Sample records for naphthols-beta

  1. Nitration of Naphthol: A Laboratory Experiment.

    ERIC Educational Resources Information Center

    Mowery, Dwight F.

    1982-01-01

    Products of nitrations, upon distillation or steam distillation, may produce dermatitis in some students. A procedure for nitration of beta-naphthol producing a relatively non-volatile product not purified by steam distillation is described. Nitration of alpha-naphthol by the same procedure yields Martius Yellow dye which dyes wool yellow or…

  2. Simultaneous analysis of naphthols, phenanthrols, and 1-hydroxypyrene in urine as biomarkers of polycyclic aromatic hydrocarbon exposure: intraindividual variance in the urinary metabolite excretion profiles caused by intervention with beta-naphthoflavone induction in the rat.

    PubMed

    Elovaara, Eivor; Väänänen, Virpi; Mikkola, Jouni

    2003-04-01

    Two fluorimetric HPLC methods are described for the quantification of naphthols, phenanthrols and 1-hydroxypyrene (1-OHP) in urine specimens obtained from male Wistar rats exposed to naphthalene, phenanthrene and pyrene. The polycyclic aromatic hydrocarbons (PAHs) were given intraperitoneally, either alone (1.0 mmol/kg body weight) or as an equimolar mixture (0.33 mmol/kg), using the same dosages for repeated treatments on week 1 and week 2. Between these treatments, PAH-metabolizing activities encoded by aryl hydrocarbon (Ah) receptor-controlled genes were induced in the rats with beta-naphthoflavone (betaNF). Chromatographic separation of five phenanthrols (1-, 2-, 3-, 4-, and 9-isomers) was accomplished using two different RP C-18 columns. Despite selective detection (programmable wavelengths), the quantification limits in the urine ranged widely: 1-OHP (0.18 microg/l) naphthol (1.5 microg/l) <1-naphthol (4 micro g/l). The relative standard deviation of the methods was good, as also was the reproducibility. The molar fraction of the dose excreted in 24-h urine as naphthols (betaNF-induced rats: naphthols, 9-phenanthrol (1- to-2-fold); 2-, 3-, and 4-phenanthrols (4- to 5-fold); 1-phenanthrol and 1-OHP (over 11-fold). The OH-metabolites were analyzed before and after enzymatic hydrolysis (beta-glucuronidase/arylsulfatase). The percentage excreted as a free phenol in urine varied for 1-OHP (2-11%), 1-naphthol (36-51%), 2-naphthol (59-65%), and the phenanthrols (29-94%). 1-Naphthyl- and 1-pyrenyl beta- d-glucuronide served as measures for the completeness of enzymatic hydrolysis. Characteristic differences observed in the urinary disposition of naphthalene, phenanthrene, and pyrene are described, as well as important factors (dose, metabolic capacity, relative urinary output) associated with biomarker validation

  3. Inhibitory effects of naphthols on the activity of mushroom tyrosinase.

    PubMed

    Lin, Yi-Fen; Hu, Yong-Hua; Jia, Yu-Long; Li, Zhi-Cong; Guo, Yun-Ji; Chen, Qing-Xi; Lin, He-Tong

    2012-01-01

    Tyrosinase (EC 1.14.18.1), a copper-containing multifunctional oxidase, was known to be a key enzyme for biosynthesis in fungi, plants and animals. In this work, the inhibition properties α-naphthol and β-naphthol toward the activity of tyrosinase have been evaluated, and the effects of α-naphthol and β-naphthol on monophenolase and diphenolase activity of tyrosinase have been investigated. The results showed that both α-naphthol and β-naphthol could potently inhibit both monophenolase activity and diphenolase activity of mushroom tyrosinase, and that β-naphthol exhibited stronger inhibitory effect against tyrosinase than α-naphthol. For monophenolase activity, β-naphthol could not only lengthen the lag time but also decrease the steady-state activity, while α-naphthol just only decreased the steady-state activity. For diphenolase activity, both α-naphthol and β-naphthol displayed revisible inhibition. Kinetic analyses showed that both α-naphthol and β-naphthol were competetive inhibitors. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Degradation of α-Naphthol by Plasma in Aqueous Solution

    NASA Astrophysics Data System (ADS)

    Gao, Jin-zhang; Hu, Zhong-ai; Wang, Xiao-yan; Hou, Jing-guo; Lu, Xiao-quan; Kang, Jing-wan

    2001-02-01

    Degradation of α-naphthol induced by plasma in aqueous solution was investigated in different initial concentration with contact glow discharge electrolysis (CGDE). The results showed that the degradation of α-naphthol obeyed the first-rate law. Some of predominant products were analyzed by a high performance liquid chromatography (HPLC). A path of α-naphthol disappearance caused by plasma was proposed according to the detected intermediate products.

  5. Peroxidase-mediated polymerization of 1-naphthol: impact of solution pH and ionic strength.

    PubMed

    Bhandari, Alok; Xu, Fangxiang; Koch, David E; Hunter, Robert P

    2009-01-01

    Peroxidase-mediated oxidation has been proposed as a treatment method for naphthol-contaminated water. However, the impact of solution chemistry on naphthol polymerization and removal has not been documented. This research investigated the impact of pH and ionic strength on peroxidase-mediated removal of 1-naphthol in completely mixed batch reactors. The impact of hydrogen peroxide to 1-naphthol ratio and activity of horseradish peroxidase was also studied. Size exclusion chromatography was used to estimate the molecular weight distribution of oligomeric products, and liquid chromatography/mass spectrometry was used to estimate product structure. Naphthol transformation decreased with ionic strength, and substrate removal was lowest at neutral pHs. Solution pH influenced the size and the composition of the oligomeric products. An equimolar ratio of H(2)O(2):naphthol was sufficient for optimal naphthol removal. Polymerization products included naphthoquinones and oligomers derived from two, three, and four naphthol molecules. Our results illustrate the importance of water chemistry when considering a peroxidase-based approach for treatment of naphthol-contaminated waters.

  6. Matrix isolation FT-IR and theoretical DFT/B3LYP spectrum of 1-naphthol.

    PubMed

    Muzomwe, Mayawila; Boeckx, Bram; Maes, Guido; Kasende, Okuma E

    2013-05-01

    The FT-IR spectrum of 1-Naphthol isolated in an argon matrix is performed and compared to the infrared spectra calculated at the DFT (B3LYP)/6-31+G(d) level for cis-1-Naphthol and trans-1-Naphthol rotamers in order to clarify the existence of both rotamers in the standard temperature. Comparison of the computed and the experimental matrix spectra reveals the presence in 1-Naphthol argon matrices in the standard temperature of both cis and trans rotameric forms of 1-Naphthol, the last predominating. The relative stability of the trans-1-Naphthol rotamer has also been supported by a fit comparison between the difference of predicted total energy (ETC) of both rotamers of 0.00195 a.u. corresponding to 5.12 kJ mol(-1) and the variation of the standard free Gibbs energy of rotamerization (ΔGr°) of 5.06 kJ mol(-1). Almost all 51 active vibrational modes of 1-Naphthol have been assigned. The stretching vibration of the OH group (νOH) appears to be the unique vibrational mode distinguishing the cis-1-NpOH rotamer from the trans-1-NpOH rotamer in FT-IR spectrum. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Adsorptive removal of 1-naphthol from water with Zeolitic imidazolate framework-67

    NASA Astrophysics Data System (ADS)

    Yan, Xinlong; Hu, Xiaoyan; Chen, Tao; Zhang, Shiyu; Zhou, Min

    2017-08-01

    1-Naphthol is widely used as an intermediate in the plastics, dyes, fibers and rubbers production areas, leading to the increasing detection of 1-naphthol in the soil and water environment, which is of particular concern due to its acute toxicity and negative environmental impacts. Considering the high surface area and good stability of ZIFs (zeolitic imidazole frameworks) material, ZIF-67 (a representative cobalt-based ZIFs material) was synthesized and applied as an adsorbent for removal of 1-naphthol from aqueous solution. The obtained ZIF-67 was characterized by XRD, TEM, XPS, N2 physisorption and TG, and the adsorption isotherm, kinetics, and regeneration of the adsorbent were studied in detail. The adsorption of 1-naphthol on ZIF-67 followed a pseudo-second-order equation kinetics and fitted Langmuir adsorption model with a maximum adsorption capacity of 339 mg/g at 313 K, which is much higher than that of the common adsorbents reported such as activated carbon and carbon nanotubes et al. The solution pH was found to be an important factor influencing the adsorption process, which could be explained by the predominant mechanism controlling the process, i.e. electrostatic attraction. In addition, the ZIF-67 showed desirable reusability toward 1-naphthol removal from alkaline aqueous solution.

  8. Utilization of Natural Zeolite from Ponorogo and Purworejo for Naphthol Substance Adsorption

    NASA Astrophysics Data System (ADS)

    Imandiani, Sundus; Indira, Christine; Johan, Anthony; Budiyono

    2018-02-01

    Indonesia has many zeolite producing areas yet untapped. Researchers developed the utilization of natural zeolites useful for the adsorption of naphthol dyes commonly found in batik waste. In this study researchers used natural zeolites from Purworejo and Ponorogo that are activated using hydrochloric acid that is used for adsorption. The purpose of this research is to know the effect of natural zeolite activation from Ponorogo and Purworejo on the effectiveness of adsorption of naphthol dyes widely used in batik industry. Natural zeolite was activated using HCl concentration of 1.3N; 1.8N; 3.2N; and 3.9N for 60 minutes. The methods are preparation of natural zeolite from Purworejo and Ponorogo, dealumination using hydrochloric acid, adsorption process of naphthol dyes using activated zeolite, and test of adsorption result with uv-vis spectrophotometry. The test results showed that the higher HCl concentration will increase adsorption capacity. This can be known from the concentration of naphthol dye which decreased both using natural zeolite Ponorogo and Purworejo. While the effectiveness of adsorption shows natural zeolite Purworejo has a greater adsorption capacity than Ponorogo with optimum conditions of dealumination using concentration HCl 3,9N.

  9. Urinary naphthol metabolites and chromosomal aberrations in 5 yr old children

    PubMed Central

    Orjuela, Manuela A.; Liu, XinHua; Miller, Rachel L.; Warburton, Dorothy; Tang, DeLiang; Jobanputra, Vaidehi; Hoepner, Lori; Suen, Ida Hui; Diaz-Carreno, Silvia; Li, Zheng; Sjodin, Andreas; Perera, Frederica P.

    2012-01-01

    Background Exposure to naphthalene, an IARC-classified possible carcinogen and polycyclic aromatic hydrocarbon (PAH), is widespread, though resulting health effects are poorly understood. Metabolites of naphthalene, 1- and 2-naphthol, are measurable in urine and are biomarkers of personal exposure. Chromosomal aberrations (CAs), including translocations, are established markers of cancer risk and a bio-dosimeter of clastogenic exposures. Although prenatal (maternal) PAH exposure predicts CAs in cord blood, few studies have examined CAs in school-age children and none has examined their association with metabolites of specific PAHs. Methods Using Whole Chromosome Paint Fluorescent in Situ Hybridization, we documented CAs including translocations, in 113 five year old urban minority children and examined their association with concurrent concentrations of PAH metabolites measured in urine. Results We report that in lymphocytes, the occurrence and frequency of CAs including translocations are associated with levels of urinary 1- and 2-naphthol. When doubling the levels of urinary naphthols, gender-adjusted Odds Ratio (OR) for CAs are 1.63 (95%CI: 1.21, 2.19) and 1.44 (95%CI: 1.02, 2.04) for 1-and 2-naphthol respectively; and for translocations: OR=1.55 (95%CI: 1.11-2.17) and 1.92 (95%CI: 1.20-3.08) for 1- and 2-naphthol respectively. Conclusion Our results demonstrate that markers of exposure to naphthalene in children are associated with translocations in a dose related manner, and that naphthalene may be a clastogen. Impact Indoor exposure to elevated levels of naphthalene is prevalent in large regions of the world. This study is the first to present an association between a marker of naphthalene exposure and a pre-carcinogenic effect in humans. PMID:22573794

  10. Simultaneous determination of 1- and 2-naphthol in human urine using on-line clean-up column-switching liquid chromatography-fluorescence detection.

    PubMed

    Preuss, Ralf; Angerer, Jürgen

    2004-03-05

    We developed a new 3-D HPLC method for on-line clean-up and simultaneous quantification of two important naphthalene metabolites, 1-naphthol and 2-naphthol, in human urine. Except an enzymatic hydrolysis no further sample pre-treatment is necessary. The metabolites are stripped from urinary matrix by on-line extraction on a restricted access material pre-column (RAM RP-8), transferred in backflush mode onto a silica-based CN-(cyano)phase column for further purification from interfering substances. By another successive column switching step both analytes are transferred with a minimum of overlapping interferences onto a C12 bonded reversed phase column with trimethylsilyl endcapping where the final separation is carried out. The entire arrangement is software controlled. Eluting analytes are quantified by fluorescence detection (227/430 nm) after an external calibration. Within a total run time of 40 min we can selectively quantify both naphthols with detection limits in the lower ppb range (1.5 and 0.5 microg/l for 1- and 2-naphthol, respectively) with excellent reliability (ensured by precision, accuracy, matrix-independency and FIOH quality assurance program participation). First results on a collective of 53 occupationally non exposed subjects showed mean levels of 11.0 microg/l (1-naphthol) and 12.9 microg/l (2-naphthol). Among smokers (n=21) a significantly elevated mean level of urinary naphthols was determined (1-naphthol: 19.2 microg/l and 2-naphthol: 23.7 microg/l) in comparison to non smokers (n=32; 1-naphthol: 5.6 microg/l, 2-naphthol: 5.6 microg/l).

  11. Isomerization of 7-oxabenzonorbornadienes into naphthols catalyzed by [RuCl(2)(CO)(3)](2).

    PubMed

    Ballantine, Melissa; Menard, Michelle L; Tam, William

    2009-10-02

    Ruthenium-catalyzed isomerization of 7-oxanorbornadienes into naphthols was investigated. Among the various ruthenium catalysts tested, [RuCl(2)(CO)(3)](2) gave the highest yields in the isomerization, and various substituted naphthols were synthesized in moderate to excellent yields. Both symmetrical and unsymmetrical 7-oxanorbornadienes were employed in the study, and moderate to excellent regioselectivities were observed.

  12. Photochemistry of 1- and 2-Naphthols and Their Water Clusters: The Role of 1 ππ*(La ) Mediated Hydrogen Transfer to Carbon Atoms.

    PubMed

    Novak, Jurica; Prlj, Antonio; Basarić, Nikola; Corminboeuf, Clémence; Došlić, Nađa

    2017-06-16

    The computational analysis of the isomer- and conformer-dependent photochemistry of 1- and 2-naphthols and their microsolvated water clusters is motivated by their very different excited state reactivities. We present evidence that 1- and 2-naphthol follow distinct excited state deactivation pathways. The deactivation of 2-naphthols, 2-naphthol water clusters, as well as of the anti conformer of 1-naphthol is mediated by the optically dark 1 πσ* state. The dynamics of the 1 πσ* surface leads to the homolytic cleavage of the OH bond. On the contrary, the excited state deactivation of syn 1-naphthol and 1-naphthol water clusters follows an uncommon reaction pathway. Upon excitation to the bright 1 ππ*(L a ) state, a highly specific excited state hydrogen transfer (ESHT) to carbon atoms C8 and C5 takes place, yielding 1,8- and 1,5-naphthoquinone methides. The ESHT pathway arises from the intrinsic electronic properties of the 1 ππ*(L a ) state of 1-naphthols. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Treatment of industrial wastewater containing Congo Red and Naphthol Green B using low-cost adsorbent.

    PubMed

    Attallah, M F; Ahmed, I M; Hamed, Mostafa M

    2013-02-01

    The present work investigates the potential use of metal hydroxides sludge (MHS) generated from hot dipping galvanizing plant for adsorption of Congo Red and Naphthol Green B dyes from aqueous solutions. Characterization of MHS included infrared and X-ray fluorescence analysis. The effect of shaking time, initial dye concentration, temperature, adsorbent dosage and pH has been investigated. The results of adsorption experiments indicate that the maximum capacity of Congo Red and Naphthol Green B dyes at equilibrium (q(e)) and percentage of removal at pH 6 are 40 mg/g, 93 %, and 10 mg/g, 52 %, respectively. Some kinetic models were used to illustrate the adsorption process of Congo Red and Naphthol Green B dyes using MHS waste. Thermodynamic parameters such as (ΔG, ΔS, and ΔH) were also determined.

  14. Enhanced transport of phenanthrene and 1-naphthol by colloidal graphene oxide nanoparticles in saturated soil.

    PubMed

    Qi, Zhichong; Hou, Lei; Zhu, Dongqiang; Ji, Rong; Chen, Wei

    2014-09-02

    With the increasing production and use of graphene oxide, the environmental implications of this new carbonaceous nanomaterial have received much attention. In this study, we found that the presence of low concentrations of graphene oxide nanoparticles (GONPs) significantly enhanced the transport of 1-naphthol in a saturated soil, but affected the transport of phenanthrene to a much smaller extent. The much stronger transport-enhancement effect on 1-naphthol was due to the significant desorption hysteresis (both thermodynamically irreversible adsorption and slow desorption kinetics) of GONP-adsorbed 1-naphthol, likely stemmed from the specific polar interactions (e.g., H-bonding) between 1-naphthol and GONPs. Increasing ionic strength or the presence of Cu(II) ion (a complexing cation) generally increased the transport-enhancement capability of GONPs, mainly by increasing the aggregation of GONPs and thus, sequestering adsorbed contaminant molecules. Interestingly, modifying GONPs with Suwannee River humic acid or sodium dodecyl sulfate had little or essentially no effect on the transport-enhancement capability of GONPs, in contrast with the previously reported profound effects of humic acids and surfactants on the transport-enhancement capability of C60 nanoparticles. Overall, the findings indicate that GONPs in the aquatic environment may serve as an effective carrier for certain organic compounds that can interact with GONPs through strong polar interactions.

  15. Protolytic dissociation of cyano derivatives of naphthol, biphenyl and phenol in the excited state: A review

    NASA Astrophysics Data System (ADS)

    Szczepanik, Beata

    2015-11-01

    The excited state proton transfer (ESPT) has been extensively studied for hydroxyarenes, phenols, naphthols, hydroxystilbenes, etc., which undergo large enhancement of acidity upon electronic excitation, thus classified as photoacids. The changes of acidic character in the excited state of cyano-substituted derivatives of phenol, hydroxybiphenyl and naphthol are reviewed in this paper. The acidity constants pKa in the ground state (S0), pKa∗ in the first singlet excited state (S1) and the change of the acidity constant in the excited state ΔpKa for the discussed compounds are summarized and compared. The results of the acidity studies show, that the "electro-withdrawing" CN group in the molecules of naphthol, hydroxybiphenyl and phenol causes dramatic increase of their acidity in the excited state in comparison to the ground state. This effect is greatest for the cyanonaphthols (the doubly substituted CN derivatives are almost as strong as a mineral acid in the excited state), comparable for cyanobiphenyls, and smaller for phenol derivatives. The increase of acidity enables proton transfer to various organic solvents, and the investigation of ESPT can be extended to a variety of solvents besides water. The results of theoretical investigations were also presented and used for understanding the protolytic equilibria of cyano derivatives of naphthol, hydroxybiphenyl and phenol.

  16. Production and optimization of bamboo hydrochars for adsorption of Congo red and 2-naphthol.

    PubMed

    Li, Yin; Meas, Arun; Shan, Shengdao; Yang, Ruiqin; Gai, Xikun

    2016-05-01

    Twelve hydrochars were produced from bamboo sawdust for adsorption of Congo red and 2-naphthol. The bamboo hydrochars have Brunauer-Emmett-Teller (BET) surface areas ranging from 2.63m(2)/g to 43.07m(2)/g, average pore diameters from 3.05nm to 3.83nm, pore volumes between 0.02cm(3)/g and 0.53cm(3)/g, and the surfaces of the hydrochars have diverse functional groups. The physico-chemical properties of the hydrochars critically depend on the hydrothermal conditions. All the hydrochars can adsorb Congo red and 2-naphthol from aqueous solutions, the largest adsorption capacity for Congo red is 33.7mg/g at the equilibrium concentration of 0.1mg/mL at 25°C, and the highest adsorption amount for 2-naphthol is 12.2mg/g at 25°C and 0.1mg/mL. Freundlich model can describe the adsorption isotherms of the both adsorbates slightly better than Langmuir model. These results provide a reference to the production and use of hydrochars as potential adsorbents in wastewater treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Enhanced degradation of 1-naphthol in landfill leachate using Arthrobacter sp.

    PubMed

    Hu, Wenyong; Min, Xiaobo; Li, Xinyu; Liu, Jingyi; Yu, Haibin; Yang, Yuan; Zhang, Jiachao; Luo, Lin; Chai, Liyuan; Zhou, Yaoyu

    2017-12-06

    Arthrobacter sp. named as JY5-1 isolated from contaminated soil of a coking plant can degrade 1-naphthol as the sole carbon source. Through identification of species, analysis of the optimal degradation condition and kinetic equation, the degradation characteristic of Arthrobacter sp. JY5-1 was obtained. Later, the acclimated strain was added into the bio-reactor to observe treatment performance of landfill leachate. The results showed that the optimal conditions for strain JY5-1 biodegradation in the study were pH 7.0 and 30 o C. The bio-reactor operation experiment declared that Arthrobacter sp. JY5-1 had a strengthened effect on COD removal of landfill leachate. Moreover, the efficiency of COD removal could be high and stable when JY5-1 was accumulated as a biofilm together with active sludge. These results demonstrate that adding 1-naphthol-degrading strain JY5-1 is a feasible technique for the enhanced treatment of sanitary landfill leachate, providing theoretical support for engineering utilization.

  18. Charge Redistribution in the β-NAPHTHOL-WATER Complex as Measured by High Resolution Stark Spectroscopy in the Gas Phase.

    NASA Astrophysics Data System (ADS)

    Fleisher, Adam J.; Pratt, David W.; Cembran, Alessandro; Gao, Jiali

    2010-06-01

    The extensively studied photoacid β-naphthol exhibits a large decrease in pKa upon irradiation with ultraviolet light, in the condensed phase. β-naphthol is almost 10 million times more acidic in the excited electronic state, compared to the ground state. Motivated by this fact, we report here the measurement of the electronic dipole moments of the β-naphthol-water complex in both electronic states, from which estimates of the charge transfer from solute to solvent in both states will be made. Comparisons to ab initio and density functional theory calculations will also be reported. N. Mataga and T. Kubota, Molecular Interactions and Electronic Spectra (Marcel Dekker, New York, 1970). Y. Mo, J. Gao, S.D. Peyerimhoff, J. Chem. Phys. 112, 5530 (2000).

  19. Dermal Exposure to Jet Fuel JP-8 Significantly Contributes to the Production of Urinary Naphthols in Fuel-Cell Maintenance Workers

    PubMed Central

    Chao, Yi-Chun E.; Kupper, Lawrence L.; Serdar, Berrin; Egeghy, Peter P.; Rappaport, Stephen M.; Nylander-French, Leena A.

    2006-01-01

    Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure. PMID:16451852

  20. Dermal exposure to jet fuel JP-8 significantly contributes to the production of urinary naphthols in fuel-cell maintenance workers.

    PubMed

    Chao, Yi-Chun E; Kupper, Lawrence L; Serdar, Berrin; Egeghy, Peter P; Rappaport, Stephen M; Nylander-French, Leena A

    2006-02-01

    Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure.

  1. Quantitative cytochemistry of nuclear and cytoplasmic proteins using the Naphthol Yellow S and dinitrofluorobenzene staining methods.

    PubMed

    Tas, J; James, J

    1981-09-01

    The 'total protein staining' of biological specimens with the electrostatically binding Naphthol Yellow S or the covalently binding dinitrofluorobenzene must be interpreted as methods which yield data on the specific amino acid pool of the proteins concerned. Both dyes bind to certain free amino-acid side-chains, giving different dye--protein ratios for various proteins. In the presence of DNA, dinitrofluorobenzene stains all proteins present in cell nuclei, whereas Naphthol Yellow S only stains the majority of the non-histone proteins. When protein staining methods are combined with the Feulgen--Pararosanile (SO2) procedure for DNA, decreased Feulgen--DNA contents were measured in dinitrofluorobenzene-stained isolated nuclei and lymphocytes.

  2. A novel copper complex supported on magnetic reduced graphene oxide: an efficient and green nanocatalyst for the synthesis of 1-amidoalkyl-2-naphthol derivatives

    NASA Astrophysics Data System (ADS)

    Kooti, M.; Karimi, M.; Nasiri, E.

    2018-02-01

    A new Cu(II) complex supported on magnetic reduced graphene oxide was prepared and characterized by various techniques, such as FT-IR, XRD, SEM, EDX, TEM, TGA, BET, ICP, and VSM. The synthesized nanocomposite, which has size distribution of 25-30 nm, was employed as catalyst in one-pot synthesis of 1-amidoalkyl-2-naphthols via three-component condensation reaction of amides, aromatic aldehydes, and 2-naphthol, under solvent-free conditions. The introduced catalysis procedure for the synthesis of 1-amidoalkyl-2-naphthol derivatives offers several advantages namely, short reaction times, high yields, facile recyclability, and cost effectiveness. [Figure not available: see fulltext.

  3. Physicochemical properties of sorbents based on silica gel modified by 1-phenylazo-2-naphtholic complexes of transition metals

    NASA Astrophysics Data System (ADS)

    Makarycheva, A. I.; Slizhov, Yu. G.

    2017-09-01

    Gas chromatography sorbents based on Silokhrom C80 and modified by 1-phenylazo-2-naphtholic complexes of 3 d metals (Co(II), Ni(II), Cu(II)) are obtained. Their structural, chromatographic, and sorption characteristics are investigated. It is found that modifying them with 1-phenylazo-2-naphthols of transition metals has a considerable effect on the chromatographic polarity and selectivity of sorption materials. The prospects for the practical application of the obtained sorbents are demonstrated by experiments on the gas chromatographic separation of mixtures of different classes of organic compounds.

  4. A SIMPLE HPLC METHOD FOR DETECTING CARBARYL AND 1-NAPHTHOL IN BIOLOGICAL TISSUES.

    EPA Science Inventory

    Carbamates are a class of pesticide used in both agricultural and residential applications. A simple HPLC method for detecting Carb and its metabolite 1-naphthol (Naph) in tissues was developed to try to correlate tissue levels of carbaryl (Carb) (a prototypical carbamate) with c...

  5. Methylation of 2-Naphthol Using Dimethyl Carbonate under Continuous-Flow Gas-Phase Conditions

    ERIC Educational Resources Information Center

    Tundo, Pietro; Rosamilia, Anthony E.; Arico, Fabio

    2010-01-01

    This experiment investigates the methylation of 2-naphthol with dimethyl carbonate. The volatility of the substrates, products, and co-products allows the reaction to be performed using a continuous-flow gas-phase setup at ambient pressure. The reaction uses catalytic quantities of base, achieves high conversion, produces little waste, and…

  6. Annulation of β-naphthols and 4-hydroxycoumarins with vinylsulfonium salts: synthesis of dihydrofuran derivatives.

    PubMed

    Chen, Zi-Cong; Tong, Lang; Du, Zhi-Bo; Mao, Zhi-Feng; Zhang, Xue-Jing; Zou, Yong; Yan, Ming

    2018-04-18

    A new synthetic approach to dihydrofuran derivatives via the annulation reaction of β-naphthols and 4-hydroxycoumarins with vinylsulfonium salts has been developed. A variety of dihydrofuran derivatives were prepared in moderate to good yields under mild conditions. The products could be readily transformed to the corresponding furans via the dehydrogenation with DDQ.

  7. Study of enhanced photogalvanic effect of Naphthol Green B in natural sunlight

    NASA Astrophysics Data System (ADS)

    Koli, Pooran

    2015-07-01

    The photogalvanic cells based on Naphthol Green B sensitizer-Fructose reductant-Sodium Lauryl Sulphate surfactant has been studied in natural sunlight. The cell has been found workable in natural sunlight with greatly enhanced optimum cell performance. The 1159.2 μW power, 4500 μA short-circuit current, 1070 mV open-circuit potential, 14.49% efficiency and 240 min storage capacity (as half change time) has been observed in optimum cell fabrication conditions.

  8. Functionalized carbon dot adorned coconut shell char derived green catalysts for the rapid synthesis of amidoalkyl naphthols.

    PubMed

    Narayanan, Divya P; Cherikallinmel, Sudha Kochiyil; Sankaran, Sugunan; Narayanan, Binitha N

    2018-06-15

    A one pot synthesis of carbon dot incorporated porous coconut shell char derived sulphonated catalyst is reported here for the first time and is effectively used in the multicomponent synthesis of amidoalkyl naphthol. Macroporous nature of the char is revealed from scanning electron microscopic (SEM) analysis, whereas the dispersion of carbon dots (CDs) on the porous coconut shell char is confirmed from the high resolution transmission electron microscopic (HRTEM) analysis. Fluorescence emission spectrum further confirmed the presence of CDs in the catalyst. Fourier-transform infrared (FTIR) spectral analysis of the materials indicated that sulphonation occurred both to the CD and to the porous char. X-ray photo electron spectroscopic (XPS) analysis of the most active catalyst confirmed the presence of both sulphonic acid and carboxylic acid groups in the catalyst. The coconut shell char derived materials prepared by varying the amount of H 2 SO 4 are successfully utilized as efficient alternative green catalysts for the multicomponent reaction, where excellent activity in amidoalkyl naphthol synthesis is obtained within short periods under solvent free reaction conditions. A maximum yield of 98% is obtained in the synthesis of N-[Phenyl-(2-hydroxy-naphthalen-1-yl)-methyl]-benzamide, the representative amidoalkyl naphthol, with the best catalyst within 3 min of reaction. The catalyst is highly active for the reactions carried out with varieties of aldehydes and amides with a product yield in the range of 88-98%. The best catalyst system retained more than 90% of its initial activity even upto 6 th repeated run. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Naphthol AS-BI (7-bromo-3-hydroxy-2-naphtho-o-anisidine) phosphatase and naphthol AS-BI. beta. -D-glucuronidase in Chinese hamster ovary cells: biochemical and flow cytometric studies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dolbeare, F.A.; Phares, W.

    1979-01-01

    Conditions for the biochemical and flow cytometric assay of 7-bromo-3-hydroxy-2-naphtho-o-anisidine phosphatase and ..beta..-D-glucuronidase activities in Chinese hamster ovary cells were studied. In the biochemical assays, the pH optimum for the phosphatase activity was pH 4.6 with a Km of 10/sup -5/ M; the pH optimum for ..beta..-D-glucuronidase activity was pH 5.0 with a Km of 2 x 10/sup -5/ M. For intact cells the derived constants were 3 to 10 times higher. The rate of hydrolysis of both substrates was also examined by flow cytometry. Cellular fluorescence increased linearly for only about 15 min. Diffusion of the fluorescent product probablymore » caused nonlinearity of the fluorescence increase and was demonstrated by mixing cells incubated with substrate with those that had not been incubated. After 15 min, cells that had not been exposed previously to product or substrate contained the fluorescent product. Cells fractionated into size classes by centrifugal elutriation also were analyzed by flow cytometry for ..beta..-D-glucuronidase activity. The activity increased linearly with the increase in cell size corresponding to the progression from G/sub 1/ through S and into G/sub 2/-M phases of the cell cycle.« less

  10. Naphthol AS-E Phosphate Inhibits the Activity of the Transcription Factor Myb by Blocking the Interaction with the KIX Domain of the Coactivator p300.

    PubMed

    Uttarkar, Sagar; Dukare, Sandeep; Bopp, Bertan; Goblirsch, Michael; Jose, Joachim; Klempnauer, Karl-Heinz

    2015-06-01

    The transcription factor c-Myb is highly expressed in hematopoietic progenitor cells and controls the transcription of genes important for lineage determination, cell proliferation, and differentiation. Deregulation of c-Myb has been implicated in the development of leukemia and certain other types of human cancer. c-Myb activity is highly dependent on the interaction of the c-Myb with the KIX domain of the coactivator p300, making the disruption of this interaction a reasonable strategy for the development of Myb inhibitors. Here, we have used bacterial Autodisplay to develop an in vitro binding assay that mimics the interaction of Myb and the KIX domain of p300. We have used this binding assay to investigate the potential of Naphthol AS-E phosphate, a compound known to bind to the KIX domain, to disrupt the interaction between Myb and p300. Our data show that Naphthol AS-E phosphate interferes with the Myb-KIX interaction in vitro and inhibits Myb activity in vivo. By using several human leukemia cell lines, we demonstrate that Naphthol AS-E phosphate suppresses the expression of Myb target genes and induces myeloid differentiation and apoptosis. Our work identifies Naphthol AS-E phosphate as the first low molecular weight compound that inhibits Myb activity by disrupting its interaction with p300, and suggests that inhibition of the Myb-KIX interaction might be a useful strategy for the treatment of leukemia and other tumors caused by deregulated c-Myb. ©2015 American Association for Cancer Research.

  11. Oxidation reactions of 1- and 2-naphthols: an experimental and theoretical study.

    PubMed

    Sreekanth, R; Prasanthkumar, Kavanal P; Sunil Paul, M M; Aravind, Usha K; Aravindakumar, C T

    2013-11-07

    The transients formed during the reactions of oxidizing radicals with 1-naphthol (1) and 2-naphthol (2) in aqueous medium have been investigated by pulse radiolysis with detection by absorption spectroscopy and density functional theory (DFT) calculations. The transient spectra formed on hydroxyl radical ((•)OH) reactions of 1 and 2 exhibited λ(max) at 340 and 350 nm at neutral pH. The rate constants of the (•)OH reactions of 1 (2) were determined from build-up kinetics at λ(max) of the transients as (9.63 ± 0.04) × 10(9) M(-1) s(-1) ((7.31 ± 0.11) × 10(9) M(-1) s(-1)). DFT calculations using the B3LYP/6-31+G(d,p) method have been performed to locate favorable reaction sites in both 1 and 2 and identification of the pertinent transients responsible for experimental results. Calculations demonstrated that (•)OH additions can occur mostly at C1 and C4 positions of 1, and at C1 and C8 positions of 2. Among several isomeric (•)OH adducts possible, the C1 adduct was found to be energetically most stable both in 1 and 2. Time-dependent density functional theory (TDDFT) calculations in the solution phase has shown that the experimental spectrum of 1 was mainly attributed by 1a4 (kinetically driven (•)OH-adduct) formed via the addition of (•)OH at the C4 position which was 0.73 kcal/mol endergonic compared to 1a1 (thermodynamic (•)OH adduct), whereas 2a1 (thermodynamic/kinetic (•)OH-adduct) was mainly responsible for the experimental spectrum of 2. Naphthoxyl radicals of 1 and 2 have been predicted as the transient formed in the reaction of (•)OH at basic pH. In addition, the same transient species resulted from the reactions of oxide radical ion (O(•-)) at pH ≈ 13 and azide radical (N3(•)) at pH 7 with 1 and 2. Further, UV photolysis of aqueous solutions of 1 and 2 containing H2O2 (UV/H2O2) were used for the (•)OH induced oxidation product formations up on 60% degradations of 1 and 2; profiling of the oxidation products were performed by

  12. Transplacental transfer of 2-naphthol in human placenta.

    PubMed

    Mirghani, Hisham; Osman, Nawal; Dhanasekaran, Subramanian; Elbiss, Hassan M; Bekdache, Gharid

    2015-01-01

    To determine the transfer of 2-naphthol (2-NPH) in fullterm human placental tissues. Six placentas were studied. The ex-vivo dual closed-loop human placental cotyledon perfusion model was used. 2-NPH was added to the perfusate in the maternal compartment. Samples were obtained from the maternal and fetal up to 360 min measuring. The mean fetal weight was 2880 ± 304.2 g. Mean perfused cotyledon weight was 26.3 (±5.5) g. All unperfused placental tissue samples contained NPH with a mean level of 7.98 (±1.73) μg\\g compared to a mean of 15.58 (±4.53) μg\\g after 360 min perfusion. A rapid drop in maternal 2-NPH concentration was observed; from 5.54 μg\\g in the first 15 min and 13.8 μg\\g in 360 min. The fetal side increased from 0.65 μg\\g in the initial 15 min to 1.5 μg\\g in 360 min. The transfer rate of NPH was much lower than that of antipyrine. 2-NPH has the ability to rapidly across the placenta from the maternal to the fetal compartment within 15 min. The placenta seems to play a role in limiting the passage of 2-NPH in the fetal compartment.

  13. Doping of polyaniline with 6-cyano-2-naphthol.

    PubMed

    Das, Debasree; Datta, Anindya; Contractor, Aliasgar Q

    2014-11-13

    The conductivity of polyaniline (PANI) is ascribed to its emeraldine salt (PANI-ES), which is formed by protonation of its emeraldine base (PANI-EB) by acids. Generally, mineral acids are used for this purpose, but the use of dopants and additives to maintain the required acidity provides an alternative method to the preparation of PANI-ES. The present work attempts to achieve the protonation by the use of a weak organic acid, namely, 6-cyano-2-naphthol (6CN2), which is generally used as a superphotoacid, as its excited state pKa is significantly smaller than its ground state pKa. The question here is if the protonation of the aniline moieties in PANI takes place and if it does, whether it takes place by dissociation of the ground state or the excited state of 6CN2. Room temperature conductance measurements were carried out to see the effect of doping. The formation of PANI-ES from PANI-EB has been monitored by UV-vis spectrophotometry. When a polar counterion is inserted into the polymer matrix, it changes the environment of the nearby chains by introducing defects, reorganization of charges as a result of interaction with the polymer. Morphological investigation was done using optical microscopy, field emission gun scanning electron microscopy (FEGSEM), and field emission gun transmission electron microscopy FEGTEM. The influence of 6CN2 on the crystallinity of the polymer was determined by X-ray diffraction (XRD).

  14. Phenol-quinone tautomerism in (arylazo)naphthols and the analogous Schiff bases: benchmark calculations.

    PubMed

    Ali, S Tahir; Antonov, Liudmil; Fabian, Walter M F

    2014-01-30

    Tautomerization energies of a series of isomeric [(4-R-phenyl)azo]naphthols and the analogous Schiff bases (R = N(CH3)2, OCH3, H, CN, NO2) are calculated by LPNO-CEPA/1-CBS using the def2-TZVPP and def2-QZVPP basis sets for extrapolation. The performance of various density functionals (B3LYP, M06-2X, PW6B95, B2PLYP, mPW2PLYP, PWPB95) as well as MP2 and SCS-MP2 is evaluated against these results. M06-2X and SCS-MP2 yield results close to the LPNO-CEPA/1-CBS values. Solvent effects (CCl4, CHCl3, CH3CN, and CH3OH) are treated by a variety of bulk solvation models (SM8, IEFPCM, COSMO, PBF, and SMD) as well as explicit solvation (Monte Carlo free energy perturbation using the OPLSAA force field).

  15. Copper/H2O2-mediated oxidation of 2'-deoxyguanosine in the presence of 2-naphthol leads to the formation of two distinct isomeric adducts.

    PubMed

    Fleming, Aaron M; Kannan, Arunkumar; Muller, James G; Liao, Yi; Burrows, Cynthia J

    2011-10-07

    Exposure of cells to phenolic compounds through exogenous and endogenous sources can lead to deleterious effects via nucleobase modifications of DNA occurring under oxidative conditions. 2'-Deoxyguanosine (dG) is the most electron rich of the four canonical bases and includes many nucleophilic sites; it is also susceptible to oxidation with numerous reactive oxygen species. In these studies, dG was allowed to react with 2-naphthol in the presence of copper or iron salts yielding two principal isomeric products. Spectroscopic analysis and reactions with alkylated nucleosides support the assignment of compound 1a/1b as a pair of atropisomer N(2) adducts and compound 2a/2b as a diastereomeric mixture of tricyclic [4.3.3.0] adducts. Both products are the result of an overall four-electron oxidation process and consequently have the same masses, though drastically different structures, providing mechanistic insight into their formation. Thus, dG alkylation by 2-naphthol under oxidative conditions yields products whose structural properties are altered, leading to potentially mutagenic effects in genomic DNA.

  16. Piper-betle-shaped nano-S-catalyzed synthesis of 1-amidoalkyl-2-naphthols under solvent-free reaction condition: a greener "nanoparticle-catalyzed organic synthesis enhancement" approach.

    PubMed

    Das, Vijay K; Borah, Madhurjya; Thakur, Ashim J

    2013-04-05

    Nano-S prepared by an annealing process showed excellent catalytic activity for the synthesis of 1-amidoalkyl-2-naphthols under solvent-free reaction condition at 50 °C. The catalyst could be reused up to the fifth cycle without loss in its action. The green-ness of the present protocol was also measured using green metrics drawing its superiority.

  17. Catalytic performance of Metal-Organic-Frameworks vs. extra-large pore zeolite UTL in condensation reactions

    PubMed Central

    Shamzhy, Mariya; Opanasenko, Maksym; Shvets, Oleksiy; Čejka, Jiří

    2013-01-01

    Catalytic behavior of isomorphously substituted B-, Al-, Ga-, and Fe-containing extra-large pore UTL zeolites was investigated in Knoevenagel condensation involving aldehydes, Pechmann condensation of 1-naphthol with ethylacetoacetate, and Prins reaction of β-pinene with formaldehyde and compared with large-pore aluminosilicate zeolite beta and representative Metal-Organic-Frameworks Cu3(BTC)2 and Fe(BTC). The yield of the target product over the investigated catalysts in Knoevenagel condensation increases in the following sequence: (Al)beta < (Al)UTL < (Ga)UTL < (Fe)UTL < Fe(BTC) < (B)UTL < Cu3(BTC)2 being mainly related to the improving selectivity with decreasing strength of active sites of the individual catalysts. The catalytic performance of Fe(BTC), containing the highest concentration of Lewis acid sites of the appropriate strength is superior over large-pore zeolite (Al)beta and B-, Al-, Ga-, Fe-substituted extra-large pore zeolites UTL in Prins reaction of β-pinene with formaldehyde and Pechmann condensation of 1-naphthol with ethylacetoacetate. PMID:24790940

  18. Static and dynamic properties of 1,1'-bi-2-naphthol and its conjugated acids and bases.

    PubMed

    Alkorta, Ibon; Cancedda, Céline; Cocinero, Emilio José; Dávalos, Juan Z; Ecija, Patrica; Elguero, José; González, Javier; Lesarri, Alberto; Ramos, Rocio; Reviriego, Felipe; Roussel, Christian; Uriarte, Iciar; Vanthuyne, Nicolas

    2014-11-03

    Several convergent techniques were used to characterize 1,1'-bi-2-naphthol (BINOL) and some of its properties. Its acidity in the gas-phase, from neutral species to monoanion, was measured by mass spectrometry. The conformation and structure of BINOL in the gas phase was determined by microwave rotational spectroscopy. NMR experiments in fluorosulfonic acid established that BINOL was monoprotonated on one of the hydroxyl oxygen atoms. The enantiomerization barriers reported in the literature for BINOL under neutral, basic, and acid conditions were analyzed with regard to the species involved. Finally, DFT calculations allowed all of these results to be gathered in a coherent picture of the BINOL structure. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Naphthol-based fluorescent sensors for aluminium ion and application to bioimaging

    NASA Astrophysics Data System (ADS)

    Liu, Bin; Wang, Pan-feng; Chai, Jie; Hu, Xiang-quan; Gao, Tingting; Chao, Jian-bin; Chen, Ting-gui; Yang, Bin-sheng

    2016-11-01

    Three naphthol Schiff base-type fluorescent sensors, 1,3-Bis(2-hydroxy-1-naphthylideneamino)propane (L1), 1,3-Bis(1-naphthylideneamino)-2-hydroxypropane (L2) and 1,3-Bis(2-hydroxy-1-naphthylideneamino)-2-hydroxypropane (L3), have been synthesized. Their recognition abilities for Al3 + are studied by fluorescence spectra. Coordination with Al3 + inhibited the Cdbnd N isomerization of Schiff base which intensely increase the fluorescence of L1-L3. Possessing a suitable space coordination structure, L3 is a best selective probe for Al3 + over other metal ions in MeOH-HEPES buffer (3/7, V/V, pH = 6.6, 25 °C, λem = 435 nm). A turn-on ratio over 140-fold is triggered with the addition of 1.0 equiv. Al3 + to L3. The binding constant Ka of L3-Al3 + is found to be 1.01 × 106.5 M- 1 in a 1:1 complex mode. The detection limit for Al3 + is 0.05 μM. Theoretical calculations have also been included in support of the configuration of the L3-Al3 + complex. Importantly, the probe L3 has been successfully used for fluorescence imaging in colon cancer SW480 cells.

  20. Selenium-mediated synthesis of biaryls through rearrangement.

    PubMed

    Shahzad, Sohail A; Vivant, Clotilde; Wirth, Thomas

    2010-03-19

    A new cyclization of beta-keto ester substituted stilbene derivatives using selenium electrophiles in the presence of Lewis acids is described. Substituted naphthols are obtained through cyclization and subsequent 1,2-rearrangement of aryl groups under very mild reaction conditions.

  1. Combination of Aryl Diselenides/Hydrogen Peroxide and Carbon Nanotube-Rhodium Nanohybrid for Naphthols Oxidation: An Efficient Route towards Trypanocidal Quinones.

    PubMed

    de Carvalho, Renato L; Jardim, Guilherme A M; Santos, Augusto; Araujo, Maria H; Oliveira, Willian X C; Bombaça, Ana Cristina; Menna-Barreto, Rubem F S; Gopi, Elumalai; Gravel, Edmond; Doris, Eric; da Silva Júnior, Eufrânio Nunes

    2018-06-14

    We report a combination of aryl diselenides/hydrogen peroxide and carbon nanotube-rhodium nanohybrid for naphthols oxidation towards synthesis of 1,4-naphthoquinones and evaluation of their relevant trypanocidal activity. Under a combination of (PhSe)2/H2O2 in the presence of O2 in i-PrOH/Hexane, several benzenoid (A-ring) substituted quinones were prepared in moderate to high yields. We also studied the contribution of RhCNT as co-catalyst in this process and, in some cases, yields were improved. This method provides an efficient and versatile alternative for preparing A-ring modified naphthoquinonoid compounds with relevant biological profile. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Photocatalytic degradation of the diazo dye naphthol blue black in water using MWCNT/Gd,N,S-TiO2 nanocomposites under simulated solar light.

    PubMed

    Mamba, Gcina; Mbianda, Xavier Yangkou; Mishra, Ajay Kumar

    2015-07-01

    A simple sol-gel method was employed to prepare gadolinium, nitrogen and sulphur tridoped titania decorated on oxidised multiwalled carbon nanotubes (MWCNT/Gd,N,S-TiO2), using titanium (IV) butoxide and thiourea as titanium and nitrogen and sulphur source, respectively. Samples of varying gadolinium loadings (0.2%, 0.6%, 1.0% and 3.0% Gd3+) relative to titania were prepared to investigate the effect of gadolinium loading and the amounts of carbon nanotubes, nitrogen and sulphur were kept constant for all the samples. Furthermore, the prepared nanocomposites were evaluated for the degradation of naphthol blue black (NBB) in water under simulated solar light irradiation. Higher degradation efficiency (95.7%) was recorded for the MWCNT/Gd,N,S-TiO2 (0.6% Gd) nanocomposites. The higher photocatalytic activity is attributed to the combined effect of improved visible light absorption and charge separation due to the synergistic effect of Gd, MWCNTs, N, S and TiO2. Total organic carbon (TOC) analysis revealed a higher degree of complete mineralisation of naphthol blue black (78.0% TOC removal) which minimises the possible formation of toxic degradation by-products such as the aromatic amines. The MWCNT/Gd,N,S-TiO2 (0.6% Gd) was fairly stable and could be re-used for five times, reaching a maximum degradation efficiency of 91.8% after the five cycles. Copyright © 2015. Published by Elsevier B.V.

  3. Spectrophotometric Determination of Nitrogen Oxides in the Air with 2-N-Ethyl-5-Naphthol-7-Sulfonic Acid

    NASA Astrophysics Data System (ADS)

    Huang, Y.; Shi, W.; Zhang, C.; Wen, H.

    2017-09-01

    For the determination of nitrogen oxides in the air, the structure of diazo and coupling compounds was studied and tested by experiments. The conditions and methods of diazo and coupling reactions were investigated. Furthermore, a spectrophotometric method using sulfanilamide as a diazo compound and 2-N-ethyl-5-naphthol-7-sulfonic acid (N-ethyl J acid) as a coupling compound was proposed. The maximum absorption wavelength of sulfanilamide-Nethyl J acid azo compound was at 478 nm. The molar absorptivity was 4.31 × 104 L/(mol × cm) with a recovery of 98.7-100.9% and RSD of 1.85%. For nitrogen oxides, the determinate limit of this measurement was 0.015 mg/m3 and the determinate range 0.024-2.0 mg/m3. Moreover, a high degree of correlation was observed between the results obtained by the proposed method and the standard methods. The proposed method can be easily applied to determine nitrogen oxides in the air.

  4. Ultrasound-Assisted Synthesis of Titania Nanoparticles, Characterization of Their Thin Films, and Activity in Photooxidation of β-Naphthol

    NASA Astrophysics Data System (ADS)

    Hurain, Syyeda Sana; Habib, Amir; Hussain, Syed Muzammil; Ul-Haq, Noaman

    2015-11-01

    Nanosized titania (TiO2) films and powders were prepared from titanium isopropoxide by ultrasonication then ultrasonic aerosol-assisted chemical vapor deposition (UAACVD). X-ray diffraction (XRD), used to study the crystal structure, phase, and crystallite size of TiO2 samples annealed at 500°C, revealed anatase was the main crystalline phase. Scanning electron microscopy and atomic force microscopy revealed the quasi-spherical morphology of the TiO2 nanoparticles; average size distribution was in the range 20-35 nm. Ultraviolet-visible spectroscopy was used to evaluate the photocatalytic activity of the anatase TiO2, on the basis of efficiency of degradation of β-naphthol. Pure TiO2 nanoparticles synthesized by use of sonication-UAACVD then calcination at 500°C enabled effective photodegradation under UV light. This method of synthesis of TiO2 is superior to the reflux-UAACVD method with titanium isopropoxide as precursor.

  5. Application of 1-(2-pyridylazo)-2-naphthol-modified nanoporous silica as a technique in simultaneous trace monitoring and removal of toxic heavy metals in food and water samples.

    PubMed

    Abolhasani, Jafar; Behbahani, Mohammad

    2015-01-01

    Solid-phase extraction is one the most useful and efficient techniques for sample preparation, purification, cleanup, preconcentration, and determination of heavy metals at trace levels. In this paper, functionalized MCM-48 nanoporous silica with 1-(2-pyridylazo)-2-naphthol was applied for trace determination of copper, lead, cadmium, and nickel in water and seafood samples. The experimental conditions such as pH, sample and eluent flow rate, type, concentration and volume of the eluent, breakthrough volume, and effect of coexisting ions were optimized for efficient solid-phase extraction of trace heavy metals in different water and seafood samples. The content of solutions containing the mentioned heavy metals was determined by flame atomic absorption spectrometry (FAAS), and the limits of detection were 0.3, 0.4, 0.6, and 0.9 ng mL(-1) for cadmium, copper, nickel, and lead, respectively. Recoveries and precisions were >98.0 and <4%, respectively. The adsorption capacity of the modified nanoporous silica was 178 mg g(-1) for cadmium, 110 mg g(-1) for copper, 98 mg g(-1) for nickel, and 210 mg g(-1) for lead, respectively. The functionalized MCM-48 nanoporous silica with 1-(2-pyridylazo)-2-naphthol was characterized by thermogravimetry analysis (TGA), differential thermal analysis (DTA), transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FT-IR), X-ray diffraction (XRD), elemental analysis (CHN), and N2 adsorption surface area measurement.

  6. Internal Dynamics of Water Attached to a Photoacidic Substrate: High Resolution Electronic Spectroscopy of β-NAPHTHOL-WATER in the Gas Phase.

    NASA Astrophysics Data System (ADS)

    Fleisher, Adam J.; Young, Justin W.; Pratt, David W.

    2010-06-01

    An understanding of the structure and internal dynamics of water attached to the photoacid β-naphthol is attainable through rotationally resolved electronic spectroscopy. Here, we present rotational constants for the 1:1 acid-base cluster in both S0 and S1, which provide the location of water within the cluster, as well as the barrier height to internal rotation of water in each electronic state. The barrier height decreases slightly upon excitation, from 206 wn in S0, to 182 wn in S1. There is also little evidence of a large change in water location, orientation, or overall hydrogen bond length upon irradiation with UV light. Thus, a single water molecule has relatively little affect on the substrate photo-acidity measured in the liquid phase.

  7. MOON for neutrino-less {beta}{beta} decays and {beta}{beta} nuclear matrix elements

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ejiri, H.

    2009-11-09

    The MOON project aims at spectroscopic 0v{beta}{beta} studies with the v-mass sensitivity of 100-30 meV by measuring two beta rays from {sup 100}Mo and/or {sup 82}Se. The detector is a compact super-module of multi-layer PL scintillator plates. R and D works made by the pro to-type MOON-1 and the small PL plate show the possible energy resolution of around {sigma}{approx}2.2%, as required for the mass sensitivity. Nuclear matrix elements M{sup 2v} for 2v{beta}{beta} are shown to be given by the sum {sigma}{sub L}M{sub k} of the 2v{beta}{beta} matrix elements M{sub k} through intermediate quasi-particle states in the Fermi-surface, where Mimore » is obtained experimentally by using the GT(J{sup {pi}} = 1{sup +}) matrix elements of M{sub i}(k) and M{sub f}(k) for the successive single-{beta} transitions through the k-th intermediate state.« less

  8. Synthesis, and spectroscopic studies of charge transfer complex of 1,2-dimethylimidazole as an electron donor with π-acceptor 2,4-dinitro-1-naphthol in different polar solvents

    NASA Astrophysics Data System (ADS)

    Miyan, Lal; Khan, Ishaat M.; Ahmad, Afaq

    2015-07-01

    The charge transfer (CT) complex of 1,2-dimethylimidazole (DMI) as an electron donor with π acceptor 2,4-dinitro-1-naphthol (DNN) has been studied spectrophotometrically in different solvents like chloroform, acetonitrile, methanol, methylene chloride, etc. at room temperature. The CT complex which is formed through the transfer of lone pair electrons from DMI to DNN exhibits well resolved CT bands and the regions of these bands were remarkably different from those of the donor and acceptor. The stoichiometry of the CT complex was found to be 1:1 by a straight-line method between donor and acceptor with maximum absorption bands. The novel CT complex has been characterized by FTIR, TGA-DTA, powder XRD, 1H NMR and 13C NMR spectroscopic techniques. The Benesi-Hildebrand equation has been used to determine the formation constant (KCT), molar extinction coefficient (εCT), standard gibbs free energy (ΔG°) and other physical parameters of the CT complex. The formation constant recorded higher values and molar extinction coefficient recorded lower values in chloroform compared with methylene chloride, methanol and acetonitrile, confirming the strong interaction between the molecular orbital's of donor and acceptor in the ground state in less polar solvent. This CT complex has been studied by absorption spectra of donor 1,2-dimethylimidazole (DMI) and acceptor 2,4-dinitro-1-naphthol (DNN) by using the spectrophotometric technique in various solvents at room temperature.

  9. Preparation of sewage sludge based activated carbon by using Fenton's reagent and their use in 2-naphthol adsorption.

    PubMed

    Gu, Lin; Wang, Yachen; Zhu, Nanwen; Zhang, Daofang; Huang, Shouqiang; Yuan, Haiping; Lou, Ziyang; Wang, Miaolin

    2013-10-01

    In this study, Fenton's reagents (H2O2/Fe(2+)) are used to activate raw sewage sludge for the preparation of the sludge based activated carbon. The effect of the amount of hydrogen peroxide addition on carbon's chemical composition, texture properties, surface chemistry and morphology are investigated. Choosing an appropriate H2O2 dosage (5 v%) (equivalent to 70.7 mM/(g VS)), it is possible to obtain a comparatively highly porous materials with SBET and the total pore volume being 321 m(2)/g and 0.414 cm(3)/g, respectively. Continuously increasing the oxidant ratio resulted in a decreased SBET value. Further adsorption experiments by using 2-naphthol as model pollutant revealed that the adoption followed a pseudo-second-order kinetics better than pseudo-first-order. The calculated adsorption capacity is 111.9 mg/g on the carbon with 5% H2O2 pretreatment while this value is just 51.5mg/g on carbons without any pretreatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Neutrophil chemotaxis in response to TGF-beta isoforms (TGF-beta 1, TGF-beta 2, TGF-beta 3) is mediated by fibronectin.

    PubMed

    Parekh, T; Saxena, B; Reibman, J; Cronstein, B N; Gold, L I

    1994-03-01

    TGF-beta isoforms regulate numerous cellular functions including cell growth and differentiation, the cellular synthesis and secretion of extracellular matrix proteins, such as fibronectin (Fn), and the immune response. We have previously shown that TGF-beta 1 is the most potent chemoattractant described for human peripheral blood neutrophils (PMNs), suggesting that TGF-beta s may play a role in the recruitment of PMNs during the initial phase of the inflammatory response. In our current studies, we demonstrate that the maximal chemotactic response was attained near 40 fM for all mammalian TGF-beta isoforms. However, there was a statistically significant difference in migratory distance of the PMNs: TGF-beta 2 (556 microM) > TGF-beta 3 (463 microM) > TGF-beta 1 (380 microM) (beta 2: beta 3, p < or = 0.010; beta 3: beta 1, p < or = 0.04; beta 2: beta 1, p < or = 0.0012). A mAb to the cell binding domain (CBD) of Fn inhibited the chemotactic response to TGF-beta 1 and TGF-beta 3 by 63% and to TGF-beta 2 by 70%, whereas the response to FMLP, a classic chemoattractant, was only inhibited by 18%. In contrast, a mAb to a C-terminal epitope of Fn did not retard migration (< 1.5%). The Arg-gly-Asp-ser tetrapeptide inhibited chemotaxis by approximately the same extent as the anti-CBD (52 to 83%). Furthermore, a mAb against the VLA-5 integrin (VLA-5; Fn receptor) also inhibited TGF-beta-induced chemotaxis. These results indicate that chemotaxis of PMNs in response to TGF-beta isoforms is mediated by the interaction of the Arg-gly-Asp-ser sequence in the CBD of Fn with an integrin on the PMN cell surface, primarily the VLA-5 integrin. TGF-beta isoforms also elicited the release of cellular Fn from PMNs; we observed a 2.3-fold increase in Fn (389 to 401 ng/ml) in the supernatants of TGF-beta-stimulated PMNs compared with unstimulated cells (173.6 ng/ml). The concentration of TGF-beta required to cause maximal release of Fn from PMNs (4000 fM) is a concentration at which TGF-beta

  11. Analysis of betaS and betaA genes in a Mexican population with African roots.

    PubMed

    Magaña, María Teresa; Ongay, Zoyla; Tagle, Juan; Bentura, Gilberto; Cobián, José G; Perea, F Javier; Casas-Castañeda, Maricela; Sánchez-López, Yoaly J; Ibarra, Bertha

    2002-01-01

    To investigate the origin of the beta(A) and beta(S) genes in a Mexican population with African roots and a high frequency of hemoglobin S, we analyzed 467 individuals (288 unrelated) from different towns in the states of Guerrero and Oaxaca in the Costa Chica region. The frequency of the sickle-cell trait was 12.8%, which may represent a public health problem. The frequencies of the beta-haplotypes were determined from 350 nonrelated chromosomes (313 beta(A) and 37 beta(S)). We observed 15 different beta(A) haplotypes, the most common of which were haplotypes 1 (48.9%), 2 (13.4%), and 3 (13.4%). The calculation of pairwise distributions and Nei's genetic distance analysis using 32 worldwide populations showed that the beta(A) genes are more closely related to those of Mexican Mestizos and North Africans. Bantu and Benin haplotypes and haplotype 9 were related to the beta(S) genes, with frequencies of 78.8, 18.2, and 3.0%, respectively. Comparison of these haplotypes with 17 other populations revealed a high similitude with the population of the Central African Republic. These data suggest distinct origins for the beta(A) and beta(S) genes in Mexican individuals from the Costa Chica region.

  12. Interaction with beta-arrestin determines the difference in internalization behavor between beta1- and beta2-adrenergic receptors.

    PubMed

    Shiina, T; Kawasaki, A; Nagao, T; Kurose, H

    2000-09-15

    The beta(1)-adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. As beta-arrestin is important for internalization, we examine the interaction of beta-arrestin with beta(1)AR with three different methods: intracellular trafficking of beta-arrestin, binding of in vitro translated beta-arrestin to intracellular domains of beta(1)- and beta(2)ARs, and inhibition of betaAR-stimulated adenylyl cyclase activities by beta-arrestin. The green fluorescent protein-tagged beta-arrestin 2 translocates to and stays at the plasma membrane by beta(2)AR stimulation. Although green fluorescent protein-tagged beta-arrestin 2 also translocates to the plasma membrane, it returns to the cytoplasm 10-30 min after beta(1)AR stimulation. The binding of in vitro translated beta-arrestin 1 and beta-arrestin 2 to the third intracellular loop and the carboxyl tail of beta(1)AR is lower than that of beta(2)AR. The fusion protein of beta-arrestin 1 with glutathione S-transferase inhibits the beta(1)- and beta(2)AR-stimulated adenylyl cyclase activities, although inhibition of the beta(1)AR-stimulated activity requires a higher concentration of the fusion protein than that of the beta(2)AR-stimulated activity. These results suggest that weak interaction of beta(1)AR with beta-arrestins explains the resistance to agonist-induced internalization. This is further supported by the finding that beta-arrestin can induce internalization of beta(1)AR when beta-arrestin 1 does not dissociate from beta(1)AR by fusing to the carboxyl tail of beta(1)AR.

  13. Removal and recovery of mercury(II) from hazardous wastes using 1-(2-thiazolylazo)-2-naphthol functionalized activated carbon as solid phase extractant.

    PubMed

    Starvin, A M; Rao, T Prasada

    2004-09-10

    As a part of removal of toxic heavy metals from hazardous wastes, solid phase extraction (SPE) of mercury(II) at trace and ultra trace levels was studied using 1-(2-thiazolylazo)-2-naphthol (TAN) functionalized activated carbon (AC). The SPE material removes traces of mercury(II) quantitatively in the pH range 6.0 +/- 0.2. Other parameters that influence quantitative recovery of mercury(II), viz. percent concentration of TAN in AC, amount of TAN-AC, preconcentration time and volume of aqueous phase were varied and optimized. The possible means of removal of Hg(II) from other metal ions that are likely to be present in the wastes of the chloroalkali industry is discussed. The potential of TAN-functionalized AC SPE material for decontaminating mercury from the brine sludge and cell house effluent of a chloralkali plant has been evaluated.

  14. Polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and polynucleotides encoding same

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Morant, Marc

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  15. Cleavage of beta,beta-carotene to flavor compounds by fungi.

    PubMed

    Zorn, H; Langhoff, S; Scheibner, M; Berger, R G

    2003-09-01

    More than 50 filamentous fungi and yeasts, known for de novo synthesis or biotransformation of mono-, sesqui-, tri-, or tetraterpenes, were screened for their ability to cleave beta,beta-carotene to flavor compounds. Ten strains discolored a beta,beta-carotene-containing growth agar, indicating efficient degradation of beta,beta-carotene. Dihydroactinidiolide was formed as the sole conversion product of beta,beta-carotene in submerged cultures of Ganoderma applanatum, Hypomyces odoratus, Kuehneromyces mutabilis, and Trametes suaveolens. When mycelium-free culture supernatants from five species were applied for the conversions, nearly complete degradation of beta,beta-carotene was observed after 12 h. Carotenoid-derived volatile products were detected in the media of Ischnoderma benzoinum, Marasmius scorodonius, and Trametes versicolor. beta-Ionone proved to be the main metabolite in each case, whereas beta-cyclocitral, dihydroactinidiolide, and 2-hydroxy-2,6,6-trimethylcyclohexanone were formed in minor quantities. Using a photometric bleaching test, the beta,beta-carotene cleaving enzyme activities of M. scorodonius were partially characterized.

  16. beta-Hexachlorocyclohexane (beta-HCH)

    Integrated Risk Information System (IRIS)

    beta - Hexachlorocyclohexane ( beta - HCH ) ; CASRN 319 - 85 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Asses

  17. Graphene oxide-labeled sandwich-type impedimetric immunoassay with sensitive enhancement based on enzymatic 4-chloro-1-naphthol oxidation.

    PubMed

    Hou, Li; Cui, Yuling; Xu, Mingdi; Gao, Zhuangqiang; Huang, Jianxin; Tang, Dianping

    2013-09-15

    A new sandwich-type impedimetric immunosensor based on functionalized graphene oxide nanosheets with a high ratio of horseradish peroxidase (HRP) and detection antibody was developed for the detection of carcinoembryonic antigen (CEA) by coupling with enzymatic biocatalytic precipitation of 4-chloro-1-naphthol (4-CN) on the captured antibody-modified glassy carbon electrode. Two molecular tags (with and without the graphene oxide nanosheets) were investigated for the detection of CEA and improved analytical features were acquired with the graphene-based labeling. With the labeling method, the performance and factors influencing the properties of the impedimetric immunosensors were also studied and evaluated. Under the optimal conditions, the dynamic concentration range of the impedimetric immunosensors spanned from 1.0pgmL(-1) to 80ngmL(-1) CEA with a detection limit (LOD) of 0.64pgmL(-1). Intra- and inter-assay coefficients of variation were less than 7.5% and 11%, respectively. Additionally, the methodology was evaluated for CEA analysis of 10 clinical serum samples and 5 diluted serum samples, receiving in a good accordance with the results obtained by the impedimetric immunoassay and the commercialized electrochemiluminescent method. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Sequence swapping does not result in conformation swapping for the beta4/beta5 and beta8/beta9 beta-hairpin turns in human acidic fibroblast growth factor.

    PubMed

    Kim, Jaewon; Lee, Jihun; Brych, Stephen R; Logan, Timothy M; Blaber, Michael

    2005-02-01

    The beta-turn is the most common type of nonrepetitive structure in globular proteins, comprising ~25% of all residues; however, a detailed understanding of effects of specific residues upon beta-turn stability and conformation is lacking. Human acidic fibroblast growth factor (FGF-1) is a member of the beta-trefoil superfold and contains a total of five beta-hairpin structures (antiparallel beta-sheets connected by a reverse turn). beta-Turns related by the characteristic threefold structural symmetry of this superfold exhibit different primary structures, and in some cases, different secondary structures. As such, they represent a useful system with which to study the role that turn sequences play in determining structure, stability, and folding of the protein. Two turns related by the threefold structural symmetry, the beta4/beta5 and beta8/beta9 turns, were subjected to both sequence-swapping and poly-glycine substitution mutations, and the effects upon stability, folding, and structure were investigated. In the wild-type protein these turns are of identical length, but exhibit different conformations. These conformations were observed to be retained during sequence-swapping and glycine substitution mutagenesis. The results indicate that the beta-turn structure at these positions is not determined by the turn sequence. Structural analysis suggests that residues flanking the turn are a primary structural determinant of the conformation within the turn.

  19. Dynamics of beta-cell turnover: evidence for beta-cell turnover and regeneration from sources of beta-cells other than beta-cell replication in the HIP rat.

    PubMed

    Manesso, Erica; Toffolo, Gianna M; Saisho, Yoshifumi; Butler, Alexandra E; Matveyenko, Aleksey V; Cobelli, Claudio; Butler, Peter C

    2009-08-01

    Type 2 diabetes is characterized by hyperglycemia, a deficit in beta-cells, increased beta-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). These characteristics are recapitulated in the human IAPP transgenic (HIP) rat. We developed a mathematical model to quantify beta-cell turnover and applied it to nondiabetic wild type (WT) vs. HIP rats from age 2 days to 10 mo to establish 1) whether beta-cell formation is derived exclusively from beta-cell replication, or whether other sources of beta-cells (OSB) are present, and 2) to what extent, if any, there is attempted beta-cell regeneration in the HIP rat and if this is through beta-cell replication or OSB. We conclude that formation and maintenance of adult beta-cells depends largely ( approximately 80%) on formation of beta-cells independent from beta-cell duplication. Moreover, this source adaptively increases in the HIP rat, implying attempted beta-cell regeneration that substantially slows loss of beta-cell mass.

  20. Inhibin/activin-betaC and -betaE subunits in the Ishikawa human endometrial adenocarcinoma cell line.

    PubMed

    Kimmich, Tanja; Brüning, Ansgar; Käufl, Stephanie D; Makovitzky, Josef; Kuhn, Christina; Jeschke, Udo; Friese, Klaus; Mylonas, Ioannis

    2010-08-01

    Inhibins and activins are important regulators of the female reproductive system. Recently, two novel inhibin subunits, named betaC and betaE, have been identified and shown to be expressed in several human tissues. However, only limited data on the expression of these novel inhibin subunits in normal human endometrial tissue and endometrial adenocarcinoma cell lines exist. Samples of proliferative and secretory human endometrium were obtained from five premenopausal, non-pregnant patients undergoing gynecological surgery for benign diseases. Normal endometrial tissue and Ishikawa endometrial adenocarcinoma cell lines were analyzed by immunohistochemistry, immunofluorescence and RT-PCR. Expression of the inhibin betaC and betaE subunits could be demonstrated at the protein level by means of immunohistochemical evaluation and at the transcriptional level by establishing a betaC- and betaE-specific RT-PCR analysis in normal human endometrial tissue and the parental Ishikawa cell line. Interestingly, in a highly de-differentiated subclone of the Ishikawa cell line lacking estrogen receptor expression, the expression of the inhibin-betaC subunit appeared strongly reduced. Here, we show for the first time that the novel inhibin/activin-betaC and -betaE subunits are expressed in normal human endometrium and the estrogen receptor positive human endometrial carcinoma cell line Ishikawa using RT-PCR and immunohistochemical detection methods. Interestingly, the Ishikawa minus cell line (lacking estrogen receptor expression) demonstrated no to minimal expression of the betaC subunit as observed with immunofluorescence and RT-PCR, suggesting a possible hormone- dependency of this subunit in human endometrial cancer cells. Moreover, because the Ishikawa cell line minus is thought to be a more malignant endometrial cell line than its estrogen receptor positive counterpart, inhibin-betaC subunit might be substantially involved in the pathogenesis and malignant transformation in

  1. Expression of transforming growth factor-beta1, -beta2 and -beta3 in normal and diseased canine mitral valves.

    PubMed

    Aupperle, H; März, I; Thielebein, J; Schoon, H-A

    2008-01-01

    The pathogenesis of chronic valvular disease (CVD) in dogs remains unclear, but activation and proliferation of valvular stromal cells (VSC) and their transdifferentiation into myofibroblast-like cells has been described. These alterations may be influenced by transforming growth factor-beta (TGF-beta), a cytokine involved in extracellular matrix (ECM) regulation and mesenchymal cell differentiation. The present study investigates immunohistochemically the expression of TGF-beta1, -beta2, -beta3 and smooth muscle alpha actin (alpha-SMA) in normal canine mitral valves (MVs) (n=10) and in the valves of dogs with mild (n=7), moderate (n=14) and severe (n=9) CVD. In normal mitral valves there was no expression of alpha-SMA but VSC displayed variable expression of TGF-beta1 (10% of VSC labelled), TGF-beta2 (1-5% labelled) and TGF-beta3 (50% labelled). In mild CVD the affected atrialis contain activated and proliferating alpha-SMA-positive VSC, which strongly expressed TGF-beta1 and -beta3, but only 10% of these cells expressed TGF-beta2. In unaffected areas of the leaflet there was selective increase in expression of TGF-beta1 and -beta3. In advanced CVD the activated subendothelial VSC strongly expressed alpha-SMA, TGF-beta1 and -beta3. Inactive VSC within the centre of the nodules had much less labelling for TGF-beta1 and -beta3. TGF-beta1 labelling was strong within the ECM. These data suggest that TGF-beta plays a role in the pathogenesis of CVD by inducing myofibroblast-like differentiation of VSC and ECM secretion. Changed haemodynamic forces and expression of matrix metalloproteinases (MMPs) may in turn regulate TGF-beta expression.

  2. Selective regulation of beta 1- and beta 2-adrenoceptors in the human heart by chronic beta-adrenoceptor antagonist treatment.

    PubMed Central

    Michel, M. C.; Pingsmann, A.; Beckeringh, J. J.; Zerkowski, H. R.; Doetsch, N.; Brodde, O. E.

    1988-01-01

    1. In 44 patients undergoing coronary artery bypass grafting, the effect of chronic administration of the beta-adrenoceptor antagonists sotalol, propranolol, pindolol, metoprolol and atenolol on beta-adrenoceptor density in right atria (containing 70% beta 1- and 30% beta 2-adrenoceptors) and in lymphocytes (having only beta 2-adrenoceptors) was studied. 2. beta-Adrenoceptor density in right atrial membranes and in intact lymphocytes was assessed by (-)-[125I]-iodocyanopindolol (ICYP) binding; the relative amount of right atrial beta 1- and beta 2-adrenoceptors was determined by inhibition of ICYP binding by the selective beta 2-adrenoceptor antagonist ICI 118,551 and analysis of the resulting competition curves by the iterative curve fitting programme LIGAND. 3. With the exception of pindolol, all beta-adrenoceptor antagonists increased right atrial beta-adrenoceptor density compared to that observed in atria from patients not treated with beta-adrenoceptor antagonists. 4. All beta-adrenoceptor antagonists increased right atrial beta 1-adrenoceptor density; on the other hand, only sotalol and propranolol also increased right atrial beta 2-adrenoceptor density, whereas metoprolol and atenolol did not affect it and pindolol decreased it. 5. Similarly, in corresponding lymphocytes, only sotalol or propranolol increased beta 2-adrenoceptor density, while metoprolol and atenolol did not affect it and pindolol decreased it. 6. It is concluded that beta-adrenoceptor antagonists subtype-selectively regulate cardiac and lymphocyte beta-adrenoceptor subtypes. The selective increase in cardiac beta 1-adrenoceptor density evoked by metoprolol and atenolol may be one of the reasons for the beneficial effects observed in patients with end-stage congestive cardiomyopathy following intermittent treatment with low doses of selective beta 1-adrenoceptor antagonists. PMID:2902891

  3. 5Beta,6beta-epoxy-17-oxoandrostan-3beta-yl acetate and 5beta,6beta-epoxy-20-oxopregnan-3beta-yl acetate.

    PubMed

    Pinto, Rui M A; Salvador, Jorge A R; Paixão, José A

    2008-05-01

    In the title compounds, C(21)H(30)O(4), (I), and C(23)H(34)O(4), (II), respectively, which are valuable intermediates in the synthesis of important steroid derivatives, rings A and B are cis-(5beta,10beta)-fused. The two molecules have similar conformations of rings A, B and C. The presence of the 5beta,6beta-epoxide group induces a significant twist of the steroid nucleus and a strong flattening of the B ring. The different C17 substituents result in different conformations for ring D. Cohesion of the molecular packing is achieved in both compounds only by weak intermolecular interactions. The geometries of the molecules in the crystalline environment are compared with those of the free molecules as given by ab initio Roothan Hartree-Fock calculations. We show in this work that quantum mechanical ab initio methods reproduce well the details of the conformation of these molecules, including a large twist of the steroid nucleus. The calculated twist values are comparable, but are larger than the observed values, indicating a possible small effect of the crystal packing on the twist angles.

  4. beta-Endorphin-induced analgesia is inhibited by synthetic analogs of beta-endorphin.

    PubMed

    Nicolas, P; Hammonds, R G; Li, C H

    1984-05-01

    Competitive antagonism of human beta-endorphin (beta h-EP)-induced analgesia by synthetic beta h-EP analogs with high in vitro opiate receptor binding to in vivo analgesic potency ratio has been demonstrated. A parallel shift of the dose-response curve for analgesia to the right was observed when either beta h-EP or [ Trp27 ] -beta h-EP was coinjected with various doses of [Gln8, Gly31 ]-beta h-EP-Gly-Gly-NH2, [Arg9,19,24,28,29]-beta h-EP, or [ Cys11 ,26, Phe27 , Gly31 ]-beta h-EP. It was estimated that the most potent antagonist, [Gln8, Gly31 ]-beta h-EP-Gly-NH2, is at least 200 times more potent than naloxone.

  5. beta-Endorphin-induced analgesia is inhibited by synthetic analogs of beta-endorphin.

    PubMed Central

    Nicolas, P; Hammonds, R G; Li, C H

    1984-01-01

    Competitive antagonism of human beta-endorphin (beta h-EP)-induced analgesia by synthetic beta h-EP analogs with high in vitro opiate receptor binding to in vivo analgesic potency ratio has been demonstrated. A parallel shift of the dose-response curve for analgesia to the right was observed when either beta h-EP or [ Trp27 ] -beta h-EP was coinjected with various doses of [Gln8, Gly31 ]-beta h-EP-Gly-Gly-NH2, [Arg9,19,24,28,29]-beta h-EP, or [ Cys11 ,26, Phe27 , Gly31 ]-beta h-EP. It was estimated that the most potent antagonist, [Gln8, Gly31 ]-beta h-EP-Gly-NH2, is at least 200 times more potent than naloxone. PMID:6328494

  6. AE activity during transient beta drops in high poloidal beta discharges

    NASA Astrophysics Data System (ADS)

    Huang, J.; Gong, X. Z.; Ren, Q. L.; Ding, S. Y.; Qian, J. P.; Pan, C. K.; Li, G. Q.; Heidbrink, W. W.; Garofalo, A. M.; McClenaghan, J.

    2016-10-01

    Enhanced AE activity has been observed during transient beta drops in high poloidal beta DIII-D discharges with internal transport barriers (ITBs). These drops in beta are believed to be caused by n=1 external kink modes. In some discharges, beta recovers within 200 ms but, in others, beta stays suppressed. A typical discharge has βP 3, qmin 3, and q95 12. The drop in beta affects both fast ions and thermal particles, and a drop is also observed in the density and rotation. The enhanced AE activity follows the instability that causes the beta drop, is largest at the lowest beta, and subsides as beta recovers. MHD stability analysis is planned. A database study of the plasma conditions associated with the collapse will be also presented. Supported in part by the US Department of Energy under DE-FC02-04ER54698, DE-AC05-06OR23100, and by the National Natural Science Foundation of China 11575249, and the National Magnetic Confinement Fusion Program of China No. 2015GB110005.

  7. Solid phase extraction of metal ions in environmental samples on 1-(2-pyridylazo)-2-naphthol impregnated activated carbon cloth.

    PubMed

    Alothman, Zeid A; Yilmaz, Erkan; Habila, Mohamed; Soylak, Mustafa

    2015-02-01

    1-(2-Pyridylazo)-2-naphthol impregnated activated carbon cloth (PAN-imp-ACC) was prepared as a solid phase sorbent and, for the first time, was used for the simultaneous separation and preconcentration of trace amounts of lead, cadmium and nickel in water, soil and sewage sludge samples prior to determination by flame atomic absorption spectrometry (FAAS). The parameters governing the efficiency of the method were optimized, including the pH, the eluent type and volume, the sample and eluent flow rates, diverse ions effects and the sample volume. A preconcentration factor of 100 was achieved for all the metal ions, with detection limits of 0.1-2.8 µg L(-1) and relative standard deviations below 6.3%. The adsorption capacity of the PAN-imp-ACC for Pb(II), Cd(II) and Ni(II) ions was found to be 45.0 mg g(-1), 45.0 mg g(-1) and 43.2 mg g(-1), respectively. The method was validated by the analysis of the certified reference materials TMDA-64.2 fortified Lake Ontario water and BCR-146R Sewage Sludge Amended Soil (Industrial Origin). The procedure was applied to determine the analytes content in real samples. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Inhibition of GSK-3beta ameliorates hepatic ischemia-reperfusion injury through GSK-3beta/beta-catenin signaling pathway in mice.

    PubMed

    Xia, Yong-Xiang; Lu, Ling; Wu, Zheng-Shan; Pu, Li-Yong; Sun, Bei-Cheng; Wang, Xue-Hao

    2012-06-01

    Glycogen synthase kinase (GSK)-3beta/beta-catenin signaling regulates ischemia-reperfusion (I/R)-induced apoptosis and proliferation, and inhibition of GSK-3beta has beneficial effects on I/R injury in the heart and the central nervous system. However, the role of this signaling in hepatic I/R injury remains unclear. The present study aimed to investigate the effects and mechanism of GSK-3beta/beta-catenin signaling in hepatic I/R injury. Male C57BL/6 mice (weighing 22-25 g) were pretreated with either SB216763, an inhibitor of GSK-3beta, or vehicle. These mice were subjected to partial hepatic I/R. Blood was collected for test of alanine aminotransferase (ALT), and liver specimen for assays of phosphorylation at the Ser9 residue of GSK-3beta, GSK-3beta activity, axin 2 and the anti-apoptotic factors Bcl-2 and survivin, as well as the proliferative factors cyclin D1 and proliferating cell nuclear antigen, and apoptotic index (TUNEL). Real-time PCR, Western blotting and immunohistochemical staining were used. SB216763 increased phospho-GSK-3beta levels and suppressed GSK-3beta activity (1880+/-229 vs 3280+/-272 cpm, P<0.01). ALT peaked at 6 hours after reperfusion. Compared with control, SB216763 decreased ALT after 6 hours of reperfusion (4451+/-424 vs 7868+/-845 IU/L, P<0.01), and alleviated hepatocyte necrosis and vacuolization. GSK-3beta inhibition led to the accumulation of beta-catenin in the cytosol (0.40+/-0.05 vs 1.31+/-0.11, P<0.05) and nucleus (0.62+/-0.14 vs 1.73+/-0.12, P<0.05), beta-catenin further upregulated the expression of axin 2. Upregulation of GSK-3beta/beta-catenin signaling increased Bcl-2, survivin and cyclin D1. Serological and histological analyses showed that SB216763 alleviated hepatic I/R-induced injury by reducing apoptosis (1.4+/-0.2% vs 3.6+/-0.4%, P<0.05) and enhanced liver proliferation (56+/-8% vs 19+/-4%, P<0.05). Inhibition of GSK-3beta ameliorates hepatic I/R injury through the GSK-3beta/beta-catenin signaling pathway.

  9. Beta experiment

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A focused laser doppler velocimeter (LDV) system was developed for the measurement of atmospheric backscatter (beta) from aerosols at infrared wavelengths. A Doppler signal generator was used in mapping the coherent sensitive focal volume of a focused LDV system. System calibration data was analyzed during the flight test activity scheduled for the Beta system. These analyses were performed to determine the acceptability of the Beta measurement system's performance.

  10. Binding of TEM-1 beta-lactamase to beta-lactam antibiotics by frontal affinity chromatography.

    PubMed

    Chen, Xiu; Li, Yuhua; Zhang, Yan; Yang, Jianting; Bian, Liujiao

    2017-04-15

    TEM-1 beta-lactamases can accurately catalyze the hydrolysis of the beta-lactam rings in beta-lactam antibiotics, which make beta-lactam antibiotics lose its activity, and the prerequisite for the hydrolysis procedure in the binding interaction of TEM-1 beta-lactamases with beta-lactam antibiotics is the beta-lactam rings in beta-lactam antibiotics. Therefore, the binding of TEM-1 beta-lactamase to three beta-lactam antibiotics including penicillin G, cefalexin as well as cefoxitin was explored here by frontal affinity chromatography in combination with fluorescence spectra, adsorption and thermodynamic data in the temperature range of 278-288K under simulated physiological conditions. The results showed that all the binding of TEM-1 beta-lactamase to the three antibiotics were spontaneously exothermic processes with the binding constants of 8.718×10 3 , 6.624×10 3 and 2.244×10 3 (mol/L), respectively at 288K. All the TEM-1 beta-lactamases were immobilized on the surface of the stationary phase in the mode of monolayer and there existed only one type of binding sites on them. Each TEM-1 beta-lactamase bound with only one beta-lactam antibiotic and hydrogen bond interaction and Van der Waals force were the main forces between them. This work provided an insight into the binding interactions between TEM-1 beta-lactamases and beta-lactam antibiotics, which may be beneficial for the designing and developing of new substrates resistant to TEM-1 beta-lactamases. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. BetaTPred: prediction of beta-TURNS in a protein using statistical algorithms.

    PubMed

    Kaur, Harpreet; Raghava, G P S

    2002-03-01

    beta-turns play an important role from a structural and functional point of view. beta-turns are the most common type of non-repetitive structures in proteins and comprise on average, 25% of the residues. In the past numerous methods have been developed to predict beta-turns in a protein. Most of these prediction methods are based on statistical approaches. In order to utilize the full potential of these methods, there is a need to develop a web server. This paper describes a web server called BetaTPred, developed for predicting beta-TURNS in a protein from its amino acid sequence. BetaTPred allows the user to predict turns in a protein using existing statistical algorithms. It also allows to predict different types of beta-TURNS e.g. type I, I', II, II', VI, VIII and non-specific. This server assists the users in predicting the consensus beta-TURNS in a protein. The server is accessible from http://imtech.res.in/raghava/betatpred/

  12. Gene encoding the human. beta. -hexosaminidase. beta. chain: Extensive homology of intron placement in the. alpha. - and. beta. -chain genes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Proia, R.L.

    1988-03-01

    Lysosomal {beta}-hexosaminidase is composed of two structurally similar chains, {alpha} and {beta}, that are the products of different genes. Mutations in either gene causing {beta}-hexosaminidase deficiency result in the lysosomal storage disease GM2-gangliosidosis. To enable the investigation of the molecular lesions in this disorder and to study the evolutionary relationship between the {alpha} and {beta} chains, the {beta}-chain gene was isolated, and its organization was characterized. The {beta}-chain coding region is divided into 14 exons distributed over {approx}40 kilobases of DNA. Comparison with the {alpha}-chain gene revealed that 12 of the 13 introns interrupt the coding regions at homologous positions.more » This extensive sharing of intron placement demonstrates that the {alpha} and {beta} chains evolved by way of the duplication of a common ancestor.« less

  13. Plasma beta-endorphin, beta-lipotropin and corticotropin in polycystic ovarian disease.

    PubMed

    Laatikainen, T; Salminen, K; Virtanen, T; Apter, D

    1987-04-01

    In 9 women with polycystic ovarian disease (PCOD) and in 11 control subjects at the follicular phase of the normal cycle, blood samples were collected at 15-min intervals during a 2 h period of bed rest for the assay of beta-endorphin, beta-lipotropin, corticotropin, cortisol and prolactin. During the study period, the plasma levels of these hormones decreased more significantly in the PCOD than in the control group, suggesting that the PCOD patients had a more significant stress response to the puncture of the vein than the control subjects. The second hour of the study period was considered to represent resting levels of hormones. The mean resting levels (+/- S.E.) of the hormones between the PCOD and control groups, respectively, were as follows: beta-E, 2.0 +/- 0.4 vs. 1.1 +/- 0.1 pmol/l, p less than 0.05; beta-LPH, 3.4 +/- 0.6 vs. 2.1 +/- 0.5 pmol/l, N.S.; corticotropin, 2.0 +/- 0.3 vs. 1.1 +/- 0.5 pmol/l, p less than 0.05; cortisol, 176 +/- 24 vs. 128 +/- 16, N.S.; and prolactin; 3.9 +/- 0.6 vs. 5.6 +/- 1.2 ng/ml, N.S. These results confirm the previous findings on increased circulating levels of beta-E in PCOD. A concomitant increase of the plasma level of corticotropin suggests that the basal secretion of both beta-E and corticotropin from the anterior pituitary gland is increased in women with PCOD.

  14. Polypeptides having beta-glucosidase and beta-xylosidase activity and polynucleotides encoding same

    DOEpatents

    Morant, Marc Dominique

    2014-05-06

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  15. Beta Emission and Bremsstrahlung

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Karpius, Peter Joseph

    2017-11-13

    Bremsstrahlung is continuous radiation produced by beta particles decelerating in matter; different beta emitters have different endpoint energies; high-energy betas interacting with high-Z materials will more likely produce bremsstrahlung; depending on the data, sometimes all you can say is that a beta emitter is present.

  16. Synthesis and cytotoxic analysis of some disodium 3beta,6beta-dihydroxysterol disulfates.

    PubMed

    Cui, Jianguo; Wang, Hui; Huang, Yanmin; Xin, Yi; Zhou, Aimin

    2009-01-01

    Disodium 3beta,6beta-dihydroxy-5alpha-cholestane disulfate (1) was synthesized in 4 steps with a high overall yield from cholesterol. First, cholesterol (4a) was converted to cholest-4-en-3,6-dione (5a) via oxidation with pyridinium chlorochromate (PCC) and then 5a was reduced by NaBH(4) in the presence of NiCl(2) to produce cholest-3beta,6beta-diol (6a). The reaction of 6a with the triethylamine-sulfur trioxide complex generated diammonium 3beta,6beta-dihydroxy-5alpha-cholestane disulfate (7a) and the treatment of 7a by cation exchange resin 732 (sodium form)(Na(+)) yielded the target steroid 1. Disodium 24-ethyl-3beta,6beta-dihydroxycholest-22-ene disulfate (2) and disodium 24-ethyl-3beta,6beta-dihydroxycholestane disulfate (3) were synthesized using a similar method. The cytotoxicity of these compounds against Sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells was investigated. Our results indicate that presence of a cholesterol-type side chain at position 17 is necessary for their biological activity.

  17. Lymphotoxin beta receptor (Lt betaR): dual roles in demyelination and remyelination and successful therapeutic intervention using Lt betaR-Ig protein.

    PubMed

    Plant, Sheila R; Iocca, Heather A; Wang, Ying; Thrash, J Cameron; O'Connor, Brian P; Arnett, Heather A; Fu, Yang-Xin; Carson, Monica J; Ting, Jenny P-Y

    2007-07-11

    Inflammation mediated by macrophages is increasingly found to play a central role in diseases and disorders that affect a myriad of organs, prominent among these are diseases of the CNS. The neurotoxicant-induced, cuprizone model of demyelination is ideally suited for the analysis of inflammatory events. Demyelination on exposure to cuprizone is accompanied by predictable microglial activation and astrogliosis, and, after cuprizone withdrawal, this activation reproducibly diminishes during remyelination. This study demonstrates enhanced expression of lymphotoxin beta receptor (Lt betaR) during the demyelination phase of this model, and Lt betaR is found in areas enriched with microglial and astroglial cells. Deletion of the Lt betaR gene (Lt betaR-/-) resulted in a significant delay in demyelination but also a slight delay in remyelination. Inhibition of Lt betaR signaling by an Lt betaR-Ig fusion decoy protein successfully delayed demyelination in wild-type mice. Unexpectedly, this Lt betaR-Ig decoy protein dramatically accelerated the rate of remyelination, even after the maximal pathological disease state had been reached. This strongly indicates the beneficial role of Lt betaR-Ig in the delay of demyelination and the acceleration of remyelination. The discrepancy between remyelination rates in these systems could be attributed to developmental abnormalities in the immune systems of Lt betaR-/- mice. These findings bode well for the use of an inhibitory Lt betaR-Ig as a candidate biological therapy in demyelinating disorders, because it is beneficial during both demyelination and remyelination.

  18. Beta-Carotene

    MedlinePlus

    ... risk of new tumors. It is unclear if dietary beta-carotene reduces the risk of colon cancer. Lung cancer. Taking beta-carotene ... mucositis during radiation therapy or chemotherapy. Osteoarthritis. Higher ... reduce the risk of ovarian cancer in women after menopause. Pancreatic ...

  19. Rapid synthesis of beta zeolites

    DOEpatents

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng

    2015-08-18

    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  20. Active-site-directed inactivation of Aspergillus oryzae beta-galactosidase with beta-D-galactopyranosylmethyl-p-nitrophenyltriazene.

    PubMed

    Mega, T; Nishijima, T; Ikenaka, T

    1990-04-01

    beta-D-Galactopyranosylmethyl-p-nitrophenyltriazene (beta-GalMNT), a specific inhibitor of beta-galactosidase, was isolated as crystals by HPLC and its chemical and physicochemical characteristics were examined. Aspergillus oryzae beta-galactosidase was inactivated by the compound. We studied the inhibition mechanism in detail. The inhibitor was hydrolyzed by the enzyme to p-nitroaniline and an active intermediate (beta-galactopyranosylmethyl carbonium or beta-galactopyranosylmethyldiazonium), which inactivated the enzyme. The efficiency of inactivation of the enzyme (the ratio of moles of inactivated enzyme to moles of beta-GalMNT hydrolyzed by the enzyme) was 3%; the efficiency of Escherichia coli beta-galactosidase was 49%. In spite of the low efficiency, the rate of inactivation of A. oryzae enzyme was not very different from that of the E. coli enzyme, because the former hydrolyzed beta-GalMNT faster than the latter did. A. oryzae beta-galactosidase was also inactivated by p-chlorophenyl, p-tolyl, and m-nitrophenyl derivatives of beta-galactopyranosylmethyltriazene. However, E. coli beta-galactosidase was not inactivated by these triazene derivatives. The results showed that the inactivation of A. oryzae and E. coli beta-galactosidases by beta-GalMNT was an enzyme-activated and active-site-directed irreversible inactivation. The possibility of inactivation by intermediates produced nonenzymatically was ruled out for E. coli, but not for the A. oryzae enzyme.

  1. Polypeptides having beta-glucosidase activity and beta-xylosidase activity and polynucleotides encoding same

    DOEpatents

    Morant, Marc Dominique

    2014-05-06

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  2. Polypeptides having beta-glucosidase activity and beta-xylosidase activity and polynucleotides encoding same

    DOEpatents

    Morant, Marc Dominique

    2014-04-29

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  3. Maternal plasma concentrations of beta-lipotrophin, beta-endorphin and gamma-lipotrophin throughout pregnancy.

    PubMed

    Browning, A J; Butt, W R; Lynch, S S; Shakespear, R A

    1983-12-01

    Plasma beta-LPH, beta-EP and gamma-LPH concentrations were measured by radioimmunoassay in 10 pregnant women from 12 weeks gestation until term and in nine women in the early follicular phase of the cycle. There was a progressive and significant rise in the concentration of all three peptides throughout pregnancy and by 32 weeks the concentrations of beta-LPH and beta-EP were greater than the corresponding concentrations in the follicular phase: gamma-LPH was greater than in the follicular phase by the end of pregnancy in those women who were delivered after 40 weeks. The ratio of beta-LPH to gamma-LPH did not change significantly throughout pregnancy, but there was a progressive fall in the beta-LPH/beta-EP ratio. The possible presence of a 'big LPH' to explain this finding is discussed.

  4. Optimized formation of detergent micelles of beta-carotene and retinal production using recombinant human beta,beta-carotene 15,15'-monooxygenase.

    PubMed

    Kim, Nam-Hee; Kim, Yeong-Su; Kim, Hye-Jung; Oh, Deok-Kun

    2008-01-01

    The formation of beta-carotene detergent micelles and their conversion into retinal by recombinant human beta,beta-carotene 15,15'-monooxygenase was optimized under aqueous conditions. Toluene was the most hydrophobic among the organic solvents tested; thus, it was used to dissolve beta-carotene, which is a hydrophobic compound. Tween 80 was selected as the detergent because it supported the highest level of retinal production among all of the detergents tested. The maximum production of retinal was achieved in detergent micelles containing 200 mg/L of beta-carotene and 2.4% (w/v) Tween 80. Under these conditions, the recombinant enzyme produced 97 mg/L of retinal after 16 h with a conversion yield of 48.5% (w/w). The amount of retinal produced, which is the highest ever reported, is a result of the ability of our system to dissolve large amounts of beta-carotene.

  5. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Feng, Ying; Tsinghua University School of Medicine, Haidian District, Beijing 100084; Yang, Shi-gao

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phasesmore » of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.« less

  6. Energetic, Structural, and Antimicrobial Analyses of [beta]-Lactam Side Chain Recognition by [beta]-Lactamases

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Caselli, E.; Powers, R.A.; Blaszczak, L.C.

    2010-03-05

    Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these {beta}-lactams, most often through bacterial expression of {beta}-lactamases, threatens public health. To understand how {beta}-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because {beta}-lactams form covalent adducts with {beta}-lactamases. This has complicated functional analyses and inhibitor design. To investigate the contribution to interaction energy of the key amide (R1) side chain of {beta}-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well asmore » four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine {beta}-lactamases. Therefore, binding energies can be calculated directly from K{sub i} values. The K{sub i} values measured span four orders of magnitude against the Group I {beta}-lactamase AmpC and three orders of magnitude against the Group II {beta}-lactamase TEM-1. The acylglycineboronic acids have K{sub i} values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of {beta}-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of {beta}-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to {beta}-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 {angstrom} and 1.75 {angstrom} resolution; these structures suggest interactions that are important to the affinity of the inhibitors. Acylglycineboronic acids allow us to begin to dissect interaction energies between {beta}-lactam side chains and {beta

  7. Exercise- and cold-induced changes in plasma beta-endorphin and beta-lipotropin in men and women.

    PubMed

    Viswanathan, M; Van Dijk, J P; Graham, T E; Bonen, A; George, J C

    1987-02-01

    The plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) response of men, eumenorrheic women, and amenorrheic women (n = 6) to 1 h of rest or to a bicycle ergometer test [20 min at 30% maximum O2 uptake (VO2max), 20 min at 60% VO2max, and at 90% VO2max to exhaustion] was studied in both normal (22 degrees C) and cold (5 degrees C) environments. beta-EP and beta-LPH was measured by radioimmunoassay in venous samples collected every 20 min during rest or after each exercise bout. Exhaustive exercise at ambient temperature (Ta) 22 degrees C induced significant increases in plasma beta-EP and beta-LPH in all subjects as did work at 60% VO2max in amenorrheic and eumenorrheic women. During work at Ta 5 degrees C, the relative increase in beta-EP and beta-LPH was suppressed in eumenorrheic women and completely prevented in amenorrheic women. Although significant lowering of beta-EP and beta-LPH was observed in men and eumenorrheic women during rest at 5 degrees C, amenorrheic women maintained precold exposure levels. These findings suggest that plasma beta-EP and beta-LPH may reflect a thermoregulatory response to heat load. There appears to be a sexual dimorphism in exercise- and cold-induced release of beta-EP and beta-LPH and amenorrhea may be accompanied by alterations in these responses.

  8. Investigation of applicability of Electro-Fenton method for the mineralization of naphthol blue black in water.

    PubMed

    Özcan, Ayça Atılır; Özcan, Ali

    2018-07-01

    In this study, mineralization and color removal performance of electro-Fenton method were examined in water containing naphthol blue black (NBB), a diazo dye. NBB was totally converted to intermediate species in a 15-min electrolysis at 60 mA, but complete de-colorization took 180 min. A very high oxidation rate constant ((3.35 ± 0.21) x 10 10  M -1 s -1 ) was obtained for NBB, showing its high reactivity towards hydroxyl radicals. A very high total organic carbon (TOC) removal value (45.23 mg L -1 ) was obtained in the first 60 min of the electro-Fenton treatment of an aqueous solution of NBB (0.25 mM) at 300 mA, indicating the mineralization efficiency of the electro-Fenton method. Mineralization current efficiency values obtained at 300 mA gradually decreased from 24.18% to 4.47% with the electrolysis time, indicating the presence of highly parasitic reactions. Gas chromatography-mass spectrometry analyses revealed that the cleavage of azo bonds of NBB led to formation of different aromatic and aliphatic oxidation intermediates. Ion chromatography analysis showed that ammonium, nitrate and sulfate were the mineralization end-products. The concentration of sulfate ion reached to its quantitative value at the 4th h of electrolysis. On the other hand, the total concentration of ammonium and nitrate ions reached to only 61% of the stoichiometric amount of initial nitrogen after a 7 h electrolysis. Finally, it can be said that the electro-Fenton method is a suitable and efficient method for the removal of NBB and its intermediates from water. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. A Synopsis of Factors Regulating Beta Cell Development and Beta Cell Mass

    PubMed Central

    Prasadan, Krishna; Shiota, Chiyo; Xiangwei, Xiao; Ricks, David; Fusco, Joseph; Gittes, George

    2016-01-01

    The insulin-secreting beta cells in the endocrine pancreas regulate blood glucose levels, and loss of functional beta cells leads to insulin deficiency, hyperglycemia (high blood glucose) and diabetes mellitus. Current treatment strategies for type-1 (autoimmune) diabetes are islet transplantation, which has significant risks and limitations, or normalization of blood glucose with insulin injections, which is clearly not ideal. The type-1 patients can lack insulin counter-regulatory mechanism; therefore, hypoglycemia is a potential risk. Hence, a cell-based therapy offers a better alternative for the treatment of diabetes. Past research was focused on attempting to generate replacement beta cells from stem cells, however, recently there has been an increasing interest in identifying mechanisms that will lead to the conversion of pre-existing differentiated endocrine cells into beta cells. The goal of this review is to provide an overview of several of the key factors that regulate new beta cell formation (neogenesis) and beta cell proliferation. PMID:27105622

  10. Beta-blocking agents in patients with insulin resistance: effects of vasodilating beta-blockers.

    PubMed

    Jacob, S; Balletshofer, B; Henriksen, E J; Volk, A; Mehnert, B; Löblein, K; Häring, H U; Rett, K

    1999-01-01

    Essential hypertension is--at least in many subjects--associated with a decrease in insulin sensitivity, while glycaemic control is (still) normal. It seems that in hypertensive patients, two major functions of insulin are impaired: there is insulin resistance of peripheral glucose uptake (primarily skeletal muscle) and insulin resistance of insulin-stimulated vasodilation. In view of some retrospective data and meta-analyses, which showed a less than expected reduction in coronary events (coronary paradox), the metabolic side effects of the antihypertensive treatment have received more attention. Many groups have shown that conventional antihypertensive treatment, both with beta-blockers and/or diuretics, decreases insulin sensitivity by various mechanisms. While low-dose diuretics seem to be free of these metabolic effects, there is no evidence for this in the beta-adrenergic blockers. However, recent metabolic studies evaluated the effects of vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. None of them decreased insulin sensitivity, as has been described for the beta-blockers with and without beta1 selectivity. This supports the idea that peripheral vascular resistance and peripheral blood flow play a central role in mediating the metabolic side effects of the beta-blocking agents, as the vasodilating action (either via beta2 stimulation or alpha1-blockade) seems to more than offset the detrimental effects of the blockade of beta (or beta1) receptors. Further studies are needed to elucidate the relevance of the radical scavenging properties of these agents and their connection to their metabolic effects. Therefore, the beneficial characteristics of these newer beta-adrenoreceptor blockers suggest that the vasodilating beta-blocking agents could be advantageous for hypertensive patients with insulin resistance or type 2 diabetes.

  11. beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0].

    PubMed

    Adams, J G; Steinberg, M H; Newman, M V; Morrison, W T; Benz, E J; Iyer, R

    1981-01-01

    Hemoglobin Vicksburg was discovered in a 6-year-old Black boy who had been anemic since infancy. Examination of his hemolysate revealed 87.5% Hb F, 2.4% Hb A2, and 7.6% Hb Vicksburg, which had the electrophoretic and chromatographic properties of Hb A. Structural analysis of Hb Vicksburg demonstrated a deletion of leucine at beta 75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The alpha/non-alpha biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and beta 0-thalassemia, Hb Vicksburg should have comprised the major portion of the hemolysate. Thus, Hb Vicksburg was synthesized at a rate considerably lower than would be expected on the basis of gene dosage. There was no reason to suspect abnormal translation of beta Vicksburg mRNA; in individuals with Hb St. Antoine (beta 74 and beta 75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of beta 75, therefore, would not in itself appear to lead to diminished synthesis. There was a profound deficit of beta Vicksburg mRNA when measured by liquid hybridization analysis with beta cDNA. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for beta +-thalassemia is present in cis to the structural mutation.

  12. Identification of functional domains within the alpha and beta subunits of beta-hexosaminidase A through the expression of alpha-beta fusion proteins.

    PubMed

    Tse, R; Wu, Y J; Vavougios, G; Hou, Y; Hinek, A; Mahuran, D J

    1996-08-20

    There are three human beta-hexosaminidase isozymes which are composed of all possible dimeric combinations of an alpha and/or a beta subunit; A (alpha beta), and B (beta beta), and S (alpha alpha). The amino acid sequences of the two subunits are 60% identical. The homology between the two chains varies with the middle > the carboxy-terminal > > the amino-terminal portions. Although dimerization is required for activity, each subunit contains its own active site and differs in its substrate specificity and thermal stability. The presence of the beta subunit in hexosaminidase A also influences the substrate specificity of the alpha subunit; e.g., in vivo only the A heterodimer can hydrolyze GM2 ganglioside. In this report, we localize functional regions in the two subunits by cellular expression of alpha/beta fusion proteins joined at adjacently aligned residues. First, a chimeric alpha/beta chain was made by replacing the least well-conserved amino-terminal section of the beta chain with the corresponding alpha section. The biochemical characteristics of this protein were nearly identical to hexosaminidase B. Therefore, the most dissimilar regions in the subunits are not responsible for their dissimilar biochemical properties. A second fusion protein was made that also included the more homologous middle section of the alpha chain. This protein expressed the substrate specificity unique to isozymes containing an alpha subunit (A and S). We conclude that the region responsible for the ability of the alpha subunit to bind negatively charged substrates is located within residues alpha 132-283. Interestingly, the remaining carboxy-terminal section from the beta chain, beta 316-556, was sufficient to allow this chimera to hydrolyze GM2 ganglioside with 10% the specific activity of heterodimeric hexosaminidase A. Thus, the carboxy-terminal section of each subunit is likely involved in subunit-subunit interactions.

  13. Degradation pathway of the naphthalene azo dye intermediate 1-diazo-2- naphthol-4-sulfonic acid using Fenton's reagent.

    PubMed

    Zhu, Nanwen; Gu, Lin; Yuan, Haiping; Lou, Ziyang; Wang, Liang; Zhang, Xin

    2012-08-01

    Degradation of naphthalene dye intermediate 1-diazo-2- naphthol-4-sulfonic acid (1,2,4-Acid) by Fenton process has been studied in depth for the purpose of learning more about the reactions involved in the oxidation of 1,2,4-Acid. During 1,2,4-Acid oxidation, the solution color initially takes on a dark red, then to dark black associated with the formation of quinodial-type structures, and then goes to dark brown and gradually disappears, indicating a fast degradation of azo group. The observed color changes of the solution are a result of main reaction intermediates, which can be an indicator of the level of oxidization reached. Nevertheless, complete TOC removal is not accomplished, in accordance with the presence of resistant carboxylic acids at the end of the reaction. The intermediates generated along the reaction time have been identified and quantified. UPLC-(ESI)-TOF-HRMS analysis allows the detection of 19 aromatic compounds of different size and complexity. Some of them share the same accurate mass but appear at different retention time, evidencing their different molecular structures. Heteroatom oxidation products like SO(4)(2-) have also been quantified and explanations of their release are proposed. Short-chain carboxylic acids are detected at long reaction time, as a previous step to complete the process of dye mineralization. Finally, considering all the findings of the present study and previous related works, the evolution from the original 1,2,4-Acid to the final products is proposed in a general reaction scheme. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. The Promiscuity of [beta]-Strand Pairing Allows for Rational Design of [beta]-Sheet Face Inversion

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Makabe, Koki; Koide, Shohei

    2009-06-17

    Recent studies suggest the dominant role of main-chain H-bond formation in specifying {beta}-sheet topology. Its essentially sequence-independent nature implies a large degree of freedom in designing {beta}-sheet-based nanomaterials. Here we show rational design of {beta}-sheet face inversions by incremental deletions of {beta}-strands from the single-layer {beta}-sheet of Borrelia outer surface protein A. We show that a {beta}-sheet structure can be maintained when a large number of native contacts are removed and that one can design large-scale conformational transitions of a {beta}-sheet such as face inversion by exploiting the promiscuity of strand-strand interactions. High-resolution X-ray crystal structures confirmed the success ofmore » the design and supported the importance of main-chain H-bonds in determining {beta}-sheet topology. This work suggests a simple but effective strategy for designing and controlling nanomaterials based on {beta}-rich peptide self-assemblies.« less

  15. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Warner-Schmid, D.; Hoshi, Suwaru; Armstrong, D.W.

    Aqueous solutions of nonionic surfactants are known to undergo phase separations at elevated temperatures. This phenomenon is known as clouding,' and the temperature at which it occurs is refereed to as the cloud point. Permethylhydroxypropyl-[beta]-cyclodextrin (PMHP-[beta]-CD) was synthesized and aqueous solutions containing it were found to undergo similar cloud-point behavior. Factors that affect the phase separation of PMHP-[beta]-CD were investigated. Subsequently, the cloud-point extractions of several aromatic compounds (i.e., acetanilide, aniline, 2,2[prime]-dihydroxybiphenyl, N-methylaniline, 2-naphthol, o-nitroaniline, m-nitroaniline, p-nitroaniline, nitrobenzene, o-nitrophenol, m-nitrophenol, p-nitrophenol, 4-phenazophenol, 3-phenylphenol, and 2-phenylbenzimidazole) from dilute aqueous solution were evaluated. Although the extraction efficiency of the compounds varied, mostmore » can be quantitatively extracted if sufficient PMHP-[beta]-CD is used. For those few compounds that are not extracted (e.g., o-nitroacetanilide), the cloud-point procedure may be an effective one-step isolation or purification method. 18 refs., 2 figs., 3 tabs.« less

  16. Integrins beta 5, beta 3 and alpha v are apically distributed in endometrial epithelium.

    PubMed

    Aplin, J D; Spanswick, C; Behzad, F; Kimber, S J; Vićovac, L

    1996-07-01

    Several adhesion molecules have been shown to occur at the surface of endometrial cells. One of these is the integrin alpha v subunit which associates with various beta chains including beta 5. We demonstrate the presence of integrin beta 5 polypeptide in human endometrial epithelial cells throughout the menstrual cycle using immunocytochemistry with monospecific antibodies, and at the mRNA level by thermal amplification from endometrial cDNA. Integrin beta 5 is also found in a population of bone marrow-derived cells. A notable feature of the distribution of the beta 5 subunit in the glandular and luminal epithelium is its apical localization, which may suggest an involvement in implantation. However, no evidence was found for regulated expression of epithelial beta 5. In mouse, the beta 5 subunit is found at both the apical and basal surface of epithelial cells and expression is essentially oestrous cycle-independent. Comparisons are made in both species with the distribution of the alpha v and beta 3 subunits which also localize to the apical epithelium.

  17. beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0].

    PubMed Central

    Adams, J G; Steinberg, M H; Newman, M V; Morrison, W T; Benz, E J; Iyer, R

    1981-01-01

    Hemoglobin Vicksburg was discovered in a 6-year-old Black boy who had been anemic since infancy. Examination of his hemolysate revealed 87.5% Hb F, 2.4% Hb A2, and 7.6% Hb Vicksburg, which had the electrophoretic and chromatographic properties of Hb A. Structural analysis of Hb Vicksburg demonstrated a deletion of leucine at beta 75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The alpha/non-alpha biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and beta 0-thalassemia, Hb Vicksburg should have comprised the major portion of the hemolysate. Thus, Hb Vicksburg was synthesized at a rate considerably lower than would be expected on the basis of gene dosage. There was no reason to suspect abnormal translation of beta Vicksburg mRNA; in individuals with Hb St. Antoine (beta 74 and beta 75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of beta 75, therefore, would not in itself appear to lead to diminished synthesis. There was a profound deficit of beta Vicksburg mRNA when measured by liquid hybridization analysis with beta cDNA. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for beta +-thalassemia is present in cis to the structural mutation. PMID:6165992

  18. Target recognition of beta2-glycoprotein I (beta2GPI)-dependent anticardiolipin antibodies: evidence for involvement of the fourth domain of beta2GPI in antibody binding.

    PubMed

    George, J; Gilburd, B; Hojnik, M; Levy, Y; Langevitz, P; Matsuura, E; Koike, T; Shoenfeld, Y

    1998-04-15

    Beta2-glycoprotein I (beta2GPI) is an absolute requirement for the binding of autoimmune anticardiolipin Abs (aCL) to cardiolipin (CL). We evaluated the target recognition of human beta2GPI by IgG derived from two patients with primary and two with secondary antiphospholipid syndrome. The total IgG serum fractions and beta2GPI affinity-purified IgGs were assessed by using various domain-deleted mutants (DM) of human beta2GPI (DMs: I-III, I-IV, II-V, III-V, IV-V, and V) and mouse mAbs against individual beta2GPI domains. The four IgGs bound slightly to CL in the absence of beta2GPI and showed increased binding in the beta2GPI presence. Following affinity purification of the IgGs on a beta2GPI column, reactivity toward CL was absent. DMs containing domain V inhibited the binding of biotinylated beta2GPI to CL. The addition to CL-coated plates of DM V, but not the other DMs, reduced the binding of all four IgGs. The anti-beta2GPI IgGs bound only to complete beta2GPI and DM I-IV coated on the plates. The binding to plate-adsorbed beta2GPI could be inhibited by complete beta2GPI and DM I-IV, the latter being a more efficient inhibitor. Further, the human anti-beta2GPI IgGs could compete with the binding to beta2GPI of Cof-21 mouse mAb (directed at domain IV), but not with the two other mouse mAbs. The results suggest that some "autoimmune:" beta2GPI-dependent anticardiolipin Abs recognize a beta2GPI target that is distinct from the CL-binding site in domain V. The target site for some antiphospholipid syndrome IgGs appear to reside in domain IV of beta2GPI.

  19. Proteopedia: Rossmann Fold: A Beta-Alpha-Beta Fold at Dinucleotide Binding Sites

    ERIC Educational Resources Information Center

    Hanukoglu, Israel

    2015-01-01

    The Rossmann fold is one of the most common and widely distributed super-secondary structures. It is composed of a series of alternating beta strand (ß) and alpha helical (a) segments wherein the ß-strands are hydrogen bonded forming a ß-sheet. The initial beta-alpha-beta (ßaß) fold is the most conserved segment of Rossmann folds. As this segment…

  20. Deletion of the human beta-globin LCR 5'HS4 or 5'HS1 differentially affects beta-like globin gene expression in beta-YAC transgenic mice.

    PubMed

    Fedosyuk, Halyna; Peterson, Kenneth R

    2007-01-01

    A 213 kb human beta-globin locus yeast artificial chromosome (beta-YAC) was modified by homologous recombination to delete 2.9 kb of cross-species conserved sequence similarity encompassing the LCR 5' hypersensitive site (HS) 4 (Delta5'HS4 beta-YAC). In three transgenic mouse lines, completion of the gamma- to beta-globin switch during definitive erythropoiesis was delayed relative to wild-type beta-YAC mice. In addition, quantitative per-copy human beta-like globin mRNA levels were similar to wild-type beta-YAC transgenic lines, although beta-globin gene expression was slightly decreased in the day 12 fetal liver of Delta5'HS4 beta-YAC mice. A 0.8 kb 5'HS1 fragment was similarly deleted in the YAC. Three Delta5'HS1 beta-YAC transgenic lines were established. epsilon-globin gene expression was markedly reduced, approximately 16 fold, during primitive erythropoiesis compared to wild-type beta-YAC mice, but gamma-globin expression levels were unaffected. However, during the fetal stage of definitive erythropoiesis, gamma-globin gene expression was decreased approximately 4 fold at day 12 and approximately 5 fold at day 14. Temporal developmental expression profiles of the beta-like globin genes were unaffected by deletion of 5'HS1. Decreased expression of the epsilon- and gamma-globin genes is the first phenotype ascribed to a 5'HS1 mutation in the human beta-globin locus, suggesting that this HS does indeed have a role in LCR function beyond simply a combined synergism with the other LCR HSs.

  1. Mechanisms of A beta plaque clearance following passive A beta immunization.

    PubMed

    Morgan, Dave

    2005-01-01

    Alzheimer's disease is a major health problem with limited available medical treatment options. Immunotherapy is one approach with the potential to slow or reverse the disease process. In transgenic mouse models of amyloid deposition, anti-A beta immunotherapy is remarkably effective at diminishing the amyloid burden and reversing the memory deficiency phenotype present in these mice. Three distinct mechanisms of antibody action have been proposed to mediate these benefits of anti-A beta immunotherapy. The first is a catalytic dissolution of the A beta fibrils, proposed by Beka Solomon and colleagues. A second mechanism is opsonization of the amyloid by the antibody and subsequent phagocytosis by macrophages proposed by Dale Schenk and the Elan group. A third mechanism proposed by DeMattos, Holtzman and colleagues is the peripheral sink hypothesis, arguing that circulating antibodies sequester A beta and favor efflux of A beta from the CNS over influx to the CNS. None of these mechanisms are mutually exclusive. Our research group has evaluated these mechanisms using intracranial injection and systemic administration of anti-A beta antibodies. We found evidence supporting all three mechanisms, and suggest they may act synergistically to achieve the large effect size of the immunotherapeutic approach. However, in aged amyloid precursor protein transgenic mice administered anti-A beta antibodies systemically, there is a redistribution of the amyloid from the parenchyma to vascular elements. This increase in congophilic angiopathy is associated with increased risk of microhemorrhage. Thus, although we favor continued testing of the immunotherapy to treat Alzheimer's disease, we believe caution should be taken to minimize the risk of vascular leakage. Copyright 2005 S. Karger AG, Basel.

  2. Beta-blockers for hypertension

    PubMed Central

    Wiysonge, Charles S; Bradley, Hazel A; Volmink, Jimmy; Mayosi, Bongani M; Opie, Lionel H

    2017-01-01

    Background Beta-blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long-term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta-blockers were thought to have similar beneficial effects when used as first-line therapy for hypertension. However, the benefit of beta-blockers as first-line therapy for hypertension without compelling indications is controversial. This review is an update of a Cochrane Review initially published in 2007 and updated in 2012. Objectives To assess the effects of beta-blockers on morbidity and mortality endpoints in adults with hypertension. Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015. Selection criteria Randomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults. Data collection and analysis We selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed-effect or random-effects meta-analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies

  3. Meprin A and meprin {alpha} generate biologically functional IL-1{beta} from pro-IL-1{beta}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herzog, Christian; University of Arkansas for Medical Sciences, Department of Medicine, Little Rock, AR 72205; Haun, Randy S.

    The present study demonstrates that both oligomeric metalloendopeptidase meprin A purified from kidney cortex and recombinant meprin {alpha} are capable of generating biologically active IL-1{beta} from its precursor pro-IL-1{beta}. Amino-acid sequencing analysis reveals that meprin A and meprin {alpha} cleave pro-IL-1{beta} at the His{sup 115}-Asp{sup 116} bond, which is one amino acid N-terminal to the caspase-1 cleavage site and five amino acids C-terminal to the meprin {beta} site. The biological activity of the pro-IL-1{beta} cleaved product produced by meprin A, determined by proliferative response of helper T-cells, was 3-fold higher to that of the IL-1{beta} product produced by meprin {beta}more » or caspase-1. In a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum IL-1{beta}, meprin inhibitor actinonin significantly reduces levels of serum IL-1{beta}. Meprin A and meprin {alpha} may therefore play a critical role in the production of active IL-1{beta} during inflammation and tissue injury.« less

  4. Examination of Urinary Beta-Naphthol as a Biomarker Indicative of Jet Fuel Exposures

    DTIC Science & Technology

    2015-04-01

    NPQ) by cytochrome P450 has been shown to alter with age, diminishing at a rate of ~ 3% per year.22 Subject age effects on cytochrome P450 enzymes ...of Ageing on cytochrome P450 enzymes : Consequences for drug biotransformation in the elderly. Current Med Chem. (2007) 14:745-757. 24. Van Winkle...naphthalene 1,2-oxide by the cytochrome P450 monooxygenase system (Fig. 1). This reaction occurs primarily in the liver, although oxidation can also

  5. 0{nu}{beta}{beta}-decay nuclear matrix elements with self-consistent short-range correlations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Simkovic, Fedor; Bogoliubov Laboratory of Theoretical Physics, JINR, RU-141 980 Dubna, Moscow region; Department of Nuclear Physics, Comenius University, Mlynska dolina F1, SK-842 15 Bratislava

    A self-consistent calculation of nuclear matrix elements of the neutrinoless double-beta decays (0{nu}{beta}{beta}) of {sup 76}Ge, {sup 82}Se, {sup 96}Zr, {sup 100}Mo, {sup 116}Cd, {sup 128}Te, {sup 130}Te, and {sup 136}Xe is presented in the framework of the renormalized quasiparticle random phase approximation (RQRPA) and the standard QRPA. The pairing and residual interactions as well as the two-nucleon short-range correlations are for the first time derived from the same modern realistic nucleon-nucleon potentials, namely, from the charge-dependent Bonn potential (CD-Bonn) and the Argonne V18 potential. In a comparison with the traditional approach of using the Miller-Spencer Jastrow correlations, matrix elementsmore » for the 0{nu}{beta}{beta} decay are obtained that are larger in magnitude. We analyze the differences among various two-nucleon correlations including those of the unitary correlation operator method (UCOM) and quantify the uncertainties in the calculated 0{nu}{beta}{beta}-decay matrix elements.« less

  6. Beta-blockers for hypertension.

    PubMed

    Wiysonge, C S; Bradley, H; Mayosi, B M; Maroney, R; Mbewu, A; Opie, L H; Volmink, J

    2007-01-24

    Two recent systematic reviews found first-line beta-blockers to be less effective in reducing the incidence of stroke and the combined endpoint of stroke, myocardial infarction, and death compared to all other antihypertensive drugs taken together. However, beta-blockers might be better or worse than a specific class of drugs for a particular outcome measure so that comparing beta-blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta-blockers relative to other antihypertensive medications. We thus undertook this review to re-assess the place of beta-blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs. To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension. We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts. We selected randomised controlled trials which assessed the effectiveness of beta-blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for hypertension, on mortality and morbidity endpoints in men and non-pregnant women aged 18 years or older. At least two authors independently applied study selection criteria, assessed study quality, and extracted data; with differences resolved by consensus. We expressed study results as relative risks (RR) with 95% confidence intervals (CI) and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity between studies (p>0.1), we performed meta-analysis using a fixed effects method. Otherwise, we used the random effects method and investigated the cause of heterogeneity

  7. Pharmacological characterization of the inhibitory activity of beta h-endorphin (beta h-EP), [Arg9,19,24,28,29]-beta h-EP, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, in the neuroeffector junction of the mouse vas deferens.

    PubMed

    Valenzuela, R; Li, C H; Huidobro-Toro, J P

    1991-08-01

    The inhibitory opioid activities of beta h-endorphin (beta h-EP), its structurally related peptide analogues [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 (Gly-Gly-beta h-EP), [Arg9,19,24,28,29]-beta h-EP (Arg-beta h-EP) and methionine enkephalin have been examined in the electrically stimulated mouse vas deferens bioassay. All four peptides behaved as full agonists; methionine enkephalin was the most potent followed by Arg-beta h-EP, beta h-EP and Gly-Gly-beta h-EP. Neither Gly-Gly-beta h-EP nor Arg-beta h-EP antagonized the inhibitory action of beta h-EP or methionine enkephalin. An hour of tissue exposure to 30 nM beta-funaltrexamine followed by thorough washing, displaced to the right, in a parallel fashion, the concentration-response curves of beta h-EP and analogues. Whereas the displacement of the concentration response curves was 8 to 10-fold for beta h-EP and Arg-beta h-EP, it was only about 3-fold for Gly-Gly-beta h-EP and methionine enkephalin. Naltrindole was the most potent antagonist of methionine enkephalin with an apparent pA2 of 9.4; its potency as an antagonist of beta h-EP and related analogues was approximately one-tenth of this with pA2 values approximately 8.5. Norbinaltorphimine also antagonized the action of the opioid peptides with pA2 values close to 7.8.

  8. 17Beta-hydroxysteroid dehydrogenase (17beta-HSD) in scleractinian corals and zooxanthellae.

    PubMed

    Blomquist, Charles H; Lima, P H; Tarrant, A M; Atkinson, M J; Atkinson, S

    2006-04-01

    Steroid metabolism studies have yielded evidence of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity in corals. This project was undertaken to clarify whether there are multiple isoforms of 17beta-HSD, whether activity levels vary seasonally, and if zooxanthellae contribute to activity. 17Beta-HSD activity was characterized in zooxanthellate and azooxanthellate coral fragments collected in summer and winter and in zooxanthellae cultured from Montipora capitata. More specifically, 17beta-HSD activity was characterized with regard to steroid substrate and inhibitor specificity, coenzyme specificity, and Michaelis constants for estradiol (E2) and NADP+. Six samples each of M. capitata and Tubastrea coccinea (three summers, three winters) were assayed with E2 and NADP+. Specific activity levels (pmol/mg protein) varied 10-fold among M. capitata samples and 6-fold among T. coccinea samples. There was overlap of activity levels between summer and winter samples. NADP+/NAD+ activity ratios varied from 1.6 to 22.2 for M. capatita, 2.3 to 3.8 for T. coccinea and 0.7 to 1.1 for zooxanthellae. Coumestrol was the most inhibitory of the steroids and phytoestrogens tested. Our data confirm that corals and zooxanthellae contain 17beta-HSD and are consistent with the presence of more than one isoform of the enzyme.

  9. Role of surfactant derived intermediates in the efficacy and mechanism for radiation chemical degradation of a hydrophobic azo dye, 1-phenylazo-2-naphthol.

    PubMed

    Das, Laboni; Chatterjee, Suchandra; Naik, Devidas B; Adhikari, Soumyakanti

    2015-11-15

    A combined methodology involving gamma and pulse radiolysis, product analysis and toxicity studies has been adopted to comprehend the degradation process of a model hydrophobic azo dye, 1-phenylazo-2-naphthol, emphasizing the role of the surfactant, which is an integral part of textile waste. Two new and important findings are underlined in this article. The first is the direct attestation of the hydrazyl radical-parent adduct, formed in the reaction of the dye with e(-)aq followed by protonation and subsequent addition to the unreacted dye molecule. This has been confirmed from concentration dependent studies. Secondly, we have clearly shown that in the reaction of hydroxyl radical with the dye in Triton X-100 media, the initially produced TX radicals cause reductive degradation of the dye. Identification and detailed analysis of HPLC and GCMS data reveals that similar products are formed in both the reactions of e(-)aq and OH radicals. Moreover, the cytotoxicity of 10(-4)moldm(-3) dye was found to be reduced significantly after irradiation. Thus, the present study not only depicts new pathways for the degradation of hydrophobic azo dye, but also demonstrates the role of a surfactant in the entire process. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Beta2- and beta3-adrenergic receptor polymorphisms and exercise hemodynamics in postmenopausal women.

    PubMed

    McCole, Steve D; Shuldiner, Alan R; Brown, Michael D; Moore, Geoffrey E; Ferrell, Robert E; Wilund, Kenneth R; Huberty, Andrea; Douglass, Larry W; Hagberg, James M

    2004-02-01

    We sought to determine whether common genetic variations at the beta2 (beta2-AR, Gln27Glu) and beta3 (beta3-AR, Trp64Arg) adrenergic receptor gene loci were associated with cardiovascular (CV) hemodynamics during maximal and submaximal exercise. CV hemodynamics were assessed in 62 healthy postmenopausal women (20 sedentary, 22 physically active, and 20 endurance athletes) during treadmill exercise at 40, 60, 80, and 100% maximal O2 uptake using acetylene rebreathing to quantify cardiac output. The beta2-AR genotype and habitual physical activity (PA) levels interacted to significantly associate with arteriovenous O2 difference (a-vDO2) during submaximal exercise (P = 0.05), with the highest submaximal exercise a-vDO2 in sedentary women homozygous for the beta2-AR Gln allele and no genotype-dependent differences in submaximal exercise a-vDO2 in physically active and athletic women. The beta2-AR genotype also was independently associated with a-vDO2 during submaximal (P = 0.004) and approximately 100% maximal O2 uptake exercise (P = 0.006), with a 1.2-2 ml/100 ml greater a-vDO2 in the Gln/Gln than in the Glu/Glu genotype women. The beta3-AR genotype, independently or interacting with habitual PA levels, was not significantly associated with any CV hemodynamic variables during submaximal or maximal exercise. Thus it appears that the beta2-AR genotype, both independently and interacting with habitual PA levels, is significantly associated with a-vDO2 during exercise in postmenopausal women, whereas the beta3-AR genotype does not appear to be associated with any maximal or submaximal exercise CV hemodynamic responses in postmenopausal women.

  11. Human APC sequesters beta-catenin even in the absence of GSK-3beta in a Drosophila model.

    PubMed

    Rao, P R; Makhijani, K; Shashidhara, L S

    2008-04-10

    There have been conflicting reports on the requirement of GSK-3beta-mediated phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) vis-à-vis its ability to bind and degrade beta-catenin. Using a unique combination of loss of function for Shaggy/GSK-3beta and a gain of function for human APC in Drosophila, we show that misexpressed human APC (hAPC) can still sequester Armadillo/beta-catenin. In addition, human APC could suppress gain of Wnt/Wingless phenotypes associated with loss of Shaggy/GSK-3beta activity, suggesting that sequestered Armadillo/beta-catenin is non-functional. Based on these studies, we propose that binding per se of beta-catenin by APC does not require phosphorylation by GSK-3beta.

  12. Genetics Home Reference: beta thalassemia

    MedlinePlus

    ... Facebook Twitter Home Health Conditions Beta thalassemia Beta thalassemia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Beta thalassemia is a blood disorder that reduces the production ...

  13. A novel NADP(+)-dependent dehydrogenase activity for 7alpha/beta- and 11beta-hydroxysteroids in human liver nuclei: A third 11beta-hydroxysteroid dehydrogenase.

    PubMed

    Robinzon, B; Prough, R A

    2009-06-15

    Human tissue from uninvolved liver of cancer patients was fractionated using differential centrifugation and characterized for 11betaHSD enzyme activity against corticosterone, dehydrocorticosterone, 7alpha- and 7beta-hydroxy-dehydroepiandrosterone, and 7-oxo-dehydroepiandrosterone. An enzyme activity was observed in nuclear protein fractions that utilized either NADP(+) or NAD(+), but not NADPH and NADH, as pyridine nucleotide cofactor with K(m) values of 12+/-2 and 390+/-2microM, compared to the K(m) for microsomal 11betaHSD1 of 43+/-8 and 264+/-24microM, respectively. The K(m) for corticosterone in the NADP(+)-dependent nuclear oxidation reaction was 102+/-16nM, compared to 4.3+/-0.8microM for 11betaHSD1. The K(cat) values for nuclear activity with NADP(+) was 1687nmol/min/mg/micromol, compared to 755nmol/min/mg/micromol for microsomal 11betaHSD1 activity. Inhibitors of 11betaHSD1 decreased both nuclear and microsomal enzyme activities, suggesting that the nuclear activity may be due to an enzyme similar to 11betaHSD Type 1 and 2.

  14. (-)-3 beta,4 beta-epoxyvalerenic acid from Valeriana officinalis.

    PubMed

    Dharmaratne, H Ranjith; Nanayakkara, N P; Khan, Ikhlas A

    2002-07-01

    Chemical investigation of the root extract of Valeriana officinalis afforded a new bicyclic sesquiterpene acid, (-)-3 beta,4 beta-epoxyvalerenic acid together with valerenic acid and hexadecanoic acid. The structure of the new compound was elucidated by spectroscopic data and confirmed by partial synthesis of its methyl ester from valerenic acid. Methyl (-)-3 alpha,4 alpha-epoxyvalerenate was obtained as a minor product from the above reaction.

  15. Evaluation of partial beta-adrenoceptor agonist activity.

    PubMed

    Lipworth, B J; Grove, A

    1997-01-01

    A partial beta-adrenoceptor (beta-AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a beta-AR agonist with higher intrinsic activity. In vivo partial beta-AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (beta 1/beta 2), inotropicity (beta 1) or peripheral vasodilatation and finger tremor (beta 2). beta-AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, beta-AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (beta 1) and potassium (beta 2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a beta-adrenoceptor blocker with partial beta 1-AR agonist activity compared with a beta-adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using beta-AR blocking drugs with partial beta 1-AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between beta 2-AR partial agonist activity and endogenous adrenergic activity. For predominantly beta 2-AR agonist such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly beta 2-AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. beta 2-AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether

  16. BETA (Bitter Electromagnet Testing Apparatus)

    NASA Astrophysics Data System (ADS)

    Bates, Evan M.; Birmingham, William J.; Rivera, William F.; Romero-Talamas, Carlos A.

    2017-10-01

    The Bitter Electromagnet Testing Apparatus (BETA) is a 1-Tesla (T) prototype of the 10-T Adjustable Long Pulse High-Field Apparatus (ALPHA). These water-cooled resistive magnets use high DC currents to produce strong uniform magnetic fields. Presented here is the successful completion of the BETA project and experimental results validating analytical magnet designing methods developed at the Dusty Plasma Laboratory (DPL). BETA's final design specifications will be highlighted which include electromagnetic, thermal and stress analyses. The magnet core design will be explained which include: Bitter Arcs, helix starters, and clamping annuli. The final version of the magnet's vessel and cooling system are also presented, as well as the electrical system of BETA, which is composed of a unique solid-state breaker circuit. Experimental results presented will show the operation of BETA at 1 T. The results are compared to both analytical design methods and finite element analysis calculations. We also explore the steady state maximums and theoretical limits of BETA's design. The completion of BETA validates the design and manufacturing techniques that will be used in the succeeding magnet, ALPHA.

  17. Specific radioimmunoassay for human. beta. -lipotropin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jeffcoate, W.J.; Rees, L.H.; Lowry, P.J.

    1978-07-01

    A homologous RIA for human ..beta..-lipotropin (..beta..hLPH) has been developed. At a final dilution of 1:24,000, the antiserum employed shows cross-reaction with ..beta..hLPH but none with human ..beta..-MSH (..beta..hMSH), and it is concluded that the antigenic determinant lies within the N-terminal 1 to 36 region of ..beta..hLPH. With extraction of 3-ml plasma samples, the assay is sufficiently sensitive to measure circulating ..beta..hLPH levels in normal individuals at 0900 h (25 to 200 pg/ml). There is a circadian variation with levels falling to (less than 20 to 80 pg/ml) at 2300 h. ..beta..hLPH levels rise after metyrapone and after insulin-induced hypoglycemia,more » and fall after administration of dexamethasone. In patients with a variety of diseases of the pituitary-adrenal axis, levels of ..beta..hLPH follow immunoreactive ACTH levels, although the two are not always secreted on a 1:1 molar basis.« less

  18. Quasiparticle random phase approximation uncertainties and their correlations in the analysis of 0{nu}{beta}{beta} decay

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Faessler, Amand; Rodin, V.; Fogli, G. L.

    2009-03-01

    The variances and covariances associated to the nuclear matrix elements of neutrinoless double beta decay (0{nu}{beta}{beta}) are estimated within the quasiparticle random phase approximation. It is shown that correlated nuclear matrix elements uncertainties play an important role in the comparison of 0{nu}{beta}{beta} decay rates for different nuclei, and that they are degenerate with the uncertainty in the reconstructed Majorana neutrino mass.

  19. TGF-beta inhibits IL-1beta-activated PAR-2 expression through multiple pathways in human primary synovial cells.

    PubMed

    Tsai, Shin-Han; Sheu, Ming-Thau; Liang, Yu-Chih; Cheng, Hsiu-Tan; Fang, Sheng-Shiung; Chen, Chien-Ho

    2009-10-23

    To investigate the mechanism how Transforming growth factor-beta(TGF-beta) represses Interleukin-1beta (IL-1beta)-induced Proteinase-Activated Receptor-2 (PAR-2) expression in human primary synovial cells (hPSCs). Human chondrocytes and hPSCs isolated from cartilages and synovium of Osteoarthritis (OA) patients were cultured with 10% fetal bovine serum media or serum free media before treatment with IL-1beta, TGF-beta1, or Connective tissue growth factor (CTGF). The expression of PAR-2 was detected using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Collagen zymography was performed to assess the activity of Matrix metalloproteinases-13 (MMP-13). It was demonstrated that IL-1beta induces PAR-2 expression via p38 pathway in hPSCs. This induction can be repressed by TGF-beta and was observed to persist for at least 48 hrs, suggesting that TGF-beta inhibits PAR-2 expression through multiple pathways. First of all, TGF-beta was able to inhibit PAR-2 activity by inhibiting IL-1beta-induced p38 signal transduction and secondly the inhibition was also indirectly due to MMP-13 inactivation. Finally, TGF-beta was able to induce CTGF, and in turn CTGF represses PAR-2 expression by inhibiting IL-1beta-induced phospho-p38 level. TGF-beta could prevent OA from progression with the anabolic ability to induce CTGF production to maintain extracellular matrix (ECM) integrity and to down regulate PAR-2 expression, and the anti-catabolic ability to induce Tissue inhibitors of metalloproteinase-3 (TIMP-3) production to inhibit MMPs leading to avoid PAR-2 over-expression. Because IL-1beta-induced PAR-2 expressed in hPSCs might play a significantly important role in early phase of OA, PAR-2 repression by exogenous TGF-beta or other agents might be an ideal therapeutic target to prevent OA from progression.

  20. Beta-decay rate and beta-delayed neutron emission probability of improved gross theory

    NASA Astrophysics Data System (ADS)

    Koura, Hiroyuki

    2014-09-01

    A theoretical study has been carried out on beta-decay rate and beta-delayed neutron emission probability. The gross theory of the beta decay is based on an idea of the sum rule of the beta-decay strength function, and has succeeded in describing beta-decay half-lives of nuclei overall nuclear mass region. The gross theory includes not only the allowed transition as the Fermi and the Gamow-Teller, but also the first-forbidden transition. In this work, some improvements are introduced as the nuclear shell correction on nuclear level densities and the nuclear deformation for nuclear strength functions, those effects were not included in the original gross theory. The shell energy and the nuclear deformation for unmeasured nuclei are adopted from the KTUY nuclear mass formula, which is based on the spherical-basis method. Considering the properties of the integrated Fermi function, we can roughly categorized energy region of excited-state of a daughter nucleus into three regions: a highly-excited energy region, which fully affect a delayed neutron probability, a middle energy region, which is estimated to contribute the decay heat, and a region neighboring the ground-state, which determines the beta-decay rate. Some results will be given in the presentation. A theoretical study has been carried out on beta-decay rate and beta-delayed neutron emission probability. The gross theory of the beta decay is based on an idea of the sum rule of the beta-decay strength function, and has succeeded in describing beta-decay half-lives of nuclei overall nuclear mass region. The gross theory includes not only the allowed transition as the Fermi and the Gamow-Teller, but also the first-forbidden transition. In this work, some improvements are introduced as the nuclear shell correction on nuclear level densities and the nuclear deformation for nuclear strength functions, those effects were not included in the original gross theory. The shell energy and the nuclear deformation for

  1. Hypersomnolence with beta-adrenergic blockers.

    PubMed

    Thachil, J; Zeller, J R; Kochar, M S

    1987-11-01

    An elderly, mildly demented, hypertensive male patient developed hypersomnolence on administration of propranolol for treatment of hypertension; no other cause for hypersomnolence was detected. Upon replacement of propranolol with atenolol, he felt better but continued to be quite somnolent. When atenolol was discontinued, he reported to have lack of sleep. On readministration of subtherapeutic doses of the same beta-adrenergic blocking agents, he once again experienced excessive sleepiness. By discontinuing beta-blocking agents and introducing captopril, he felt much better, became pleasant and talkative, and blood pressure was well controlled. Beta antagonists are important drugs in the management of many cardiovascular problems. Propranolol, a lipophilic beta-blocking agent, and atenolol, a hydrophilic beta-blocking agent, are two of the major agents currently used clinically in the United States. Numerous neuropsychiatric side-effects of the beta-adrenergic blocking drugs have been reported, but hypersomnolence is not readily recognized as one of them.

  2. Procollagen C-proteinase enhancer-1 (PCPE-1) interacts with beta2-microglobulin (beta2-m) and may help initiate beta2-m amyloid fibril formation in connective tissues.

    PubMed

    Morimoto, Hisanori; Wada, Jun; Font, Bernard; Mott, Joni D; Hulmes, David J S; Ookoshi, Tadakazu; Naiki, Hironobu; Yasuhara, Akihiro; Nakatsuka, Atsuko; Fukuoka, Kousuke; Takatori, Yuji; Ichikawa, Haruo; Akagi, Shigeru; Nakao, Kazushi; Makino, Hirofumi

    2008-04-01

    Dialysis related amyloidosis (DRA) is a progressive and serious complication in patients under long-term hemodialysis and mainly leads to osteo-articular diseases. Although beta(2)-microglobulin (beta2-m) is the major structural component of beta2-m amyloid fibrils, the initiation of amyloid formation is not clearly understood. Here, we have identified procollagen C-proteinase enhancer-1 (PCPE-1) as a new interacting protein with beta2-m by screening a human synovium cDNA library. The interaction of beta2-m with full-length PCPE-1 was confirmed by immunoprecipitation, solid-phase binding and pull-down assays. By yeast two-hybrid analysis and pull-down assay, beta2-m appeared to interact with PCPE-1 via the NTR (netrin-like) domain and not via the CUB (C1r/C1s, Uegf and BMP-1) domain region. In synovial tissues derived from hemodialysis patients with DRA, beta2-m co-localized and formed a complex with PCPE-1. beta2-m did not alter the basal activity of bone morphogenetic protein-1/procollagen C-proteinase (BMP-1/PCP) nor BMP-1/PCP activity enhanced by PCPE-1. PCPE-1 did not stimulate beta2-m amyloid fibril formation from monomeric beta2-m in vitro under acidic and neutral conditions as revealed by thioflavin T fluorescence spectroscopy and electron microscopy. Since PCPE-1 is abundantly expressed in connective tissues rich in type I collagen, it may be involved in the initial accumulation of beta2-m in selected tissues such as tendon, synovium and bone. Furthermore, since such preferential deposition of beta2-m may be linked to subsequent beta2-m amyloid fibril formation, the disruption of the interaction between beta2-m and PCPE-1 may prevent beta2-m amyloid fibril formation and therefore PCPE-1 could be a new target for the treatment of DRA.

  3. Ca2+-dependent dephosphorylation of kinesin heavy chain on beta-granules in pancreatic beta-cells. Implications for regulated beta-granule transport and insulin exocytosis

    NASA Technical Reports Server (NTRS)

    Donelan, Matthew J.; Morfini, Gerardo; Julyan, Richard; Sommers, Scott; Hays, Lori; Kajio, Hiroshi; Briaud, Isabelle; Easom, Richard A.; Molkentin, Jeffery D.; Brady, Scott T.; hide

    2002-01-01

    The specific biochemical steps required for glucose-regulated insulin exocytosis from beta-cells are not well defined. Elevation of glucose leads to increases in cytosolic [Ca2+]i and biphasic release of insulin from both a readily releasable and a storage pool of beta-granules. The effect of elevated [Ca2+]i on phosphorylation of isolated beta-granule membrane proteins was evaluated, and the phosphorylation of four proteins was found to be altered by [Ca2+]i. One (a 18/20-kDa doublet) was a Ca2+-dependent increase in phosphorylation, and, surprisingly, three others (138, 42, and 36 kDa) were Ca2+-dependent dephosphorylations. The 138-kDa beta-granule phosphoprotein was found to be kinesin heavy chain (KHC). At low levels of [Ca2+]i KHC was phosphorylated by casein kinase 2, but KHC was rapidly dephosphorylated by protein phosphatase 2B beta (PP2Bbeta) as [Ca2+]i increased. Inhibitors of PP2B specifically reduced the second, microtubule-dependent, phase of insulin secretion, suggesting that dephosphorylation of KHC was required for transport of beta-granules from the storage pool to replenish the readily releasable pool of beta-granules. This is distinct from synaptic vesicle exocytosis, because neurotransmitter release from synaptosomes did not require a Ca2+-dependent KHC dephosphorylation. These results suggest a novel mechanism for regulating KHC function and beta-granule transport in beta-cells that is mediated by casein kinase 2 and PP2B. They also implicate a novel regulatory role for PP2B/calcineurin in the control of insulin secretion downstream of a rise in [Ca2+]i.

  4. Bucindolol, a nonselective beta 1- and beta 2-adrenergic receptor antagonist, decreases beta-adrenergic receptor density in cultured embryonic chick cardiac myocyte membranes.

    PubMed

    Asano, K; Zisman, L S; Yoshikawa, T; Headley, V; Bristow, M R; Port, J D

    2001-06-01

    Bucindolol and carvedilol, nonselective beta1- and beta2-adrenergic receptor antagonists, have been widely used in clinical therapeutic trials of congestive heart failure. The aim of the current study was to investigate long-term effects of bucindolol or carvedilol on beta-adrenergic receptor protein and gene expression in cardiac myocytes. Embryonic chick cardiac myocytes were cultured and incubated with bucindolol (1 microM), carvedilol (1 microM), or norepinephrine (1 microM) for 24 h. 125I-iodocyanopindolol binding assays demonstrated that incubation with norepinephrine or bucindolol, but not carvedilol, significantly decreased beta-adrenergic receptor density in crude membranes prepared from the myocytes. Neither bucindolol nor carvedilol significantly stimulated adenylyl cyclase activity in membranes from drug-untreated cells. Unlike by norepinephrine, the receptor density reduction by bucindolol incubation was not accompanied by a change in beta1-adrenergic receptor messenger RNA abundance. A decrease in membrane beta-adrenergic receptor density without a change in cognate messenger RNA abundance was also observed in hamster DDT1 MF2 cell line incubated with bucindolol (1 microM, 24 h). We conclude that incubation with bucindolol, but not carvedilol, results in true reduction of beta-adrenergic receptor density in chick cardiac myocyte membranes by mechanisms that are distinct from those responsible for receptor density reduction by the agonist norepinephrine.

  5. The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade.

    PubMed

    Wheeldon, N M; McDevitt, D G; Lipworth, B J

    1994-08-01

    1. The aim of the present study was to evaluate the relative beta 1/beta 2 antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2. Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover design. beta 1-adrenoceptor antagonism was assessed by attenuation of exercise tachycardia, and beta 2-adrenoceptor blockade by effects on salbutamol-induced chronotropic, hypokalaemic and finger tremor responses. The relative percentage attenuation of beta 2 and beta 1-mediated responses was calculated and expressed as beta 2:beta 1 selectivity ratios. 3. Nadolol produced dose-related reductions in exercise tachycardia in keeping with increasing beta 1-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta 2-mediated effects and significantly increase exercise hyperkalaemia; peak exercise hyperkalaemia (mmol l-1) (means and 95% CI): PL 4.88 (4.68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta 2:beta 1 selectivity ratios significantly increased as the dose of nadolol was reduced. 4. These data suggest that whereas in the clinical dose range nadolol behaves as a non-selective beta-adrenoceptor antagonist, as the dose is reduced this drug demonstrates an increasing degree of selectivity for the beta 2-adrenoceptor.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Beta-glucosidase I variants with improved properties

    DOEpatents

    Bott, Richard R.; Kaper, Thijs; Kelemen, Bradley; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus; Kralj, Slavko; Kruithof, Paulien; Nikolaev, Igor; Van Der Kley, Wilhelmus Antonious Hendricus; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander

    2016-09-20

    The present disclosure is generally directed to enzymes and in particular beta-glucosidase variants. Also described are nucleic acids encoding beta-glucosidase variants, compositions comprising beta-glucosidase variants, methods of using beta-glucosidase variants, and methods of identifying additional useful beta-glucosidase variants.

  7. Characterization of a beta-glycosidase highly active on disaccharides and of a beta-galactosidase from Tenebrio molitor midgut lumen.

    PubMed

    Ferreira, Alexandre H P; Terra, Walter R; Ferreira, Clélia

    2003-02-01

    The midgut of the yellow mealworm, Tenebrio molitor L. (Coleoptera: Tenebrionidae) larvae has four beta-glycosidases. The properties of two of these enzymes (betaGly1 and betaGly2) have been described elsewhere. In this paper, the characterization of the other two glycosidases (betaGly3 and betaGly4) is described. BetaGly3 has one active site, hydrolyzes disaccharides, cellodextrins, synthetic substrates and beta-glucosides produced by plants. The enzyme is inhibited by amygdalin, cellotriose, cellotetraose and cellopentaose in high concentrations, probably due to transglycosylation. betaGly3 hydrolyzes beta 1,4-glycosidic linkages with a catalytic rate independent of the substrate polymerization degree (k(int)) of 11.9 s(-1). Its active site is formed by four subsites, where subsites +1 and -1 bind glucose residues with higher affinity than subsite +2. The main role of betaGly3 seems to be disaccharide hydrolysis. BetaGly4 is a beta-galactosidase, since it has highest activity against beta-galactosides. It can also hydrolyze fucosides, but not glucosides, and has Triton X-100 as a non-essential activator (K(a)=15 microM, pH 4.5). betaGly4 has two active sites that can hydrolyze p-nitrophenyl beta-galactoside (NPbetaGal). The one hydrolyzing NPbetaGal with more efficiency is also active against methylumbellipheryl beta-D-galactoside and lactose. The other active site hydrolyzes NPbetaFucoside and binds NPbetaGal weakly. BetaGly4 hydrolyzes hydrophobic substrates with high catalytical efficiency and is able to bind octyl-beta-thiogalactoside in its active site with high affinity. The betaGly4 physiological role is supposed to be the hydrolysis of galactolipids that are found in membranes from vegetal tissues. As the enzyme has a hydrophobic site where Triton X-100 can bind, it might be activated by membrane lipids, thus becoming fully active only at the surface of cell membranes.

  8. [Characterization of microstructure of ibuprofen-hydroxypropyl-beta-cyclodextrin and ibuprofen-beta-cyclodextrin by atomic force microscope].

    PubMed

    Wang, Li-juan; Zhu, Zhao-jing; Che, Ke-ke; Ju, Feng-ge

    2008-09-01

    The microstructures of ibuprofen-hydroxypropyl-bets-cyclodextrin (IBU-HP-beta-CyD) and ibuprofen-beta-cyclodextrin (IBU-beta-CyD) were observed by atomic force microscope (AFM). The high resolving capability of AFM has the tungsten filament probe with the spring constant of 0.06 N x m(-1). Samples were observed in a small scale scanning area of 10.5 nm x 10.5 nm and 800 x 800 pixels. The original scanning images were gained by tapping mode at room temperature. Their three-dimensional reconstruction of microstructure was performed by G3DR software. The outer diameters of HP-beta-CyD and beta-CyD are 1.53 nm. The benzene diameter of IBU is 0.62 nm, fitting to the inner diameters of HP-beta-CyD and beta-CyD. The benzene and hydrophobic chain of IBU enter into the hole of cyclodextrin at 1:1 ratio. The results were evidenced by IR, X-ray diffraction and the phase solubility.

  9. Temperature Dependence of Positron Annihilation in beta-Cyclodextrin and beta-Cyclodextrin Complexes

    NASA Astrophysics Data System (ADS)

    Hu, Y.; Hsu Hadley, F. H., Jr.; Trinh, T.

    1996-11-01

    The effects of temperature on positron annihilation in beta-cyclodextrin and beta-cyclodextrin complexed with benzyl salicylate, benzyl acetate, ethyl salicylate, geraniol, linalool and nerol were studied. Samples were prepared by slurry, air-dried and freeze-dried methods. Lifetime spectra were measured as a function of temperature for each sample. Comparison of the annihilation rate and intensity of the longer-lived component showed that positronium formation was affected by guest molecules, preparation methods and temperature variations. Results can be used to explain beta-cyclodextrin complex formation with different guest molecules.

  10. Investigation of charge-transfer hydrogen bonding interaction of 1-(2-pyridylazo)-2-naphthol (PAN) and 4-(2-Pyridylazo)resorcinol (PAR) with chloranilic acid through experimental and DFT studies

    NASA Astrophysics Data System (ADS)

    Karmakar, Animesh; Singh, Bula

    2018-07-01

    The H-bonding interaction of 1-(2-pyridylazo)-2-naphthol (PAN) and 4-(2-Pyridylazo) resorcinol (PAR) with chloranilic acid (CLA) have been considered spectroscopically in methanol solvent. PAN and PAR were used as a ligand and this two ligands has diverse application in spectrophotometric, chelatometric analysis of different metal ions. However, it is seen as of the literature analysis that no molecular complex of PAN and PAR with CLA was reported. The creation of charge-transfer H-bonded adduct gives a outlook to progress the physico-chemical scenery of the donor. So the complex of PAN and PAR with chloranilic acid was recounted in this work in methanol medium. Both the hydrogen-bonded molecular complexes have been prepared and identified using 1H NMR, FT-IR, and elemental analysis. Spectroscopic data point out that PAN and PAR discretely interact with CLA by a physically potent H-bonding interaction. The thermal constancy of the above molecular complexes has been determined by TGA-DTA analysis. The computational calculation also supported the development of the H-bonded charge-transfer adduct.

  11. Equine endometrial fibrosis correlates with 11beta-HSD2, TGF-beta1 and ACE activities.

    PubMed

    Ganjam, V K; Evans, T J

    2006-03-27

    Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss in mares. Equine EPF correlates inversely with conception and successful gestation. In the modified Kenney endometrial biopsy classification system, EPF categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe fibrosis (+/-inflammation), respectively. Paraffin sections of biopsy specimens were stained with H&E, and picrosirius red (specific for fibrillar collagens types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF-beta1 and 11beta-HSD2 activities were also measured. Ultrastructural changes in EPF categories IIB and III endometria strongly suggested myofibroblastic transformation. ACE-binding activity was highest in EPF category IIB; however, endometrial TGF-beta1 and 11beta-HSD2 activities were significantly correlated to the severity of EPF (P<0.05). We conclude that, locally generated angiotensin II initiates the expression of TGF-beta1 resulting in myofibroblastic transformation. 11Beta-HSD2 in concert appears to modulate the severity of endometrial fibrosis.

  12. A comparison of heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major.

    PubMed

    Amoozgar, Hamid; Zeighami, Samaneh; Haghpanah, Sezaneh; Karimi, Mehran

    2017-01-01

    The goal of this study was to compare heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major. In this cross-sectional study, 60 patients with beta thalassemia major and 60 patients with beta thalassemia intermedia who had clinically no symptoms of arrhythmia and clinically normal heart function were evaluated using 24-hour ambulatory electrocardiogram monitoring and echocardiography. For data analysis SPSS ver.20 software was used. A P-value of less than 0.05 was considered statistically significant. The mean age of the beta thalassemia intermedia patients was 24.18 ± 7.9 years and the mean age in beta thalassemia major was 24.38 ± 7.7 years (P>0.05). Premature atrial contractions (PACs) were observed in 14 (23.3%) patients with beta thalassemia intermedia and in 22 (36.6%) beta thalassemia major patients. Premature ventricular contractions (PVCs) were detected in 8 (13.3%) patients in the beta thalassemia intermediate group and 16 (26.6) patients in the beta thalassemia major group, respectively. The left ventricular diastolic dimension, end-diastolic volume, and stroke volume were significantly higher in beta thalassemia intermedia group (P<0.05). Pulmonary acceleration time as an indicator of pulmonary pressure was lower in beta thalassemia intermedia group. Both atrial and ventricular arrhythmias were more common in the beta thalassemia major group. Higher end-diastolic volume and stroke volume were detected in the beta thalassemia intermedia group. Pulmonary acceleration time was lower in the beta thalassemia intermedia group, which can be an indicator of higher pulmonary pressure.

  13. Molecular analysis of the beta-thalassemia phenotype associated with inheritance of hemoglobin E (alpha 2 beta2(26)Glu leads to Lys).

    PubMed Central

    Benz, E J; Berman, B W; Tonkonow, B L; Coupal, E; Coates, T; Boxer, L A; Altman, A; Adams, J G

    1981-01-01

    Inheritance of the gene for betaE-globin is associated with hypochromia and microcytosis, reminiscent of typical heterozygous beta-thalassemia. Patients with hemoglobin (Hb)E-beta-thalassemia exhibit clinical phenotypes of severe beta-thalassemia, a circumstance not encountered in other compound heterozygous states for structural beta-chain mutations and beta-thalassemia. We have analyzed the kinetics of globin synthesis and the levels of globin messenger (m) RNA accumulation in patients with Hb E-beta-thalassemia and Hb E trait. The initial rate of beta-globin synthesis (betaE/alpha=0.20-0.34) was less than expected on the basis of gene dosage, or comparable studies of other compound heterozygous states for beta-thalassemia and structurally abnormal beta-chains. betaE-globin synthesis was not only reduced during short-term incubations (1-5 min), but also remained relatively unchanged during long-term pulse or chase incubations up to 5h. Analysis of globin mRNA by cell-free translation and molecular hybridization confirmed that the unexpectedly low levels of betaE-globin synthesis were associated with comparable reduction in the levels of beta-globin mRNA. In Hb E-beta-thalassemia the betaA + betaE (alpha globin nRNA ratio observed were substantially lower than those obtained from reticulocytes of patients with heterozygous beta-thalassemia, or Hb S-betaO-thalassemia, while in Hb E trait, the betaA + betaE/alpha mRNA ratio was in the ranged observed for beta-thalassemia trait. The betaE-globin gene specifies reduced accumulation of betaE-globin mRNA, a property characteristic of other forms of beta-thalassemia. The beta-thalassemia phenotype associated with inheritance of Hb E is thus determined at the level of beta-globin mRNA metabolism. PMID:6166632

  14. Tyrosine residues 654 and 670 in {beta}-cat enin are crucial in regulation of Met-{beta}-catenin interactions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zeng, Gang; Apte, Udayan; Micsenyi, Amanda

    2006-11-01

    {beta}-catenin, a key component of the canonical Wnt pathway, is also regulated by tyrosine phosphorylation that regulates its association to E-cadherin. Previously, we reported its association with the hepatocyte growth factor (HGF) receptor Met at the membrane. HGF induced Met-{beta}-catenin dissociation and nuclear translocation of {beta}-catenin, which was tyrosine-phosphorylation-dependent. Here, we further investigate the Met-{beta}-catenin interaction by selectively mutating several tyrosine residues, alone or in combination, in {beta}-catenin. The mutants were subcloned into FLAG-CMV vector and stably transfected into rat hepatoma cells, which were treated with HGF. All single or double-mutant-transfected cells continued to show HGF-induced nuclear translocation of FLAG-{beta}-cateninmore » except the mutations affecting 654 and 670 simultaneously (Y654/670F), which coincided with the lack of formation of {beta}-catenin-TCF complex and DNA synthesis, in response to the HGF treatment. In addition, the Y654/670F-transfected cells also showed no phosphorylation of {beta}-catenin or dissociation from Met in response to HGF. Thus, intact 654 and 670 tyrosine residues in {beta}-catenin are crucial in HGF-mediated {beta}-catenin translocation, activation and mitogenesis.« less

  15. The H,K-ATPase beta-subunit can act as a surrogate for the beta-subunit of Na,K-pumps.

    PubMed

    Horisberger, J D; Jaunin, P; Reuben, M A; Lasater, L S; Chow, D C; Forte, J G; Sachs, G; Rossier, B C; Geering, K

    1991-10-15

    Na,K-ATPase and H,K-ATPase are the only members of the P-type ATPases in which a glycosylated beta-subunit is part of the purified active enzyme. In this study, we have followed the synthesis and the posttranslational processing of the beta-subunit of H,K-ATPase (beta HK) in Xenopus oocytes injected with beta HK cRNA and have tested whether it can act as a surrogate for the beta-subunit of Na,K-ATPase (beta NaK) to support the functional expression of Na,K-pumps. In Xenopus oocytes, beta HK is processed from an Endo H-sensitive 51-kDa coreglycosylated form to an Endo H-resistant 71-kDa fully glycosylated form. Similar to beta NaK, beta HK can stabilize and increase the trypsin resistance of alpha-subunits of Na,K-ATPase (alpha NaK). Finally, expression of beta HK together with alpha NaK leads to an increased number of ouabain binding sites at the plasma membrane accompanied by an increased Rb+ uptake and Na,K-pump current. Our data suggest that beta HK, similar to beta NaK, can assemble to alpha NaK, support the structural maturation and the intracellular transport of catalytic alpha NaK, and ultimately form active alpha NaK-beta HK complexes with Na,K-pump transport properties.

  16. Molecular analysis of beta-globin gene mutations among Thai beta-thalassemia children: results from a single center study

    PubMed Central

    Boonyawat, Boonchai; Monsereenusorn, Chalinee; Traivaree, Chanchai

    2014-01-01

    Background Beta-thalassemia is one of the most common genetic disorders in Thailand. Clinical phenotype ranges from silent carrier to clinically manifested conditions including severe beta-thalassemia major and mild beta-thalassemia intermedia. Objective This study aimed to characterize the spectrum of beta-globin gene mutations in pediatric patients who were followed-up in Phramongkutklao Hospital. Patients and methods Eighty unrelated beta-thalassemia patients were enrolled in this study including 57 with beta-thalassemia/hemoglobin E, eight with homozygous beta-thalassemia, and 15 with heterozygous beta-thalassemia. Mutation analysis was performed by multiplex amplification refractory mutation system (M-ARMS), direct DNA sequencing of beta-globin gene, and gap polymerase chain reaction for 3.4 kb deletion detection, respectively. Results A total of 13 different beta-thalassemia mutations were identified among 88 alleles. The most common mutation was codon 41/42 (-TCTT) (37.5%), followed by codon 17 (A>T) (26.1%), IVS-I-5 (G>C) (8%), IVS-II-654 (C>T) (6.8%), IVS-I-1 (G>T) (4.5%), and codon 71/72 (+A) (2.3%), and all these six common mutations (85.2%) were detected by M-ARMS. Six uncommon mutations (10.2%) were identified by DNA sequencing including 4.5% for codon 35 (C>A) and 1.1% initiation codon mutation (ATG>AGG), codon 15 (G>A), codon 19 (A>G), codon 27/28 (+C), and codon 123/124/125 (-ACCCCACC), respectively. The 3.4 kb deletion was detected at 4.5%. The most common genotype of beta-thalassemia major patients was codon 41/42 (-TCTT)/codon 26 (G>A) or betaE accounting for 40%. Conclusion All of the beta-thalassemia alleles have been characterized by a combination of techniques including M-ARMS, DNA sequencing, and gap polymerase chain reaction for 3.4 kb deletion detection. Thirteen mutations account for 100% of the beta-thalassemia genes among the pediatric patients in our study. PMID:25525381

  17. In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus.

    PubMed Central

    Kobayashi, S; Arai, S; Hayashi, S; Sakaguchi, T

    1989-01-01

    The effects of combinations of beta-lactams with two beta-lactamase inhibitors, sulbactam and clavulanic acid, were determined in vitro against 22 clinical isolates of methicillin-resistant Staphylococcus aureus. Combinations of cefpirome, cefotaxime, and cefazolin with sulbactam (10 micrograms/ml) showed synergistic effects against more than 70% of the strains. Combinations of methicillin and penicillin G with sulbactam also showed synergistic effects against 50 and 68% of the strains, respectively, while cefotiam, moxalactam, flomoxef, and cefmetazole in combination with sulbactam showed such effects against only 40% or fewer. Clavulanic acid was synergistic only when combined with penicillin G, the effect probably being due to the beta-lactamase inhibition by the inhibitor. Sulbactam did not improve the antimicrobial activities of the beta-lactams against methicillin-susceptible S. aureus strains. At 42 degrees C the MICs of cefotaxime, methicillin, and flomoxef alone were markedly decreased from the values at 35 degrees C, and no synergy between these beta-lactams and sulbactam appeared. The resistance to penicillin G was not inhibited by incubation at 42 degrees C, and combinations of penicillin G with sulbactam and clavulanic acid showed synergy. The amounts of beta-lactamase produced were not related to the decreases in the MICs of the beta-lactams, except for penicillin G combined with sulbactam. Clavulanic acid showed slightly stronger beta-lactamase-inhibiting activity than sulbactam did. These results suggest that the synergy between sulbactam and the beta-lactams, except for penicillin G, may not be due to beta-lactamase inhibition but to suppression of the methicillin-resistant S. aureus-specific resistance based on other factors. PMID:2786369

  18. Misleading Betas: An Educational Example

    ERIC Educational Resources Information Center

    Chong, James; Halcoussis, Dennis; Phillips, G. Michael

    2012-01-01

    The dual-beta model is a generalization of the CAPM model. In the dual-beta model, separate beta estimates are provided for up-market and down-market days. This paper uses the historical "Anscombe quartet" results which illustrated how very different datasets can produce the same regression coefficients to motivate a discussion of the…

  19. Beta-glucosidase variants and polynucleotides encoding same

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wogulis, Mark; Harris, Paul; Osborn, David

    The present invention relates to beta-glucosidase variants, e.g. beta-glucosidase variants of a parent Family GH3A beta-glucosidase from Aspergillus fumigatus. The present invention also relates to polynucleotides encoding the beta-glucosidase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the beta-glucosidase variants.

  20. Activities of beta-lactam antibiotics against Escherichia coli strains producing extended-spectrum beta-lactamases.

    PubMed Central

    Jacoby, G A; Carreras, I

    1990-01-01

    Seven extended-spectrum beta-lactamases related to TEM and four enzymes derived from SHV-1 were transferred to a common Escherichia coli host so that the activity of a variety of beta-lactams could be tested in a uniform genetic environment. For most derivatives, penicillinase activity was 10% or less than that of strains making TEM-1, TEM-2, or SHV-1 beta-lactamase, suggesting that reduced catalytic efficiency accompanied the broader substrate spectrum. Despite this deficit, resistance to aztreonam, carumonam, cefdinir, cefepime, cefixime, cefmenoxime, cefotaxime, cefotiam, cefpirome, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime, and E1040 was enhanced. For strains producing TEM-type enzymes, however, MICs of carumonam, cefepime, cefmenoxime, cefotiam, cefpirome, and ceftibuten were 8 micrograms/ml or less. Susceptibilities of cefmetazole, cefotetan, cefoxitin, flomoxef, imipenem, meropenem, moxalactam, temocillin, FCE 22101, and Sch 34343 were unaffected. FCE 22101, imipenem, meropenem, and Sch 34343 were inhibitory for all strains at 1 microgram/ml or less. In E. coli an OmpF- porin mutation in combination with an extended-spectrum beta-lactamase enhanced resistance to many of these agents, but generally by only fourfold. Hyperproduction of chromosomal AmpC beta-lactamase increased resistance to 7-alpha-methoxy beta-lactams but not that to temocillin. When tested at 8 micrograms/ml, clavulanate was more potent than sulbactam or tazobactam in overcoming resistance to ampicillin, while cefoperazone-sulbactam was more active than ticarcillin-clavulanate or piperacillin-tazobactam, especially against TEM-type extended-spectrum beta-lactamases. PMID:2193623

  1. TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chung, Eun Jee; Chun, Ji Na; Jung, Sun-Ah

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology inmore » pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful

  2. Beta-glucuronidase and Beta-glucosidase activity in stool specimens of children with inflammatory bowel disease.

    PubMed

    Mroczyńska, Marta; Galecka, Miroslawa; Szachta, Patrycja; Kamoda, Dorota; Libudzisz, Zdzislawa; Roszak, Dorota

    2013-01-01

    The aim of the study was to analyze the differences in the activity of beta-glucuronidase and beta-glucosidase in stool specimens of children with Inflammatory Bowel Diseases (IBD) and healthy subjects. The disease activity was determined according to the PCDAI scale (Crohn disease) and Truelove-Witts scale (Ulcerative colitis). Enzyme activity was determined by spectrophotometry. There was a correlation between the level of beta - glucosidase activity in stool and patient's age in the group of healthy controls, but not in the IBD group. beta-glucosidase activity in IBD and healthy subjects stool specimens did not differ significantly. The activity of beta-glucuronidase in children with IBD was two times lower than in the healthy group and was correlated with age in children with IBD, but not in the group of healthy ones.

  3. Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)-mediated signal transduction pathway: role of GSK-3beta in myocardial protection against ischemia/reperfusion injury.

    PubMed

    Miura, Tetsuji; Nishihara, Masahiro; Miki, Takayuki

    2009-02-01

    Although reperfusion is required to salvage ischemic myocardium from necrosis, reperfusion per se induces myocardial necrosis. In this "lethal reperfusion injury", opening of the mitochondrial permeability transition pore (mPTP) upon reperfusion is crucially involved. The mPTP primarily consists of adenine nucleotide translocator (ANT) and voltage-dependent anion channel, and its opening is triggered by binding of cyclophilin-D (CyP-D) to ANT, which increases Ca(2+) sensitivity of the mPTP. Recent studies have shown that inactivation of glycogen synthase kinase-3beta (GSK-3beta) suppresses mPTP opening and protects cardiomyocytes. Multiple intracellular signals relevant to cardiomyocyte protection converge to GSK-3beta and inactivate this kinase by phosphorylation. Although the effect of GSK-3beta phosphorylation on mPTP structure and function remains unclear, suppression of ANT-CyP-D interaction by binding of phospho-GSK-3beta to ANT and reduction in GSK-3beta-mediated phosphorylation of p53 may contribute to elevation of the threshold for mPTP opening. Furthermore, a significant inverse correlation was observed between level of phospho-GSK-3beta at the time of reperfusion and the extent of myocardium infarction in heart. Together with the infarct size-limiting effect of GSK-3beta inhibitors, this finding indicates that phospho-GSK-3beta is a determinant of myocardial tolerance against reperfusion-induced necrosis. Thus, GSK-3beta appears to be a target of novel therapy for cardioprotection upon reperfusion.

  4. Milk Intolerance, Beta-Casein and Lactose.

    PubMed

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen

    2015-08-31

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  5. Milk Intolerance, Beta-Casein and Lactose

    PubMed Central

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen

    2015-01-01

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed. PMID:26404362

  6. Spectroscopic Studies of Double Beta Decays and MOON

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ejiri, H.; Nuclear Science, Czech Technical University, Brehova, Prague, Czech Republic, National Institute of Radiological Sciences, Chiba, 263-8555

    2007-10-12

    This is a brief review of future spectroscopic experiments of neutrino-less double beta decays (0{nu}{beta}{beta}) and the MOON (Mo Observatory Of Neutrinos) project. Spectroscopic 0{nu}{beta}{beta} experiments of MOON, SuperNEMO and DCBA are planned to study Majorana masses in the quasi-degenerate (QD) and inverted mass hierarchy (IH) regions. MOON aims at 0{nu}{beta}{beta} studies with the {nu}-mass sensitivities of 100-30 meV by means of a super ensemble of multi-layer modules, each being consist of a scintillator plate, two tracking detector planes and a thin {beta}{beta} source film.

  7. Variants of beta-glucosidase

    DOEpatents

    Fidantsef, Ana; Lamsa, Michael; Gorre-Clancy, Brian

    2015-07-14

    The present invention relates to variants of a parent beta-glucosidase, comprising a substitution at one or more positions corresponding to positions 142, 183, 266, and 703 of amino acids 1 to 842 of SEQ ID NO: 2 or corresponding to positions 142, 183, 266, and 705 of amino acids 1 to 844 of SEQ ID NO: 70, wherein the variant has beta-glucosidase activity. The present invention also relates to nucleotide sequences encoding the variant beta-glucosidases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  8. Variants of beta-glucosidases

    DOEpatents

    Fidantsef, Ana; Lamsa, Michael; Gorre-Clancy, Brian

    2014-10-07

    The present invention relates to variants of a parent beta-glucosidase, comprising a substitution at one or more positions corresponding to positions 142, 183, 266, and 703 of amino acids 1 to 842 of SEQ ID NO: 2 or corresponding to positions 142, 183, 266, and 705 of amino acids 1 to 844 of SEQ ID NO: 70, wherein the variant has beta-glucosidase activity. The present invention also relates to nucleotide sequences encoding the variant beta-glucosidases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  9. Variants of beta-glucosidase

    DOEpatents

    Fidantsef, Ana [Davis, CA; Lamsa, Michael [Davis, CA; Gorre-Clancy, Brian [Elk Grove, CA

    2009-12-29

    The present invention relates to variants of a parent beta-glucosidase, comprising a substitution at one or more positions corresponding to positions 142, 183, 266, and 703 of amino acids 1 to 842 of SEQ ID NO: 2 or corresponding to positions 142, 183, 266, and 705 of amino acids 1 to 844 of SEQ ID NO: 70, wherein the variant has beta-glucosidase activity. The present invention also relates to nucleotide sequences encoding the variant beta-glucosidases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  10. Extracellular heat shock protein HSP90{beta} secreted by MG63 osteosarcoma cells inhibits activation of latent TGF-{beta}1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Suzuki, Shigeki; Kulkarni, Ashok B., E-mail: ak40m@nih.gov

    2010-07-30

    Transforming growth factor-beta 1 (TGF-{beta}1) is secreted as a latent complex, which consists of latency-associated peptide (LAP) and the mature ligand. The release of the mature ligand from LAP usually occurs through conformational change of the latent complex and is therefore considered to be the first step in the activation of the TGF-{beta} signaling pathway. So far, factors such as heat, pH changes, and proteolytic cleavage are reportedly involved in this activation process, but the precise molecular mechanism is still far from clear. Identification and characterization of the cell surface proteins that bind to LAP are important to our understandingmore » of the latent TGF-{beta} activation process. In this study, we have identified heat shock protein 90 {beta} (HSP90{beta}) from the cell surface of the MG63 osteosarcoma cell line as a LAP binding protein. We have also found that MG63 cells secrete HSP90{beta} into extracellular space which inhibits the activation of latent TGF-{beta}1, and that there is a subsequent decrease in cell proliferation. TGF-{beta}1-mediated stimulation of MG63 cells resulted in the increased cell surface expression of HSP90{beta}. Thus, extracellular HSP90{beta} is a negative regulator for the activation of latent TGF-{beta}1 modulating TGF-{beta} signaling in the extracellular domain. -- Research highlights: {yields} Transforming growth factor-beta 1 (TGF-{beta}1) is secreted as a latent complex. {yields} This complex consists of latency-associated peptide (LAP) and the mature ligand. {yields} The release of the mature ligand from LAP is the first step in TGF-{beta} activation. {yields} We identified for the first time a novel mechanism for this activation process. {yields} Heat shock protein 90 {beta} is discovered as a negative regulator for this process.« less

  11. Cross-class resistance to non-beta-lactam antimicrobials in extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.

    PubMed

    Procop, Gary W; Tuohy, Marion J; Wilson, Deborah A; Williams, Delisa; Hadziyannis, Emilia; Hall, Gerri S

    2003-08-01

    Extended spectrum beta-lactamases are modified beta-lactamase enzymes that impart resistance to third-generation cephalosporins and make all beta-lactam antibiotics and cephalosporins useless for therapy. We compared the antimicrobial susceptibility profiles of extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing isolates of Klebsiella pneumoniae. The ESBL producers had significantly diminished susceptibility compared with the non-ESBL producers for gentamicin (P < .001), tobramycin (P < .001), amikacin (P < .005), trimethoprim-sulfamethoxazole (P < .01), ciprofloxacin (P < .001), and nitrofurantoin (P < .001). All isolates were susceptible to imipenem. ESBL-producing K pneumoniae may also be resistant to non-beta-lactam antibiotics. Therefore, susceptibility testing of these isolates is critical for guiding therapy.

  12. Beta-1-Selective Beta-Blockers and Cognitive Functions in Patients With Coronary Artery Disease: A Cross-Sectional Study.

    PubMed

    Burkauskas, Julius; Noreikaite, Aurelija; Bunevicius, Adomas; Brozaitiene, Julija; Neverauskas, Julius; Mickuviene, Narseta; Bunevicius, Robertas

    2016-01-01

    The association between current beta-1-selective beta-blocker use and cognitive function was evaluated in 722 patients with coronary artery disease without dementia. Beta-1-selective beta-blocker use was associated with worse incidental learning independently of sociodemographic characteristics, clinical coronary artery disease severity, and depression/anxiety.

  13. beta. -lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant. beta. -endorphin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liotta, A.S.; Suda, T.; Krieger, D.T.

    1978-06-01

    ..beta..-Lipotropin is the predominant opioid peptide of the human pituitary and rat pars distalis and is present in concentrations essentially equimolar with corticotropin. When freshly obtained nonfrozen rat anterior pituitaries were homogenized with 0.2 M HCl, approximately 98% of the immunoreactivity detected utilizing an antiserum that crossreacts equally with ..beta..-lipotropin and ..beta..-endorphin coeluted with /sup 125/I-labeled human ..beta..-lipotropin upon molecular sieve chromatography. The remainder of the activity eluted with synthetic human ..beta..-endorphin. Similar results were obtained for human pituitary. HCl homogenization of thawed tissue or homogenization of fresh tissue with acetic acid yielded substantially greater concentrations of ..beta..-endorphin and decreasedmore » concentrations of ..beta..-lipotropin. In human subjects, acute anterior pituitary stimulation using either insulin-induced hypoglycemia or vasopressin administration was associated with increased plasma ..beta..-lipotropin and corticotropin levels. At the time of peak concentrations, no significant levels of ..beta..-endorphin were detectable. These data indicate the lack of significant amounts of ..beta..-endorphin in human pituitary. Additionally, there appears to be no specific intrapituitary conversion of ..beta..-lipotropin to ..beta..-endorphin.« less

  14. Chromosome mapping of the human arrestin (SAG), {beta}-arrestin 2 (ARRB2), and {beta}-adrenergic receptor kinase 2 (ADRBK2) genes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Calabrese, G.; Sallese, M.; Stornaiuolo, A.

    1994-09-01

    Two types of proteins play a major role in determining homologous desensitization of G-coupled receptors: {beta}-adrenergic receptor kinase ({beta}ARK), which phosphorylates the agonist-occupied receptor and its functional cofactor, {beta}-arrestin. Both {beta}ARK and {beta}-arrestin are members of multigene families. The family of G-protein-coupled receptor kinases includes rhodopsin kinase, {beta}ARK1, {beta}ARK2, IT11-A (GRK4), GRK5, and GRK6. The arrestin/{beta}-arrestin gene family includes arrestin (also known as S-antigen), {beta}-arrestin 1, and {beta}-arrestin 2. Here we report the chromosome mapping of the human genes for arrestin (SAG), {beta}arrestin 2 (ARRB2), and {beta}ARK2 (ADRBK2) by fluorescence in situ hybridization (FISH). FISH results confirmed the assignment ofmore » the gene coding for arrestin (SAG) to chromosome 2 and allowed us to refine its localization to band q37. The gene coding for {beta}-arrestin 2 (ARRB2) was mapped to chromosome 17p13 and that coding for {beta}ARK2 (ADRBK2) to chromosome 22q11. 17 refs., 1 fig.« less

  15. Substance P-induced trafficking of beta-arrestins. The role of beta-arrestins in endocytosis of the neurokinin-1 receptor.

    PubMed

    McConalogue, K; Déry, O; Lovett, M; Wong, H; Walsh, J H; Grady, E F; Bunnett, N W

    1999-06-04

    Agonist-induced redistribution of G-protein-coupled receptors (GPCRs) and beta-arrestins determines the subsequent cellular responsiveness to agonists and is important for signal transduction. We examined substance P (SP)-induced trafficking of beta-arrestin1 and the neurokinin-1 receptor (NK1R) in KNRK cells in real time using green fluorescent protein. Green fluorescent protein did not alter function or localization of the NK1R or beta-arrestin1. SP induced (a) striking and rapid (<1 min) translocation of beta-arrestin1 from the cytosol to the plasma membrane, which preceded NK1R endocytosis; (b) redistribution of the NK1R and beta-arrestin1 into the same endosomes containing SP and the transferrin receptor (2-10 min); (c) prolonged colocalization of the NK1R and beta-arrestin1 in endosomes (>60 min); (d) gradual resumption of the steady state distribution of the NK1R at the plasma membrane and beta-arrestin1 in the cytosol (4-6 h). SP stimulated a similar redistribution of immunoreactive beta-arrestin1 and beta-arrestin2. In contrast, SP did not affect Galphaq/11 distribution, which remained at the plasma membrane. Expression of the dominant negative beta-arrestin319-418 inhibited SP-induced endocytosis of the NK1R. Thus, SP induces rapid translocation of beta-arrestins to the plasma membrane, where they participate in NK1R endocytosis. beta-Arrestins colocalize with the NK1R in endosomes until the NK1R recycles and beta-arrestins return to the cytosol.

  16. Origin of a sensitive dependence of calculated {beta}{beta}-decay amplitudes on the particle-particle residual interaction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rodin, Vadim; Faessler, Amand

    2011-07-15

    In the present work the sensitivity of calculated {beta}{beta}-decay amplitudes to a realistic residual interaction is analyzed in the framework of the approach of O. A. Rumyantsev and M. H. Urin, Phys. Lett. B 443, 51 (1998). and V. A. Rodin, M. H. Urin, and A. Faessler, Nucl. Phys. A 747, 297 (2005). Both the Gamow-Teller (GT) and Fermi (F) matrix elements M{sup 2}{nu} for two-neutrino {beta}{beta} decay (2{nu}{beta}{beta} decay), along with the monopole transition contributions to the total matrix elements M{sup 0{nu}} of neutrinoless {beta}{beta} decay (0{nu}{beta}{beta} decay), are calculated within the quasiparticle random-phase approximation (QRPA). In the aforementionedmore » approach decompositions of M{sup 2{nu}} and M{sup 0{nu}} can be obtained in terms of the corresponding energy-weighted sum rules S. It is shown that in most of the cases almost the whole dependence of M{sup 2{nu}} and M{sup 0{nu}} on the particle-particle (p-p) renormalization parameter g{sub pp} is accounted for by the g{sub pp} dependence of the corresponding sum rules S. General expressions relating S to a realistic residual particle-particle interaction are derived, which show a pronounced sensitivity of S to the singlet-channel interaction in the case of F transitions and to the triplet-channel interaction in the case of GT transitions. Thus, the sensitivity of M{sup 2{nu}} and M{sup 0{nu}} to the SU(4)-symmetry-breaking part of the p-p residual interaction is dictated by the generic structure of the {beta}{beta}-decay amplitudes. Therefore, a choice of this part in a particular calculation needs a special caution. Finally, a better isospin-consistent way of renormalization of a realistic residual p-p interaction to use in QRPA calculations is suggested.« less

  17. A new compound heterozygous frameshift mutation in the type II 3{beta}-hydroxysteroid dehydrogenase 3{beta}-HSD gene causes salt-wasting 3{beta}-HSD deficiency congenital adrenal hyperplasia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, L.; Sakkal-Alkaddour, S.; Chang, Ying T.

    1996-01-01

    We report a new compound heterozygous frameshift mutation in the type II 3{Beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) gene in a Pakistanian female child with the salt-wasting form of 3{Beta}-HSD deficiency congenital adrenal hyperplasia. The etiology for her congenital adrenal hyperplasia was not defined. Although the family history suggested possible 3{beta}-HSd deficiency disorder, suppressed adrenal function caused by excess glucocorticoid therapy in this child at 7 yr of age did not allow hormonal diagnosis. To confirm 3{beta}-HSD deficiency, we sequenced the type II 3{beta}-HSD gene in the patient, her family, and the parents of her deceased paternal cousins. The type II 3{beta}-HSD genemore » region of a putative promotor, exons I, II, III, and IV, and exon-intron boundaries were amplified by PCR and sequenced in all subjects. The DNA sequence of the child revealed a single nucleotide deletion at codon 318 [ACA(Thr){r_arrow}AA] in exon IV in one allele, and two nucleotide deletions at codon 273 [AAA(Lys){r_arrow}A] in exon IV in the other allele. The remaining gene sequences were normal. The codon 318 mutation was found in one allele from the father, brother, and parents of the deceased paternal cousins. The codon 273 mutation was found in one allele of the mother and a sister. These findings confirmed inherited 3{beta}-HSD deficiency in the child caused by the compound heterozygous type II 3{beta}-HSD gene mutation. Both codons at codons 279 and 367, respectively, are predicted to result in an altered and truncated type II 3{beta}-HSD protein, thereby causing salt-wasting 3{beta}-HSD deficiency in the patient. 21 refs., 2 figs., 1 tab.« less

  18. Simultaneous beta and gamma spectroscopy

    DOEpatents

    Farsoni, Abdollah T.; Hamby, David M.

    2010-03-23

    A phoswich radiation detector for simultaneous spectroscopy of beta rays and gamma rays includes three scintillators with different decay time characteristics. Two of the three scintillators are used for beta detection and the third scintillator is used for gamma detection. A pulse induced by an interaction of radiation with the detector is digitally analyzed to classify the type of event as beta, gamma, or unknown. A pulse is classified as a beta event if the pulse originated from just the first scintillator alone or from just the first and the second scintillator. A pulse from just the third scintillator is recorded as gamma event. Other pulses are rejected as unknown events.

  19. Double beta decays of {sup 106}Cd

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Suhonen, Jouni

    2011-12-16

    The two-neutrino (2{nu}2{beta}) and neutrinoless (0{nu}2{beta}) double beta decays of {sup 106}Cd are studied for the transitions to the ground state 0{sub gs}{sup +} and 0{sup +} and 2{sup +} excited states in {sup 106}Pd by using realistic many-body wave functions calculated in the framework of the quasiparticle random-phase approximation. Effective, G-matrix-derived nuclear forces are used in realistic single-particle model spaces. All the possible channels, {beta}{sup +}{beta}{sup +}, {beta}{sup +}EC, and ECEC, are discussed for both the 2{nu}2{beta} and 0{nu}2{beta} decays. The associated half-lives are computed and particular attention is devoted to the study of the detectability of the resonantmore » neutrinoless double electron capture (R0{nu}ECEC) process in {sup 106}Cd. The calculations of the present article constitute the thus far most complete and up-to-date investigation of the double-beta-decay properties of {sup 106}Cd.« less

  20. Beta-catenin is required for memory consolidation.

    PubMed

    Maguschak, Kimberly A; Ressler, Kerry J

    2008-11-01

    beta-catenin has been implicated in neuronal synapse regulation and remodeling. Here we have examined beta-catenin expression in the adult mouse brain and its role in amygdala-dependent learning and memory. We found alterations in beta-catenin mRNA and protein phosphorylation during fear-memory consolidation. Such alterations correlated with a change in the association of beta-catenin with cadherin. Pharmacologically, this consolidation was enhanced by lithium-mediated facilitation of beta-catenin. Genetically, the role of beta-catenin was confirmed with site-specific deletions of loxP-flanked Ctnnb1 (encoding beta-catenin) in the amygdala. Baseline locomotion, anxiety-related behaviors and acquisition or expression of conditioned fear were normal. However, amygdala-specific deletion of Ctnnb1 prevented the normal transfer of newly formed fear learning into long-term memory. Thus, beta-catenin may be required in the amygdala for the normal consolidation, but not acquisition, of fear memory. This suggests a general role for beta-catenin in the synaptic remodeling and stabilization underlying long-term memory in adults.

  1. Self-assembled nanoparticle of common food constituents that carries a sparingly soluble small molecule.

    PubMed

    Bhopatkar, Deepak; Feng, Tao; Chen, Feng; Zhang, Genyi; Carignano, Marcelo; Park, Sung Hyun; Zhuang, Haining; Campanella, Osvaldo H; Hamaker, Bruce R

    2015-05-06

    A previously reported nanoparticle formed through the self-assembly of common food constituents (amylose, protein, and fatty acids) was shown to have the capacity to carry a sparingly soluble small molecule (1-naphthol) in a dispersed system. Potentiometric titration showed that 1-naphthol locates in the lumen of the amylose helix of the nanoparticle. This finding was further supported by calorimetric measurements, showing higher enthalpies of dissociation and reassociation in the presence of 1-naphthol. Visually, the 1-naphthol-loaded nanoparticle appeared to be well-dispersed in aqueous solution. Molecular dynamics simulation showed that the self-assembly was favorable, and at 500 ns, the 1-naphthol molecule resided in the helix of the amylose lumen in proximity to the hydrophobic tail of the fatty acid. Thus, sparingly soluble small molecules, such as some nutraceuticals or drugs, could be incorporated and delivered by this soft nanoparticle carrier.

  2. Chromosome-encoded beta-lactamases of Citrobacter diversus. Interaction with beta-iodopenicillanate and labelling of the active site.

    PubMed Central

    Amicosante, G; Oratore, A; Joris, B; Galleni, M; Frère, J M; Van Beeumen, J

    1988-01-01

    Both forms of the chromosome-encoded beta-lactamase of Citrobacter diversus react with beta-iodopenicillanate at a rate characteristic of class A beta-lactamases. The active site of form I was labelled with the same reagent. The sequence of the peptide obtained after trypsin hydrolysis is identical with that of a peptide obtained in a similar manner from the chromosome-encoded beta-lactamase of Klebsiella pneumoniae. PMID:2848500

  3. Organocatalysed asymmetric beta-amination and multicomponent syn-selective diamination of alpha,beta-unsaturated aldehydes.

    PubMed

    Jiang, Hao; Nielsen, Johanne B; Nielsen, Martin; Jørgensen, Karl Anker

    2007-01-01

    An easy and affordable route for obtaining chiral beta-aminated- and alpha,beta-diaminated aldehydes, 1,3-aminoalcohols, and related compounds by using organocatalysis is presented. The chiral secondary amine (S)-2-[bis(3,5-bistrifluoromethylphenyl)trimethylsilanyloxymethyl]pyrrolidine is used as the catalyst to activate alpha,beta-unsaturated aldehydes, which allows succinimide to add in a 1,4-regio- and stereoselective fashion thereby forming N-protected 1,3-aminoaldehydes in good yields and enantioselectivities. This is followed by two easy transformations giving rise to optically active 1,3-aminoalcohols, a common motif in many biologically active compounds, for example, fibrinogen receptor antagonists. Furthermore, optically active alpha,beta-syn-diaminated aldehydes were obtained by the addition of diethyl azodicarboxylate in a one-pot reaction.

  4. Identification of beta-Lactamases and beta-Lactam-Related Proteins in Human Pathogenic Bacteria using a Computational Search Approach.

    PubMed

    Brambila-Tapia, Aniel Jessica Leticia; Perez-Rueda, Ernesto; Barrios, Humberto; Dávalos-Rodríguez, Nory Omayra; Dávalos-Rodríguez, Ingrid Patricia; Cardona-Muñoz, Ernesto Germán; Salazar-Páramo, Mario

    2017-08-01

    A systematic analysis of beta-lactamases based on comparative proteomics has not been performed thus far. In this report, we searched for the presence of beta-lactam-related proteins in 591 bacterial proteomes belonging to 52 species that are pathogenic to humans. The amino acid sequences for 19 different types of beta-lactamases (ACT, CARB, CifA, CMY, CTX, FOX, GES, GOB, IMP, IND, KPC, LEN, OKP, OXA, OXY, SHV, TEM, NDM, and VIM) were obtained from the ARG-ANNOT database and were used to construct 19 HMM profiles, which were used to identify potential beta-lactamases in the completely sequenced bacterial proteomes. A total of 2877 matches that included the word "beta-lactamase" and/or "penicillin" in the functional annotation and/or in any of its regions were obtained. These enzymes were mainly described as "penicillin-binding proteins," "beta-lactamases," and "metallo-beta-lactamases" and were observed in 47 of the 52 species studied. In addition, proteins classified as "beta-lactamases" were observed in 39 of the species included. A positive correlation between the number of beta-lactam-related proteins per species and the proteome size was observed (R 0.78, P < 0.00001). This correlation partially explains the high presence of beta-lactam-related proteins in large proteomes, such as Nocardia brasiliensis, Bacillus anthracis, and Mycobacterium tuberculosis, along with their absence in small proteomes, such as Chlamydia spp. and Mycoplasma spp. We detected only five types of beta-lactamases (TEM, SHV, CTX, IMP, and OXA) and other related proteins in particular species that corresponded with those reported in the literature. We additionally detected other potential species-specific beta-lactamases that have not yet been reported. In the future, better results will be achieved due to more accurate sequence annotations and a greater number of sequenced genomes.

  5. Role of estrogen receptors alpha, beta and GPER1/GPR30 in pancreatic beta-cells.

    PubMed

    Nadal, Angel; Alonso-Magdalena, Paloma; Soriano, Sergi; Ripoll, Cristina; Fuentes, Esther; Quesada, Ivan; Ropero, Ana Belen

    2011-01-01

    Estrogen receptors (ER) are emerging as important molecules involved in the adaptation of beta-cells to insulin resistance. The onset of type 2 diabetes is marked by insulin secretory dysfunction and decreased beta-cell mass. During pregnancy, puberty and obesity there is increased metabolic demand and insulin resistance is developed. This metabolic state increases the demand on beta-cells to augment insulin biosynthesis and release. In this respect, ERalpha is directly implicated in the E2-regulation of insulin content and secretion, while ERbeta is in the E2-potentiation of glucose-induced insulin release. Both receptors develop their actions within the physiological range of E2. In addition, the G protein-coupled estrogen receptor (GPER1/GPR30) seems to be implicated in the E2-regulation of stimulus-secretion coupling in the three cell types of the islet. The increased demand of insulin production for long time may lead to beta-cell stress and apoptosis. ERalpha, ERbeta and GPER1/GPR30 are involved in preventing beta-cell apoptosis, impeding the loss of critical beta-cell mass. Therefore, estrogen receptors may play an essential role in the adaptation of the pancreas to insulin resistant periods.

  6. Anti-inflammatory, analgesic and ulcerogenic properties of S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin.

    PubMed

    Bole-Vunduk, B; Verhnjak, K; Zmitek, J

    1996-11-01

    The anti-inflammatory, analgesic and gastric mucosal damage-inducing activities of S-(+)-ibuproxam, and S-(+)-ibuproxam-beta-cyclodextrin, new propionic acid derivatives, and racemic ibuproxam-beta-cyclodextrin were investigated in three animal models and compared with those of racemic ibuproxam, racemic ibuprofen and its optical enantiomer S-(+)-ibuprofen. The anti-inflammatory activities of racemic ibuprofen, S-(+)-ibuprofen and racemic ibuproxam in carrageenan-induced paw oedema in rats were almost equipotent and slightly greater than those of S-(+)-ibuproxam and S-(+)-ibuproxam-beta-cyclodextrin, and significantly greater than that of racemic ibuproxam-beta-cyclodextrin. In abdominal constriction tests in mice, the analgesic effects of racemic ibuproxam, S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin were significantly less pronounced than those of racemic ibuprofen and S-(+)-ibuprofen. Ulcerogenic activity of S-(+)-ibuproxam-beta-cyclodextrin in rats was found to be significantly weaker than that of racemic ibuproxam-beta-cyclodextrin, racemic ibuproxam and S-(+)-ibuproxam and, most notably, weaker than those of racemic ibuprofen and S-(+)ibuprofen. These results indicate that S-(+)-ibuproxam-beta-cyclodextrin could be a novel potent anti-inflammatory and analgesic agent with a therapeutic index more favourable than that of the classical non-steroid anti-inflammatory drugs ibuprofen and ibuproxam.

  7. Ab initio study of excited state electronic circular dichroism. Two prototype cases: methyl oxirane and R-(+)-1,1'-bi(2-naphthol).

    PubMed

    Rizzo, Antonio; Vahtras, Olav

    2011-06-28

    A computational approach to the calculation of excited state electronic circular dichroism (ESECD) spectra of chiral molecules is discussed. Frequency dependent quadratic response theory is employed to compute the rotatory strength for transitions between excited electronic states, by employing both a magnetic gauge dependent and a (velocity-based) magnetic gauge independent approach. Application is made to the lowest excited states of two prototypical chiral molecules, propylene oxide, also known as 1,2-epoxypropane or methyl oxirane, and R-(+)-1,1'-bi(2-naphthol), or BINOL. The dependence of the rotatory strength for transitions between the lowest three excited states of methyl oxirane upon the quality and extension of the basis set is analyzed, by employing a hierarchy of correlation consistent basis sets. Once established that basis sets of at least triple zeta quality, and at least doubly augmented, are sufficient to ensure sufficiently converged results, at least at the Hartree-Fock self-consistent field (HF-SCF) level, the rotatory strengths for all transitions between the lowest excited electronic states of methyl oxirane are computed and analyzed, employing HF-SCF, and density functional theory (DFT) electronic structure models. For DFT, both the popular B3LYP and its recently highly successful CAM-B3LYP extension are exploited. The strong dependence of the spectra upon electron correlation is highlighted. A HF-SCF and DFT study is carried out also for BINOL, a system where excited states show the typical pairing structure arising from the interaction of the two monomeric moieties, and whose conformational changes following photoexcitation were studied recently with via time-resolved CD.

  8. Neutralizing Antibodies against IFN-[Beta] in Multiple Sclerosis: Antagonization of IFN-[Beta] Mediated Suppression of MMPs

    ERIC Educational Resources Information Center

    Gilli, Francesca; Bertolotto, Antonio; Sala, Arianna; Hoffmann, Francine; Capobianco, Marco; Malucchi, Simona; Glass, Tracy; Kappos, Ludwig; Lindberg, Raija L. P.; Leppert, David

    2004-01-01

    Neutralizing antibodies (NAb) against interferon-[Beta] (IFN-Beta) develop in about a third of treated multiple sclerosis patients and are believed to reduce therapeutic efficacy of IFN-[Beta] on clinical and MRI measures. The expression of the interferon acute-response protein, myxovirus resistance protein A (MxA) is a sensitive measure of the…

  9. Selectivity of beta-adrenergic stimulating and blocking agents.

    PubMed

    Löfdahl, C G; Svedmyr, N

    1984-01-01

    Studies have been performed to answer two questions: whether there are subgroups of beta 2-receptors separating effects in bronchial and skeletal muscle and whether beta 1-receptors in asthmatic airways mediate bronchoconstriction. Asthmatic patients have been studied in randomised cross-over trials. Effects on FEV1, heart rate and skeletal muscle tremor have been monitored. In some experimental studies, two new compounds, D2343 and QH-25, have shown a selectivity for beta 2-receptors in bronchial muscle compared to skeletal muscle. Studies in asthmatics did not confirm this. Thus, the beta 2-receptors in the two organs appear to be identical. The clinical effect of beta 1-receptors in the the airways was studied by giving selective beta 1-receptor blocking agents. It was shown that pafenolol , a beta-blocker more beta 1-selective than metoprolol, had less effect on FEV1 than metoprolol given in equipotent beta 1-blocking doses. Beta 1-receptor stimulation with a new selective beta 1-stimulating agent, prenalterol, did not give bronchodilation in doses which gave a significant increase of heart rate. Thus, beta 1-receptors do not contribute to bronchodilation in asthmatic patients.

  10. Gamma-ray blind beta particle probe

    DOEpatents

    Weisenberger, Andrew G.

    2001-01-01

    An intra-operative beta particle probe is provided by placing a suitable photomultiplier tube (PMT), micro channel plate (MCP) or other electron multiplier device within a vacuum housing equipped with: 1) an appropriate beta particle permeable window; and 2) electron detection circuitry. Beta particles emitted in the immediate vicinity of the probe window will be received by the electron multiplier device and amplified to produce a detectable signal. Such a device is useful as a gamma insensitive, intra-operative, beta particle probe in surgeries where the patient has been injected with a beta emitting radiopharmaceutical. The method of use of such a device is also described, as is a position sensitive such device.

  11. Beta genus papillomaviruses and skin cancer.

    PubMed

    Howley, Peter M; Pfister, Herbert J

    2015-05-01

    A role for the beta genus HPVs in keratinocyte carcinoma (KC) remains to be established. In this article we examine the potential role of the beta HPVs in cancer revealed by the epidemiology associating these viruses with KC and supported by oncogenic properties of the beta HPV proteins. Unlike the cancer associated alpha genus HPVs, in which transcriptionally active viral genomes are invariably found associated with the cancers, that is not the case for the beta genus HPVs and keratinocyte carcinomas. Thus a role for the beta HPVs in KC would necessarily be in the carcinogenesis initiation and not in the maintenance of the tumor. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Beta particle monitor for surfaces

    DOEpatents

    MacArthur, Duncan W.

    1997-01-01

    A beta radiation detector which is capable of reliably detecting beta radiation emitted from a surface. An electrically conductive signal collector is adjustably mounted inside an electrically conductive enclosure which may define a single large opening for placing against a surface. The adjustable mounting of the electrically conductive signal collector can be based on the distance from the surface or on the expected beta energy range. A voltage source is connected to the signal collector through an electrometer or other display means for creating an electric field between the signal collector and the enclosure. Air ions created by the beta radiation are collected and the current produced is indicated on the electrometer or other display means.

  13. Beta particle monitor for surfaces

    DOEpatents

    MacArthur, D.W.

    1997-10-21

    A beta radiation detector which is capable of reliably detecting beta radiation emitted from a surface. An electrically conductive signal collector is adjustably mounted inside an electrically conductive enclosure which may define a single large opening for placing against a surface. The adjustable mounting of the electrically conductive signal collector can be based on the distance from the surface or on the expected beta energy range. A voltage source is connected to the signal collector through an electrometer or other display means for creating an electric field between the signal collector and the enclosure. Air ions created by the beta radiation are collected and the current produced is indicated on the electrometer or other display means. 2 figs.

  14. The changes in beta-adrenoceptor-mediated cardiac function in experimental hypothyroidism: the possible contribution of cardiac beta3-adrenoceptors.

    PubMed

    Arioglu, E; Guner, S; Ozakca, I; Altan, V M; Ozcelikay, A T

    2010-02-01

    Thyroid hormone deficiency has been reported to decrease expression and function of both beta(1)- and beta(2)-adrenoceptor in different tissues including heart. The purpose of this study was to examine the possible contribution of beta(3)-adrenoceptors to cardiac dysfunction in hypothyroidism. In addition, effect of this pathology on beta(1)- and beta(2)-adrenoceptor was investigated. Hypothyroidism was induced by adding methimazole (300 mg/l) to drinking water of rats for 8 weeks. Cardiac hemodynamic parameters were measured in anesthetised rats in vivo. Responses to beta-adrenoceptor agonists were examined in rat papillary muscle in vitro. We also studied the effect of hypotyroidism on mRNA expression of beta-adrenoceptors, Gialpha, GRK, and eNOS in rat heart. All of the hemodynamic parameters (systolic, diastolic and mean arterial pressure, left ventricular pressure, heart rate, +dp/dt, and -dp/dt) were significantly reduced by the methimazole treatment. The negative inotropic effect elicited by BRL 37344 (a beta(3)-adrenoceptor preferential agonist) and positive inotropic effects produced by isoprenaline and noradrenaline, respectively, were significantly decreased in papillary muscle of hypothyroid rats as compared to those of controls. On the other hand, hypothyroidism resulted in increased cardiac beta(2)- and beta(3)-adrenoceptor, Gialpha(2), Gialpha(3), GRK3, and eNOS mRNA expressions. However, beta(1)-adrenoceptor and GRK2 mRNA expressions were not changed significantly in this pathology. These results show that mRNA expression of beta(3)-adrenoceptors as well as the signalling pathway components mediated through beta(3)-adrenoceptors are significantly increased in hypothyroid rat heart. Since we could not correlate these alternates with the decreased negative inotropic response mediated by this receptor subtype, it is not clear whether these changes are important for hypothyroid induced reduction in cardiac function.

  15. Minimalist design of water-soluble cross-beta architecture.

    PubMed

    Biancalana, Matthew; Makabe, Koki; Koide, Shohei

    2010-02-23

    Demonstrated successes of protein design and engineering suggest significant potential to produce diverse protein architectures and assemblies beyond those found in nature. Here, we describe a new class of synthetic protein architecture through the successful design and atomic structures of water-soluble cross-beta proteins. The cross-beta motif is formed from the lamination of successive beta-sheet layers, and it is abundantly observed in the core of insoluble amyloid fibrils associated with protein-misfolding diseases. Despite its prominence, cross-beta has been designed only in the context of insoluble aggregates of peptides or proteins. Cross-beta's recalcitrance to protein engineering and conspicuous absence among the known atomic structures of natural proteins thus makes it a challenging target for design in a water-soluble form. Through comparative analysis of the cross-beta structures of fibril-forming peptides, we identified rows of hydrophobic residues ("ladders") running across beta-strands of each beta-sheet layer as a minimal component of the cross-beta motif. Grafting a single ladder of hydrophobic residues designed from the Alzheimer's amyloid-beta peptide onto a large beta-sheet protein formed a dimeric protein with a cross-beta architecture that remained water-soluble, as revealed by solution analysis and x-ray crystal structures. These results demonstrate that the cross-beta motif is a stable architecture in water-soluble polypeptides and can be readily designed. Our results provide a new route for accessing the cross-beta structure and expanding the scope of protein design.

  16. Double Beta Decays and Neutrinos - Experiments and MOON

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ejiri, H.; National Institute of Radiological Sciences, Chiba, 263-8555

    2008-01-24

    This is a brief review of the present and future experiments of neutrino-less double beta decays (0{nu}{beta}{beta}) and the MOON (Mo Observatory Of Neutrinos) project. High sensitivity 0{nu}{beta}{beta} experiments are unique and realistic probes for studying the Majorana nature of neutrinos and the absolute mass scale as suggested by neutrino oscillation experiments. MOON aims at spectroscopic 0{nu}{beta}{beta} studies with the {nu}-mass sensitivity of 100-30 meV by means of a super ensemble of multilayer modules of scintillator plates and tracking detector planes.

  17. Functional overload increases beta-MHC promoter activity in rodent fast muscle via the proximal MCAT (betae3) site.

    PubMed

    Giger, Julia M; Haddad, Fadia; Qin, Anqi X; Baldwin, Kenneth M

    2002-03-01

    Functional overload (OL) of the rat plantaris muscle by the removal of synergistic muscles induces a shift in the myosin heavy chain (MHC) isoform expression profile from the fast isoforms toward the slow type I, or, beta-MHC isoform. Different length rat beta-MHC promoters were linked to a firefly luciferase reporter gene and injected in control and OL plantaris muscles. Reporter activities of -3,500, -914, -408, and -215 bp promoters increased in response to 1 wk of OL. The smallest -171 bp promoter was not responsive to OL. Mutation analyses of putative regulatory elements within the -171 and -408 bp region were performed. The -408 bp promoters containing mutations of the betae1, distal muscle CAT (MCAT; betae2), CACC, or A/T-rich (GATA), were still responsive to OL. Only the proximal MCAT (betae3) mutation abolished the OL response. Gel mobility shift assays revealed a significantly higher level of complex formation of the betae3 probe with nuclear protein from OL plantaris compared with control plantaris. These results suggest that the betae3 site functions as a putative OL-responsive element in the rat beta-MHC gene promoter.

  18. [S632A3 promotes LPS-induced IFN-beta production through inhibiting the activation of GSK-3beta].

    PubMed

    Zhang, Na; Yang, Xin; Xu, Rong; Wang, Zhen; Song, Dan-Qing; Li, Dian-Dong; Deng, Hong-Bin

    2013-07-01

    LPS stimulation of macrophages production of IFN-beta plays a key role in innate immunity defending the microbial invasion. In this study, the effect of S632A3 promoting LPS-induced IFN-beta production and the underlying mechanism were investigated, mRNA level was measured by real-time PCR, cytokine production was determined by ELISA, GSK-3beta activity was investigated by kinase assay, protein phosphorylation and expression were evaluated by Western blotting. The results revealed that S632A3 significantly augmented IFN-beta production by LPS-stimulated macrophages. S632A3 inhibition of the activation of GSK-3beta, reduced the threonine 239 phosphorylation of transcription factor c-Jun but increased the total level of c-Jun in LPS-stimulated macrophages. Moreover, small interfering RNA-mediated knockdown of c-Jun level abrogated the ability of S632A3 to augment IFN-beta. The study thus demonstrates S632A3 being a new anti-inflammation lead compound and provides a molecular mechanism by which S632A3 promoted LPS-induced IFN-beta production in macrophages through inhibiting the activation of GSK-3beta.

  19. Beta-lactamase production in Prevotella and in vitro susceptibilities to selected beta-lactam antibiotics [corrected].

    PubMed

    Dubreuil, L; Behra-Miellet, J; Vouillot, C; Bland, S; Sedallian, A; Mory, F

    2003-03-01

    This study looked for beta-lactamase production in 100 Prevotella isolates. MICs were determined for amoxycillin, ticarcillin, amoxycillin+clavulanate, cephalothin, cefuroxime, cefixime, cefpodoxime and cefotaxime using the reference agar dilution method (standard M11 A4, NCCLS). Beta-lactamase activity was detected in 58 of the 100 isolates, 24 of 46 black-pigmented Provotella and 34 of 54 non-pigmented Prevotella. All beta-lactamase-negative strains were susceptible to all beta-lactam antibiotics with the exception of cefuroxime and cefixime. Overall, resistance rates of Prevotella strains were lower for ticarcillin (8%) and celefotaxime (12%) than for the other cephalosporins. All Prevotella isolates were susceptible to amoxycillin and were all inhibited by 2 mg/l or less amoxycillin [corrected].

  20. Direct ethanol production from barley beta-glucan by sake yeast displaying Aspergillus oryzae beta-glucosidase and endoglucanase.

    PubMed

    Kotaka, Atsushi; Bando, Hiroki; Kaya, Masahiko; Kato-Murai, Michiko; Kuroda, Kouichi; Sahara, Hiroshi; Hata, Yoji; Kondo, Akihiko; Ueda, Mitsuyoshi

    2008-06-01

    Three beta-glucosidase- and two endoglucanase-encoding genes were cloned from Aspergillus oryzae, and their gene products were displayed on the cell surface of the sake yeast, Saccharomyces cerevisiae GRI-117-UK. GRI-117-UK/pUDB7 displaying beta-glucosidase AO090009000356 showed the highest activity against various substrates and efficiently produced ethanol from cellobiose. On the other hand, GRI-117-UK/pUDCB displaying endoglucanase AO090010000314 efficiently degraded barley beta-glucan to glucose and smaller cellooligosaccharides. GRI-117-UK/pUDB7CB codisplaying both beta-glucosidase AO090009000356 and endoglucanase AO090010000314 was constructed. When direct ethanol fermentation from 20 g/l barley beta-glucan as a model substrate was performed with the codisplaying strain, the ethanol concentration reached 7.94 g/l after 24 h of fermentation. The conversion ratio of ethanol from beta-glucan was 69.6% of the theoretical ethanol concentration produced from 20 g/l barley beta-glucan. These results showed that sake yeast displaying A. oryzae cellulolytic enzymes can be used to produce ethanol from cellulosic materials. Our constructs have higher ethanol production potential than the laboratory constructs previously reported.

  1. High power beta electron device - Beyond betavoltaics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ayers, William M.; Gentile, Charles A.

    Developing watt level power sources with beta emitting radioisotopes has been limited by the inability to utilize high energy (> 100 KeV) beta emitters at high radioisotope loadings without damaging the energy conversion materials. A new type of beta electron power source is described that removes those restrictions. This approach contains the radioisotope in a beta transparent titanium tube and confines beta electrons emitted through the tube wall to spiral trajectories around the tube with an axial magnetic field. The confined beta electrons dissipate energy though multiple interactions with surrounding excimer precursor gas atoms to efficiently generate photons. Photovoltaic cellsmore » convert the photons to electrical power. Since the beta electrons dissipate energy in the excimer precursor gas, the device can be loaded with more than 10 13 Bq of radioisotope to generate 100 milliwatt to watt levels of electrical power without damaging the device materials or degrading its performance. Furthermore, the power source can use a variety of beta radioisotopes and scales by stacking the devices.« less

  2. High power beta electron device - Beyond betavoltaics

    DOE PAGES

    Ayers, William M.; Gentile, Charles A.

    2017-11-10

    Developing watt level power sources with beta emitting radioisotopes has been limited by the inability to utilize high energy (> 100 KeV) beta emitters at high radioisotope loadings without damaging the energy conversion materials. A new type of beta electron power source is described that removes those restrictions. This approach contains the radioisotope in a beta transparent titanium tube and confines beta electrons emitted through the tube wall to spiral trajectories around the tube with an axial magnetic field. The confined beta electrons dissipate energy though multiple interactions with surrounding excimer precursor gas atoms to efficiently generate photons. Photovoltaic cellsmore » convert the photons to electrical power. Since the beta electrons dissipate energy in the excimer precursor gas, the device can be loaded with more than 10 13 Bq of radioisotope to generate 100 milliwatt to watt levels of electrical power without damaging the device materials or degrading its performance. Furthermore, the power source can use a variety of beta radioisotopes and scales by stacking the devices.« less

  3. High power beta electron device - Beyond betavoltaics.

    PubMed

    Ayers, William M; Gentile, Charles A

    2018-01-01

    Developing watt level power sources with beta emitting radioisotopes has been limited by the inability to utilize high energy (> 100KeV) beta emitters at high radioisotope loadings without damaging the energy conversion materials. A new type of beta electron power source is described that removes those restrictions. The approach contains the radioisotope in a beta transparent titanium tube and confines beta electrons emitted through the tube wall to spiral trajectories around the tube with an axial magnetic field. The confined beta electrons dissipate energy though multiple interactions with surrounding excimer precursor gas atoms to efficiently generate photons. Photovoltaic cells convert the photons to electrical power. Since the beta electrons dissipate energy in the excimer precursor gas, the device can be loaded with more than 10 13 Bq of radioisotope to generate 100 milliwatt to watt levels of electrical power without damaging the device materials or degrading its performance. The power source can use a variety of beta radioisotopes and scales by stacking the devices. Copyright © 2017. Published by Elsevier Ltd.

  4. Calmodulin is a phospholipase C-beta interacting protein.

    PubMed

    McCullar, Jennifer S; Larsen, Shana A; Millimaki, Ryan A; Filtz, Theresa M

    2003-09-05

    Phospholipase C-beta 3 (PLC beta 3) is an important effector enzyme in G protein-coupled signaling pathways. Activation of PLC beta 3 by G alpha and G beta gamma subunits has been fairly well characterized, but little is known about other protein interactions that may also regulate PLC beta 3 function. A yeast two-hybrid screen of a mouse brain cDNA library with the amino terminus of PLC beta 3 has yielded potential PLC beta 3 interacting proteins including calmodulin (CaM). Physical interaction between CaM and PLC beta 3 is supported by a positive secondary screen in yeast and the identification of a CaM binding site in the amino terminus of PLC beta 3. Co-precipitation of in vitro translated and transcribed amino- and carboxyl-terminal PLC beta 3 revealed CaM binding at a putative amino-terminal binding site. Direct physical interaction of PLC beta 3 and PLC beta 1 isoforms with CaM is supported by pull-down of both isoenzymes with CaM-Sepharose beads from 1321N1 cell lysates. CaM inhibitors reduced M1-muscarinic receptor stimulation of inositol phospholipid hydrolysis in 1321N1 astrocytoma cells consistent with a physiologic role for CaM in modulation of PLC beta activity. There was no effect of CaM kinase II inhibitors, KN-93 and KN-62, on M1-muscarinic receptor stimulation of inositol phosphate hydrolysis, consistent with a direct interaction between PLC beta isoforms and CaM.

  5. Minimalist design of water-soluble cross-[beta] architecture

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Biancalana, Matthew; Makabe, Koki; Koide, Shohei

    Demonstrated successes of protein design and engineering suggest significant potential to produce diverse protein architectures and assemblies beyond those found in nature. Here, we describe a new class of synthetic protein architecture through the successful design and atomic structures of water-soluble cross-{beta} proteins. The cross-{beta} motif is formed from the lamination of successive {beta}-sheet layers, and it is abundantly observed in the core of insoluble amyloid fibrils associated with protein-misfolding diseases. Despite its prominence, cross-{beta} has been designed only in the context of insoluble aggregates of peptides or proteins. Cross-{beta}'s recalcitrance to protein engineering and conspicuous absence among the knownmore » atomic structures of natural proteins thus makes it a challenging target for design in a water-soluble form. Through comparative analysis of the cross-{beta} structures of fibril-forming peptides, we identified rows of hydrophobic residues ('ladders') running across {beta}-strands of each {beta}-sheet layer as a minimal component of the cross-{beta} motif. Grafting a single ladder of hydrophobic residues designed from the Alzheimer's amyloid-{beta} peptide onto a large {beta}-sheet protein formed a dimeric protein with a cross-{beta} architecture that remained water-soluble, as revealed by solution analysis and x-ray crystal structures. These results demonstrate that the cross-{beta} motif is a stable architecture in water-soluble polypeptides and can be readily designed. Our results provide a new route for accessing the cross-{beta} structure and expanding the scope of protein design.« less

  6. The beta2- and beta3-adrenoceptor-mediated relaxation induced by fenoterol in guinea pig taenia caecum.

    PubMed

    Akimoto, Yurie; Horinouchi, Takahiro; Tanaka, Yoshio; Koike, Katsuo

    2002-10-01

    Fenoterol, a beta2-adrenoceptor selective agonist, belongs to the arylethanolamine class. To understand the receptor subtypes responsible for beta-adrenoceptor-mediated relaxation of guinea pig taenia caecum, we investigated the effect of fenoterol. Fenoterol caused concentration-dependent relaxation of the guinea pig taenia caecum. Propranolol, bupranolol and butoxamine produced shifts of the concentration-response curve for fenoterol. Schild regression analyses carried out for propranolol, butoxamine and bupranolol against fenoterol gave pA2 values of 8.41, 6.33 and 8.44, respectively. However, in the presence of 3 x 10(-4) M atenolol, 10(-4) M butoxamine and 10(-6) M phentolamine to block the beta1-, beta2- and a-adrenoceptor effects, respectively, Schild regression analysis carried out for bupranolol against fenoterol gave pA2 values of 5.80. These results suggest that the relaxant response to fenoterol in the guinea pig taenia caecum is mediated by both the beta2- and the beta3-adrenoceptors.

  7. MetroBeta: Beta Spectrometry with Metallic Magnetic Calorimeters in the Framework of the European Program of Ionizing Radiation Metrology

    NASA Astrophysics Data System (ADS)

    Loidl, M.; Beyer, J.; Bockhorn, L.; Enss, C.; Györi, D.; Kempf, S.; Kossert, K.; Mariam, R.; Nähle, O.; Paulsen, M.; Rodrigues, M.; Schmidt, M.

    2018-05-01

    MetroBeta is a European project aiming at the improvement of the knowledge of the shapes of beta spectra, both in terms of theoretical calculations and measurements. It is part of a common European program of ionizing radiation metrology. Metallic magnetic calorimeters (MMCs) with the beta emitter embedded in the absorber have in the past proven to be among the best beta spectrometers, in particular for low-energy beta transitions. Within this project, new designs of MMCs optimized for five different beta energy ranges were developed. A new detector module with thermal decoupling of MMC and SQUID chips was designed. An important aspect of the research and development concerns the source/absorber preparation techniques. Four beta spectra with maximum energies ranging from 76 to 709 keV will be measured. Improved theoretical calculation methods and complementary measurement techniques complete the project.

  8. Analysis of interleukin (IL)-1 beta and transforming growth factor (TGF)-beta-induced signal transduction pathways in IL-2 and TGF-beta secretion and proliferation in the thymoma cell line EL4.NOB-1.

    PubMed

    Siese, A; Jaros, P P; Willig, A

    1999-02-01

    In the present study we investigated the interleukin (IL)-1beta and transforming growth factor-beta1 (TGF-beta1)-mediated proliferation, and production of IL-2 and TGF-beta, in the murine T-cell line, EL4.NOB-1. This cell line is resistant to TGF-beta concerning growth arrest but not autoinduction or suppression of IL-1-induced IL-2 production. When cocultured with IL-1beta, TGF-beta showed growth-promoting activity that could be antagonized by adding the phosphatidyl choline-dependent phospholipase C (PC-PLC) inhibitor, D609. Using specific enzyme inhibitors of protein kinases (PK) C and A, mitogen-activated protein kinase (MAPK), phospholipase A2 (PLA2), phosphatidylinositol-dependent (PI)-PLC and PC-PLC, we showed that IL-1beta-induced IL-2 synthesis was dependent on all investigated kinases and phospholipases, except PC-PLC. TGF-beta1 was able to inhibit IL-2 synthesis by the activation of PKA and MAPK. The same kinases are involved in TGF-beta autoinduction that is accompanied by a secretion of the active but not the latent growth factor and is antagonized by IL-1beta. Addition of the PI-PLC inhibitor, ET 18OCH3, or the PLA2 inhibitor (quinacrine) alone, resulted in secretion of latent TGF-beta and, in the case of ET 18OCH3, active TGF-beta. These data implicate a role for PI-PLC and PLA2 in the control of latency and secretion. Analysis of specific tyrosine activity and c-Fos expression showed synergistic but no antagonistic effects. These events are therefore not involved in IL- and TGF-beta-regulated IL-2 and TGF-beta production, but might participate in IL-1/TGF-beta-induced growth promotion.

  9. Molecular structures of the inclusion complexes beta-cyclodextrin-1,2-bis(4-aminophenyl)ethane and beta-cyclodextrin-4,4'-diaminobiphenyl; packing of dimeric beta-cyclodextrin inclusion complexes.

    PubMed

    Giastas, Petros; Yannakopoulou, Konstantina; Mavridis, Irene M

    2003-04-01

    The present investigation is part of an ongoing study on the influence of the long end-functonalized guest molecules DBA and BNZ in the crystal packing of beta-cyclodextrin (betaCD) dimeric complexes. The title compounds are 2:2 host:guest complexes showing limited host-guest hydrogen bonding at the primary faces of the betaCD dimers. Within the betaCD cavity the guests exhibit mutual pi...pi interactions and between betaCD dimers perpendicular NH...pi interactions. The DBA guest molecule exhibits one extended and two bent conformations in the complex. The BNZ guest molecule is not planar inside betaCD, in contrast to the structure of BNZ itself, which indicates that the cavity isolates the molecules and forbids the pi...pi stacking of the aromatic rings. NMR spectroscopy studies show that in aqueous solution both DBA and BNZ form strong complexes that have 1:1 stoichiometry and structures similar to the solid state ones. The relative packing of the dimers is the same in both complexes. The axes of two adjacent dimers form an angle close to 20 degrees and have a lateral displacement approximately 2.45 A, both of which characterize the screw-channel mode of packing. Although the betaCD/BNZ complex indeed crystallizes in a space group characterizing the latter mode, the betaCD/DBA complex crystallizes in a space group with novel dimensions not resembling any of the packing modes reported so far. The new lattice is attributed to the three conformations exhibited by the guest in the crystals. However, this lattice can be transformed into another, which is isostructural to that of the betaCD/BNZ inclusion complex, if the conformation of the guest is not taken into account.

  10. Potentiating role of interleukin-1beta (IL-1beta) and IL-1beta type 1 receptors in the medial hypothalamus in defensive rage behavior in the cat.

    PubMed

    Hassanain, M; Bhatt, S; Zalcman, S; Siegel, A

    2005-06-28

    Recently, this laboratory provided evidence that interleukin-1beta (IL-1beta), an immune and brain-derived cytokine, microinjected into the medial hypothalamus, potentiates defensive rage behavior in the cat elicited from the midbrain periaqueductal gray (PAG), and that such effects are blocked by a 5-HT2 receptor antagonist. Since this finding represents the first time that a brain cytokine has been shown to affect defensive rage behavior, the present study replicated and extended these findings by documenting the specific potentiating role played by IL-1beta Type 1 receptor (IL-1RI), and the anatomical relationship between IL-1beta and 5-HT2 receptors in the medial hypothalamus. IL-1beta (10 ng) microinjected into the medial hypothalamus induced two separate phases of facilitation, one at 60 min and another at 180 min, post-injection. In turn, these effects were blocked with pretreatment of the selective IL-1 Type I receptor antagonist (IL-1ra) (10 ng), demonstrating the selectivity of the effects of IL-1beta on medial hypothalamic neurons upon PAG-elicited defensive rage behavior. The next stage of the study utilized immunohistochemical methods to demonstrate that IL-1beta and 5-HT2 receptors were present on the same neurons within regions of the medial hypothalamus where IL-1beta and the IL-1beta receptor antagonists were administered. This provided anatomical evidence suggesting a relationship between IL-1RI and 5-HT2 receptors in the medial hypothalamus that is consistent with the previous pharmacological observations in our laboratory. The overall findings show that activation of IL-1RI in the medial hypothalamus potentiates defensive rage behavior in the cat and that these effects may also be linked to the presence of 5-HT2 receptors on the same groups of neurons in this region of hypothalamus.

  11. Delta-catenin/NPRAP: A new member of the glycogen synthase kinase-3beta signaling complex that promotes beta-catenin turnover in neurons.

    PubMed

    Bareiss, Sonja; Kim, Kwonseop; Lu, Qun

    2010-08-15

    Through a multiprotein complex, glycogen synthase kinase-3beta (GSK-3beta) phosphorylates and destabilizes beta-catenin, an important signaling event for neuronal growth and proper synaptic function. delta-Catenin, or NPRAP (CTNND2), is a neural enriched member of the beta-catenin superfamily and is also known to modulate neurite outgrowth and synaptic activity. In this study, we investigated the possibility that delta-catenin expression is also affected by GSK-3beta signaling and participates in the molecular complex regulating beta-catenin turnover in neurons. Immunofluorescent light microscopy revealed colocalization of delta-catenin with members of the molecular destruction complex: GSK-3beta, beta-catenin, and adenomatous polyposis coli proteins in rat primary neurons. GSK-3beta formed a complex with delta-catenin, and its inhibition resulted in increased delta-catenin and beta-catenin expression levels. LY294002 and amyloid peptide, known activators of GSK-3beta signaling, reduced delta-catenin expression levels. Furthermore, delta-catenin immunoreactivity increased and protein turnover decreased when neurons were treated with proteasome inhibitors, suggesting that the stability of delta-catenin, like that of beta-catenin, is regulated by proteasome-mediated degradation. Coimmunoprecipitation experiments showed that delta-catenin overexpression promoted GSK-3beta and beta-catenin interactions. Primary cortical neurons and PC12 cells expressing delta-catenin treated with proteasome inhibitors showed increased ubiquitinated beta-catenin forms. Consistent with the hypothesis that delta-catenin promotes the interaction of the destruction complex molecules, cycloheximide treatment of cells overexpressing delta-catenin showed enhanced beta-catenin turnover. These studies identify delta-catenin as a new member of the GSK-3beta signaling pathway and further suggest that delta-catenin is potentially involved in facilitating the interaction, ubiquitination, and

  12. Beta-structures in fibrous proteins.

    PubMed

    Kajava, Andrey V; Squire, John M; Parry, David A D

    2006-01-01

    The beta-form of protein folding, one of the earliest protein structures to be defined, was originally observed in studies of silks. It was then seen in early studies of synthetic polypeptides and, of course, is now known to be present in a variety of guises as an essential component of globular protein structures. However, in the last decade or so it has become clear that the beta-conformation of chains is present not only in many of the amyloid structures associated with, for example, Alzheimer's Disease, but also in the prion structures associated with the spongiform encephalopathies. Furthermore, X-ray crystallography studies have revealed the high incidence of the beta-fibrous proteins among virulence factors of pathogenic bacteria and viruses. Here we describe the basic forms of the beta-fold, summarize the many different new forms of beta-structural fibrous arrangements that have been discovered, and review advances in structural studies of amyloid and prion fibrils. These and other issues are described in detail in later chapters.

  13. [Therapy of heart failure with beta-blockers?].

    PubMed

    Osterziel, K J; Dietz, R

    1997-01-01

    In heart failure the chronic sympathetic stimulation alters the cardiac beta-adrenergic pathway. This alteration leads to a diminished contractile response to stimulation of the cardiac beta 1 receptor. A blockade of the beta 1 receptor partly restores the physiologic response to sympathetic stimulation at rest and during exercise. Several mechanisms resulting from the competitive blockade of the beta 1 receptor may be important. The major effect of beta-blockers seems to be triggered by a reduction of the heart rate at rest resulting in an increase of the left ventricular ejection fraction on the average by 7-8%. Patients with heart failure who are treated with a beta-blocker experience initially a slight decrease of the left ventricular function. beta-blocker therapy should therefore be initiated only in patients with stable heart failure. The starting dose of the beta-blocker has to be very small, e.g, 5 mg Metoprolol, 1.25 mg Bisoprolol or 3.125 mg Carvedilol. In a stepwise fashion the dose has to be increased to a full beta blocking effect over a period of 4-8 weeks. Despite a careful dose titration only 90% of the patients tolerate this regimen. Patients with high resting heart rates and/or dilated cardiomyopathy will have the greatest benefit. The two main reasons for withdrawal of the beta-blocker are deterioration of heart failure or symptomatic hypotension. Symptomatic improvement and a significant increase of exercise capacity appear gradually and can be measured only after more than 1 month duration of therapy. Three multicenter studies (MDC. CIBIS I, Carvedilol) evaluated the influence of beta-blockers on prognosis of heart failure. The MDC trial demonstrated a slower progression of heart failure with Metoprolol. The MDC and the CIBIS I trial could not show a significant improvement of prognosis. The larger trial with carvedilol was the first study to demonstrate a decreased mortality in patients who initially tolerate the beta-blocker therapy. One

  14. Partitioning diversity into independent alpha and beta components.

    PubMed

    Jost, Lou

    2007-10-01

    Existing general definitions of beta diversity often produce a beta with a hidden dependence on alpha. Such a beta cannot be used to compare regions that differ in alpha diversity. To avoid misinterpretation, existing definitions of alpha and beta must be replaced by a definition that partitions diversity into independent alpha and beta components. Such a unique definition is derived here. When these new alpha and beta components are transformed into their numbers equivalents (effective numbers of elements), Whittaker's multiplicative law (alpha x beta = gamma) is necessarily true for all indices. The new beta gives the effective number of distinct communities. The most popular similarity and overlap measures of ecology (Jaccard, Sorensen, Horn, and Morisita-Horn indices) are monotonic transformations of the new beta diversity. Shannon measures follow deductively from this formalism and do not need to be borrowed from information theory; they are shown to be the only standard diversity measures which can be decomposed into meaningful independent alpha and beta components when community weights are unequal.

  15. Increased mature interleukin-1beta (IL-1beta) secretion from THP-1 cells induced by nigericin is a result of activation of p45 IL-1beta-converting enzyme processing.

    PubMed

    Cheneval, D; Ramage, P; Kastelic, T; Szelestenyi, T; Niggli, H; Hemmig, R; Bachmann, M; MacKenzie, A

    1998-07-10

    Perregaux and Gabel (Perregaux, D., and Gabel, C. A. (1994) J. Biol. Chem. 269, 15195-15203) reported that potassium depletion of lipopolysaccharide-stimulated mouse macrophages induced by the potassium ionophore, nigericin, leads to the rapid release of mature interleukin-1beta (IL-1beta). We have now shown a similar phenomenon in lipopolysaccharide-stimulated human monocytic leukemia THP-1 cells. Rapid secretion of mature, 17-kDa IL-1beta occurred, in the presence of nigericin (4-16 microM). No effects on the release of tumor necrosis factor-alpha, IL-6, or proIL-1beta were seen. Addition of the irreversible interleukin-1beta-converting enzyme (ICE) inhibitor, Z-Val-Ala-Asp-dichlorobenzoate, or a radicicol analog, inhibited nigericin-induced mature IL-1beta release and activation of p45 ICE precursor. The radicicol analog itself did not inhibit ICE, but markedly, and very rapidly depleted intracellular levels of 31-kDa proIL-1beta. By contrast, dexamethasone, cycloheximide, and the Na+/H+ antiporter inhibitor, 5-(N-ethyl-N-isopropyl)amiloride, had no effect on nigericin-induced release of IL-1beta. We have therefore shown conclusively, for the first time, that nigericin-induced release of IL-1beta is dependent upon activation of p45 ICE processing. So far, the mechanism by which reduced intracellular potassium ion concentration triggers p45 ICE processing is not known, but further investigation in this area could lead to the discovery of novel molecular targets whereby control of IL-1beta production might be effected.

  16. Effects of Asp-179 mutations in TEMpUC19 beta-lactamase on susceptibility to beta-lactams.

    PubMed Central

    Vakulenko, S B; Tóth, M; Taibi, P; Mobashery, S; Lerner, S A

    1995-01-01

    To examine the effect of disruption of the salt bridge (between Arg-164 and Asp-179 [numbering of Ambler et al. (Biochem J. 267:269-272, 1991)]) that anchors the conserved omega-loop in class A beta-lactamases, we obtained mutant enzymes with each of the 19 other amino acid residues replacing Asp-179 in the TEM beta-lactamase encoded by pUC19 and studied the level of resistance to various beta-lactams conferred by each enzyme. All mutations of Asp-179 compromised the level of resistance to ampicillin, but most of them enhanced resistance to ceftazidime. In contrast, mutations of Asp-179 generally impaired the low levels of resistance to cefepime and aztreonam. One might expect to find clinical isolates with mutant TEM beta-lactamases with replacements of Asp-179 that express an expanded spectrum of resistance to beta-lactams including ceftazidime. PMID:7486939

  17. Basal Ganglia Beta Oscillations Accompany Cue Utilization

    PubMed Central

    Leventhal, Daniel K.; Gage, Gregory J.; Schmidt, Robert; Pettibone, Jeffrey R.; Case, Alaina C.; Berke, Joshua D.

    2012-01-01

    SUMMARY Beta oscillations in cortical-basal ganglia (BG) circuits have been implicated in normal movement suppression and motor impairment in Parkinson’s disease. To dissect the functional correlates of these rhythms we compared neural activity during four distinct variants of a cued choice task in rats. Brief beta (~20 Hz) oscillations occurred simultaneously throughout the cortical-BG network, both spontaneously and at precise moments of task performance. Beta phase was rapidly reset in response to salient cues, yet increases in beta power were not rigidly linked to cues, movements, or movement suppression. Rather, beta power was enhanced after cues were used to determine motor output. We suggest that beta oscillations reflect a postdecision stabilized state of cortical-BG networks, which normally reduces interference from alternative potential actions. The abnormally strong beta seen in Parkinson’s Disease may reflect overstabilization of these networks, producing pathological persistence of the current motor state. PMID:22325204

  18. Adverse CNS-effects of beta-adrenoceptor blockers.

    PubMed

    Gleiter, C H; Deckert, J

    1996-11-01

    In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

  19. Neurotensin protects pancreatic beta cells from apoptosis.

    PubMed

    Coppola, Thierry; Béraud-Dufour, Sophie; Antoine, Aurélie; Vincent, Jean-Pierre; Mazella, Jean

    2008-01-01

    The survival of pancreatic beta cells depends on the balance between external cytotoxic and protective molecular systems. The neuropeptide neurotensin (NT) has been shown to regulate certain functions of the endocrine pancreas including insulin and glucagon release. However, the mechanism of action of NT as well as the identification of receptors involved in the pancreatic functions of the peptide remained to be studied. We demonstrate here that NT is an efficient protective agent of pancreatic beta cells against cytotoxic agents. Both beta-TC3 and INS-1E cell lines and the mouse pancreatic islet cells express the three known NT receptors. The incubation of beta cells with NT protects cells from apoptosis induced either by staurosporine or by IL-1beta. In beta-TC3 cells, NT activates both MAP and PI-3 kinases pathways and strongly reduces the staurosporine or the Il-1beta-induced caspase-3 activity by a mechanism involving Akt activation. The NTSR2 agonist levocabastine displays the same protective effect than NT whereas the NTSR1 antagonist is unable to block the effect of NT suggesting the predominant involvement of the NTSR2 in the action of NT on beta cells. These results clearly indicate for the first time that NT is able to protect endocrine beta cells from external cytotoxic agents, a role well correlated with its release in the circulation after a meal.

  20. Polymorphisms of the IL-1beta and IL-1beta-inducible genes in ulcerative colitis.

    PubMed

    Nohara, Hiroaki; Saito, Yuki; Higaki, Singo; Okayama, Naoko; Hamanaka, Yuichiro; Okita, Kiwamu; Hinoda, Yuji

    2002-11-01

    Ulcerative colitis (UC) is a chronic disorder of undetermined etiology, but a genetic predisposition to UC is well recognized. Among cytokines induced in UC, interleukin 1 (IL-1) appears to have a central role because of its immunological upregulatory and proinflammatory activities. The aim of this study was to assess whether UC is associated with polymorphisms of the IL-1beta gene and three additional genes inducible with IL-1beta in Japanese subjects. A total of 96 patients with UC and 106 ethnically matched controls were genotyped at polymorphic sites in IL-1beta, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 3 (MMP-3), and inducible nitric oxide synthase (iNOS) genes, using polymerase chain reaction (PCR)-based methods. There was no significant difference in genotype distributions of IL-1beta, MMP-1, MMP-3, and iNOS genes between controls and UC patients in a Japanese population. Also, no significant association of those polymorphisms with various clinical parameters of the patients was found. However, concerning association of age at onset with clinical factors in UC, the frequency of pancolitis was significantly higher in UC patients with age at onset being less than 30 years than in those more than 30 years of age (P = 0.049). No association of the IL-1beta and three IL-1beta-inducible gene polymorphisms with UC was observed in a Japanese population.

  1. Genotype–phenotype correlation among beta-thalassemia and beta-thalassemia/HbE disease in Thai children: predictable clinical spectrum using genotypic analysis

    PubMed Central

    Traivaree, Chanchai; Monsereenusorn, Chalinee; Rujkijyanont, Piya; Prasertsin, Warakorn; Boonyawat, Boonchai

    2018-01-01

    Introduction Beta-thalassemia is a group of inherited hemolytic anemias and one of the most common genetic disorders in Thailand. The clinical spectrum of beta-thalassemia disease ranges from mild to severe clinical symptoms including mild beta-thalassemia intermedia (TI) and severe beta-thalassemia major (TM). Objective This study aimed to determine the correlation between beta-globin gene (HBB) mutations and their phenotypic manifestations by evaluating patients’ clinical characteristics, transfusion requirements, growth and hematologic parameters, and hemoglobin typing among pediatric patients treated at Phramongkutklao Hospital. Materials and methods Seventy beta-thalassemia patients, including 63 with beta-thalassemia/hemoglobin E (HbE) and 7 with either homozygous or compound heterozygous beta-thalassemia, were enrolled in this study. Their clinical presentation, growth parameters and laboratory findings were reviewed and analyzed. The mean follow-up time was 10.52±5.62 years. Mutation analysis in each individual was performed using multiplex amplification refractory mutation system (M-ARMS), direct DNA sequencing of beta-globin gene and gap PCR for 3.4 kb deletion detection. Results All 7 homozygous and compound heterozygous beta-thalassemia patients were classified in TM. Among 63 patients with beta-thalassemia/HbE, 58 were classified in TM and 4 were classified in TI. Mean age at diagnosis was 0.8±0.49 years for homozygous or compound heterozygous beta-thalassemia and 3.43±3.5 years for beta-thalassemia/HbE. The most common HBB mutation was HBB:c.126_129delCTTT [codon 41/42 (-TCTT)] found in 34 alleles (48.6%). The height for age was also lower in homozygous beta-thalassemia patients (<3rd percentile) compared to compound heterozygous beta-thalassemia patients (25–50th percentile). Conclusion This study revealed a genotype–phenotype correlation of the most prevalent beta-thalassemia in Thai children using diagnostic capacity in genotypic analysis

  2. Treatment with unsaponifiable extracts of avocado and soybean increases TGF-beta1 and TGF-beta2 levels in canine joint fluid.

    PubMed

    Altinel, Levent; Saritas, Z Kadir; Kose, Kamil Cagri; Pamuk, Kamuran; Aksoy, Yusuf; Serteser, Mustafa

    2007-02-01

    Avocado and soya unsaponifiables (ASU) are plant extracts used as a slow-acting antiarthritic agent. ASU stimulate the synthesis of matrix components by chondrocytes, probably by increasing the production of transforming growth factor-beta (TGF-beta). TGF-beta is expressed by chondrocytes and osteoblasts and is present in cartilage matrix. This study investigates the effect of ASU treatment on the levels of two isoforms of TGFbeta, TGF-beta1 and TGF-beta2, in the knee joint fluid using a canine model. Twenty-four outbred dogs were divided into three groups. The control animals were given a normal diet, while the treated animals were given 300 mg ASU every three days or every day. Joint fluid samples were obtained prior to treatment, and at the end of every month (up to three months). TGF-beta1 and TGF-beta2 levels were measured using a quantitative sandwich enzyme immunoassay technique. ASU treatment caused an increase in TGF-beta1 and TGF-beta2 levels in the joint fluid when compared to controls. The different doses did not cause a significant difference in joint fluid TGF levels. TGF-beta1 levels in the treated animals reached maximum values at the end of the second month and then decreased after the third month, while TGF-beta2 levels showed a marginal increase during the first two months, followed by a marked increase at the end of the third month. In conclusion, ASU increased both TGF-beta1 and TGF-beta2 levels in knee joint fluid.

  3. Discovery of isonicotinamide derived beta-secretase inhibitors: in vivo reduction of beta-amyloid.

    PubMed

    Stanton, Matthew G; Stauffer, Shaun R; Gregro, Alison R; Steinbeiser, Melissa; Nantermet, Philippe; Sankaranarayanan, Sethu; Price, Eric A; Wu, Guoxin; Crouthamel, Ming-Chih; Ellis, Joan; Lai, Ming-Tain; Espeseth, Amy S; Shi, Xiao-Ping; Jin, Lixia; Colussi, Dennis; Pietrak, Beth; Huang, Qian; Xu, Min; Simon, Adam J; Graham, Samuel L; Vacca, Joseph P; Selnick, Harold

    2007-07-26

    beta-Secretase inhibition offers an exciting opportunity for therapeutic intervention in the progression of Alzheimer's disease. A series of isonicotinamides derived from traditional aspartyl protease transition state isostere inhibitors has been optimized to yield low nanomolar inhibitors with sufficient penetration across the blood-brain barrier to demonstrate beta-amyloid lowering in a murine model.

  4. Immunogenicity of an interferon-beta1a product.

    PubMed

    Kauffman, M A; Sterin-Prync, A; Papouchado, M; González, E; Vidal, A J; Grossberg, S E; Chuppa, S; Odoriz, B; Vrech, C; Diez, R A; Ferro, H H

    2011-01-01

    In order to determine whether Blastoferon®, a biosimilar interferon (IFN)- beta 1a formulation, shares epitopes with other known IFN-beta products, a series of neutralization bioassays were performed with a set of well-characterized anti-IFN- beta monoclonal antibodies and human sera (World Health Organization Reference Reagents). The bioassay was the interferon-induced inhibition of virus cytopathic effect on human cells in culture (EMC virus and A-549 cells). Computer-calculated results were reported as Tenfold Reduction Units (TRU)/ml. To further assess Blastoferon® immunogenicity, in vivo production of anti-IFN beta antibodies was determined in sera of patients included in the pharmacovigilance plan of Blastoferon® by the level of IFN- beta 1a binding antibodies (by enzyme immunoassay -EIA) and neutralizing antibodies (in the Wish-VSV system). The highly characterized neutralizing monoclonal antibodies A1 and A5 that bind to specific regions of the IFN- beta molecule reacted positively with the three beta 1a IFNs: Blastoferon®, Rebif®, and the IFN- beta WHO Second International Standard 00/572. As expected, the non-neutralizing monoclonal antibodies B4 and B7 did not neutralize any of the IFN- beta preparations. The commercially available monoclonal antibody B-02 reacted essentially equally with Rebif® and Blastoferon®. The WHO Reference Reagent human serum anti-IFN- beta polyclonal antibody neutralized all the IFN- beta products, whereas the WHO Reference Reagent human serum anti-IFN-alpha polyclonal antibody G037-501-572 appropriately failed to react with any of the IFN- beta products. On the basis of in vitro reactivity with known, well-characterized monoclonal and polyclonal antibody preparations, Blastoferon® shares immunological determinants with other human interferon- beta products, especially IFN- beta 1a. In vivo antibodies were detected by EIA in 72.9% of 37 chronically treated multiple sclerosis patients, whereas neutralizing antibodies were

  5. Beta-phenylethylamine inhibits K+ currents in neocortical neurons of the rat: a possible mechanism of beta-phenylethylamine-induced seizures.

    PubMed

    Kitamura, Taro; Munakata, Mitsutoshi; Haginoya, Kazuhiro; Tsuchiya, Shigeru; Iinuma, Kazuie

    2008-08-01

    beta-Phenylethylamine (beta-PEA), an endogenous amine synthesized in the brain, serves as a neuromodulator and is involved in the pathophysiology of various neurological disorders such as depression, schizophrenia, and attention-deficit hyperactivity disorder. beta-PEA fully exerts the physiological effects within the nanomolar concentration range via the trace amine receptors, but beta-PEA also causes convulsions at much higher concentrations via an as yet unknown mechanism. To investigate the electrophysiological mechanism by which beta-PEA induces convulsions, we examined the effect of beta-PEA on ionic currents passing through the cell membrane of dissociated rat cerebral cortical neurons, using a patch-clamp technique. The external application of beta-PEA suppressed ionic currents which continuously flowed when the membrane potential was held at -25 mV. The suppression was in a concentration-dependent manner and a half-maximal effective concentration was 540 muM. These currents suppressed by beta-PEA consisted of two K(+) currents: a time- and voltage-dependent K(+) current (M-current) and a leakage K(+) current. The suppression of the M-current reduces the efficacy of the current in limiting excessive neuronal firing, and the suppression of the leakage K(+) current can cause membrane depolarization and thus promote neuronal excitation. Reducing both of these currents in concert may produce neuronal seizing activity, which could conceivably underlie the convulsions induced by high-dose beta-PEA.

  6. Specific radioimmunoassay of human. beta. -endorphin in unextracted plasma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wiedemann, E.; Saito, T.; Linfoot, J.A.

    1979-09-01

    With an antiserum against human ..beta..-endorphin (..beta..-EP) crossreacting <2% with human ..beta..-lipotropin (..beta..-LPH) by weight we have developed a radioimmunoassay that can detect 1 pg ..beta..-EP in diluted raw plasma. In a.m. fasting plasma of 14 normal subjects ..beta..-EP ranged from <5 to 45 pg/ml. ..beta..-EP was elevated in untreated, but normal in successfully treated Cushing's disease; undetectable in a patient with adrenal adenoma; extremely high in Nelson's syndrome; and elevated in a patient with bronchogenic carcinoma before, but undetectable after tumor resection. In subjects with intact hypothalamic-pituitary-adrenal axis, ..beta..-EP was undectectable after dexamethasone and increased after metyrapone administration andmore » insulin-induced hypoglycemia. ..beta..-EP concentration was considerably lower in serum than in simultaneously collected plasma, but increased in serum left unfrozen for several hours after clot removal. Thus, ..beta..-EP behaves like a hormone responding to the same stimuli as ACTH and ..beta..-LPH and blood appears to contain enzymes both generating and destroying immunoreactive ..beta..-EP.« less

  7. Immunological characterization of eristostatin and echistatin binding sites on alpha IIb beta 3 and alpha V beta 3 integrins.

    PubMed Central

    Marcinkiewicz, C; Rosenthal, L A; Mosser, D M; Kunicki, T J; Niewiarowski, S

    1996-01-01

    Two disintegrins with a high degree of amino acid sequence similarity, echistatin and eristostatin, showed a low level of interaction with Chinese hamster ovary (CHO) cells, but they bound to CHO cells transfected with alpha IIb beta 3 genes (A5 cells) and to CHO cells transfected with alpha v beta 3 genes (VNRC3 cells) in a reversible and saturable manner. Scatchard analysis revealed that eristostatin bound to 816000 sites per A5 cell (Kd 28 nM) and to 200000 sites (Kd 14 nM) per VNRC3 cell respectively. However, VNRC3 cells did not bind to immobilized eristostatin. Echistatin bound to 495000 sites (Kd 53 nM) per A5 cell and to 443000 sites (Kd 20 nM) per VNRC3 cell. As determined by flow cytometry, radiobinding assay and adhesion studies, binding of both disintegrins to A5 cells and resting platelets and binding of echistatin to VNRC3 cells resulted in the expression of ligand-induced binding sites (LIBS) on the beta 3 subunit. Eristostatin inhibited, more strongly than echistatin, the binding of three monoclonal antibodies: OPG2 (RGD motif dependent), A2A9 (alpha IIb beta 3 complex dependent) and 7E3 (alpha IIb beta 3 and alpha v beta 3 complex dependent) to A5 cells, to resting and to activated platelets and to purified alpha IIb beta 3. Experiments in which echistatin and eristostatin were used alone or in combination to inhibit the binding of 7E3 and OPG2 antibodies to resting platelets suggested that these two disintegrins bind to different but overlapping sites on alpha IIb beta 3 integrin. Monoclonal antibody LM 609 and echistatin seemed to bind to different sites on alpha v beta 3 integrin. However, echistatin inhibited binding of 7E3 antibody to VNRC3 cells and to purified alpha v beta 3 suggesting that alpha v beta 3 and alpha IIb beta 3 might share the same epitope to which both echistatin and 7E3 bind. Eristostatin had no effect in these systems, providing further evidence that it binds to a different epitope on alpha v beta 3. PMID:8760368

  8. Clostridium perfringens enterotoxin is a superantigen reactive with human T cell receptors V beta 6.9 and V beta 22

    PubMed Central

    1992-01-01

    Candidate superantigens were screened for their ability to induce lysis of human histocompatibility leukocyte antigen class II-positive targets by human CD8+ influenza-specific cytotoxic T cell (CTL) lines. Clostridium perfringens enterotoxin (CPET) induced major histocompatibility complex unrestricted killing by some but not all CTL lines. Using "anchored" polymerase chain reactions, CPET was shown to selectively stimulate peripheral blood lymphocytes bearing T cell receptor V beta 6.9 and V beta 22 in five healthy donors. V beta 24, V beta 21, V beta 18, V beta 5, and V beta 6.1-5 appeared to be weakly stimulated. Antigen processing was not required for CPET to induce proliferation. Like the staphylococcal enterotoxins, CPET is a major cause of food poisoning. These data suggest that superantigenic and enterotoxigenic properties may be closely linked. PMID:1512551

  9. Invariant glycines and prolines flanking in loops the strand beta 2 of various (alpha/beta)8-barrel enzymes: a hidden homology?

    PubMed Central

    Janecek, S.

    1996-01-01

    The question of parallel (alpha/beta)8-barrel fold evolution remains unclear, owing mainly to the lack of sequence homology throughout the amino acid sequences of (alpha/beta)8-barrel enzymes. The "classical" approaches used in the search for homologies among (alpha/beta)8-barrels (e.g., production of structurally based alignments) have yielded alignments perfect from the structural point of view, but the approaches have been unable to reveal the homologies. These are proposed to be "hidden" in (alpha/beta)8-barrel enzymes. The term "hidden homology" means that the alignment of sequence stretches proposed to be homologous need not be structurally fully satisfactory. This is due to the very long evolutionary history of all (alpha/beta)8-barrels. This work identifies so-called hidden homology around the strand beta 2 that is flanked by loops containing invariant glycines and prolines in 17 different (alpha/beta)8-barrel enzymes, i.e., roughly in half of all currently known (alpha/beta)8-barrel proteins. The search was based on the idea that a conserved sequence region of an (alpha/beta)8-barrel enzyme should be more or less conserved also in the equivalent part of the structure of the other enzymes with this folding motif, given their mutual evolutionary relatedness. For this purpose, the sequence region around the well-conserved second beta-strand of alpha-amylase flanked by the invariant glycine and proline (56_GFTAIWITP, Aspergillus oryzae alpha-amylase numbering), was used as the sequence-structural template. The proposal that the second beta-strand of (alpha/beta)8-barrel fold is important from the evolutionary point of view is strongly supported by the increasing trend of the observed beta 2-strand structural similarity for the pairs of (alpha/beta)8-barrel enzymes: alpha-amylase and the alpha-subunit of tryptophan synthase, alpha-amylase and mandelate racemase, and alpha-amylase and cyclodextrin glycosyltransferase. This trend is also in agreement with the

  10. Invariant glycines and prolines flanking in loops the strand beta 2 of various (alpha/beta)8-barrel enzymes: a hidden homology?

    PubMed

    Janecek, S

    1996-06-01

    The question of parallel (alpha/beta)8-barrel fold evolution remains unclear, owing mainly to the lack of sequence homology throughout the amino acid sequences of (alpha/beta)8-barrel enzymes. The "classical" approaches used in the search for homologies among (alpha/beta)8-barrels (e.g., production of structurally based alignments) have yielded alignments perfect from the structural point of view, but the approaches have been unable to reveal the homologies. These are proposed to be "hidden" in (alpha/beta)8-barrel enzymes. The term "hidden homology" means that the alignment of sequence stretches proposed to be homologous need not be structurally fully satisfactory. This is due to the very long evolutionary history of all (alpha/beta)8-barrels. This work identifies so-called hidden homology around the strand beta 2 that is flanked by loops containing invariant glycines and prolines in 17 different (alpha/beta)8-barrel enzymes, i.e., roughly in half of all currently known (alpha/beta)8-barrel proteins. The search was based on the idea that a conserved sequence region of an (alpha/beta)8-barrel enzyme should be more or less conserved also in the equivalent part of the structure of the other enzymes with this folding motif, given their mutual evolutionary relatedness. For this purpose, the sequence region around the well-conserved second beta-strand of alpha-amylase flanked by the invariant glycine and proline (56_GFTAIWITP, Aspergillus oryzae alpha-amylase numbering), was used as the sequence-structural template. The proposal that the second beta-strand of (alpha/beta)8-barrel fold is important from the evolutionary point of view is strongly supported by the increasing trend of the observed beta 2-strand structural similarity for the pairs of (alpha/beta)8-barrel enzymes: alpha-amylase and the alpha-subunit of tryptophan synthase, alpha-amylase and mandelate racemase, and alpha-amylase and cyclodextrin glycosyltransferase. This trend is also in agreement with the

  11. Use of beta-methylphenylalanine (beta MeF) residues to probe the nature of the interaction of substance P with its receptor: effects of beta MeF-containing substance P analogs on rabbit iris smooth muscle contraction.

    PubMed

    Birney, D M; Cole, D C; Crosson, C E; Kahl, B F; Neff, B W; Reid, T W; Ren, K; Walkup, R D

    1995-06-23

    The effects of substituting (2S,3S)-beta-methylphenylalanine (S-beta MeF) or (2S,3R)-beta-methylphenylalanine (R-beta MeF) for the Phe7 and/or Phe8 residues of the tachykinin substance P (SP, RPKPQQFFGLM-NH2) upon the ability of SP to stimulate contraction of the rabbit iris smooth muscle were investigated. The eight beta MeF-containing SP analogs (four monosubstituted analogs, four disubstituted analogs) 1-8 were synthesized and found to be agonsts of SP in the smooth muscle contraction assay, having EC50 values ranging from 0.15 to 10.0 nM. Three analogs are significantly more active than SP [8R-(beta MeF)SP (4), 7S,8S-(beta MeF)2SP (5), and 7R,8S-(beta MeF)2SP (6)], three analogs are approximately equipotent with SP [7S-(beta MeF)SP (1), 7R-(beta MeF)SP (2), and 7S,8R-(beta MeF)2SP (8)], and two analogs are significantly less active than SP [8S-(beta MeF)SP (3) and 7R,8R-(beta MeF)2SP (7)]. The effects of the beta MeF substitutions upon the activity of SP are not additive and cannot be explained using simple conformational models which focus only on the side chain conformations of the beta MeF residues. It is postulated that the beta MeF residues induce minor distortions in the peptide backbone with resultant consequences upon peptide-receptor binding which are not dictated soley by the side chain conformations. This idea is consistent with 1H-NMR data for the monosubstituted analogs 1-4, which imply that the beta MeF substitutions cause slight distortions in the peptide backbone and that the beta MeF side chains are assuming trans or gauche(-) conformations.

  12. Maternal and cord plasma concentrations of beta-lipotrophin, beta-endorphin and gamma-lipotrophin at delivery; effect of analgesia.

    PubMed

    Browning, A J; Butt, W R; Lynch, S S; Shakespear, R A; Crawford, J S

    1983-12-01

    Maternal venous plasma concentrations of beta-LPH, beta-EP and gamma-LPH were compared in (i) patients undergoing vaginal delivery, 11 with an epidural block and 13 with pethidine and nitrous oxide or no analgesics; (ii) patients delivered by caesarean section, 7 under epidural block and 8 under general anaesthesia. Patients delivered by either method under epidural block had significantly lower levels of all three peptides than those receiving no epidural. There were significant negative correlations between umbilical vein beta-LPH, beta-EP and gamma-LPH concentrations and umbilical artery pH and positive correlations between beta-LPH and beta-EP but not gamma-LPH and cord PCO2 in 29 patients. There was no relation between cord levels of any of the three peptides and the method of analgesia or the route of delivery. Although concentrations of all three peptides were closely correlated to one another in either maternal or cord plasma, there was no relationship between maternal and fetal levels.

  13. Spotlight on agalsidase beta in Fabry disease.

    PubMed

    Keating, Gillian M; Simpson, Dene

    2007-01-01

    Agalsidase beta (Fabrazyme) is a recombinant human alpha-galactosidase A enzyme approved for intravenous use in the treatment of Fabry disease. Fabry disease is a progressive, multisystemic, potentially life-threatening disorder caused by a deficiency of alpha-galactosidase A. This deficiency results in accumulation of glycosphingolipids, particularly globotriaosylceramide (GL-3), in the lysosomes of various tissues. This accumulation is the underlying driver of disease progression. Agalsidase beta provides an exogenous source of alpha-galactosidase A. Intravenous agalsidase beta is effective and well tolerated in patients with Fabry disease. In a phase III trial, agalsidase beta was shown to clear GL-3 from various target cells and, in a subsequent extension of this trial, prevent GL-3 reaccumulation. In a post-approval trial, agalsidase beta was shown to provide significant clinical benefit by reducing the risk of a major clinical event. Thus, agalsidase beta represents an important advance in the treatment of Fabry disease, and agalsidase beta therapy should be strongly considered in patients with Fabry disease who are suitable candidates.

  14. Prediction of beta-turns with learning machines.

    PubMed

    Cai, Yu-Dong; Liu, Xiao-Jun; Li, Yi-Xue; Xu, Xue-biao; Chou, Kuo-Chen

    2003-05-01

    The support vector machine approach was introduced to predict the beta-turns in proteins. The overall self-consistency rate by the re-substitution test for the training or learning dataset reached 100%. Both the training dataset and independent testing dataset were taken from Chou [J. Pept. Res. 49 (1997) 120]. The success prediction rates by the jackknife test for the beta-turn subset of 455 tetrapeptides and non-beta-turn subset of 3807 tetrapeptides in the training dataset were 58.1 and 98.4%, respectively. The success rates with the independent dataset test for the beta-turn subset of 110 tetrapeptides and non-beta-turn subset of 30,231 tetrapeptides were 69.1 and 97.3%, respectively. The results obtained from this study support the conclusion that the residue-coupled effect along a tetrapeptide is important for the formation of a beta-turn.

  15. “Too Many betas do not Spoil the Broth”: The Role of Beta Brain Oscillations in Language Processing

    PubMed Central

    Weiss, Sabine; Mueller, Horst M.

    2012-01-01

    Over the past 20 years, brain oscillations have proven to be a gateway to the understanding of cognitive processes. It has been shown that different neurocognitive aspects of language processing are associated with brain oscillations at various frequencies. Frequencies in the beta range (13–30 Hz) turned out to be particularly important with respect to cognitive and linguistic manipulations during language processing. Beta activity has been involved in higher-order linguistic functions such as the discrimination of word categories and the retrieval of action semantics as well as semantic memory, and syntactic binding processes, which support meaning construction during sentence processing. From a neurophysiological point of view, the important role of the beta frequencies for such a complex cognitive task as language processing seems reasonable. Experimental evidence suggests that frequencies in the beta range are ideal for maintaining and preserving the activity of neuronal assemblies over time. In particular, recent computational and experimental evidence suggest that beta frequencies are important for linking past and present input and the detection of novelty of stimuli, which are essential processes for language perception as well as production. In addition, the beta frequency’s role in the formation of cell assemblies underlying short-term memory seems indispensable for language analysis. Probably the most important point is the well-known relation of beta oscillations with motor processes. It can be speculated that beta activities reflect the close relationship between language comprehension and motor functions, which is one of the core claims of current theories on embodied cognition. In this article, the importance of beta oscillations for language processing is reviewed based both on findings in psychophysiological and neurophysiological literature. PMID:22737138

  16. Similarity of different beta-strands flanked in loops by glycines and prolines from distinct (alpha/beta)8-barrel enzymes: chance or a homology?

    PubMed Central

    Janecek, S.

    1995-01-01

    Many (alpha/beta)8-barrel enzymes contain their conserved sequence regions at or around the beta-strand segments that are often preceded and succeeded by glycines and prolines, respectively. alpha-Amylase is one of these enzymes. Its sequences exhibit a very low degree of similarity, but strong conservation is seen around its beta-strands. These conserved regions were used in the search for similarities with beta-strands of other (alpha/beta)8-barrel enzymes. The analysis revealed an interesting similarity between the segment around the beta 2-strand of alpha-amylase and the one around the beta 4-strand of glycolate oxidase that are flanked in loops by glycines and prolines. The similarity can be further extended on other members of the alpha-amylase and glycolate oxidase subfamilies, i.e., cyclodextrin glycosyltransferase and oligo-1,6-glucosidase, and flavocytochrome b2, respectively. Moreover, the alpha-subunit of tryptophan synthase, the (alpha/beta)8-barrel enzyme belonging to the other subfamily of (alpha/beta)8-barrels, has both investigated strands, beta 2 and beta 4, similar to beta 2 of alpha-amylase and beta 4 of glycolate oxidase. The possibilities of whether this similarity exists only by chance or is a consequence of some processes during the evolution of (alpha/beta)8-barrel proteins are briefly discussed. PMID:7549888

  17. Similarity of different beta-strands flanked in loops by glycines and prolines from distinct (alpha/beta)8-barrel enzymes: chance or a homology?

    PubMed

    Janecek, S

    1995-06-01

    Many (alpha/beta)8-barrel enzymes contain their conserved sequence regions at or around the beta-strand segments that are often preceded and succeeded by glycines and prolines, respectively. alpha-Amylase is one of these enzymes. Its sequences exhibit a very low degree of similarity, but strong conservation is seen around its beta-strands. These conserved regions were used in the search for similarities with beta-strands of other (alpha/beta)8-barrel enzymes. The analysis revealed an interesting similarity between the segment around the beta 2-strand of alpha-amylase and the one around the beta 4-strand of glycolate oxidase that are flanked in loops by glycines and prolines. The similarity can be further extended on other members of the alpha-amylase and glycolate oxidase subfamilies, i.e., cyclodextrin glycosyltransferase and oligo-1,6-glucosidase, and flavocytochrome b2, respectively. Moreover, the alpha-subunit of tryptophan synthase, the (alpha/beta)8-barrel enzyme belonging to the other subfamily of (alpha/beta)8-barrels, has both investigated strands, beta 2 and beta 4, similar to beta 2 of alpha-amylase and beta 4 of glycolate oxidase. The possibilities of whether this similarity exists only by chance or is a consequence of some processes during the evolution of (alpha/beta)8-barrel proteins are briefly discussed.

  18. Transforming growth factor-{beta}-inducible phosphorylation of Smad3.

    PubMed

    Wang, Guannan; Matsuura, Isao; He, Dongming; Liu, Fang

    2009-04-10

    Smad proteins transduce the transforming growth factor-beta (TGF-beta) signal at the cell surface into gene regulation in the nucleus. Upon TGF-beta treatment, the highly homologous Smad2 and Smad3 are phosphorylated by the TGF-beta receptor at the SSXS motif in the C-terminal tail. Here we show that in addition to the C-tail, three (S/T)-P sites in the Smad3 linker region, Ser(208), Ser(204), and Thr(179) are phosphorylated in response to TGF-beta. The linker phosphorylation peaks at 1 h after TGF-beta treatment, behind the peak of the C-tail phosphorylation. We provide evidence suggesting that the C-tail phosphorylation by the TGF-beta receptor is necessary for the TGF-beta-induced linker phosphorylation. Although the TGF-beta receptor is necessary for the linker phosphorylation, the receptor itself does not phosphorylate these sites. We further show that ERK is not responsible for TGF-beta-dependent phosphorylation of these three sites. We show that GSK3 accounts for TGF-beta-inducible Ser(204) phosphorylation. Flavopiridol, a pan-CDK inhibitor, abolishes TGF-beta-induced phosphorylation of Thr(179) and Ser(208), suggesting that the CDK family is responsible for phosphorylation of Thr(179) and Ser(208) in response to TGF-beta. Mutation of the linker phosphorylation sites to nonphosphorylatable residues increases the ability of Smad3 to activate a TGF-beta/Smad-target gene as well as the growth-inhibitory function of Smad3. Thus, these observations suggest that TGF-beta-induced phosphorylation of Smad3 linker sites inhibits its antiproliferative activity.

  19. Hypothermia blocks beta-catenin degradation after focal ischemia in rats.

    PubMed

    Zhang, Hanfeng; Ren, Chuancheng; Gao, Xuwen; Takahashi, Tetsuya; Sapolsky, Robert M; Steinberg, Gary K; Zhao, Heng

    2008-03-10

    Dephosphorylated and activated glycogen synthase kinase (GSK) 3beta hyperphosphorylates beta-catenin, leading to its ubiquitin-proteosome-mediated degradation. beta-catenin-knockdown increases while beta-catenin overexpression prevents neuronal death in vitro; in addition, protein levels of beta-catenin are reduced in the brain of Alzheimer's patients. However, whether beta-catenin degradation is involved in stroke-induced brain injury is unknown. Here we studied activities of GSK 3beta and beta-catenin, and the protective effect of moderate hypothermia (30 degrees C) on these activities after focal ischemia in rats. The results of Western blot showed that GSK 3beta was dephosphorylated at 5 and 24 h after stroke in the normothermic (37 degrees C) brain; hypothermia augmented GSK 3beta dephosphorylation. Because hypothermia reduces infarction, these results contradict with previous studies showing that GSK 3beta dephosphorylation worsens neuronal death. Nevertheless, hypothermia blocked degradation of total GSK 3beta protein. Corresponding to GSK 3beta activity in normothermic rats, beta-catenin phosphorylation transiently increased at 5 h in both the ischemic penumbra and core, and the total protein level of beta-catenin degraded after normothermic stroke. Hypothermia did not inhibit beta-catenin phosphorylation, but it blocked beta-catenin degradation in the ischemic penumbra. In conclusion, moderate hypothermia can stabilize beta-catenin, which may contribute to the protective effect of moderate hypothermia.

  20. Selective inhibition of sheep kidney 11 beta-hydroxysteroid dehydrogenase isoform 2 activity by 5 alpha-reduced (but not 5 beta) derivatives of adrenocorticosteroids.

    PubMed

    Latif, S A; Sheff, M F; Ribeiro, C E; Morris, D J

    1997-02-01

    We have previously reported that 5 alpha and 5 beta pathways of steroid metabolism are controlled in vivo by dietary Na+ and glycyrrhetinic acid, see Gorsline et al. 1988; Latif et al. 1990. The present investigations provide evidence supporting the suggestion that endogenous substances may regulate the glucocorticoid inactivating isoenzymes, 11 beta-HSD (hydroxysteroid dehydrogenase) 1 (liver) and 11 beta-HSD2 (kidney). The activity of 11 beta-HSD is impaired in essential hypertension, following licorice ingestion, and in patients with apparent mineralocorticoid excess where 11 beta-HSD2 is particularly affected. In all three conditions, excretion of the less common 5 alpha metabolites is elevated in urine. We now report on the differential abilities of a series of Ring A reduced (5 alpha and 5 beta) adrenocorticosteroid and progesterone metabolites to inhibit these isoenzymes. Using liver microsomes with NADP+ as co-factor (11 beta-HSD1), and sheep kidney microsomes with NAD+ as co-factor (11 beta-HSD2), we have systematically investigated the abilities of a number of adrenocorticosteroids and their derivatives to inhibit the individual isoforms of 11 beta-HSD. A striking feature is the differential sensitivity of the two isoenzymes to inhibition by 5 alpha and 5 beta derivatives. 11 beta-HSD1 is inhibited by both 5 alpha and certain 5 beta derivatives. 11 beta-HSD-2 was selectively inhibited only by 5 alpha derivatives: 5 beta derivatives were without inhibitory activity toward this isoform of 11 beta-HSD. These results indicate the importance of the structural conformation of the A and B Rings in conferring specific inhibitory properties on these compounds. In addition, we discuss the effects of additions or substitutions of other functional groups on the inhibitory potency of these steroid molecules against 11 beta-HSD1 and 11 beta-HSD2.

  1. Discordant changes in plasma ACTH and beta-lipotropin/beta-endorphin levels in Cushing's disease patients with depression.

    PubMed

    Starkman, M N; Schteingart, D E; Schork, M A

    1992-11-01

    Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and beta-lipotropin/beta-endorphin (beta-LPH/beta-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean [+/- SD] depressed mood score = 0.17 +/- 0.4; modified Hamilton Depression scale score = 7.6 +/- 4.5) and five as severely depressed (mean depressed mood score = 2.4 +/- 0.5; modified Hamilton Depression scale score = 15 +/- 5.6) (p < 0.05). ACTH and beta-LPH/beta-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and beta-LPH/beta-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed = 90.0 +/- 16.7; severely depressed = 34.6 +/- 8.7 (p < 0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0 mg dexamethasone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Synthesis of 3-O-(beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl)-3'-O-(beta-D-glucopyranosyl)tamarixetin, the putative structure of aescuflavoside A from the seeds of Aesculus chinensis.

    PubMed

    Zhu, Cunsheng; Peng, Wenjie; Li, Yuwen; Han, Xiuwen; Yu, Biao

    2006-06-12

    3-O-(beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl)-3'-O-(beta-D-glucopyranosyl)tamarixetin, the putative flavonal glycoside named aescuflavoside A, isolated from the seeds of Aesculus chinensis, is synthesized via regioselective glycosylation of 7-O-benzyltamarixetin with glycosyl bromides under phase-transfer-catalyzed conditions.

  3. Beta-lactamases of Mycobacterium tuberculosis and Mycobacterium kansasii.

    PubMed

    Segura, C; Salvadó, M

    1997-09-01

    Re-emergence of infectious diseases caused by mycobacteria as well as the emergence of multiresistant strains of Mycobacterium has promoted the research on the use of beta-lactames in the treatment of such diseases. Mycobacteria produce beta-lactamases: M. tuberculosis produces a wide-spectrum beta-lactamase whose behaviour mimicks those of Gram-negative bacteria. M. kansasii produces also beta-lactamase which can be inhibited by clavulanic acid. An overview on beta-lactamases from both species is reported.

  4. {beta}-Catenin regulates airway smooth muscle contraction.

    PubMed

    Jansen, Sepp R; Van Ziel, Anna M; Baarsma, Hoeke A; Gosens, Reinoud

    2010-08-01

    beta-Catenin is an 88-kDa member of the armadillo family of proteins that is associated with the cadherin-catenin complex in the plasma membrane. This complex interacts dynamically with the actin cytoskeleton to stabilize adherens junctions, which play a central role in force transmission by smooth muscle cells. Therefore, in the present study, we hypothesized a role for beta-catenin in the regulation of smooth muscle force production. beta-Catenin colocalized with smooth muscle alpha-actin (sm-alpha-actin) and N-cadherin in plasma membrane fractions and coimmunoprecipitated with sm-alpha-actin and N-cadherin in lysates of bovine tracheal smooth muscle (BTSM) strips. Moreover, immunocytochemistry of cultured BTSM cells revealed clear and specific colocalization of sm-alpha-actin and beta-catenin at the sites of cell-cell contact. Treatment of BTSM strips with the pharmacological beta-catenin/T cell factor-4 (TCF4) inhibitor PKF115-584 (100 nM) reduced beta-catenin expression in BTSM whole tissue lysates and in plasma membrane fractions and reduced maximal KCl- and methacholine-induced force production. These changes in force production were not accompanied by changes in the expression of sm-alpha-actin or sm-myosin heavy chain (MHC). Likewise, small interfering RNA (siRNA) knockdown of beta-catenin in BTSM strips reduced beta-catenin expression and attenuated maximal KCl- and methacholine-induced contractions without affecting sm-alpha-actin or sm-MHC expression. Conversely, pharmacological (SB-216763, LiCl) or insulin-induced inhibition of glycogen synthase kinase-3 (GSK-3) enhanced the expression of beta-catenin and augmented maximal KCl- and methacholine-induced contractions. We conclude that beta-catenin is a plasma membrane-associated protein in airway smooth muscle that regulates active tension development, presumably by stabilizing cell-cell contacts and thereby supporting force transmission between neighboring cells.

  5. Deficient "sensory" beta synchronization in Parkinson's disease.

    PubMed

    Degardin, A; Houdayer, E; Bourriez, J-L; Destée, A; Defebvre, L; Derambure, P; Devos, D

    2009-03-01

    Beta rhythm movement-related synchronization (beta synchronization) reflects motor cortex deactivation and sensory afference processing. In Parkinson's disease (PD), decreased beta synchronization after active movement reflects abnormal motor cortex idling and may be involved in the pathophysiology of akinesia. The objectives of the present study were to (i) compare event-related synchronization after active and passive movement and electrical nerve stimulation in PD patients and healthy, age-matched volunteers and (ii) evaluate the effect of levodopa. Using a 128-electrode EEG system, we studied beta synchronization after active and passive index finger movement and electrical median nerve stimulation in 13 patients and 12 control subjects. Patients were recorded before and after 150% of their usual morning dose of levodopa. The peak beta synchronization magnitude in the contralateral primary sensorimotor (PSM) cortex was significantly lower in PD patients after active movement, passive movement and electrical median nerve stimulation, compared with controls. Levodopa partially reversed the drop in beta synchronization after active movement but not after passive movement or electrical median nerve stimulation. If one considers that beta synchronization reflects sensory processing, our results suggest that integration of somaesthetic afferences in the PSM cortex is abnormal in PD during active and passive movement execution and after simple electrical median nerve stimulation. Better understanding of the mechanisms involved in the deficient beta synchronization observed here could prompt the development of new therapeutic approaches aimed at strengthening defective processes. The lack of full beta synchronization restoration by levodopa might be related to the involvement of non-dopaminergic pathways.

  6. Imaging of alpha(v)beta(3) expression by a bifunctional chimeric RGD peptide not cross-reacting with alpha(v)beta(5).

    PubMed

    Zannetti, Antonella; Del Vecchio, Silvana; Iommelli, Francesca; Del Gatto, Annarita; De Luca, Stefania; Zaccaro, Laura; Papaccioli, Angela; Sommella, Jvana; Panico, Mariarosaria; Speranza, Antonio; Grieco, Paolo; Novellino, Ettore; Saviano, Michele; Pedone, Carlo; Salvatore, Marco

    2009-08-15

    To test whether a novel bifunctional chimeric peptide comprising a cyclic Arg-Gly-Asp pentapeptide covalently bound to an echistatin domain can discriminate alpha(v)beta(3) from alpha(v)beta(5) integrin, thus allowing the in vivo selective visualization of alpha(v)beta(3) expression by single-photon and positron emission tomography (PET) imaging. The chimeric peptide was preliminarily tested for inhibition of alpha(v)beta(3)-dependent cell adhesion and competition of 125I-echistatin binding to membrane of stably transfected K562 cells expressing alpha(v)beta(3) (Kalpha(v)beta(3)) or alpha(v)beta(5) (Kalpha(v)beta(5)) integrin. The chimeric peptide was then conjugated with diethylenetriaminepentaacetic acid and labeled with 111In for single-photon imaging, whereas a one-step procedure was used for labeling the full-length peptide and a truncated derivative, lacking the last five C-terminal amino acids, with 18F for PET imaging. Nude mice bearing tumors from Kalpha(v)beta(3), Kalpha(v)beta(5), U87MG human glioblastoma, and A431 human epidermoid cells were subjected to single-photon and PET imaging. Adhesion and competitive binding assays showed that the novel chimeric peptide selectively binds to alpha(v)beta(3) integrin and does not cross-react with alpha(v)beta(5). In agreement with in vitro findings, single-photon and PET imaging studies showed that the radiolabeled chimeric peptide selectively localizes in tumor xenografts expressing alphavbeta3 and fails to accumulate in those expressing alpha(v)beta(5) integrin. When 18F-labeled truncated derivative was used for PET imaging, alphavbeta3- and alpha(v)beta(5)-expressing tumors were visualized, indicating that the five C-terminal amino acids are required to differentially bind the two integrins. Our findings indicate that the novel chimeric Arg-Gly-Asp peptide, having no cross-reaction with alphavbeta5 integrin, allows highly selective alphavbeta3 expression imaging and monitoring.

  7. Characterization and inhibition of beta-adrenergic receptor kinase in intact myocytes.

    PubMed

    Laugwitz, K L; Kronsbein, K; Schmitt, M; Hoffmann, K; Seyfarth, M; Schömig, A; Ungerer, M

    1997-08-01

    beta-Adrenergic receptor kinase (beta ARK) phosphorylates and thereby inactivates agonist-occupied beta-adrenergic receptors (beta AR). beta ARK is thought to play an important role in the regulation of cardiac function. Therefore, we studied beta ARK activation and its inhibition in intact smooth muscle cells and in cardiomyoblasts. beta AR agonist-stimulated translocation of beta ARK was monitored by immunofluorescence labelling with specific antibodies and confocal laser scanning microscopy in DDT-MF 2 hamster smooth muscle cells and in H9c2 rat cardiomyoblasts. In unstimulated cells. beta ARK was mainly located in the cytosol. After beta AR agonist stimulation, the beta ARK signal was partially translocated to the membranes. Liposomal gene transfer of the COOH-terminus of beta ARK ('beta ARKmini') as a beta ARK inhibitor led to functional expression of this protein in both cell lines with high efficiency. Western blots with beta ARK antibodies showed a gene concentration-dependent immunoreactivity of the 'beta ARKmini' protein. 'beta ARKmini'-transfected myocytes demonstrated reduced membrane targeting of the beta ARK immuno-fluorescence signal. Additionally, the effect of 'beta ARKmini' on beta AR-induced desensitization of myocytic cAMP accumulation was investigated. In control cells, desensitization with isoproterenol led to a subsequent reduction of beta AR-induced cAMP accumulation. In 'beta ARKmini'-transfected myocytes, this beta AR-induced desensitization was significantly diminished, whereas normal beta AR-induced cAMP accumulation was unaffected. A gene concentration of 2 micrograms 'beta ARKmini' DNA/100,000 cardiomyoblasts, and of 0.7 microgram 'beta ARKmini' DNA/100,000 DDT-MF2 smooth muscle cells led to approximately 5.9- and approximately 5.6-fold overexpressions of 'beta ARKmini' vs. native beta ARK, respectively. These gene doses proved sufficient to attenuate beta-adrenergic desensitization significantly. (1) beta ARK translocation was

  8. Towards Alzheimer's beta-amyloid vaccination.

    PubMed

    Frenkel, D; Solomon, B

    2001-01-01

    Beta-amyloid pathology, the main hallmark of Alzheimer's disease (AD), has been linked to its conformational status and aggregation. We recently showed that site-directed monoclonal antibodies (mAbs) towards the N-terminal region of the human beta-amyloid peptide bind to preformed beta-amyloid fibrils (Abeta), leading to disaggregation and inhibition of their neurotoxic effect. Here we report the development of a novel immunization procedure to raise effective anti-aggregating amyloid beta-protein (AbetaP) antibodies, using as antigen filamentous phages displaying the only EFRH peptide found to be the epitope of these antibodies. Due to the high antigenicity of the phage no adjuvant is required to obtain high affinity anti-aggregating IgG antibodies in animals model, that exhibit identity to human AbetaP. Such antibodies are able to sequester peripheral AbetaP, thus avoiding passage through the blood brain barrier (BBB) and, as recently shown in a transgenic mouse model, to cross the BBB and dissolve already formed beta-amyloid plaques. To our knowledge, this is the first attempt to use as a vaccine a self-anti-aggregating epitope displayed on a phage, and this may pave the way to treat abnormal accumulation-peptide diseases, such as Alzheimer's disease or other amyloidogenic diseases. Copyright 2001 The International Association for Biologicals.

  9. Urinary biomarkers of occupational jet fuel exposure among Air Force personnel.

    PubMed

    Smith, Kristen W; Proctor, Susan P; Ozonoff, A L; McClean, Michael D

    2012-01-01

    There is a potential for widespread occupational exposure to jet fuel among military and civilian personnel. Urinary metabolites of naphthalene have been suggested for use as short-term biomarkers of exposure to jet fuel (jet propulsion fuel 8 (JP8)). In this study, urinary biomarkers of JP8 were evaluated among US Air Force personnel. Personnel (n=24) were divided a priori into high, moderate, and low exposure groups. Pre- and post-shift urine samples were collected from each worker over three workdays and analyzed for metabolites of naphthalene (1- and 2-naphthol). Questionnaires and breathing-zone naphthalene samples were collected from each worker during the same workdays. Linear mixed-effects models were used to evaluate the exposure data. Post-shift levels of 1- and 2-naphthol varied significantly by a priori exposure group (levels in high group>moderate group>low group), and breathing-zone naphthalene was a significant predictor of post-shift levels of 1- and 2-naphthol, indicating that for every unit increase in breathing-zone naphthalene, there was an increase in naphthol levels. These results indicate that post-shift levels of urinary 1- and 2-naphthol reflect JP8 exposure during the work-shift and may be useful surrogates of JP8 exposure. Among the high exposed workers, significant job-related predictors of post-shift levels of 1- and 2-naphthol included entering the fuel tank, repairing leaks, direct skin contact with JP8, and not wearing gloves during the work-shift. The job-related predictors of 1- and 2-naphthol emphasize the importance of reducing inhalation and dermal exposure through the use of personal protective equipment while working in an environment with JP8.

  10. Dynamics of beta-amyloid peptide in cholesterol superlattice domain

    NASA Astrophysics Data System (ADS)

    Smirnov, Anton; Zhu, Qing; Vaughn, Mark; Khare, Rajesh; Cheng, K.

    2006-10-01

    Presence of beta-amyloid peptide (beta-A) plagues in membranes of neuron cells is a clinical signature of Alzheimer disease. The onset of beta-A peptide aggregation occurs via a conformational transition from an alpha-helix state to a beta-sheet state. A gradual build-up of beta-A content in the neuronal extracellular space is another characteristic of the beta-A plague formation. Hypothetically, both the pathological conformation and the predominant localization of the beta-A can be a result of specific dynamic characteristics of the interphase between cellular membrane and extracellular milieu. In this study, the beta-A interphase problem has been investigated using a virtual membrane model implemented on the base of GROMACS molecular dynamics simulation package. The detailed folding pattern of beta-A has been examined using a novice interphase model comprised of a cholesterol supperlattice membrane and two water layers.

  11. Nonessential role of beta3 and beta5 integrin subunits for efficient clearance of cellular debris after light-induced photoreceptor degeneration.

    PubMed

    Joly, Sandrine; Samardzija, Marijana; Wenzel, Andreas; Thiersch, Markus; Grimm, Christian

    2009-03-01

    During light-induced photoreceptor degeneration, large amounts of cellular debris are formed that must be cleared from the subretinal space. The integrins alphavbeta5 and alphavbeta3 are involved in the normal physiological process of phagocytosis in the retina. This study was conducted to investigate the question of whether the lack of beta5 and/or beta3 integrin subunits might influence the course of retinal degeneration and/or clearance of photoreceptor debris induced by acute exposure to light. Wild-type, beta5(-/-) and beta3(-/-) single-knockout, and beta3(-/-)/beta5(-/-) Ccl2(-/-)/beta5(-/-) double-knockout mice were exposed to 13,000 lux of white light for 2 hours to induce severe photoreceptor degeneration. Real-time PCR and Western blot analysis were used to analyze gene and protein expression, light- and electron microscopy to judge retinal morphology, and immunofluorescence to study retinal distribution of proteins. Individual or combined deletion of beta3 and beta5 integrin subunits did not affect the pattern of photoreceptor cell loss or the clearance of photoreceptor debris in mice compared with that in wild-type mice. Invading macrophages may contribute to efficient phagocytosis. However, ablation of the MCP-1 gene did not prevent macrophage recruitment. Several chemokines in addition to MCP-1 were induced after light-induced damage that may have compensated for the deletion of MCP-1. Acute clearance of a large amount of cellular debris from the subretinal space involves invading macrophages and does not depend on beta3 and beta5 integrins.

  12. Mode identification in Beta Cephei stars

    NASA Technical Reports Server (NTRS)

    Aizenmen, M. L.; Lesh, J. R.

    1980-01-01

    The essential observational characteristics related to mode identification are summarized. Major emphasis is placed on the following: both light and velocity amplitudes; typical periods in both light and radial velocity; the light curve for Beta Cephei stars in comparison to the classical Cepheids and RR Lyrae stars; the van Hoof effect with respect to the radial velocity curves in many Beta Cephei stars; and the line profiles of many Beta Cephei stars.

  13. Ferulic acid destabilizes preformed {beta}-amyloid fibrils in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ono, Kenjiro; Hirohata, Mie; Yamada, Masahito

    2005-10-21

    Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that curcumin (Cur) inhibits fA{beta} formation from A{beta} and destabilizes preformed fA{beta} in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of ferulic acid (FA) on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of FA with Cur, rifampicin, and tetracycline. Ferulic acid dose-dependentlymore » inhibited fA{beta} formation from amyloid {beta}-peptide, as well as their extension. Moreover, it destabilized preformed fA{beta}s. The overall activity of the molecules examined was in the order of: Cur > FA > rifampicin = tetracycline. FA could be a key molecule for the development of therapeutics for AD.« less

  14. Central beta-adrenergic modulation of cognitive flexibility.

    PubMed

    Beversdorf, David Q; White, Dawn M; Chever, Daquesha C; Hughes, John D; Bornstein, Robert A

    2002-12-20

    Situational stressors and anxiety impede performance on creativity tests requiring cognitive flexibility. Preliminary research revealed better performance on a task requiring cognitive flexibility, the anagram task, after propranolol (beta-adrenergic antagonist) than after ephedrine (beta-adrenergic agonist). However, propranolol and ephedrine have both peripheral and central beta-adrenergic effects. In order to determine whether noradrenergic modulation of cognitive flexibility is a centrally or peripherally mediated phenomenon, we compared the effects of propranolol (peripheral and central beta-blocker), nadolol (peripheral beta-blocker), and placebo on anagram task performance. Solution latency scores for each subject were compared across the drug conditions. Anagram solution latency scores after propranolol were significantly lower than after nadolol. This suggests a centrally mediated modulatory influence of the noradrenergic system on cognitive flexibility.

  15. Reduced Expression of the Liver/Beta-Cell Glucose Transporter Isoform in Glucose-Insensitive Pancreatic Beta Cells of Diabetic Rats

    NASA Astrophysics Data System (ADS)

    Thorens, Bernard; Weir, Gordon C.; Leahy, John L.; Lodish, Harvey F.; Bonner-Weir, Susan

    1990-09-01

    Rats injected with a single dose of streptozocin at 2 days of age develop non-insulin-dependent diabetes 6 weeks later. The pancreatic beta islet cells of these diabetic rats display a loss of glucose-induced insulin secretion while maintaining sensitivity to other secretagogues such as arginine. We analyzed the level of expression of the liver/beta-cell glucose transporter isoform in diabetic islets by immunofluorescence staining of pancreas sections and by Western blotting of islet lysates. Islets from diabetic animals have a reduced expression of this beta-cell-specific glucose transporter isoform and the extent of reduction is correlated with the severity of hyperglycemia. In contrast, expression of this transporter isoform in liver is minimally modified by the diabetes. Thus a decreased expression of the liver/beta-cell glucose transporter isoform in beta cells is associated with the impaired glucose sensing characteristic of diabetic islets; our data suggest that this glucose transporter may be part of the beta-cell glucose sensor.

  16. The responses of the estuarine bivalve mollusc Scrobicularia to the first hydrolytic product of the insecticide Sevin ®

    NASA Astrophysics Data System (ADS)

    Akberali, H. B.; Trueman, E. R.; Black, J. E.; Hewitt, C.

    1982-10-01

    The effects of 1-naphthol, the first hydrolytic product of the insecticide Sevin ®, have been studied on the estuarine bivalve Scrobicularia. Median lethal times for 5 and 10 mg l -1 1-naphthol were 15 and 9 days respectively. Final concentrations of 1, 5, 10 and 20 mg l -1 of 1-naphthol resulted in the immediate contraction of the isolated siphon. The contractions were more pronounced at higher concentrations. Application of the same range of concentrations of 1-naphthol to intact Scrobicularia resulted in valve closure and bradycardia. The similarity between the results of median lethal time experiments and the isolated siphonal and behavioural responses of Scrobicularia indicates the feasibility of the use of the isolated siphon preparations to make rapid assessments of environmental stress conditions.

  17. Pin1 down-regulates transforming growth factor-beta (TGF-beta) signaling by inducing degradation of Smad proteins.

    PubMed

    Nakano, Ayako; Koinuma, Daizo; Miyazawa, Keiji; Uchida, Takafumi; Saitoh, Masao; Kawabata, Masahiro; Hanai, Jun-ichi; Akiyama, Hirotada; Abe, Masahiro; Miyazono, Kohei; Matsumoto, Toshio; Imamura, Takeshi

    2009-03-06

    Transforming growth factor-beta (TGF-beta) is crucial in numerous cellular processes, such as proliferation, differentiation, migration, and apoptosis. TGF-beta signaling is transduced by intracellular Smad proteins that are regulated by the ubiquitin-proteasome system. Smad ubiquitin regulatory factor 2 (Smurf2) prevents TGF-beta and bone morphogenetic protein signaling by interacting with Smads and inducing their ubiquitin-mediated degradation. Here we identified Pin1, a peptidylprolyl cis-trans isomerase, as a novel protein binding Smads. Pin1 interacted with Smad2 and Smad3 but not Smad4; this interaction was enhanced by the phosphorylation of (S/T)P motifs in the Smad linker region. (S/T)P motif phosphorylation also enhanced the interaction of Smad2/3 with Smurf2. Pin1 reduced Smad2/3 protein levels in a manner dependent on its peptidyl-prolyl cis-trans isomerase activity. Knockdown of Pin1 increased the protein levels of endogenous Smad2/3. In addition, Pin1 both enhanced the interaction of Smurf2 with Smads and enhanced Smad ubiquitination. Pin1 inhibited TGF-beta-induced transcription and gene expression, suggesting that Pin1 negatively regulates TGF-beta signaling by down-regulating Smad2/3 protein levels via induction of Smurf2-mediated ubiquitin-proteasomal degradation.

  18. Release of IL-1beta via IL-1beta-converting enzyme in a skin dendritic cell line exposed to 2,4-dinitrofluorobenzene.

    PubMed

    Matos, Teresa J; Jaleco, Sara P; Gonçalo, Margarida; Duarte, Carlos B; Lopes, M Celeste

    2005-08-14

    We used a mouse fetal skin dendritic cell line (FSDC) to study the effect of the strong allergen 2,4-dinitrofluorobenzene (DNFB) on interleukin (IL)-1beta release and IL-1beta receptor immunoreactivity. Stimulation with DNFB (30 minutes) increased IL-1 release without changing the mRNA levels of the protein. Furthermore, DNFB increased transiently the interleukin-1beta-converting enzyme (ICE) activity, as measured with its fluorogenic substrate Z-Tyr-Val-Ala-Asp-AFC. The ICE inhibitor Z-YVAD-FMK prevented the release of IL-1beta evoked by DNFB. Incubation of the cells with DNFB (30 minutes) strongly increased IL-1beta receptor immunoreactivity. The rapid effect of DNFB on the release of mature IL-1beta, without inducing an increase of IL-1beta mRNA in FSDC, suggests a posttranslational modification of pro-IL-1beta by ICE activity.

  19. Hydroxyurea responses in clinically varied beta, HbE-beta thalassaemia and sickle cell anaemia patients of Eastern India.

    PubMed

    Chatterjee, Tridip; Chakravarty, Amit; Chakravarty, Sudipa

    2018-05-01

    The haematological and clinical response to hydroxyurea was estimated in HbE-beta, beta thalassaemia and sickle cell anaemia patients of Eastern India, with variable clinical severity and transfusion requirement to determine whether hydroxyurea can help these patients to maintain their steady haemoglobin level without blood transfusions. Three hundred patients (189 HbE-beta thalassaemia, 95 beta thalassaemia and 16 other haemoglobinopathies including sickle cell anaemia) were selected for hydroxyurea therapy and were followed up for 48-60 months. Results suggest significant response to hydroxyurea therapy in 19 beta and 99 HbE-beta patients in the transfusion-dependent group (GR-I). All of them became transfusion-independent while on hydroxyurea therapy. The majority of responding patients were IVS1-5(G-C) in one of their alleles in HbE-beta cases (83 out of 119). Though IVS1-5(G-C) was found to be the commonest mutation in our selected patients, the mutational background of the patients does not found to have any significant correlation with the response category towards hydroxyurea as per the results observed in our study. But, the drug works pretty well in most of the transfusion-dependent patients, as these patients were withdrawn from regular blood transfusion. At the same time, partial or no response to the drug hydroxyurea was also recorded in our study.

  20. Formulary considerations in selection of beta-blockers.

    PubMed

    Yedinak, K C

    1993-08-01

    Selection of beta-adrenergic blockers for formulary addition can be a difficult task, especially with the increasing availability of new beta-blockers, as well as the numerous differences in pharmacodynamic and pharmacokinetic properties of currently available agents. Nevertheless, appropriate evaluation of the important characteristics of beta-blockers should allow selection of the most cost-effective agents for formulary addition. Most importantly, differences in efficacy, product formulation and cost should be carefully considered when making formulary decisions. Notably, evidence from clinical trials indicates differences in efficacy among beta-blockers for post-myocardial infarction prophylaxis, situational anxiety, essential tremor, thyrotoxicosis, migraine prophylaxis and prevention of bleeding associated with oesophageal varices. For many clinical situations, it is also important to select an effective agent that is available in both an oral and intravenous formulation, especially for cardioprotection after acute myocardial infarction and for use in supraventricular arrhythmias. In addition, availability of sustained release products and generic formulations should be considered for their potential to increase compliance and decrease cost, respectively. Comparative drug costs, as well as costs associated with decreased compliance, should also be carefully evaluated. Differences in beta-receptor selectivity, duration of action and presence of intrinsic sympathomimetic activity (ISA) are also important considerations in the selection of beta-blockers for formulary consideration. Although degree of selectivity is relative, beta 1-selective agents may be less likely to induce bronchospasm in patients with chronic obstructive pulmonary disease (COPD) and may be less likely to affect glucose homeostasis in patients with diabetes mellitus. Duration of action of a beta-blocker is an important consideration for evaluation of efficacy throughout the recommended

  1. Beta cell device using icosahedral boride compounds

    DOEpatents

    Aselage, Terrence L.; Emin, David

    2002-01-01

    A beta cell for converting beta-particle energies into electrical energy having a semiconductor junction that incorporates an icosahedral boride compound selected from B.sub.12 As.sub.2, B.sub.12 P.sub.2, elemental boron having an .alpha.-rhombohedral structure, elemental boron having a .beta.-rhombohedral structure, and boron carbides of the chemical formula B.sub.12-x C.sub.3-x, where 0.15beta radiation source, and means for transmitting electrical energy to an outside load. The icosahedral boride compound self-heals, resisting degradation from radiation damage.

  2. Beta-Endorphin: dissociation of receptor binding activity from analgesic potency.

    PubMed

    Li, C H; Tseng, L F; Ferrara, P; Yamashiro, D

    1980-04-01

    Biological activities of synthetic camel beta-endorphin and human beta-endorphin (beta h-EP) have been measured by the radioreceptor binding assay, using [Tyr27-3H]-beta h-EP as the primary ligand and by the tail-flick test for analgesic potency. Four synthetic analogs of beta h-EP, namely [Gly31]-beta h-EP-Gly-NH2, [Gly31]-beta h-EP-Gly-Gly-NH2, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, and [CH3(CH2)4NH231]-beta h-EP, have also been assayed by the same procedures. Results indicate a clear dissociation of radioreceptor binding activity from analgesic potency.

  3. Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells.

    PubMed

    Belkin, A M; Zhidkova, N I; Balzac, F; Altruda, F; Tomatis, D; Maier, A; Tarone, G; Koteliansky, V E; Burridge, K

    1996-01-01

    The cytoplasmic domains of integrins provide attachment of these extracellular matrix receptors to the cytoskeleton and play a critical role in integrin-mediated signal transduction. In this report we describe the identification, expression, localization, and initial functional characterization of a novel form of beta 1 integrin, termed beta 1D. This isoform contains a unique alternatively spliced cytoplasmic domain of 50 amino acids, with the last 24 amino acids encoded by an additional exon. Of these 24 amino acids, 11 are conserved when compared to the beta 1A isoform, but 13 are unique (Zhidkova, N. I., A. M. Belkin, and R. Mayne. 1995. Biochem. Biophys. Res. Commun. 214:279-285; van der Flier, A., I. Kuikman, C. Baudoin, R, van der Neuf, and A. Sonnenberg. 1995. FEBS Lett. 369:340-344). Using an anti-peptide antibody against the beta 1D integrin subunit, we demonstrated that the beta 1D isoform is synthesized only in skeletal and cardiac muscles, while very low amounts of beta 1A were detected by immunoblot in striated muscles. Whereas beta 1A could not be detected in adult skeletal muscle fibers and cardiomyocytes by immunofluorescence, beta 1D was localized to the sarcolemma of both cell types. In skeletal muscle, beta 1D was concentrated in costameres, myotendinous, and neuromuscular junctions. In cardiac muscle this beta 1 isoform was found in costamers and intercalated discs. beta 1D was associated with alpha 7A and alpha 7B in adult skeletal muscle. In cardiomyocytes of adult heart, alpha 7B was the major partner for the beta 1D isoform. beta 1D could not be detected in proliferating C2C12 myoblasts, but it appeared immediately after myoblast fusion and its amount continued to rise during myotube growth and maturation. In contrast, expression of the beta 1A isoform was downregulated during myodifferentiation in culture and it was completely displaced by beta 1D in mature differentiated myotubes. We also analyzed some functional properties of the beta 1D

  4. [Effects of beta blockers on lipoprotein metabolism].

    PubMed

    Ritter, M M; Richter, W O; Schwandt, P

    1992-10-10

    With respect to prevention of its most common complication--mortality from coronary heart disease--treatment of hypertension had disappointed. It is possible that this is due to negative effects of antihypertensives on lipid metabolism. The effects of beta blockers on lipid metabolism can be differentiated principally, in accordance with the classification of beta blockers into those with and those without intrinsic sympathomimetic activity (ISA), as also selectivity and non-selectivity. Thus, non-selective beta blockers with no ISA usually lead to an increase in triglycerides of 25% to 30%, and a decrease in HDL cholesterol of about 15%. On average, beta-1 selective blockers result in a smaller increase in triglycerides. Beta blockers with ISA, in contrast, are largely neutral vis-à-vis lipid metabolism. In the individual case, in particular in the presence of hyperlipoproteinemia, the effects cannot be reliably predicted. Lipoprotein concentrations should be monitored during treatment with beta blockers. If necessary, a change in the agent employed is recommended. In the case of prevention of a second myocardial infarction, for which various studies have unequivocally shown a reduction in mortality associated with treatment with beta blockers with no ISA, these side effects will, however, be accepted--with the exception of extreme changes--for a limited period of time.

  5. High beta-N experiments at JET

    NASA Astrophysics Data System (ADS)

    Challis, Clive

    2007-11-01

    JET has investigated the performance potential and limitations of highly triangular plasmas relevant to fully non-inductive tokamak operation. The q-profile shape has been varied from cases with highly negative core magnetic shear to low shear with q0 close to 1, allowing the effect on confinement and stability to be studied. Operation with beta-N above the no-wall `limit' has been demonstrated for durations comparable with the resistive time and direct measurements of the no-wall beta have been developed as a tool for systematic performance optimization. Regimes have been developed with ITBs at reduced plasma current and toroidal field (1.2-1.5MA/2.3-2.7T) to obtain high values of beta-N and beta-P with either impurity seeding or quasi-double-null plasma configurations used to mitigate ELMs. The importance of the q-profile shape for performance optimization has been demonstrated in plasmas without ITBs (1.2MA/1.8T) with low values of minimum q (1-2) providing access to the highest beta-N (above 3).

  6. Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.

    2011-03-11

    Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomicsmore » screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.« less

  7. How Should Beta-Diversity Inform Biodiversity Conservation?

    PubMed

    Socolar, Jacob B; Gilroy, James J; Kunin, William E; Edwards, David P

    2016-01-01

    To design robust protected area networks, accurately measure species losses, or understand the processes that maintain species diversity, conservation science must consider the organization of biodiversity in space. Central is beta-diversity--the component of regional diversity that accumulates from compositional differences between local species assemblages. We review how beta-diversity is impacted by human activities, including farming, selective logging, urbanization, species invasions, overhunting, and climate change. Beta-diversity increases, decreases, or remains unchanged by these impacts, depending on the balance of processes that cause species composition to become more different (biotic heterogenization) or more similar (biotic homogenization) between sites. While maintaining high beta-diversity is not always a desirable conservation outcome, understanding beta-diversity is essential for protecting regional diversity and can directly assist conservation planning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

    1986-10-07

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

  9. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

    1986-01-01

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

  10. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, G.G.; Kato, T.R.; Schonegg, E.

    1985-04-11

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed. 5 tabs.

  11. Metabolic Stress and Compromised Identity of Pancreatic Beta Cells.

    PubMed

    Swisa, Avital; Glaser, Benjamin; Dor, Yuval

    2017-01-01

    Beta cell failure is a central feature of type 2 diabetes (T2D), but the molecular underpinnings of the process remain only partly understood. It has been suggested that beta cell failure in T2D involves massive cell death. Other studies ascribe beta cell failure to cell exhaustion, due to chronic oxidative or endoplasmic reticulum stress leading to cellular dysfunction. More recently it was proposed that beta cells in T2D may lose their differentiated identity, possibly even gaining features of other islet cell types. The loss of beta cell identity appears to be driven by glucotoxicity inhibiting the activity of key beta cell transcription factors including Pdx1, Nkx6.1, MafA and Pax6, thereby silencing beta cell genes and derepressing alternative islet cell genes. The loss of beta cell identity is at least partly reversible upon normalization of glycemia, with implications for the reversibility of T2D, although it is not known if beta cell failure reaches eventually a point of no return. In this review we discuss current evidence for metabolism-driven compromised beta cell identity, key knowledge gaps and opportunities for utility in the treatment of T2D.

  12. Molecular basis of beta-thalassemia in the Maldives.

    PubMed

    Furuumi, H; Firdous, N; Inoue, T; Ohta, H; Winichagoon, P; Fucharoen, S; Fukumaki, Y

    1998-03-01

    We have systematically analyzed beta-thalassemia genes using polymerase chain reaction-related techniques, dot-blot hybridization with oligonucleotide probes, allele specific-polymerase chain reaction, and sequencing of amplified DNA fragments from 41 unrelated patients, including 37 beta-thalassemia homozygotes, three with beta-thalassemia/Hb E, and one with beta-thalassemia/Hb S. Four different beta-thalassemia mutations were detected in 78 alleles. These are the IVS-I-5 (G-->C), codon 30 (AGG-->ACG) [also indicated as IVS-I (-1)], IVS-I-1 (G-->A), and codons 41/42 (-TTCT) mutations. The distribution of the beta-thalassemia mutations in the Maldives is 58 alleles (74.3%) with the IVS-I-5 (G-->C) mutation, 12 (15.4%) with the codon 30 (AGG-->ACG) mutation, seven (9%) with the IVS-I-1 (G-->A) mutation, and one with the codons 41/42 (-TTCT) mutation. The first three mutations account for 98.7% of the total number of beta-thalassemia chromosomes studied. These mutations are clustered in the region spanning 6 bp around the junction of exon 1 and the first intervening sequence of the beta-globin gene. These observations have significant implications for setting up a thalassemia prevention and control program in the Maldives. Analysis of haplotypes and frameworks of chromosomes bearing each beta-thalassemia mutation suggested that the origin and spread of these mutations were reflected by the historical record.

  13. Toward beta cell replacement for diabetes

    PubMed Central

    Johannesson, Bjarki; Sui, Lina; Freytes, Donald O; Creusot, Remi J; Egli, Dieter

    2015-01-01

    The discovery of insulin more than 90 years ago introduced a life-saving treatment for patients with type 1 diabetes, and since then, significant progress has been made in clinical care for all forms of diabetes. However, no method of insulin delivery matches the ability of the human pancreas to reliably and automatically maintain glucose levels within a tight range. Transplantation of human islets or of an intact pancreas can in principle cure diabetes, but this approach is generally reserved for cases with simultaneous transplantation of a kidney, where immunosuppression is already a requirement. Recent advances in cell reprogramming and beta cell differentiation now allow the generation of personalized stem cells, providing an unlimited source of beta cells for research and for developing autologous cell therapies. In this review, we will discuss the utility of stem cell-derived beta cells to investigate the mechanisms of beta cell failure in diabetes, and the challenges to develop beta cell replacement therapies. These challenges include appropriate quality controls of the cells being used, the ability to generate beta cell grafts of stable cellular composition, and in the case of type 1 diabetes, protecting implanted cells from autoimmune destruction without compromising other aspects of the immune system or the functionality of the graft. Such novel treatments will need to match or exceed the relative safety and efficacy of available care for diabetes. PMID:25733347

  14. Beta-Endorphin: dissociation of receptor binding activity from analgesic potency.

    PubMed Central

    Li, C H; Tseng, L F; Ferrara, P; Yamashiro, D

    1980-01-01

    Biological activities of synthetic camel beta-endorphin and human beta-endorphin (beta h-EP) have been measured by the radioreceptor binding assay, using [Tyr27-3H]-beta h-EP as the primary ligand and by the tail-flick test for analgesic potency. Four synthetic analogs of beta h-EP, namely [Gly31]-beta h-EP-Gly-NH2, [Gly31]-beta h-EP-Gly-Gly-NH2, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, and [CH3(CH2)4NH231]-beta h-EP, have also been assayed by the same procedures. Results indicate a clear dissociation of radioreceptor binding activity from analgesic potency. PMID:6246537

  15. Energy response of diamond sensor to beta radiation.

    PubMed

    Tchouaso, Modeste Tchakoua; Kasiwattanawut, Haruetai; Prelas, Mark A

    2018-04-26

    This paper demonstrates the ability of diamond sensors to respond to beta radiation. A Chemical Vapor Deposition (CVD) single crystal diamond was used in this work. The diamond crystal has a dimension of 4.5×4.5 by 0.5 mm thick. Metal contacts were fabricated on both sides of the diamond using titanium and palladium metals with thicknesses of 50 nm and 150 nm, respectively. The energy response of the diamond sensor was experimentally measured using three beta isotopes that cover the entire range of beta energy: 147 Pm, a weak beta radiation with a maximum energy of 0.225 MeV, 2 ° 4 Tl, a medium energy beta radiation with a maximum energy of 0.763 MeV, and 9 °Sr/ 9 °Y, with both a medium energy beta radiation with a maximum energy of 0.546 MeV, and a high energy beta radiation with a maximum energy of 2.274 MeV. The beta measurements indicate that diamond sensors are sensitive to beta radiation and are suitable for beta spectroscopy. This is important in estimating dose since diamond is tissue equivalent, and the absorbed dose is easily determined from the energy and the mass of the active volume. The high energy betas from 2 ° 4 Tl and 90 Sr/ 90 Y penetrates the sensor without depositing sufficient energy in the active area because their range is larger than the thickness of sensor. The sensitivity of the detector is limited because of its small volume and can be improved by combining smaller area sensors since growing large size diamond is currently a challenge. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Amyloid Beta Mediates Memory Formation

    ERIC Educational Resources Information Center

    Garcia-Osta, Ana; Alberini, Cristina M.

    2009-01-01

    The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid [beta] (1-42) peptide (A[beta][1-42]), which is believed to play a major role in amyloid plaque formation in Alzheimer's disease (AD). Here we provide evidence that, in contrast with its pathological role when accumulated,…

  17. Beta-agonists and animal welfare

    USDA-ARS?s Scientific Manuscript database

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  18. Loss of c-myc repression coincides with ovarian cancer resistance to transforming growth factor beta growth arrest independent of transforming growth factor beta/Smad signaling.

    PubMed

    Baldwin, Rae Lynn; Tran, Hang; Karlan, Beth Y

    2003-03-15

    Many epithelial carcinomas, including ovarian, are refractory to the antiproliferative effects of transforming growth factor (TGF) beta. In some cancers, TGF-beta resistance has been linked to TGF-beta receptor II (TbetaR-II) and Smad4 mutations; however, in ovarian cancer, the mechanism of resistance remains unclear. Primary ovarian epithelial cell cultures were used as a model system to determine the mechanisms of TGF-beta resistance. To simulate in vivo responses to TGF-beta, primary cultures derived from normal human ovarian surface epithelium (HOSE) and from ovarian carcinomas (CSOC) were grown on collagen I gel, the predominant matrix molecule in the ovarian tumor milieu. When treated with 5 ng/ml TGF-beta for 72 h, HOSE (n = 11) proliferation was inhibited by 20 +/- 21% on average. In contrast, CSOC (n = 10) proliferation was stimulated 5 +/- 10% in response to TGF-beta (a statistically significant difference in response when compared with HOSE; P = 0.001). To dissect the TGF-beta/Smad signaling pathway we used a quantitative RNase protection assay (RPA) for measuring mRNA levels of TGF-beta pathway components in 20 HOSE and 20 CSOC cultures. Basal mRNA levels of TGF-beta receptors I and II, downstream signaling components Smad2, 3, 4, 6, 7, and the transcriptional corepressors Ski and SnoN did not show a statistically significant difference between HOSE and CSOC, and cannot explain their differential susceptibility to TGF-beta-induced cell cycle arrest. To assess functional differences of the TGF-beta pathway in TGF-beta-sensitive HOSE and TGF-beta-resistant CSOC, we measured Smad2/4 and 3/4 complex induction after TGF-beta treatment. HOSE and CSOC showed equivalent Smad2/4 and 3/4 complex induction after TGF-beta exposure for 0, 0.5, 2, and 4 h. It has been proposed that SnoN and Ski are corepressors of the TGF-beta/Smad pathway and undergo TGF-beta-induced degradation followed by reinduction of SnoN mRNA. However, our data show equivalent SnoN degradation

  19. Desensitization in patients with beta-lactam drug allergy.

    PubMed

    Yusin, J S; Klaustermeyer, W; Simmons, C W; Baum, M

    2013-01-01

    Patients with a history of beta-lactam antibiotic allergy are often admitted to the hospital with severe or life-threatening infections requiring beta-lactam antibiotics. Strict avoidance of beta lactams to such patients may prevent them from getting adequate coverage and can lead to an increase in the use of alternative antibiotics, which can predispose to antibiotic resistance. Past studies revealed a lower incidence of pen allergy then patients' histories suggest. Fortunately today, there are three options for patients presenting with a history of beta-lactam allergy. Penicillin skin testing, beta-lactam challenge or beta-lactam desensitization. Recently Pre Pen has been FDA re-approved and when combined with Pen G is a valid way to determine if patients are able to tolerate beta-lactam antibiotic. When these agents are not available one must decide about desensitization or challenge. When a patient has a positive penicillin skin test, desensitization or beta-lactam avoidance are the only options. This paper reviews the safety of beta-lactam desensitization. To perform a chart review on patients desensitised with beta lactam to determine if desensitizations can be performed safely without minimal complications. A retrospective chart review was performed on allergy and immunology inpatient consultations for beta-lactam desensitization between September 2003 and August 2006 at the Cedars-Sinai Medical Centre in Los Angeles. Patient data and outcomes of desensitization were analysed. A total of 13 intravenous desensitizations were performed on 12 patients. The patients consisted of eight females and four males with an average age of 65 years. Age range was 36-92 years old. All 13 intravenous desensitizations were completed without complications. No patient required a slower rate of desensitization or discontinuance of the desensitization. Patients were able to tolerate the initial therapeutic dose of their beta-lactam antibiotic and were then able to complete full

  20. Genetics Home Reference: beta-ketothiolase deficiency

    MedlinePlus

    ... Beta Ketothiolase Deficiency Orphanet: Beta-ketothiolase deficiency Screening, Technology And Research in Genetics Virginia Department of Health (PDF) Patient Support and Advocacy Resources (2 links) Children Living with Inherited Metabolic Diseases Organic Acidemia Association ...

  1. Interactions of Plakoglobin and [beta]-Catenin with Desmosomal Cadherins BASIS OF SELECTIVE EXCLUSION OF [alpha]- AND [beta]-CATENIN FROM DESMOSOMES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Choi, Hee-Jung; Gross, Julia C.; Pokutta, Sabine

    2009-11-18

    Plakoglobin and {beta}-catenin are homologous armadillo repeat proteins found in adherens junctions, where they interact with the cytoplasmic domain of classical cadherins and with {alpha}-catenin. Plakoglobin, but normally not {beta}-catenin, is also a structural constituent of desmosomes, where it binds to the cytoplasmic domains of the desmosomal cadherins, desmogleins and desmocollins. Here, we report structural, biophysical, and biochemical studies aimed at understanding the molecular basis of selective exclusion of {beta}-catenin and {alpha}-catenin from desmosomes. The crystal structure of the plakoglobin armadillo domain bound to phosphorylated E-cadherin shows virtually identical interactions to those observed between {beta}-catenin and E-cadherin. Trypsin sensitivity experimentsmore » indicate that the plakoglobin arm domain by itself is more flexible than that of {beta}-catenin. Binding of plakoglobin and {beta}-catenin to the intracellular regions of E-cadherin, desmoglein1, and desmocollin1 was measured by isothermal titration calorimetry. Plakoglobin and {beta}-catenin bind strongly and with similar thermodynamic parameters to E-cadherin. In contrast, {beta}-catenin binds to desmoglein-1 more weakly than does plakoglobin. {beta}-Catenin and plakoglobin bind with similar weak affinities to desmocollin-1. Full affinity binding of desmoglein-1 requires sequences C-terminal to the region homologous to the catenin-binding domain of classical cadherins. Although pulldown assays suggest that the presence of N- and C-terminal {beta}-catenin 'tails' that flank the armadillo repeat region reduces the affinity for desmosomal cadherins, calorimetric measurements show no significant effects of the tails on binding to the cadherins. Using purified proteins, we show that desmosomal cadherins and {alpha}-catenin compete directly for binding to plakoglobin, consistent with the absence of {alpha}-catenin in desmosomes.« less

  2. Corticosteroidogenesis in the toad Bufo arenarum H: evidence for a precursor role for an aldosterone 3 beta-hydroxy-5-ene analogue (3 beta, 11 beta, 21-trihydroxy-20-oxo-5-pregnen-18-al).

    PubMed Central

    Ceballos, N R; Shackleton, C H; Harnik, M; Cozza, E N; Gros, E G; Lantos, C P

    1993-01-01

    A material isolated following pregnenolone incubations with toad (Bufo arenarum) inter-renal tissue at 28 degrees C has been identified as a 3 beta-hydroxy-5-ene analogue of aldosterone (3 beta, 11 beta, 21-trihydroxy-20-oxo-5-pregnen-18-al). The initial identification was made by enzymic and m.s. methods, and structural confirmation was achieved through comparison with chemically synthesized authentic material. The relative efficacy of corticosterone, 18-hydroxycorticosterone and the 3 beta-hydroxy-5-ene aldosterone analogue as aldosterone precursors was evaluated. In the in vitro situation studied, the 3 beta-hydroxy-5-ene steroid was by far the best precursor. PMID:8503841

  3. Corticosteroidogenesis in the toad Bufo arenarum H: evidence for a precursor role for an aldosterone 3 beta-hydroxy-5-ene analogue (3 beta, 11 beta, 21-trihydroxy-20-oxo-5-pregnen-18-al).

    PubMed

    Ceballos, N R; Shackleton, C H; Harnik, M; Cozza, E N; Gros, E G; Lantos, C P

    1993-05-15

    A material isolated following pregnenolone incubations with toad (Bufo arenarum) inter-renal tissue at 28 degrees C has been identified as a 3 beta-hydroxy-5-ene analogue of aldosterone (3 beta, 11 beta, 21-trihydroxy-20-oxo-5-pregnen-18-al). The initial identification was made by enzymic and m.s. methods, and structural confirmation was achieved through comparison with chemically synthesized authentic material. The relative efficacy of corticosterone, 18-hydroxycorticosterone and the 3 beta-hydroxy-5-ene aldosterone analogue as aldosterone precursors was evaluated. In the in vitro situation studied, the 3 beta-hydroxy-5-ene steroid was by far the best precursor.

  4. POCKET $beta$ AND $gamma$ RADIOMETER (in Russian)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Markelov, V.V.; Lushikhin, A.M.; Nikoforov, V.I.

    A pocket BETA and gamma rate meter was designed by the Academy of Medical Sciences of U.S.S.R. for detecting gamma radiation of 0.25 to 2 Mev and for BETA particles of 0 to 50 and 0 to 500 particles/cm/sup 2/sec, with energies of 0.5 to 2 Mev. Measurements of BETA particles are made through the hack wall opening in the appuratus. The opening is closed durtng the recording of gamma radiation, which permits differentiation between the BETA and gamma radiation. The accuracy of the counter is within plus or minus 15%. (R.V.J.)

  5. Stabilization of beta-catenin impacts pancreas growth.

    PubMed

    Heiser, Patrick W; Lau, Janet; Taketo, Makoto M; Herrera, Pedro L; Hebrok, Matthias

    2006-05-01

    A recent study has shown that deletion of beta-catenin within the pancreatic epithelium results in a loss of pancreas mass. Here, we show that ectopic stabilization of beta-catenin within mouse pancreatic epithelium can have divergent effects on both organ formation and growth. Robust stabilization of beta-catenin during early organogenesis drives changes in hedgehog and Fgf10 signaling and induces a loss of Pdx1 expression in early pancreatic progenitor cells. Together, these perturbations in early pancreatic specification culminate in a severe reduction of pancreas mass and postnatal lethality. By contrast, inducing the stabilized form of beta-catenin at a later time point in pancreas development causes enhanced proliferation that results in a dramatic increase in pancreas organ size. Taken together, these data suggest a previously unappreciated temporal/spatial role for beta-catenin signaling in the regulation of pancreas organ growth.

  6. Metabolic Stress and Compromised Identity of Pancreatic Beta Cells

    PubMed Central

    Swisa, Avital; Glaser, Benjamin; Dor, Yuval

    2017-01-01

    Beta cell failure is a central feature of type 2 diabetes (T2D), but the molecular underpinnings of the process remain only partly understood. It has been suggested that beta cell failure in T2D involves massive cell death. Other studies ascribe beta cell failure to cell exhaustion, due to chronic oxidative or endoplasmic reticulum stress leading to cellular dysfunction. More recently it was proposed that beta cells in T2D may lose their differentiated identity, possibly even gaining features of other islet cell types. The loss of beta cell identity appears to be driven by glucotoxicity inhibiting the activity of key beta cell transcription factors including Pdx1, Nkx6.1, MafA and Pax6, thereby silencing beta cell genes and derepressing alternative islet cell genes. The loss of beta cell identity is at least partly reversible upon normalization of glycemia, with implications for the reversibility of T2D, although it is not known if beta cell failure reaches eventually a point of no return. In this review we discuss current evidence for metabolism-driven compromised beta cell identity, key knowledge gaps and opportunities for utility in the treatment of T2D. PMID:28270834

  7. Ionic liquid-based dispersive liquid-liquid microextraction with back-extraction coupled with capillary electrophoresis to determine phenolic compounds.

    PubMed

    Zhou, Caihong; Tong, Shanshan; Chang, Yunxia; Jia, Qiong; Zhou, Weihong

    2012-04-01

    Ionic liquid (IL) based dispersive liquid-liquid microextraction (DLLME) with back-extraction coupled with capillary electrophoresis ultraviolet detection was developed to determine four phenolic compounds (bisphenol-A, β-naphthol, α-naphthol, 2, 4-dichlorophenol) in aqueous cosmetics. The developed method was used to preconcentrate and clean up the four phenolic compounds including two steps. The analytes were transferred into room temperature ionic liquid (1-octyl-3-methylimidazolium hexafluorophosphate, [C(8) MIM][PF(6) ]) rich-phase in the first step. In the second step, the analytes were back-extracted into the alkaline aqueous phase. The effects of extraction parameters, such as type and volume of extraction solvent, type and volume of disperser, extraction and centrifugal time, sample pH, salt addition, and concentration and volume of NaOH in back-extraction were investigated. Under the optimal experimental conditions, the preconcentration factors were 60.1 for bisphenol-A, 52.7 for β-naphthol, 49.2 for α-naphthol, and 18.0 for 2, 4-dichlorophenol. The limits of detection for bisphenol-A, β-naphthol, α-naphthol and 2, 4-dichlorophenol were 5, 5, 8, and 100 ng mL(-1), respectively. Four kinds of aqueous cosmetics including toner, soften lotion, make-up remover, and perfume were analyzed and yielded recoveries ranging from 81.6% to 119.4%. The main advantages of the proposed method are quick, easy, cheap, and effective. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Expression of the barley stripe mosaic virus RNA beta "triple gene block".

    PubMed

    Zhou, H; Jackson, A O

    1996-02-15

    Genomic RNA beta of barley strip mosaic virus (BSMV) contains four defined open reading frames (ORFs). These include the coat protein (beta a) and a "triple gene block" consisting of the beta b, beta c, and beta d ORFs that overlap one another. Two subgenomic beta RNAs (sgRNA beta 1 and sgRNA beta 2) with sizes of 2.5 and 0.96 kb were identified in BSMV-infected protoplasts, and their transcription initiation sites were mapped to nucleotides 789 and 2327, respectively, of RNA beta by primer extension experiments. In a cell-free wheat germ translation system, genomic RNA beta served as a mRNA only for the 22-kDa coat protein, and sgRNA beta 1 directed synthesis of only the 58-kDA beta b protein. However, with sgRNA beta 2, three proteins with sizes of 14, 17, and 23 kDa were synthesized. Both the 14- and the 23-kDa proteins were recognized by the beta d antibodies in vitro and in vivo. These results demonstrated that the 14-kDa protein was encoded by the beta d ORF and suggested that the 23-kDa protein, designated beta d', is a readthrough product of the amber stop codon of the beta d ORF. Mutagenesis of sgRNA beta 2 revealed that the 17-kDa protein was a product of the beta c ORF. Expression of sgRNA beta 1 and sgRNA beta 2 was also investigated with the chloramphenicol acetyl transferase (CAT) reporter gene in protoplasts coinfected with RNAs alpha and gamma plus chimeric RNA beta derivatives containing the CAT gene in-frame with the beta b, beta c, beta d, or beta d' ORFs. Elimination of the sgRNA beta 1 promoter abolished CAT expression from the beta b-CAT chimeric RNA, and removal of the sgRNA beta 2 promoter prevented CAT expression from the beta c-CAT, beta d-CAT, and beta d'-CAT chimeric RNAs. Taken together, these results demonstrate that the BSMV coat protein is the sole translation product of the genomic RNA beta, whereas sgRNA beta 1 serves as a messenger for translation of the beta b protein, and sgRNA beta 2 functions as a messenger for translation of

  9. GLP-1 mediates antiapoptotic effect by phosphorylating Bad through a beta-arrestin 1-mediated ERK1/2 activation in pancreatic beta-cells.

    PubMed

    Quoyer, Julie; Longuet, Christine; Broca, Christophe; Linck, Nathalie; Costes, Safia; Varin, Elodie; Bockaert, Joël; Bertrand, Gyslaine; Dalle, Stéphane

    2010-01-15

    Strategies based on activating GLP-1 receptor (GLP-1R) are intensively developed for the treatment of type 2 diabetes. The exhaustive knowledge of the signaling pathways linked to activated GLP-1R within the beta-cells is of major importance. In beta-cells, GLP-1 activates the ERK1/2 cascade by diverse pathways dependent on either Galpha(s)/cAMP/cAMP-dependent protein kinase (PKA) or beta-arrestin 1, a scaffold protein. Using pharmacological inhibitors, beta-arrestin 1 small interfering RNA, and islets isolated from beta-arrestin 1 knock-out mice, we demonstrate that GLP-1 stimulates ERK1/2 by two temporally distinct pathways. The PKA-dependent pathway mediates rapid and transient ERK1/2 phosphorylation that leads to nuclear translocation of the activated kinases. In contrast, the beta-arrestin 1-dependent pathway produces a late ERK1/2 activity that is restricted to the beta-cell cytoplasm. We further observe that GLP-1 phosphorylates the cytoplasmic proapoptotic protein Bad at Ser-112 but not at Ser-155. We find that the beta-arrestin 1-dependent ERK1/2 activation engaged by GLP-1 mediates the Ser-112 phosphorylation of Bad, through p90RSK activation, allowing the association of Bad with the scaffold protein 14-3-3, leading to its inactivation. beta-Arrestin 1 is further found to mediate the antiapoptotic effect of GLP-1 in beta-cells through the ERK1/2-p90RSK-phosphorylation of Bad. This new regulatory mechanism engaged by activated GLP-1R involving a beta-arrestin 1-dependent spatiotemporal regulation of the ERK1/2-p90RSK activity is now suspected to participate in the protection of beta-cells against apoptosis. Such signaling mechanism may serve as a prototype to generate new therapeutic GLP-1R ligands.

  10. Osteoblast gene expression is differentially regulated by TGF-beta isoforms.

    PubMed

    Fagenholz, P J; Warren, S M; Greenwald, J A; Bouletreau, P J; Spector, J A; Crisera, F E; Longaker, M T

    2001-03-01

    The transforming growth factor beta (TGF-beta) superfamily encompasses a number of important growth factors including several TGF-beta isoforms, the bone morphogenetic proteins, activins, inhibins, and growth and differentiation factors. TGF-beta 1, -beta 2, and -beta 3 are three closely related isoforms that are widely expressed during skeletal morphogenesis and bone repair. Numerous studies suggest that each isoform has unique in vivo functions; however, the effects of these TGF-beta isoforms on osteoblast gene expression and maturation have never been directly compared. In the current study, we treated undifferentiated neonatal rat calvaria osteoblast-enriched cell cultures with 2.5 ng/ml of each TGF-beta isoform and analyzed gene expression at 0, 3, 6, and 24 hours. We demonstrated unique isoform-specific regulation of endogenous TGF-beta 1 and type I collagen mRNA transcription. To assess the effects of extended TGF-beta treatment on osteoblast maturation, we differentiated osteoblast cultures in the presence of 2.5 ng/ml of each TGF-beta isoform. Analysis of collagen I, alkaline phosphatase, and osteocalcin demonstrated that each TGF-beta isoform uniquely suppressed the transcription of these osteoblast differentiation markers. Interestingly, TGF-beta isoform treatment increased osteopontin expression in primary osteoblasts after 4 and 10 days of differentiation. To our knowledge, these data provide the first direct comparison of the effects of the TGF-beta isoforms on osteoblast gene expression in vitro. Furthermore, these data suggest that TGF-beta isoforms may exert their unique in vivo effects by differentially regulating osteoblast cytokine secretion, extracellular matrix production, and the rate of cellular maturation.

  11. Movement-related beta oscillations show high intra-individual reliability.

    PubMed

    Espenhahn, Svenja; de Berker, Archy O; van Wijk, Bernadette C M; Rossiter, Holly E; Ward, Nick S

    2017-02-15

    Oscillatory activity in the beta frequency range (15-30Hz) recorded from human sensorimotor cortex is of increasing interest as a putative biomarker of motor system function and dysfunction. Despite its increasing use in basic and clinical research, surprisingly little is known about the test-retest reliability of spectral power and peak frequency measures of beta oscillatory signals from sensorimotor cortex. Establishing that these beta measures are stable over time in healthy populations is a necessary precursor to their use in the clinic. Here, we used scalp electroencephalography (EEG) to evaluate intra-individual reliability of beta-band oscillations over six sessions, focusing on changes in beta activity during movement (Movement-Related Beta Desynchronization, MRBD) and after movement termination (Post-Movement Beta Rebound, PMBR). Subjects performed visually-cued unimanual wrist flexion and extension. We assessed Intraclass Correlation Coefficients (ICC) and between-session correlations for spectral power and peak frequency measures of movement-related and resting beta activity. Movement-related and resting beta power from both sensorimotor cortices was highly reliable across sessions. Resting beta power yielded highest reliability (average ICC=0.903), followed by MRBD (average ICC=0.886) and PMBR (average ICC=0.663). Notably, peak frequency measures yielded lower ICC values compared to the assessment of spectral power, particularly for movement-related beta activity (ICC=0.386-0.402). Our data highlight that power measures of movement-related beta oscillations are highly reliable, while corresponding peak frequency measures show greater intra-individual variability across sessions. Importantly, our finding that beta power estimates show high intra-individual reliability over time serves to validate the notion that these measures reflect meaningful individual differences that can be utilised in basic research and clinical studies. Copyright © 2016 The

  12. A novel solution for hydroxylated PAHs removal by oxidative coupling reaction using Mn oxide.

    PubMed

    Kang, Ki-Hoon; Lim, Dong-Min; Shin, Hyun-Sang

    2008-01-01

    In this study, removals of 1-naphthol by oxidative-coupling reaction using birnessite, one of the natural Mn oxides present in soil, was investigated in various experimental conditions (reaction time, Mn oxide loadings, pH). The removal efficiency of 1-naphthol by birnessite was high in all the experimental conditions, and UV-visible and mass spectrometric analyses on the supernatant after reaction confirmed that the reaction products were oligomers formed by oxidative-coupling reaction. Pseudo-first order rate constants, k, for the oxidative transformation of 1-naphthol by birnessite was derived from the kinetic experiments under various amounts of birnessite loadings, and using the observed pseudo-first order rate constants with respect to birnessite loadings, the surface area normalised specific rate constant, k(surf), was also determined to be 9.3 x 10(-4) (L/m(2).min) for 1-naphthol. In addition, the oxidative transformation of 1-naphthol was found to be dependent on solution pH, and the pseudo-first order rate constants were increased from 0.129 at pH 10 to 0.187 at pH 4. (c) IWA Publishing 2008.

  13. [beta]-Glucan Synthesis in the Cotton Fiber (III. Identification of UDP-Glucose-Binding Subunits of [beta]-Glucan Synthases by Photoaffinity Labeling with [[beta]-32P]5[prime]-N3-UDP-Glucose.

    PubMed Central

    Li, L.; Drake, R. R.; Clement, S.; Brown, R. M.

    1993-01-01

    Using differential product entrapment and photolabeling under specifying conditions, we identifIed a 37-kD polypeptide as the best candidate among the UDP-glucose-binding polypeptides for the catalytic subunit of cotton (Gossypium hirsutum) cellulose synthase. This polypeptide is enriched by entrapment under conditions favoring [beta]-1,4-glucan synthesis, and it is magnesium dependent and sensitive to unlabeled UDP-glucose. A 52-kD polypeptide was identified as the most likely candidate for the catalytic subunit of [beta]-1,3-glucan synthase because this polypeptide is the most abundant protein in the entrapment fraction obtained under conditions favoring [beta]-1,3-glucan synthesis, is coincident with [beta]-1,3-glucan synthase activity, and is calcium dependent. The possible involvement of other polypeptides in the synthesis of [beta]-1,3-glucan is discussed. PMID:12231766

  14. Increasing protein stability by improving beta-turns.

    PubMed

    Fu, Hailong; Grimsley, Gerald R; Razvi, Abbas; Scholtz, J Martin; Pace, C Nick

    2009-11-15

    Our goal was to gain a better understanding of how protein stability can be increased by improving beta-turns. We studied 22 beta-turns in nine proteins with 66-370 residues by replacing other residues with proline and glycine and measuring the stability. These two residues are statistically preferred in some beta-turn positions. We studied: Cold shock protein B (CspB), Histidine-containing phosphocarrier protein, Ubiquitin, Ribonucleases Sa2, Sa3, T1, and HI, Tryptophan synthetase alpha-subunit, and Maltose binding protein. Of the 15 single proline mutations, 11 increased stability (Average = 0.8 +/- 0.3; Range = 0.3-1.5 kcal/mol), and the stabilizing effect of double proline mutants was additive. On the basis of this and our previous work, we conclude that proteins can generally be stabilized by replacing nonproline residues with proline residues at the i + 1 position of Type I and II beta-turns and at the i position in Type II beta-turns. Other turn positions can sometimes be used if the phi angle is near -60 degrees for the residue replaced. It is important that the side chain of the residue replaced is less than 50% buried. Identical substitutions in beta-turns in related proteins give similar results. Proline substitutions increase stability mainly by decreasing the entropy of the denatured state. In contrast, the large, diverse group of proteins considered here had almost no residues in beta-turns that could be replaced by Gly to increase protein stability. Improving beta-turns by substituting Pro residues is a generally useful way of increasing protein stability. 2009 Wiley-Liss, Inc.

  15. Carotenoids: more than just beta-carotene.

    PubMed

    Gellenbeck, K W

    1998-12-01

    Fruits and vegetables of the human diet contain many of the over 600 carotenoid pigments that have been identified in plants. Led by work with beta-carotene, researchers have constantly been learning more about the metabolism of these compounds in the human body. Research work is now expanding beyond beta-carotene in an effort to understand what happens to all the pigments found in the human diet. This discussion briefly looks at research results on the carotenoids found in human serum as well as the effects of supplementation. Recent confusing results from large intervention trials with beta-carotene and lung cancer incidence are emphasized in relation to supplementation doses and beta-carotene source (synthetic vs. natural). The summation of results emphasizes the importance of the broad spectrum of carotenoids in the diet and relates to supplementation products currently being designed for the marketplace.

  16. Computerized tomography platform using beta rays

    NASA Astrophysics Data System (ADS)

    Paetkau, Owen; Parsons, Zachary; Paetkau, Mark

    2017-12-01

    A computerized tomography (CT) system using a 0.1 μCi Sr-90 beta source, Geiger counter, and low density foam samples was developed. A simple algorithm was used to construct images from the data collected with the beta CT scanner. The beta CT system is analogous to X-ray CT as both types of radiation are sensitive to density variations. This system offers a platform for learning opportunities in an undergraduate laboratory, covering topics such as image reconstruction algorithms, radiation exposure, and the energy dependence of absorption.

  17. Right ventricular beneficial effects of beta adrenergic receptor kinase inhibitor (betaARKct) gene transfer in a rat model of severe pressure overload.

    PubMed

    Molina, Ezequiel J; Gupta, Dipin; Palma, Jon; Gaughan, John P; Macha, Mahender

    2009-06-01

    Heart failure is associated with abnormalities in betaAR cascade regulation, calcium cycling, expression of inflammatory mediators and apoptosis. Adenoviral mediated gene transfer of betaARKct has beneficial indirect effects on these pathologic processes upon the left ventricular myocardium. The concomitant biochemical changes that occur in the right ventricle have not been well characterized. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After a decrease in fractional shortening of 25% from baseline, intracoronary injection of adenoviral-betaARKct (n=14) or adenoviral-beta-galactosidase (control, n=13) was performed. Rats were randomly euthanized on post-operative day 7, 14 or 21. Protein analysis including RV myocardial levels of betaARKct, betaARK1, SERCA(2a), inflammatory tissue mediators (IL-1, IL-6 and TNF-alpha), apoptotic markers (bax and bak), and MAP kinases (jnk, p38 and erk) was performed. ANOVA was employed for group comparison. Adenoviral-betaARKct treated animals showed increased expression of betaARKct and decreased levels of betaARK1 compared with controls. This treatment group also demonstrated normalization of SERCA(2a) expression and decreased levels of the inflammatory markers IL-1, IL-6 and TNF-alpha. The pro-apoptotic markers bax and bak were similarly improved. Ventricular levels of the MAP kinase jnk were increased. Differences were most significant 7 days after gene transfer, but the majority of these changes persisted at 21 days. These results suggest that attenuation of the pathologic mechanisms of beta adrenergic receptor desensitization, SERCA(2a) expression, inflammation and apoptosis, not only occur in the left ventricle but also in the right ventricular myocardium after intracoronary gene transfer of betaARKct during heart failure.

  18. Beta-blocker use in decompensated heart failure.

    PubMed

    Alharethi, Rami; Hershberger, Ray E

    2006-06-01

    Despite the current advances in treatment, acute decompensated heart failure accounts for more than 1 million hospital admissions annually. Many of the patients hospitalized are already receiving long-term treatment with beta-blockers. For patients who receive full dose beta-blocker therapy and suffer acute decompensated heart failure, clinicians face two key questions: what to do, if anything, with the dosage of beta-blocker and what is the best way to integrate inotropic and beta-blocker therapies for patients who require inotropes. This article discusses these issues and reviews the available literature. Because these topics have received little systematic evaluation, we also present our clinical approaches to these problems.

  19. Expression of beta 3-adrenoceptor mRNA in rat tissues.

    PubMed

    Evans, B A; Papaioannou, M; Bonazzi, V R; Summers, R J

    1996-01-01

    1. This study examines the expression of beta 3-adrenoceptor messenger RNA (beta 3-AR mRNA) in rat tissues to allow comparison with atypical beta-adrenoceptors determined by functional and radioligand binding techniques. 2. A reverse transcription/polymerase chain reaction protocol has been developed for determining the relative amounts of beta 3-AR mRNA in rat tissues. 3. Measurement of adipsin and uncoupling protein (UCP) mRNA was used to examine all tissues for the presence of white and brown adipose tissue which may contribute beta 3-AR mRNA. 4. The beta 3-AR mRNA is expressed at high levels in brown and white adipose tissue, stomach fundus, the longitudinal/circular smooth muscle of both colon and ileum, and colon submucosa. There was substantial expression of adipsin in colon submucosa and moderate expression in fundus, suggesting that in these regions at least some of the beta 3-AR signal may be contributed by fat. Pylorus and colon mucosa showed moderate levels of beta 3-AR mRNA with lower levels of adipsin. Ileum mucosa and submucosa showed low but readily detectable levels of beta 3-AR. 5. Expression of adipsin in rat skeletal muscles coupled to very low levels of beta 3-AR mRNA indicates that the observed beta 3-AR may be due to the presence of intrinsic fat. beta 3-AR mRNA was virtually undetectable in heart, lung and liver. These results raise the possibility that the atypical beta-AR demonstrated by functional and/or binding studies in muscle and in heart is not the beta 3-AR. 6. By use of two different sets of primers for amplification of beta 3-AR cDNA, no evidence was found for differential splicing of the mRNA in any of the tissues examined. 7. The detection of beta 3-AR mRNA in the gut mucosa and submucosa suggests that in addition to its established roles in lipolysis, thermogenesis and regulation of gut motility beta 3-AR may subserve other functions in the gastrointestinal tract. The absence of beta 3-AR mRNA in rat heart or its presence with

  20. The BetaCage: Ultrasensitive Screener for Radioactive Backgrounds

    NASA Astrophysics Data System (ADS)

    Thompson, Michael; BetaCage Collaboration

    2017-09-01

    Rare event searches, such as dark matter detection and neutrinoless double beta decay, require screening of materials for backgrounds such as beta emission and alpha decaying isotopes. The BetaCage is a proposed ultra-sensitive time-projection chamber to screen for alpha-emitting and low energy beta-emitting (10-200 keV) contaminants. The expected sensitivity is 0.1 beta particles (perkeV -m2 - day) and 0.1 alpha particles (perm2 - day) , where the former will be limited by Compton scattering of external photons in the screening samples and the latter is expected to be signal-limited. The prototype BetaCage under commissioning at South Dakota School of Mines & Technology is filled with P10 gas (10% methane, 90% argon) in place of neon and is 40×40×20 cm in size. Details on design, construction and characterization will be presented.

  1. 17betaE2 promotes cell proliferation in endometriosis by decreasing PTEN via NFkappaB-dependent pathway.

    PubMed

    Zhang, Hui; Zhao, Xingbo; Liu, Shu; Li, Jijun; Wen, Zeqing; Li, Mingjiang

    2010-04-12

    The objective of this study was to explore the mechanism of phosphatase and tensin homolog (PTEN) loss in endometriosis. We found that aberrant PTEN expression and mitogen-activated protein kinases (MAPK)/ERK, phosphoinositide 3-kinase (PI3K)/AKt, and nuclear factor-kappaB (NFkappaB) signaling overactivities coexisted in endometriosis. In vitro, 17beta-estradiol rapidly activated the 3 pathways in endometriotic cells and specific inhibitions on the 3 pathways respectively blocked 17beta-estradiol-induced cell proliferation. 17beta-estradiol suppressed PTEN transcription and expression in endometriotic cells which was abolished by specific NFkappaB inhibition. Total/nuclear PTEN-loss and MAPK/ERK, PI3K/AKt, and NFkappaB signal overactivities coexist in endometriosis. In vitro, 17beta-estradiol can promotes cell proliferation in endometriosis by activating PI3K/AKt pathway via an NFkappaB/PTEN-dependent pathway. For the first time we propose the possibility of the presence of a positive feedback-loop: 17beta-estradiol-->high NFkappaB-->low PTEN-->high PI3K-->high NFkappaB, in endometriosis, which may finally promote the proliferation of ectopic endometrial epithelial cells and in turn contributes to the progression of the disease.

  2. Stabilization of beta-catenin induces pancreas tumor formation.

    PubMed

    Heiser, Patrick W; Cano, David A; Landsman, Limor; Kim, Grace E; Kench, James G; Klimstra, David S; Taketo, Maketo M; Biankin, Andrew V; Hebrok, Matthias

    2008-10-01

    beta-Catenin signaling within the canonical Wnt pathway is essential for pancreas development. However, the pathway is normally down-regulated in the adult organ. Increased cytoplasmic and nuclear localization of beta-catenin can be detected in nearly all human solid pseudopapillary neoplasms (SPN), a rare tumor with low malignant potential. Conversely, pancreatic ductal adenocarcinoma (PDA) accounts for the majority of pancreatic tumors and is among the leading causes of cancer death. Whereas activating mutations within beta-catenin and other members of the canonical Wnt pathway are rare, recent reports have implicated Wnt signaling in the development and progression of human PDA. Here, we sought to address the role of beta-catenin signaling in pancreas tumorigenesis. Using Cre/lox technology, we conditionally activated beta-catenin in a subset of murine pancreatic cells in vivo. Activation of beta-catenin results in the formation of large pancreatic tumors at a high frequency in adult mice. These tumors resemble human SPN based on morphologic and immunohistochemical comparisons. Interestingly, stabilization of beta-catenin blocks the formation of pancreatic intraepithelial neoplasia (PanIN) in the presence of an activating mutation in Kras that is known to predispose individuals to PDA. Instead, mice in which beta-catenin and Kras are concurrently activated develop distinct ductal neoplasms that do not resemble PanIN lesions. These results demonstrate that activation of beta-catenin is sufficient to induce pancreas tumorigenesis. Moreover, they indicate that the sequence in which oncogenic mutations are acquired has profound consequences on the phenotype of the resulting tumor.

  3. Polypeptides having beta-glucosidase activity and polynucleotides encoding same

    DOEpatents

    Morant, Marc Dominique

    2014-10-14

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  4. beta-Propiolactone

    Integrated Risk Information System (IRIS)

    beta - Propiolactone ; CASRN 57 - 57 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  5. beta-Chloronaphthalene

    Integrated Risk Information System (IRIS)

    beta - Chloronaphthalene ; CASRN 91 - 58 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcin

  6. Why Downside Beta Is Better: An Educational Example

    ERIC Educational Resources Information Center

    Chong, James T.; Jennings, William P.; Phillips, G. Michael

    2013-01-01

    An educational example is presented that is an effective teaching illustration to help students understand the difference between traditional CAPM beta and downside (or down-market) beta and why downside beta is a superior measure for use in personal financial planning investment policy statements.

  7. Beta-Cryptoxanthin as a source of Vitamin A.

    USDA-ARS?s Scientific Manuscript database

    Beta-cryptoxanthin is a common carotenoid that is found in fruit, and in human blood and tissues. Foods that are rich in beta-cryptoxanthin include tangerines, persimmons, and oranges. Beta-cryptoxanthin has several functions that are important for human health, including roles in antioxidant defens...

  8. Alpha- and beta-keratins of the snake epidermis.

    PubMed

    Toni, Mattia; Alibardi, Lorenzo

    2007-01-01

    Snake scales contain specialized hard keratins (beta-keratins) and alpha- or cyto-keratins in their epidermis. The number, isoelectric point, and the evolution of these proteins in snakes and their similarity with those of other vertebrates are not known. In the present study, alpha- and beta-keratins of snake molts and of the whole epidermis have been studied by using two-dimensional electrophoresis and immunocytochemistry. Specific keratins in snake epidermis have been identified by using antibodies that recognize acidic and basic cytokeratins and avian or lizard scale beta-keratin. Alpha keratins of 40-70 kDa and isoelectric point (pI) at 4.5-7.0 are present in molts. The study suggests that cytokeratins in snakes are acidic or neutral, in contrast to mammals and birds where basic keratins are also present. Beta keratins of 10-15 kDa and a pI of 6.5-8.5 are found in molts. Some beta-keratins appear as basic proteins (pI 8.2) comparable to those present in the epidermis of other reptiles. Some basic "beta-keratins" associate with cytokeratins as matrix proteins and replace cytokeratins forming the corneous material of the mature beta-layer of snake scales, as in other reptiles. The study also suggests that more forms of beta-keratins (more than three different types) are present in the epidermis of snakes.

  9. Bioavailabilty of beta-amino acid and C-terminally derived PK/PBAN analogs

    USDA-ARS?s Scientific Manuscript database

    The ability of linear beta amino-acid-substituted peptides (PK-betaA-1: Ac-YFT[beta3-P]RLa; PK-betaA-2: Ac-Y[beta2-homoF]TPRLa; PK-betaA-3: Ac-Y[beta3-F]TPRLa and PK-betaA-4: Ac-[beta3-F]FT[beta3-P]RLa) and unsubstituted analogs (Ac-YFTPRLa and YFTPRLa) of the pyrokinin(PK)/pheromone biosynthesis-ac...

  10. Fragrant dioxane derivatives identify beta1-subunit-containing GABAA receptors.

    PubMed

    Sergeeva, Olga A; Kletke, Olaf; Kragler, Andrea; Poppek, Anja; Fleischer, Wiebke; Schubring, Stephan R; Görg, Boris; Haas, Helmut L; Zhu, Xin-Ran; Lübbert, Hermann; Gisselmann, Günter; Hatt, Hanns

    2010-07-30

    Nineteen GABA(A) receptor (GABA(A)R) subunits are known in mammals with only a restricted number of functionally identified native combinations. The physiological role of beta1-subunit-containing GABA(A)Rs is unknown. Here we report the discovery of a new structural class of GABA(A)R positive modulators with unique beta1-subunit selectivity: fragrant dioxane derivatives (FDD). At heterologously expressed alpha1betaxgamma2L (x-for 1,2,3) GABA(A)R FDD were 6 times more potent at beta1- versus beta2- and beta3-containing receptors. Serine at position 265 was essential for the high sensitivity of the beta1-subunit to FDD and the beta1N286W mutation nearly abolished modulation; vice versa the mutation beta3N265S shifted FDD sensitivity toward the beta1-type. In posterior hypothalamic neurons controlling wakefulness GABA-mediated whole-cell responses and GABAergic synaptic currents were highly sensitive to FDD, in contrast to beta1-negative cerebellar Purkinje neurons. Immunostaining for the beta1-subunit and the potency of FDD to modulate GABA responses in cultured hypothalamic neurons was drastically diminished by beta1-siRNA treatment. In conclusion, with the help of FDDs we reveal a functional expression of beta1-containing GABA(A)Rs in the hypothalamus, offering a new tool for studies on the functional diversity of native GABA(A)Rs.

  11. Hypertrophic stimulation increases beta-actin dynamics in adult feline cardiomyocytes.

    PubMed

    Balasubramanian, Sundaravadivel; Mani, Santhosh K; Kasiganesan, Harinath; Baicu, Catalin C; Kuppuswamy, Dhandapani

    2010-07-12

    The myocardium responds to hemodynamic stress through cellular growth and organ hypertrophy. The impact of cytoskeletal elements on this process, however, is not fully understood. While alpha-actin in cardiomyocytes governs muscle contraction in combination with the myosin motor, the exact role of beta-actin has not been established. We hypothesized that in adult cardiomyocytes, as in non-myocytes, beta-actin can facilitate cytoskeletal rearrangement within cytoskeletal structures such as Z-discs. Using a feline right ventricular pressure overload (RVPO) model, we measured the level and distribution of beta-actin in normal and pressure overloaded myocardium. Resulting data demonstrated enriched levels of beta-actin and enhanced translocation to the Triton-insoluble cytoskeletal and membrane skeletal complexes. In addition, RVPO in vivo and in vitro hypertrophic stimulation with endothelin (ET) or insulin in isolated adult cardiomyocytes enhanced the content of polymerized fraction (F-actin) of beta-actin. To determine the localization and dynamics of beta-actin, we adenovirally expressed GFP-tagged beta-actin in isolated adult cardiomyocytes. The ectopically expressed beta-actin-GFP localized to the Z-discs, costameres, and cell termini. Fluorescence recovery after photobleaching (FRAP) measurements of beta-actin dynamics revealed that beta-actin at the Z-discs is constantly being exchanged with beta-actin from cytoplasmic pools and that this exchange is faster upon hypertrophic stimulation with ET or insulin. In addition, in electrically stimulated isolated adult cardiomyocytes, while beta-actin overexpression improved cardiomyocyte contractility, immunoneutralization of beta-actin resulted in a reduced contractility suggesting that beta-actin could be important for the contractile function of adult cardiomyocytes. These studies demonstrate the presence and dynamics of beta-actin in the adult cardiomyocyte and reinforce its usefulness in measuring cardiac

  12. Redox-mediated activation of latent transforming growth factor-beta 1

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Dix, T. A.; Chatterjee, A. (Principal Investigator)

    1996-01-01

    Transforming growth factor beta 1 (TGF beta) is a multifunctional cytokine that orchestrates response to injury via ubiquitous cell surface receptors. The biological activity of TGF beta is restrained by its secretion as a latent complex (LTGF beta) such that activation determines the extent of TGF beta activity during physiological and pathological events. TGF beta action has been implicated in a variety of reactive oxygen-mediated tissue processes, particularly inflammation, and in pathologies such as reperfusion injury, rheumatoid arthritis, and atherosclerosis. It was recently shown to be rapidly activated after in vivo radiation exposure, which also generates reactive oxygen species (ROS). In the present studies, the potential for redox-mediated LTGF beta activation was investigated using a cell-free system in which ROS were generated in solution by ionizing radiation or metal ion-catalyzed ascorbate reaction. Irradiation (100 Gray) of recombinant human LTGF beta in solution induced 26% activation compared with that elicited by standard thermal activation. Metal-catalyzed ascorbate oxidation elicited extremely efficient recombinant LTGF beta activation that matched or exceeded thermal activation. The efficiency of ascorbate activation depended on ascorbate concentrations and the presence of transition metal ions. We postulate that oxidation of specific amino acids in the latency-conferring peptide leads to a conformation change in the latent complex that allows release of TGF beta. Oxidative activation offers a novel route for the involvement of TGF beta in tissue processes in which ROS are implicated and endows LTGF beta with the ability to act as a sensor of oxidative stress and, by releasing TGF beta, to function as a signal for orchestrating the response of multiple cell types. LTGF beta redox sensitivity is presumably directed toward recovery of homeostasis; however, oxidation may also be a mechanism of LTGF beta activation that can be deleterious during

  13. Expression and structural features of endoglin (CD105), a transforming growth factor beta1 and beta3 binding protein, in human melanoma.

    PubMed Central

    Altomonte, M.; Montagner, R.; Fonsatti, E.; Colizzi, F.; Cattarossi, I.; Brasoveanu, L. I.; Nicotra, M. R.; Cattelan, A.; Natali, P. G.; Maio, M.

    1996-01-01

    Human endoglin (CD105) is a member of the transforming growth factor beta (TGF-beta) receptor family that binds TGF-beta1 and -beta3, but not TGF-beta2, on human endothelial cells. Immunohistochemical analyses demonstrated that CD105 is expressed on normal and neoplastic cells of the melanocytic lineage. The anti-CD105 MAb, MAEND3, stained 50, 25 and 34% of intradermal naevi, primary and metastatic melanomas investigated, respectively, and nine out of 12 melanoma cell lines. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that CD105 expressed by melanoma cells consists of a homodimeric protein with an apparent molecular weight of 180 and 95 kDa under non-reducing and reducing conditions. Cross-linking of 125I-labelled TGF-beta1 to melanoma cells, Mel 97, by disuccinimidyl suberate (DSS) demonstrated that CD105 expressed on pigmented cells binds TGF-beta1; the pattern of binding of TGF-beta1 to melanoma cells was found to be similar to that of human umbilical vein endothelial cells. The addition of exogenous, bioactive TGF-beta1 significantly (P<0.05) inhibited the growth of CD105-positive melanoma cells, Mel 97, but did not affect that of CD105-negative melanoma cells, F0-1. These data, altogether, demonstrate that CD105 is expressed on pigmented cells and might play a functionally relevant role in the biology of human melanoma cells by regulating their sensitivity to TGF-betas. Images Figure 1 Figure 3 Figure 4 PMID:8932339

  14. Phenotypic Characterization of Multidrug-resistant Escherichia Coli with Special Reference to Extended-spectrum-beta-lactamases and Metallo-beta-lactamases in a Tertiary Care Center.

    PubMed

    Shrestha, B; Shrestha, S; Mishra, S K; Kattel, H P; Tada, T; Ohara, H; Kirikae, T; Rijal, B P; Sherchand, J B; Pokhrel, B M

    2015-01-01

    The increasing reports on extended-spectrum-beta-lactamase and metallo-beta-lactamase producing Escherichia coli have addressed a potential threat to global health since it is found to be highly resistance to most of the currently available antibiotics including carbapenems. The present study was aimed to determine the antibiogram of extended-spectrum-beta-lactamase and metallo-beta-lactamase producing MDR E. coli isolates from various clinical samples. This was a cross-sectional study conducted over a period of seven months from December 2013 to July 2014 at bacteriology laboratory of Tribhuvan University Teaching Hospital. A total of 250 clinical specimens (urine, pus, sputum, blood, body fluid, bile, tissue and central venous pressure line tip) were processed from inpatients, with multidrug-resistant Escherichia coli infections. Standard microbiological techniques were used for isolation and identification of the isolates. The presence of extended-spectrum-beta-lactamase was detected by phenotypic confirmatory test recommended by Clinical and Laboratory Standards Institute and imipenem (IMP) /EDTA combined disc method was performed to detect metallo-beta-lactamase mediated resistance mechanism. We found high level of beta lactamase mediated resistance mechanism as part of multidrug resistance. Among 250 MDR isolates, 60% isolates were extended-spectrum-beta-lactamase producers and 17.2% isolates were metallo-beta-lactamase producers. Co-existence of extended-spectrum-beta-lactamase and metallo-beta-lactamase identified in 6.8% isolates. Beta-lactamase mediated resistance mechanisms are accounting very high in the multidrug resistant isolates of E. coli. Therefore, early detection of beta lactamase mediated resistant strains and their current antibiotic susceptibility pattern is necessary to avoid treatment failure and prevent the spread of MDR.

  15. Beta-catenin phosphorylated at serine 45 is spatially uncoupled from beta-catenin phosphorylated in the GSK3 domain: implications for signaling.

    PubMed

    Maher, Meghan T; Mo, Rigen; Flozak, Annette S; Peled, Ofra N; Gottardi, Cara J

    2010-04-16

    C. elegans and Drosophila generate distinct signaling and adhesive forms of beta-catenin at the level of gene expression. Whether vertebrates, which rely on a single beta-catenin gene, generate unique adhesive and signaling forms at the level of protein modification remains unresolved. We show that beta-catenin unphosphorylated at serine 37 (S37) and threonine 41 (T41), commonly referred to as transcriptionally Active beta-Catenin (ABC), is a minor nuclear-enriched monomeric form of beta-catenin in SW480 cells, which express low levels of E-cadherin. Despite earlier indications, the superior signaling activity of ABC is not due to reduced cadherin binding, as ABC is readily incorporated into cadherin contacts in E-cadherin-restored cells. Beta-catenin phosphorylated at serine 45 (S45) or threonine 41 (T41) (T41/S45) or along the GSK3 regulatory cassette S33, S37 or T41 (S33/37/T41), however, is largely unable to associate with cadherins. Beta-catenin phosphorylated at T41/S45 and unphosphorylated at S37 and T41 is predominantly nuclear, while beta-catenin phosphorylated at S33/37/T41 is mostly cytoplasmic, suggesting that beta-catenin hypophosphorylated at S37 and T41 may be more active in transcription due to its enhanced nuclear accumulation. Evidence that phosphorylation at T41/S45 can be spatially separated from phosphorylations at S33/37/T41 suggests that these phosphorylations may not always be coupled, raising the possibility that phosphorylation at S45 serves a distinct nuclear function.

  16. Proteolytic processing of the pro beta chain of beta-hexosaminidase occurs at basic residues contained within an exposed disulfide loop structure.

    PubMed

    Sagherian, C; Poroszlay, S; Vavougios, G; Mahuran, D

    1993-01-01

    Lysosomal beta-hexosaminidase (EC 3.2.1.52) occurs as two major isozymes, Hex A (alpha beta) and Hex B (beta beta). The alpha and beta subunits are encoded by the HEXA and HEXB genes, respectively. Extensive homology in both the gene structures and deduced primary sequences demonstrate their common evolutionary origin. While undergoing similar proteolytic modifications in the lysosome, the pro beta polypeptide is additionally cleaved internally to produce the mature 24-30 kilodalton beta b and beta a chains. Previous data have suggested that this processing event occurs somewhere between residues Ser311 and Lys315. In this report we demonstrate that this area is located in a hydrophilic disulfide-loop structure (between Cys309 and Cys360). The cleavage event is prevented by the deletion through in vitro mutagenesis of the Arg312-Gln-Asn-Lys tetrapeptide or by its substitution with the aligned alpha residues (Gly-Ser-Glu-Pro). Reintroduction of either Arg312 or Lys315 reinstates the processing. Furthermore, we show that this area is not involved in lysosomal targeting of pro-Hex B, or in the increased stability or the variation in substrate specificity of the beta as compared with the alpha subunit. Our data suggest the presence of a novel lysosomal endoprotease. Like other endoproteases it is specific for basic amino acids; however, it cleaves on the amino-terminal side rather than the conventional carboxy-terminal side of such residues and then only if they are fully exposed to the lysosomal environment.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. 21 CFR 886.5100 - Ophthalmic beta radiation source.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ophthalmic beta radiation source. 886.5100 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5100 Ophthalmic beta radiation source. (a) Identification. An ophthalmic beta radiation source is a device intended to apply superficial...

  18. 21 CFR 886.5100 - Ophthalmic beta radiation source.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ophthalmic beta radiation source. 886.5100 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5100 Ophthalmic beta radiation source. (a) Identification. An ophthalmic beta radiation source is a device intended to apply superficial...

  19. 21 CFR 886.5100 - Ophthalmic beta radiation source.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ophthalmic beta radiation source. 886.5100 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5100 Ophthalmic beta radiation source. (a) Identification. An ophthalmic beta radiation source is a device intended to apply superficial...

  20. 21 CFR 886.5100 - Ophthalmic beta radiation source.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ophthalmic beta radiation source. 886.5100 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5100 Ophthalmic beta radiation source. (a) Identification. An ophthalmic beta radiation source is a device intended to apply superficial...

  1. 21 CFR 886.5100 - Ophthalmic beta radiation source.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic beta radiation source. 886.5100 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5100 Ophthalmic beta radiation source. (a) Identification. An ophthalmic beta radiation source is a device intended to apply superficial...

  2. Method for conversion of .beta.-hydroxy carbonyl compounds

    DOEpatents

    Lilga, Michael A.; White, James F.; Holladay, Johnathan E.; Zacher, Alan H.; Muzatko, Danielle S.; Orth, Rick J.

    2010-03-30

    A process is disclosed for conversion of salts of .beta.-hydroxy carbonyl compounds forming useful conversion products including, e.g., .alpha.,.beta.-unsaturated carbonyl compounds and/or salts of .alpha.,.beta.-unsaturated carbonyl compounds. Conversion products find use, e.g., as feedstock and/or end-use chemicals.

  3. Preparation and physical characterization of pure beta-carotene.

    PubMed

    Laughlin, Robert G; Bunke, Gregory M; Eads, Charles D; Laidig, William D; Shelley, John C

    2002-05-01

    Pure all-trans beta-carotene has been prepared on the 10's of grams scale by isothermal Fractional Dissolution (FD) of commercial laboratory samples in tetrahydrofuran (THF). beta-Carotene purified in this way is black, with a faint brownish tinge. The electronic spectra of black samples extend into the near infrared, with end-absorption past 750 nm. Black samples react directly with dioxygen under mild conditions to yield the familiar orange or red powders. Pure beta-carotene rigorously obeys Beer's Law in octane over the entire UV-Vis spectral range, while commercial laboratory samples and recrystallized samples do not. NMR self-diffusion coefficient data demonstrate that beta-carotene exists as simple molecular solutions in octane and toluene. The anomalously high crystallinity of beta-carotene can be attributed (from analysis using molecular mechanics) to the facts that: (1) the number of theoretically possible conformers of beta-carotene is extremely small, and (2) only a small fraction of these (ca. 12%, or 127) may actually exist in fluid phases.

  4. Isolation of a new class of cysteine-glycine-proline-rich beta-proteins (beta-keratins) and their expression in snake epidermis.

    PubMed

    Dalla Valle, Luisa; Nardi, Alessia; Alibardi, Lorenzo

    2010-03-01

    Scales of snakes contain hard proteins (beta-keratins), now referred to as keratin-associated beta-proteins. In the present study we report the isolation, sequencing, and expression of a new group of these proteins from snake epidermis, designated cysteine-glycine-proline-rich proteins. One deduced protein from expressed mRNAs contains 128 amino acids (12.5 kDa) with a theoretical pI at 7.95, containing 10.2% cysteine and 15.6% glycine. The sequences of two more snake cysteine-proline-rich proteins have been identified from genomic DNA. In situ hybridization shows that the messengers for these proteins are present in the suprabasal and early differentiating beta-cells of the renewing scale epidermis. The present study shows that snake scales, as previously seen in scales of lizards, contain cysteine-rich beta-proteins in addition to glycine-rich beta-proteins. These keratin-associated beta-proteins mix with intermediate filament keratins (alpha-keratins) to produce the resistant corneous layer of snake scales. The specific proportion of these two subfamilies of proteins in different scales can determine various degrees of hardness in scales.

  5. Beta-papillomaviruses in anogenital hairs plucked from healthy individuals.

    PubMed

    Potocnik, Marko; Kocjan, Bostjan J; Seme, Katja; Luzar, Bostjan; Babic, Dunja Z; Poljak, Mario

    2006-12-01

    A total of 150 specimens of anogenital hairs plucked from the scrotal, pubic, and perianal region of 51 immunocompetent healthy male individuals were tested for the presence of beta-papillomaviruses (beta-HPV) using the nested M(a)/H(a) polymerase chain reaction. Beta-HPV were found in a total of 38 (25.3%) of 150 hair samples. According to the sampling sites, beta-HPV were detected in 18/51 (35.3%), 13/50 (26.0%), and 7/49 (14.3%) plucked hair samples obtained from the pubic, scrotal, and perianal region, respectively. The prevalence of beta-HPV in the plucked pubic hairs was significantly higher than in the perianal hairs (P = 0.013). In contrast, the difference in the prevalence of beta-HPV in the pubic and scrotal hairs as well as in scrotal and perianal hairs did not reach statistical significance (P = 0.302 and P = 0.227, respectively). The difference in the lifetime-cumulative sun exposure is the most likely explanation for the differences obtained on beta-HPV prevalence. Beta-HPV genotype HPV-38 was detected most frequently, followed by HPV-36, HPV-15, and HPV-14D. In addition to the beta-HPV recognized officially five partial DNA sequences suggesting putative new HPV genotypes were identified. (c) 2006 Wiley-Liss, Inc.

  6. The aCORN backscatter-suppressed beta spectrometer

    DOE PAGES

    Hassan, M. T.; Bateman, F.; Collett, B.; ...

    2017-06-16

    Backscatter of electrons from a beta detector, with incomplete energy deposition, can lead to undesirable effects in many types of experiments. We present and discuss the design and operation of a backscatter-suppressed beta spectrometer that was developed as part of a program to measure the electron–antineutrino correlation coefficient in neutron beta decay (aCORN). An array of backscatter veto detectors surrounds a plastic scintillator beta energy detector. The spectrometer contains an axial magnetic field gradient, so electrons are efficiently admitted but have a low probability for escaping back through the entrance after backscattering. Lastly, the design, construction, calibration, and performance ofmore » the spectrometer are discussed.« less

  7. A recombinant tail-less integrin beta 4 subunit disrupts hemidesmosomes, but does not suppress alpha 6 beta 4-mediated cell adhesion to laminins

    PubMed Central

    1995-01-01

    To examine the function of the alpha 6 beta 4 integrin we have determined its ligand-binding ability and overexpressed two potentially dominant negative mutant beta 4 subunits, lacking either the cytoplasmic or extracellular domain, in bladder epithelial 804G cells. The results of cell adhesion and radioligand-binding assays showed that alpha 6 beta 4 is a receptor for several laminin isoforms, including laminin 1, 2, 4, and 5. Overexpression of the tail-less or head-less mutant beta 4 subunit did not suppress alpha 6 beta 4-mediated adhesion to laminins, as both types of transfectants adhered to these ligands in the presence of blocking anti-beta 1 antibodies as well as the controls. However, immunofluorescence experiments indicated that the endogenous alpha 6 beta 4 integrin and other hemidesmosomal markers were not concentrated in hemidesmosomes in cells overexpressing tail- less beta 4, while the distribution of these molecules was not altered in cells overexpressing the head-less subunit. Electron microscopic studies confirmed that cells overexpressing tail-less beta 4 had a drastically reduced number of hemidesmosomes, while cells expressing the head-less subunit had a normal number of these structures. Thus, expression of a tail-less, but not a head-less mutant beta 4 subunit leads to a dominant negative effect on hemidesmosome assembly without suppressing initial adhesion to laminins. We conclude that the alpha 6 beta 4 integrin binds to several laminins and plays an essential role in the assembly and/or stability of hemidesmosomes, that alpha 6 beta 4- mediated adhesion and hemidesmosome assembly have distinct requirements, and that it is possible to use a dominant negative approach to selectively interfere with a specific function of an integrin. PMID:7721947

  8. Effects of beta-lactamases and omp mutation on susceptibility to beta-lactam antibiotics in Escherichia coli.

    PubMed Central

    Hiraoka, M; Okamoto, R; Inoue, M; Mitsuhashi, S

    1989-01-01

    Four types of beta-lactamases consisting of a penicillinase type I (TEM-1), a penicillinase type II (OXA-1), a cephalosporinase of Citrobacter freundii, and a cephalosporinase of Proteus vulgaris were introduced into Escherichia coli MC4100 and its omp mutants, MH1160 (MC4100 ompR1) and MH760 (MC4100 ompR2), by transformation. Effects of the combination of the omp mutations and these beta-lactamases on the susceptibility of E. coli strains were studied with 15 beta-lactam antibiotics including cephalosporins, cephamycins, penicillins, imipenem, and aztreonam. The ompR1 mutant, MH1160, lacks OmpF and OmpC, and it showed reduced susceptibility to 11 of the 15 beta-lactam agents. The reduction in susceptibility to cefoxitin, moxalactam, and flomoxef was much greater than reduction in susceptibility to the other agents. When the ompR1 mutant produced the cephalosporinase of C. freundii, the susceptibility of the mutant to 12 of the 15 beta-lactam antibiotics decreased. The reduction in susceptibility of MH1160 to 10 of the 12 agents affected by the enzyme was two- to fourfold greater than that observed in MC4100. Such a synergistic effect was also observed with the cephalosporinase of P. vulgaris and ompR1 mutation against six cephalosporins, moxalactam, and aztreonam. Images PMID:2658786

  9. Beta/alpha continuous air monitor

    DOEpatents

    Becker, Gregory K.; Martz, Dowell E.

    1989-01-01

    A single deep layer silicon detector in combination with a microcomputer, recording both alpha and beta activity and the energy of each pulse, distinguishing energy peaks using a novel curve fitting technique to reduce the natural alpha counts in the energy region where plutonium and other transuranic alpha emitters are present, and using a novel algorithm to strip out radon daughter contribution to actual beta counts.

  10. Both conditional ablation and overexpression of E2 SUMO-conjugating enzyme (UBC9) in mouse pancreatic beta cells result in impaired beta cell function.

    PubMed

    He, Xiaoyu; Lai, Qiaohong; Chen, Cai; Li, Na; Sun, Fei; Huang, Wenting; Zhang, Shu; Yu, Qilin; Yang, Ping; Xiong, Fei; Chen, Zhishui; Gong, Quan; Ren, Boxu; Weng, Jianping; Eizirik, Décio L; Zhou, Zhiguang; Wang, Cong-Yi

    2018-04-01

    Post-translational attachment of a small ubiquitin-like modifier (SUMO) to the lysine (K) residue(s) of target proteins (SUMOylation) is an evolutionary conserved regulatory mechanism. This modification has previously been demonstrated to be implicated in the control of a remarkably versatile regulatory mechanism of cellular processes. However, the exact regulatory role and biological actions of the E2 SUMO-conjugating enzyme (UBC9)-mediated SUMOylation function in pancreatic beta cells has remained elusive. Inducible beta cell-specific Ubc9 (also known as Ube2i) knockout (KO; Ubc9 Δbeta ) and transgenic (Ubc9 Tg ) mice were employed to address the impact of SUMOylation on beta cell viability and functionality. Ubc9 deficiency or overexpression was induced at 8 weeks of age using tamoxifen. To study the mechanism involved, we closely examined the regulation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) through SUMOylation in beta cells. Upon induction of Ubc9 deficiency, Ubc9 Δbeta islets exhibited a 3.5-fold higher accumulation of reactive oxygen species (ROS) than Ubc9 f/f control islets. Islets from Ubc9 Δbeta mice also had decreased insulin content and loss of beta cell mass after tamoxifen treatment. Specifically, at day 45 after Ubc9 deletion only 40% of beta cell mass remained in Ubc9 Δbeta mice, while 90% of beta cell mass was lost by day 75. Diabetes onset was noted in some Ubc9 Δbeta mice 8 weeks after induction of Ubc9 deficiency and all mice developed diabetes by 10 weeks following tamoxifen treatment. In contrast, Ubc9 Tg beta cells displayed an increased antioxidant ability but impaired insulin secretion. Unlike Ubc9 Δbeta mice, which spontaneously developed diabetes, Ubc9 Tg mice preserved normal non-fasting blood glucose levels without developing diabetes. It was noted that SUMOylation of NRF2 promoted its nuclear expression along with enhanced transcriptional activity, thereby preventing ROS accumulation in

  11. The islet beta-cell: fuel responsive and vulnerable.

    PubMed

    Nolan, Christopher J; Prentki, Marc

    2008-10-01

    The pancreatic beta-cell senses blood nutrient levels and is modulated by neurohormonal signals so that it secretes insulin according to the need of the organism. Nutrient sensing involves marked metabolic activation, resulting in the production of coupling signals that promote insulin biosynthesis and secretion. The beta-cell's high capacity for nutrient sensing, however, necessitates reduced protection to nutrient toxicity. This potentially explains why in susceptible individuals, chronic fuel surfeit results in beta-cell failure and type 2 diabetes. Here we discuss recent insights into first, the biochemical basis of beta-cell signaling in response to glucose, amino acids and fatty acids, and second, beta-cell nutrient detoxification. We emphasize the emerging role of glycerolipid/fatty acid cycling in these processes.

  12. Cell surface expression of beta 2-microglobulin (beta 2m) correlates with stages of differentiation in B cell tumours.

    PubMed Central

    Jones, R A; Scott, C S; Norfolk, D R; Stark, A N; Child, J A

    1987-01-01

    Cell surface beta 2-microglobulin (beta 2m) densities of malignant B cells were determined by enzyme immunoassay in 97 cases of immunologically defined lymphoproliferative disease. Absolute beta 2m densities were found to depend on disease category with the lowest levels found on cells from chronic lymphocytic leukaemia (mean = 5.6 ng/10(6) cells, n = 27); atypical chronic lymphocytic leukaemia (mean = 5.9 ng/10(6) cells, n = 8); and prolymphocytoid chronic lymphocytic leukaemia variant (mean = 6.0 ng/10(6) cells, n = 16). beta 2m densities for B non-Hodgkin's lymphoma (n = 14) and B prolymphocytic leukaemia (n = 17) cases were 8.1 and 10.0 ng/10(6) cells, respectively, and the highest densities were found on cells from "late-B cell" tumours (mean = 14.3 ng/10(6) cells). Plasma cells from cases of Ig secreting tumours expressed unexpectedly low beta 2m densities (mean = 9.3 ng/10(6) cells; n = 6). PMID:3108331

  13. Beta-adrenergic blockade for the treatment of hyperthyroidism.

    PubMed

    Geffner, D L; Hershman, J M

    1992-07-01

    To review the clinical and biochemical effects of beta-adrenergic blocking drugs on hyperthyroidism. Studies published since 1972 were identified through a computerized search of MEDLINE and extensive searching of the bibliographies of the articles identified. Based on an understanding of the differences in beta-blocker metabolism in euthyroid and hyperthyroid patients, we reviewed the differences in pharmacokinetics and metabolic and clinical outcomes during their use in hyperthyroidism, as reported in the articles reviewed. beta Blockers have been used to modify the severity of the hyperadrenergic symptoms of hyperthyroidism for the past 20 years. The clinical efficacy of these agents is affected by hyperthyroid-induced alterations in their gastrointestinal absorption, hepatic metabolism, and renal excretion. The mechanisms whereby these clinical changes are effected is unknown. The agents differ in their beta 1 cardioselectivity, membrane-stabilizing activity, intrinsic sympathomimetic activity, and lipid solubility. They do not appear to alter synthesis or secretion of thyroid hormone by the thyroid gland. Their effects on thyroxine metabolism are contradictory. Decreased thyroxine to triiodothyronine conversion is caused by some, but not all, beta blockers, and this appears to correlate with membrane-stabilizing activity. There does not appear to be any alteration in catecholamine sensitivity during beta-adrenergic blockade. The principal mechanism of action of beta blockers in hyperthyroidism is to antagonize beta-receptor-mediated effects of catecholamines. beta Blockers are effective in treating hypermetabolic symptoms in a variety of hyperthyroid states. Used alone, they offer significant symptomatic relief. They are also useful adjuvants to antithyroid medications, surgery, and radioactive iodide treatment in patients with Graves' disease and toxic nodular goiters.

  14. Asymmetric functional organozinc additions to aldehydes catalyzed by 1,1'-bi-2-naphthols (BINOLs).

    PubMed

    Pu, Lin

    2014-05-20

    Chiral alcohols are ubiquitous in organic structures. One efficient method to generate chiral alcohols is the catalytic asymmetric addition of a carbon nucleophile to a carbonyl compound since this process produces a C-C bond and a chiral center simultaneously. In comparison with the carbon nucleophiles such as an organolithium or a Grignard reagent, an organozinc reagent possesses the advantages of functional group tolerance and more mild reaction conditions. Catalytic asymmetric reactions of aldehydes with arylzincs, vinylzincs, and alkynylzincs to generate functional chiral alcohols are discussed in this Account. Our laboratory has developed a series of 1,1'-bi-2-naphthol (BINOL)-based chiral catalysts for the asymmetric organozinc addition to aldehydes. It is found that the 3,3'-dianisyl-substituted BINOLs are not only highly enantioselective for the alkylzinc addition to aldehydes, but also highly enantioselective for the diphenylzinc addition to aldehydes. A one-step synthesis has been achieved to incorporate Lewis basic amine groups into the 3,3'-positions of the partially hydrogenated H8BINOL. These H8BINOL-amine compounds have become more generally enantioselective and efficient catalysts for the diphenylzinc addition to aldehydes to produce various types of chiral benzylic alcohols. The application of the H8BINOL-amine catalysts is expanded by using in situ generated diarylzinc reagents from the reaction of aryl iodides with ZnEt2, which still gives high enantioselectivity and good catalytic activity. Such a H8BINOL-amine compound is further found to catalyze the highly enantioselective addition of vinylzincs, in situ generated from the treatment of vinyl iodides with ZnEt2, to aldehydes to give the synthetically very useful chiral allylic alcohols. We have discovered that the unfunctionalized BINOL in combination with ZnEt2 and Ti(O(i)Pr)4 can catalyze the terminal alkyne addition to aldehydes to produce chiral propargylic alcohols of high synthetic

  15. High Temperature Stability of Potassium Beta Alumina

    NASA Technical Reports Server (NTRS)

    Williams, R. M.; Kisor, A.; Ryan, M. A.

    1996-01-01

    None. From Objectives section: Evaluate the stability of potassium beta alumina under potassium AMTEC operating conditions. Evaluate the stability regime in which potassium beta alumina can be fabricated.

  16. Method for preparing Pb-. beta. ''-alumina ceramic

    DOEpatents

    Hellstrom, E.E.

    1984-08-30

    A process is disclosed for preparing impermeable, polycrystalline samples of Pb-..beta..''-alumina ceramic from Na-..beta..''-alumina ceramic by ion exchange. The process comprises two steps. The first step is a high-temperature vapor phase exchange of Na by K, followed by substitution of Pb for K by immersing the sample in a molten Pb salt bath. The result is a polycrystalline Pb-..beta..''-alumina ceramic that is substantially crack-free.

  17. Method for preparing Pb-.beta."-alumina ceramic

    DOEpatents

    Hellstrom, Eric E.

    1986-01-01

    A process is disclosed for preparing impermeable, polycrystalline samples of Pb-.beta."-alumina ceramic from Na-.beta."-alumina ceramic by ion exchange. The process comprises two steps. The first step is a high-temperature vapor phase exchange of Na by K, followed by substitution of Pb for K by immersing the sample in a molten Pb salt bath. The result is a polycrystalline Pb-.beta."-alumina ceramic that is substantially crack-free.

  18. Synthesis, (1-->3)-beta-D-glucanase-binding ability, and phytoalexin-elicitor activity of a mixture of 3,4-epoxybutyl (1-->3)-beta-D-oligoglucosides.

    PubMed

    Huang, Gang-Liang; Liu, Man-Xi; Mei, Xin-Ya

    2004-06-01

    We describe a approach for the synthesis of a mixture of 3,4-epoxybutyl (1-->3)-beta-D-oligoglucosides. The particular (1-->3)-beta-D-glucan isolated from the cell walls of Saccharomyces cerevisiae was recovered from the aqueous medium as water-insoluble particles by the spray drying (GS) method, and it was characterized by FTIR spectroscopy. The acid-solubilized (1-->3)-beta-D-oligoglucosides were prepared by partial acid hydrolysis of glucan particles, which were qualitatively analyzed by fluorophore-assisted carbohydrate electrophoresis (FACE). The peracetylated 3-butenyl (1-->3)-beta-D-oligoglucosides were synthesized by treating peracetylated (1-->3)-beta-D-oligoglucosides with the 3-butenyl alcohols and a Lewis acid (SnCl4) catalyst. Epoxidation of the peracetylated 3-butenyl oligoglucosides took place with m-chloroperoxybenzoic acid (m-CPBA). NaOMe in dry methanol was used for the deacetylation of the blocked derivatives, to give the 3,4-epoxybutyl (1-->3)-beta-D-oligoglucoside mixture in an overall yield of 21%. The sample was analyzed by positive-ion electrospray ionization mass spectrometry (ESIMS). In a 3,4-epoxybutyl (1-->3)-beta-D-oligoglucoside-binding (1-->3)-beta-D-glucanase assay, we found that the (1-->3)-beta-D-glucanase was obviously inactivated by the 3,4-epoxybutyl (1-->3)-beta-D-oligoglucosides. At the same time, we found the 3,4-epoxybutyl (1-->3)-beta-D-oligoglucoside mixture was more active as compared to the underivatized oligoglucoside mixture in eliciting phytoalexin accumulation in tobacco cotyledon tissue. Furthermore, it could be kept for a longer time than a (1-->3)-beta-D-oligoglucoside mixture, which indicated it is much more stable than (1-->3)-beta-D-oligoglucosides. Copyright 2004 Elsevier Ltd.

  19. Natural polypeptide scaffolds: beta-sheets, beta-turns, and beta-hairpins.

    PubMed

    Rotondi, Kenneth S; Gierasch, Lila M

    2006-01-01

    This paper provides an introduction to fundamental conformational states of polypeptides in the beta-region of phi,psi space, in which the backbone is extended near to its maximal length, and to more complex architectures in which extended segments are linked by turns and loops. There are several variants on these conformations, and they comprise versatile scaffolds for presentation of side chains and backbone amides for molecular recognition and designed catalysts. In addition, the geometry of these fundamental folds can be readily mimicked in peptidomimetics. Copyright 2005 Wiley Periodicals, Inc.

  20. Beta-lactamase targeted enzyme activatable photosensitizers for antimicrobial PDT

    NASA Astrophysics Data System (ADS)

    Zheng, Xiang; Verma, Sarika; Sallum, Ulysses W.; Hasan, Tayyaba

    2009-06-01

    Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed.

  1. Double heterozygosity for Hb New York [beta 113 GTG-->GAG; VAL-->GLU] and beta degrees-thalassemia mutations manifests as a thalassemia trait.

    PubMed

    Lee, Anselm C W; Ma, Edmond S K; Chan, Amy Y Y; Szeto, S C; Chan, L C

    2008-01-01

    An extended family with three individuals affected by two different forms of double heterozygosity for beta-thalassemia and Hb New York is reported. Double heterozygosity of Hb New York [beta 113 GTG-->GAG; VAL-->GLU] and beta degrees codon 17 was detected in a fetus following prenatal screening for thalassemia. The father and a paternal aunt were also found to be heterozygous for Hb New York and beta degrees IVSII-654. Both adults had clinical and hematological features consistent with beta-thalassemia trait. The affected child was followed up after birth and manifested the typical course of a thalassemia trait, with no signs of organomegaly or overt hemolysis. Observations strongly suggest that double heterozygosity of Hb New York and beta degrees thalassemia has mild, if any, clinical symptoms, and is not an indication of therapeutic abortion when detected antenatally.

  2. Lack of mixed agonist-antagonist properties of [Gln8-Gly31]-beta h-EP-Gly-Gly-NH2 and [Arg9,19,24,28,29]-beta h-EP in the rat vas deferens neuroeffector junction: studies with naloxone, beta-funaltrexamine and ICI 174,864.

    PubMed

    Valenzuela, R; Li, C H; Huidobro-Toro, J P

    1989-02-01

    The 1-27 truncated fragment of beta h-endorphin (beta h-EP) as well as [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 or [Arg9,19,24,28,29]-beta h-EP exhibited opiate agonist activity in the rat vas deferens bioassay; the potency of these peptides was 3 to 6 times less than that of beta h-EP. None of these compounds exhibited any degree of antagonism towards the inhibitory action of beta h-EP. Naloxone antagonized and reversed the inhibitory action of beta h-EP and its analogues though with varying potencies. The apparent naloxone-pA2 value for beta h-EP was 8.94; that for [Gln8-Gly31]-beta h-EP-Gly-Gly-NH2 was 8.08 and that for [Arg9,19,24,28,29]-beta h-EP was 8.38. beta-Funaltrexamine (beta-FNA) potently antagonized the inhibitory action of beta h-EP following non-equilibrium kinetics. Tissue preincubation with 10 nM beta-FNA for 60 min followed by extensive washing caused a 10-fold increase in the beta h-EP IC50. However, 10 nM beta-FNA caused only a 1.2 increase in the IC50 of [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 and a 4.1-fold increase in the IC50 of [Arg9,19,24,28,29]-beta h-EP. In contrast, preincubation of the tissue with 3 microM ICI 174,864 did not modify the potency of beta h-EP or its structural analogues. However, a 60 min pretreatment with 10 microM beta-FNA followed by the addition of 3 microM ICI 174,864 revealed a further decrease in the potency of the opiopeptins compared with tissues exposed to beta-FNA alone or ICI 174,864 alone. In conclusion, the inhibitory action of these peptides is remarkably sensitive to beta-FNA antagonism; in addition the peptides act as pure opiate agonists in marked contrast with the agonist-antagonist properties described in the CNS.

  3. Hydrolyses of alpha-naphthyl acetate, beta-naphthyl acetate, and acetyl-DL-phenylalanine beta-naphthyl ester.

    PubMed

    Kirkeby, S; Moe, D

    1983-01-01

    Using simultaneous coupling azo dye techniques kidney enzymes active against alpha-naphthyl acetate, beta-naphthyl acetate, and acetyl-DL-phenylalanine beta-naphthyl ester are characterized. The enzymes show identical distribution in the section. The banding patterns in zymograms are the same after incubation with the different substrates. The enzymes might, however, be separated by difference in pH optimum, initial velocity and sensitivity to inhibitors and activators.

  4. Circulating form of beta-2-microglobulin in dialysis patients.

    PubMed

    Gagnon, R F; Somerville, P; Thomson, D M

    1988-01-01

    The circulating profile of beta-2-microglobulin (beta 2M) was determined in 8 end-stage renal disease patients on long-term dialysis (6 on hemodialysis, 2 on CAPD) by measuring beta 2M in different fraction after molecular sieve separation of their sera. Four patients had carpal tunnel syndrome with demonstrated amyloid in excised wrist tissues of which 2 were positive for beta 2M. In all patients despite very high blood levels (34.3-63.1 mg/l), beta 2M eluted exclusively as a single peak in the molecular weight region of about 12,000 daltons on a calibrated Sephacryl S-200 column. Recoveries from within the peak accounted for 96% of the applied beta 2M serum concentrations. These results were confirmed by molecular sieve separation of the enriched beta 2M-containing fractions by high-pressure liquid chromatography. We conclude that immunoreactive beta 2M in dialysis patients circulates as an intact monomer without evidence for the formation of aggregates or fragments. The pathogenesis of tissue deposition of this low-molecular-weight protein and its polymerisation to form a specific amyloid remains to be defined.

  5. Soft epidermis of a scaleless snake lacks beta-keratin.

    PubMed

    Toni, M; Alibardi, L

    2007-01-01

    Beta-keratins are responsible for the mechanical resistance of scales in reptiles. In a scaleless crotalus snake (Crotalus atrox), large areas of the skin are completely devoid of scales, and the skin appears delicate and wrinkled. The epidermis of this snake has been assessed for the presence of beta-keratin by immunocytochemistry and immunoblotting using an antibody against chicken scale beta-keratin. This antibody recognizes beta-keratins in normal snake scales with molecular weights of 15-18 kDa and isoelectric points at 6.8, 7.5, 8.3 and 9.4. This indicates that beta-keratins of the stratum corneum are mainly basic proteins, so may interact with cytokeratins of the epidermis, most of which appear acidic (isoelectric points 4.5-5.5). A beta-layer and beta-keratin immunoreactivity are completely absent in moults of the scaleless mutant, and the corneous layer comprises a multi-layered alpha-layer covered by a flat oberhautchen. In conclusion, the present study shows that a lack of beta-keratins is correlated with the loss of scales and mechanical protection in the skin of this mutant snake.

  6. Autoradiographic localization of beta-adrenoceptors in asthmatic human lung

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Spina, D.; Rigby, P.J.; Paterson, J.W.

    1989-11-01

    The autoradiographic distribution and density of beta-adrenoceptors in human non-diseased and asthmatic bronchi were investigated using (125I)iodocyanopindolol (I-CYP). Analysis of the effects of the beta-adrenoceptor antagonists on I-CYP binding demonstrated that betaxolol (20 nM, beta 1-selective) had no significant effect on specific grain density in either nonasthmatic or asthmatic human bronchus, whereas ICI-118551 (20 nM, beta 2-selective) inhibited I-CYP binding by 85 +/- 9% and 89 +/- 3%, respectively. Thus, homogeneous populations of beta 2-adrenoceptors existed in bronchi from both sources. Large populations of beta-adrenoceptors were localized to the bronchial epithelium, submucosal glands, and airway smooth muscle. Asthmatic bronchial tissuemore » featured epithelial damage with exfoliated cells associated with luminal mucus plugs. A thickened basement membrane and airway smooth muscle hyperplasia were also evident. High levels of specific I-CYP binding were also detected over asthmatic bronchial smooth muscle, as assessed by autoradiography and quantitation of specific grain densities. Isoproterenol and fenoterol were 10- and 13-fold less potent, respectively, in bronchi from asthmatic lung than in those from nonasthmatic lung. However, this attenuated responsiveness to beta-adrenoceptor agonists was not caused by reduced beta-adrenoceptor density in asthmatic airways. A defect may exist in the coupling between beta-adrenoceptors and postreceptor mechanisms in severely asthmatic lung.« less

  7. Milk composition and lactation of beta-casein-deficient mice.

    PubMed Central

    Kumar, S; Clarke, A R; Hooper, M L; Horne, D S; Law, A J; Leaver, J; Springbett, A; Stevenson, E; Simons, J P

    1994-01-01

    beta-Casein is a major protein component of milk and, in conjunction with the other caseins, it is assembled into micelles. The casein micelles determine many of the physical characteristics of milk, which are important for stability during storage and for milk-processing properties. There is evidence that suggests that beta-casein may also possess other, nonnutritional functions. To address the function of beta-casein, the mouse beta-casein gene was disrupted by gene targeting in embryonic stem cells. Homozygous beta-casein mutant mice are viable and fertile; females can lactate and successfully rear young. beta-Casein was expressed at a reduced level in heterozygotes and was completely absent from the milk of homozygous mutant mice. Despite the deficiency of beta-casein, casein micelles were assembled in heterozygous and homozygous mutants, albeit with reduced diameters. The absence of beta-casein expression was reflected in a reduced total protein concentration in milk, although this was partially compensated for by an increased concentration of other proteins. The growth of pups feeding on the milk of homozygous mutants was reduced relative to those feeding on the milk of wild-type mice. Various genetic manipulations of caseins have been proposed for the qualitative improvement of cow's milk composition. The results presented here demonstrate that beta-casein has no essential function and that the casein micelle is remarkably tolerant of changes in composition. Images PMID:8016126

  8. Review of modern double beta decay experiments

    NASA Astrophysics Data System (ADS)

    Barabash, A. S.

    2015-10-01

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T1/2(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino ( < 0.46 eV) and a coupling constant of Majoron to neutrino ( < 1.3 . 10-5) are obtained. Prospects of search for neutrinoless double beta decay in new experiments with sensitivity to at the level of ˜ 0.01-0.1 eV are discussed.

  9. aCORN Beta Spectrometer and Electrostatic Mirror

    NASA Astrophysics Data System (ADS)

    Hassan, Md; aCORN Collaboration

    2013-10-01

    aCORN uses a high efficiency backscatter suppressed beta spectrometer to measure the electron-antineutrino correlation in neutron beta decay. We measure the correlation by counting protons and beta electrons in coincidence with precisely determined electron energy. There are 19 photomultiplier tubes arranged in a hexagonal array coupled to a single phosphor doped polystyrene scintillator. The magnetic field is shaped so that electrons that backscatter without depositing their full energy strike a tulip-shaped array of scintillator paddles and these events are vetoed. The detailed construction, performance and calibration of this beta spectrometer will be presented. I will also present the simulation, construction, and features of our novel electrostatic mirror. This work was supported by the National Science Foundation and the NIST Center for Neutron Research.

  10. [Beta-endorphin and obesity. Possible pathogenetic implications].

    PubMed

    Giugliano, D; Saccomanno, F; Quatraro, A; Ceriello, A; Torella, R

    1990-01-01

    Several experimental data have documented the ability of both opiates and opioid peptides to stimulate food intake. On the other hand, the plasma beta-endorphin levels found in obese patients are higher than those observed in normal-weight controls, which may have pathogenetic implications. We have investigated the responses of plasma glucose, insulin, C-peptide and glucagon to an infusion of human beta-endorphin in formerly obese subjects who had obtained by dieting the normalization of body weight and in lean controls. The data show that: a) the increased plasma beta-endorphin concentrations found in human obesity are not corrected by normalization of body weight; b) formerly obese subjects behave as obese subjects in their metabolic and hormonal responses to beta-endorphin.

  11. Rate-dependent inverse-addition beta-selective mannosylation and contiguous sequential glycosylation involving beta-mannosidic bond formation.

    PubMed

    Chang, Shih-Sheng; Shih, Che-Hao; Lai, Kwun-Cheng; Mong, Kwok-Kong Tony

    2010-05-03

    The beta-selectivity of mannosylation has been found to be dependent on the addition rate of the mannosyl trichloroacetimidate donor in an inverse-addition (I-A) procedure. This rate dependent I-A procedure can improve the selectivity of direct beta-mannosylation and is applicable to orthogonal glycosylations of thioglycoside acceptors. Further elaboration of this novel procedure enables the development of the contiguous sequential glycosylation strategy, which streamlines the preparation of oligosaccharides invoking beta-mannosidic bond formation. The synthetic utility of the contiguous glycosylation strategy was demonstrated by the preparation of the trisaccharide core of human N-linked glycoproteins and the trisaccharide repeating unit of the O-specific polysaccharide found in the cellular capsule of Salmonelle bacteria.

  12. Beta/alpha continuous air monitor

    DOEpatents

    Becker, G.K.; Martz, D.E.

    1988-06-27

    A single deep layer silicon detector in combination with a microcomputer, recording both alpha and beta activity and the energy of each pulse, distinquishing energy peaks using a novel curve fitting technique to reduce the natural alpha counts in the energy region where plutonium and other transuranic alpha emitters are present, and using a novel algorithm to strip out radon daughter contribution to actual beta counts. 7 figs.

  13. Double Beta Decay

    NASA Astrophysics Data System (ADS)

    Shirai, Junpei

    Double beta decay is a key process to reveal a fundamental property of neutrinos. If neutrinos are Majorana particles, that is they are equivalent to their antiparticles, neutrinoless double beta (0νββ) decay, (A,Z) → (A,Z + 2) + 2e‑, would occur. The process is beyond the standard model and would lead to a scenario which can explain the extremely small masses of neutrinos and provide a solution to the current matter dominance of the world. In this talk experimental efforts searching for 0νββ decays are presented. Then, major 0νββ experiments together with searches using 136Xe nuclei are described, followed by the current status of the KamLAND-Zen experiment.

  14. [Study of beta-turns in globular proteins].

    PubMed

    Amirova, S R; Milchevskiĭ, Iu V; Filatov, I V; Esipova, N G; Tumanian, V G

    2005-01-01

    The formation of beta-turns in globular proteins has been studied by the method of molecular mechanics. Statistical method of discriminant analysis was applied to calculate energy components and sequences of oligopeptide segments, and after this prediction of I type beta-turns has been drawn. The accuracy of true positive prediction is 65%. Components of conformational energy considerably affecting beta-turn formation were delineated. There are torsional energy, energy of hydrogen bonds, and van der Waals energy.

  15. Changes in immune and metabolic gut response in broilers fed beta-mannanase in beta-mannan containing diets

    USDA-ARS?s Scientific Manuscript database

    Beta-mannans, found in soy-based broiler feed, are known to cause physiological effects that are hypothesized to be related to gut inflammation. Previous studies have shown that the incorporation of beta-mannanase in the diet or as a supplement results in improvements to certain performance paramet...

  16. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of Beta-hydroxy-Beta-methylbutyrate

    USDA-ARS?s Scientific Manuscript database

    Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite Beta-hydroxy-Beta-methylbutyrate (HMB). To determine the effects of HMB on protein synthesi...

  17. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of beta-hydroxy-beta-methylbutyrate

    USDA-ARS?s Scientific Manuscript database

    Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB). To determine the effects of HMB on protein synthesi...

  18. Parallel multireference configuration interaction calculations on mini-beta-carotenes and beta-carotene.

    PubMed

    Kleinschmidt, Martin; Marian, Christel M; Waletzke, Mirko; Grimme, Stefan

    2009-01-28

    We present a parallelized version of a direct selecting multireference configuration interaction (MRCI) code [S. Grimme and M. Waletzke, J. Chem. Phys. 111, 5645 (1999)]. The program can be run either in ab initio mode or as semiempirical procedure combined with density functional theory (DFT/MRCI). We have investigated the efficiency of the parallelization in case studies on carotenoids and porphyrins. The performance is found to depend heavily on the cluster architecture. While the speed-up on the older Intel Netburst technology is close to linear for up to 12-16 processes, our results indicate that it is not favorable to use all cores of modern Intel Dual Core or Quad Core processors simultaneously for memory intensive tasks. Due to saturation of the memory bandwidth, we recommend to run less demanding tasks on the latter architectures in parallel to two (Dual Core) or four (Quad Core) MRCI processes per node. The DFT/MRCI branch has been employed to study the low-lying singlet and triplet states of mini-n-beta-carotenes (n=3, 5, 7, 9) and beta-carotene (n=11) at the geometries of the ground state, the first excited triplet state, and the optically bright singlet state. The order of states depends heavily on the conjugation length and the nuclear geometry. The (1)B(u) (+) state constitutes the S(1) state in the vertical absorption spectrum of mini-3-beta-carotene but switches order with the 2 (1)A(g) (-) state upon excited state relaxation. In the longer carotenes, near degeneracy or even root flipping between the (1)B(u) (+) and (1)B(u) (-) states is observed whereas the 3 (1)A(g) (-) state is found to remain energetically above the optically bright (1)B(u) (+) state at all nuclear geometries investigated here. The DFT/MRCI method is seen to underestimate the absolute excitation energies of the longer mini-beta-carotenes but the energy gaps between the excited states are reproduced well. In addition to singlet data, triplet-triplet absorption energies are

  19. Single dosing comparison of the relative cardiac beta 1/beta 2 activity of inhaled fenoterol and salbutamol in normal subjects.

    PubMed Central

    Newnham, D M; Wheeldon, N M; Lipworth, B J; McDevitt, D G

    1993-01-01

    BACKGROUND--The aim of the present study was to compare the dose related effects of fenoterol and salbutamol on cardiac beta 1 and beta 2 receptors using the beta 1 selective antagonist atenolol, in order to dissect out relative beta 1/beta 2 mediated responses. METHODS--Fourteen normal volunteers were randomised to receive pretreatment with either atenolol 25 mg or placebo, followed by inhaled fenoterol or salbutamol in equal doses by weight (cumulative doses of 1 mg and 4 mg). Measurements were made 30 minutes after inhaling each dose of beta 2 agonist. Values (mean and 95% CI) were expressed as a change from baseline. RESULTS--At 4 mg fenoterol produced equivalent falls in serum potassium and increases in tremor to salbutamol. The mean (95% CI) increase in heart rate (beats/min) with fenoterol at 4 mg after placebo was 47 (41-53) and after atenolol was 34 (28-40), with values for salbutamol being 46 (40-52) after placebo and 30 (24-36) after atenolol. The inotropic response (stroke distance) after atenolol at the 4 mg dose was 5.0 (3.9-6.1) cm for fenoterol and 4.7 (3.5-5.9) cm for salbutamol. There were no significant differences in heart rate or stroke distance response between the two drugs after either placebo or atenolol. Furthermore, ECG effects (Q-Tc and T wave) of fenoterol and salbutamol were comparable at both doses. CONCLUSIONS--These results show that there is no difference in the respective chronotropic or inotropic activities of fenoterol and salbutamol on cardiac beta 1 or beta 2 receptors when given at higher than conventional doses. PMID:8102213

  20. Evidence for novel beta-sheet structures in Iowa mutant beta-amyloid fibrils.

    PubMed

    Tycko, Robert; Sciarretta, Kimberly L; Orgel, Joseph P R O; Meredith, Stephen C

    2009-07-07

    Asp23-to-Asn mutation within the coding sequence of beta-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-Abeta40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-Abeta40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10(-3) min(-1) and 1.07 x 10(-4) min(-1) for D23N-Abeta40 and the wild-type peptide WT-Abeta40, respectively) and without a lag phase. Electron microscopy shows that D23N-Abeta40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-beta pattern, with a sharp reflection at 4.7 A and a broad reflection at 9.4 A, which is notably smaller than the value for WT-Abeta40 fibrils (10.4 A). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-Abeta40 fibrils containing the in-register, parallel beta-sheet structure commonly found in WT-Abeta40 fibrils and most other amyloid fibrils. Antiparallel beta-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through (13)C-(13)C and (15)N-(13)C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-Abeta40 fibrils and the unusual vasculotropic clinical picture in these patients.

  1. Purification and properties of beta-galactosidase from Aspergillus nidulans.

    PubMed

    Díaz, M; Pedregosa, A M; de Lucas, J R; Torralba, S; Monistrol, I F; Laborda, F

    1996-12-01

    Beta-Galactosidase from mycelial extract of Aspergillus nidulans has been purified by substrate affinity chromatography and used to obtain anti-beta-galactosidase polyclonal antibodies. A. nidulans growing in lactose as carbon source synthesizes one active form of beta-galactosidase which seems to be a multimeric enzyme of 450 kDa composed of monomers with 120 and 97 kDa. Although the enzyme was not released to the culture medium, some enzymatic activity was detected in a cell-wall extract, thus suggesting that it can be an extracellular enzyme. Beta-Galactosidase of A. nidulans is a very unstable enzyme with an optimum pH value of 7.5 and an optimum temperature of 30 degrees C. It was only active against beta-galactoside substrates like lactose and p-nitrophenyl-beta-D-galactoside (PNPG).

  2. Isolation of a new class of cysteine–glycine–proline-rich beta-proteins (beta-keratins) and their expression in snake epidermis

    PubMed Central

    Dalla Valle, Luisa; Nardi, Alessia; Alibardi, Lorenzo

    2010-01-01

    Scales of snakes contain hard proteins (beta-keratins), now referred to as keratin-associated beta-proteins. In the present study we report the isolation, sequencing, and expression of a new group of these proteins from snake epidermis, designated cysteine–glycine–proline-rich proteins. One deduced protein from expressed mRNAs contains 128 amino acids (12.5 kDa) with a theoretical pI at 7.95, containing 10.2% cysteine and 15.6% glycine. The sequences of two more snake cysteine–proline-rich proteins have been identified from genomic DNA. In situ hybridization shows that the messengers for these proteins are present in the suprabasal and early differentiating beta-cells of the renewing scale epidermis. The present study shows that snake scales, as previously seen in scales of lizards, contain cysteine-rich beta-proteins in addition to glycine-rich beta-proteins. These keratin-associated beta-proteins mix with intermediate filament keratins (alpha-keratins) to produce the resistant corneous layer of snake scales. The specific proportion of these two subfamilies of proteins in different scales can determine various degrees of hardness in scales. PMID:20070430

  3. Beta-propellers: associated functions and their role in human diseases.

    PubMed

    Pons, Tirso; Gómez, Raú; Chinea, Glay; Valencia, Alfonso

    2003-03-01

    The beta-propeller fold appears as a very fascinating architecture based on four-stranded antiparallel and twisted beta-sheets, radially arranged around a central tunnel. Similar to the alpha/beta-barrel (TIM-barrel) fold, the beta-propeller has a wide range of different functions, and is gaining substantial attention. Some proteins containing beta-propeller domains have been implicated in the pathogenesis of a variety of diseases such as cancer, Alzheimer, Huntington, arthritis, familial hypercholesterolemia, retinitis pigmentosa, osteogenesis, hypertension, and microbial and viral infections. This article reviews some aspects of 3D structure, amino acids sequence regularities, and biological functions of the proteins containing beta-propeller domains. Major emphasis has been laid on beta-propellers whose functions are associated to human diseases. Recent research efforts reported in the fields of protein engineering, drug design, and protein structure-function relationship studies, concerning the beta-propeller architecture, have also been discussed.

  4. Beta-lactams against methicillin-resistant Staphylococcus aureus.

    PubMed

    Guignard, Bertrand; Entenza, José M; Moreillon, Philippe

    2005-10-01

    Methicillin-resistant Staphylococcus aureus (MRSA) have developed resistance to virtually all non-experimental antibiotics. They are intrinsically resistant to beta-lactams by virtue of newly acquired low-affinity penicillin-binding protein 2A (PBP2A). Because PBP2A can build the wall when other PBPs are blocked by beta-lactams, designing beta-lactams capable of blocking this additional target should help solve the issue. Older molecules including penicillin G, amoxicillin and ampicillin had relatively good PBP2A affinities, and successfully treated experimental endocarditis caused by MRSA, provided that the bacterial penicillinase could be inhibited. Newer anti-PBP2A beta-lactams with over 10-fold greater PBP2A affinities and low minimal inhibitory concentrations were developed, primarily in the cephem and carbapenem classes. They are also very resistant to penicillinase. Most have demonstrated anti-MRSA activity in animal models of infection, and two--the carbapenem CS-023 and the cephalosporin ceftopibrole medocaril--have proceeded to Phase II and Phase III clinical evaluation. Thus, clinically useful anti-MRSA beta-lactams are imminent.

  5. The Beta Pictoris circumstellar disk. XV - Highly ionized species near Beta Pictoris

    NASA Technical Reports Server (NTRS)

    Deleuil, M.; Gry, C.; Lagrange-Henri, A.-M.; Vidal-Madjar, A.; Beust, H.; Ferlet, R.; Moos, H. W.; Livengood, T. A.; Ziskin, D.; Feldman, P. D.

    1993-01-01

    Temporal variations of the Fe II, Mg II, and Al III circumstellar lines towards Beta Pictoris have been detected and monitored since 1985. However, the unusual presence of Al III ions is still puzzling, since the UV stellar flux from an A5V star such as Beta Pic is insufficient to produce such an ion. In order to better define the origin of such a phenomenon, new observations have been carried out to detect faint signatures of other highly ionized species in the short UV wavelength range, where the stellar continuum flux is low. These observations reveal variations not only near the C IV doublet lines, but also in C I and Al II lines, two weakly ionized species, not clearly detectable until now. In the framework of an infalling body scenario, highly ionized species would be created in the tail, far from the comet head, by collisions with ambient gas surrounding the star, or a weak stellar wind. Spectral changes have also been detected near a CO molecular band location, which, if confirmed, would provide the first molecular signature around Beta Pictoris.

  6. Hypercrosslinked poly(styrene-co-divinylbenzene) resin as a specific polymeric adsorbent for purification of berberine hydrochloride from aqueous solutions.

    PubMed

    Li, Yin; Cao, Ruofan; Wu, Xiaofei; Huang, Jianhan; Deng, Shuguang; Lu, Xiuyang

    2013-06-15

    A hypercrosslinked poly(styrene-co-divinylbenzene) resin (TEPA) was synthesized and characterized as a specific polymeric adsorbent for concentrating berberine hydrochloride from aqueous solutions. Three organic molecules of different sizes (2-naphthol, berberine hydrochloride, and Congo red) were used as target molecules to elucidate the molecular sieving effect of the TEPA adsorbent. Because the TEPA adsorbent has a pore structure consisting mainly of micropores and mesopores, the adsorption of 2-naphthol from aqueous solutions is very efficient due to the micropore filling effect. The adsorption of berberine hydrochloride mostly takes place in the mesopores as well as macropores, while the adsorption of Congo red mainly occurs in the macropores. The smaller adsorbate molecule (2-naphthol) reaches the adsorption equilibrium much faster than the larger ones (berberine hydrochloride and Congo red). An adsorption breakthrough experiment with an aqueous solution containing 2-naphthol and berberine hydrochloride demonstrated that the TEPA adsorbent could effectively remove 2-naphthol from berberine hydrochloride at 0-107 BV (bed volume, 1 BV=10 ml), and the berberine hydrochloride concentration was increased from 66.7% to 99.4%, suggesting that this polymeric adsorbent is promising for purifying berberine hydrochloride and similar alkaloids from herbal plant extracts. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Beta-lactamase induction and cell wall metabolism in Gram-negative bacteria

    PubMed Central

    Zeng, Ximin; Lin, Jun

    2013-01-01

    Production of beta-lactamases, the enzymes that degrade beta-lactam antibiotics, is the most widespread and threatening mechanism of antibiotic resistance. In the past, extensive research has focused on the structure, function, and ecology of beta-lactamases while limited efforts were placed on the regulatory mechanisms of beta-lactamases. Recently, increasing evidence demonstrate a direct link between beta-lactamase induction and cell wall metabolism in Gram-negative bacteria. Specifically, expression of beta-lactamase could be induced by the liberated murein fragments, such as muropeptides. This article summarizes current knowledge on cell wall metabolism, beta-lactam antibiotics, and beta-lactamases. In particular, we comprehensively reviewed recent studies on the beta-lactamase induction by muropeptides via two major molecular mechanisms (the AmpG–AmpR–AmpC pathway and BlrAB-like two-component regulatory system) in Gram-negative bacteria. The signaling pathways for beta-lactamase induction offer a broad array of promising targets for the discovery of new antibacterial drugs used for combination therapies. Therefore, to develop effective mitigation strategies against the widespread beta-lactam resistance, examination of the molecular basis of beta-lactamase induction by cell wall fragment is highly warranted. PMID:23734147

  8. Stability of human interferon-beta 1: oligomeric human interferon-beta 1 is inactive but is reactivated by monomerization.

    PubMed

    Utsumi, J; Yamazaki, S; Kawaguchi, K; Kimura, S; Shimizu, H

    1989-10-05

    Human interferon-beta 1 is extremely stable is a low ionic strength solution of pH 2 such as 10 mM HCl at 37 degrees C. However, the presence of 0.15 M NaCl led to a remarkable loss of antiviral activity. The molecular-sieve high-performance liquid chromatography revealed that, whereas completely active human interferon-beta 1 eluted as a 25 kDa species (monomeric form), the inactivated preparation eluted primarily as a 90 kDa species (oligomeric form). The specific activity (units per mg protein) of the oligomeric form was approx. 10% of that of the monomeric form. This observation shows that oligomeric human interferon-beta 1 is apparently in an inactive form. When the oligomeric eluate was resolved by polyacrylamide gel containing sodium dodecyl sulphate (SDS), it appeared to be monomeric under non-reducing conditions. Monomerization of the oligomeric human interferon-beta 1 by treatment with 1% SDS, fully regenerated its antiviral activity. These results suggest that the inactivation of the human interferon-beta 1 preparation was caused by its oligomerization via hydrophobic interactions without the formation of intermolecular disulphide bonds. These oligomers can be dissociated by SDS to restore biological activity.

  9. Fabrication of thin layer beta alumina

    NASA Technical Reports Server (NTRS)

    Tennenhouse, G. J.

    1977-01-01

    Beta alumina tubes having walls 700 microns, 300 microns, and 140 microns were processed by extrusion and sintering utilizing Ford proprietary binder and fabrication systems. Tubes prepared by this method have properties similar to tubes prepared by isostatic pressing and sintering, i.e. density greater than 98% of theoretical and a helium leak rate less than 3 x 10 to the -9th power cc/sq cm/sec. Ford ultrasonic bonding techniques were used for bonding beta alumina end caps to open ended beta -alumina tubes prior to sintering. After sintering, the bond was hermetic, and the integrity of the bonded area was comparable to the body of the tube.

  10. Separation, preconcentration and inductively coupled plasma-mass spectrometric (ICP-MS) determination of thorium(IV), titanium(IV), iron(III), lead(II) and chromium(III) on 2-nitroso-1-naphthol impregnated MCI GEL CHP20P resin.

    PubMed

    Aydin, Funda Armagan; Soylak, Mustafa

    2010-01-15

    A simple and effective method is presented for the separation and preconcentration of Th(IV), Ti(IV), Fe(III), Pb(II) and Cr(III) by solid phase extraction on 2-nitroso-1-naphthol impregnated MCI GEL CHP20P resin prior to their inductively coupled plasma-mass spectrometric determinations. The influence of analytical parameters including pH of the aqueous solution, flow rates of sample and eluent solutions and sample volume on the quantitative recoveries of analyte ions was investigated. Matrix effects caused by the presence of alkali, earth alkali and some metal ions in the analyzed solutions were investigated. The presented solid phase extraction method was applied to BCR-144R Sewage Sludge (domestic origin), BCR-141R Calcareous Loam Soil, NIST 1568a Rice Flour and NIST 1577b Bovine Liver certified reference materials (CRMs) for the determination of analyte ions and the results were in good agreement with the certified values. The separation procedure presented was also applied to the various natural water samples collected from Turkey with satisfactory results.

  11. Contribution of beta 1- and beta 2-adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (-)-atenolol.

    PubMed Central

    Lemoine, H.; Schönell, H.; Kaumann, A. J.

    1988-01-01

    1. (-)-Atenolol was used as a tool to assess the function of beta 1- and beta 2-adrenoceptors in human heart. Right atrial and left ventricular preparations from patients undergoing open heart surgery were set up to contract isometrically. Membrane particles were prepared for beta-adrenoceptor labelling with [3H]-(-)-bupranolol and adenylate cyclase assays. 2. The positive inotropic effects of (-)-noradrenaline were antagonized to a similar extent by (-)-atenolol in atrial and ventricular preparations. (-)-Atenolol consistently antagonized the effects of (-)-adrenaline to a lesser extent than those of (-)-noradrenaline in atrial preparations. In ventricular preparations (-)-atenolol antagonized the effects of low concentrations of (-)-adrenaline to a lesser extent than those of high concentrations. 3. pKB values (M) of (-)-atenolol, estimated with non-linear analysis from the blockade of the positive inotropic effects of the catecholamines, were 7.4 for beta 1-adrenoceptors and 6.0 for beta 2-adrenoceptors. 4. (-)-Atenolol inhibited the binding of [3H]-(-)-bupranolol to ventricular beta 1-adrenoceptors with a pKD (M) of 5.9 and to ventricular beta 2-adrenoceptors with a pKD of 4.6. 5. (-)-Atenolol inhibited the catecholamine-induced adenylate cyclase stimulation in the atrium and ventricle with pKB values of 5.8-6.4 for beta 1- and pKB values of 4.7-5.7 for beta 2-adrenoceptors. The binding and cyclase assays suggest a partial affinity loss for (-)-atenolol inherent to membrane preparations. 6. beta 1-Adrenoceptors mediate the maximum positive inotropic effects of (-)-noradrenaline in both the atrium and ventricle of man. beta 2-Adrenoceptors appear to be capable of mediating maximal positive inotropic effects of (-)-adrenaline in atrium. In contrast, ventricular beta 2-adrenoceptors mediated only submaximal effects of (-)-adrenaline. PMID:2851354

  12. SPECT-evaluation of the monoamine uptake site ligand [123I](1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I]beta-CIT) in untreated patients with suspicion of Parkinson disease.

    PubMed

    Eising, E G; Müller, T T; Zander, C; Kuhn, W; Farahati, J; Reiners, C; Coenen, H H

    1997-10-01

    For a few years, data on SPECT-imaging of dopamine transporters with the cocaine derivate [123I](1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I] beta-CIT) have been reported mostly in healthy subjects or animals. This study reflects our preliminary results with SPECT-imaging of dopamine transporters using the cocaine analogue 123-beta-CIT in patients with untreated (de novo) parkinsonism. In 33 patients with clinical suspicion of Parkinson disease and 5 healthy controls, SPECT-imaging of dopamine transporters was performed 1, 4, and 24 hours after injection of 180 MBq of 123I-beta-CIT, which was generated by iododestannylation. None of the patients or controls had been treated before with neuroleptical drugs or any other pharmaceuticals with known binding to the dopamine transporters. Clinical symptoms were staged by the scales Hoehn-Yahr (HYS), Unified Parkinson Disease Rating Scale (UPDRS), and the self-rating scale of Beck depression inventory (BDI). For evaluation, striatal/cerebellar ratios were calculated to every time point. Significant correlations of 123I-beta-CIT uptake could be stated compared to UPDRS, HYS, and BDI values (Spearman correlation, p < 0.05). The symptoms of rigor and akinesia showed a significant correlation with the beta-CIT uptake, whereas the symptom of tremor failed, which may be caused by the location of tremor symptoms out of the striatum. Comparing the controls, a significant (p < 0.01) decrease of tracer uptake in parkinsonian patients is stated on the images at 24 hours p.i. In our patients, tracer uptake does not depend significantly on duration of disease and age. 123I-beta-CIT seems to be a promising tool in imaging of untreated parkinsonian patient.

  13. Inactivation of beta-lactam antibiotics by Legionella pneumophila.

    PubMed Central

    Fu, K P; Neu, H C

    1979-01-01

    Beta-lactam-inactivating activity has been found in all sero-groups of Legionella pneumophila. The beta-lactamase activity could be detected in intact cells and released by ethylenediaminetetraacetic acid treatment, indicating that it is located in the periplasmic space. The enzyme acted primarily as a cephalosporinase hydrolyzing cefamandole, cephalothin, cephaloridine, and also penicillin G and ampicillin. Cefoxitin and cefuroxime were not hydrolyzed. Clavulanic acid and CP-45,899, beta-lactamase inhibitors, prevented the hydrolysis of cephalosporins and penicillins. The beta-lactamase activity appears to be different from that found in Enterobacteriaceae and Pseudomonas. Images PMID:316686

  14. How Do Beta Blocker Drugs Affect Exercise?

    MedlinePlus

    ... for Heart.org CPR & ECC for Heart.org Shop for Heart.org Causes for Heart.org Advocate ... Thromboembolism Aortic Aneurysm More How do beta blocker drugs affect exercise? Updated:Aug 22,2017 Beta blockers ...

  15. BETA-GAMMA PERSONNEL DOSIMETER

    DOEpatents

    Davis, D.M.; Gupton, E.D.; Hart, J.C.; Hull, A.P.

    1961-01-17

    A personnel dosimeter is offered which is sensitive to both gamma and soft beta radiations from all directions within a hemisphere. The device is in the shape of a small pill box which is worn on a worker-s wrist. The top and sides of the device are provided with 50 per cent void areas to give 50 per cent response to the beta rays and complete response to the gamma rays. The device is so constructed as to have a response which will approximate the dose received by the basal layer of the human epidermis.

  16. Expression of mammalian beta-adrenergic receptors in Xenopus laevis oocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bahouth, S.W.; Malbon, C.C.

    1987-05-01

    Xenopus laevis oocytes are a useful transcription and expression system for DNA and RNA, respectively. Total cellular RNA was extracted from mouse lymphoma S49 cells and poly(A)/sup +/mRNA prepared by affinity chromatography of RNA on oligo(dT) cellulose. The membranes of S49 cells contain beta-adrenergic receptors that display pharmacological characteristics of beta/sub 2/-subtype. Xenopus laevis oocytes were injected with 50 ng of mRNA/oocyte. Expression of beta-adrenergic receptors in oocytes incubated for 30 hr after microinjection was assessed in membranes by radioligand binding using (/sup 3/H) dihydroalprenolol. The injected oocytes displayed 0.34 fmol receptor/oocyte as compared to 0.02 fmol receptor/oocyte in themore » control oocytes. The affinity of beta-adrenergic receptors in injected oocytes for this radioligand was 2 nM, a value similar to the affinity of beta-adrenergic receptors for DHA in S49 cell membranes. The potency of beta-adrenergic agonists in competing for DHA binding to oocytes membranes was isoproterenol > epinephrine > norepineprine, indicating that the expressed beta-adrenergic receptors were of the beta/sub 2/-subtype. The K/sub I/ of these agonists for the beta-adrenergic receptor in oocyte membranes was 0.03, 0.15 and 1.2 ..mu..M, respectively. The role of post-translational modification in dictating receptor subtype is analyzed using mRNA of beta/sub 1/- as well as beta/sub 2/-adrenergic receptors.« less

  17. Proteolytic processing of endogenous and recombinant beta 4 integrin subunit

    PubMed Central

    1992-01-01

    The alpha 6 beta 4 integrin is a receptor involved in the interaction of epithelial cells with basement membranes. This integrin is unique among the known integrins in that its beta 4 subunit has a large cytoplasmic domain. The function of this cytoplasmic domain is not known. In this paper we show that the beta 4 subunit undergoes proteolytic processing in cultured cells and provide evidence that this also happens in tissues. Immunoprecipitation experiments indicated that the cytoplasmic domain of beta 4 is susceptible to a calcium-dependent protease present in cellular extracts. In vitro assays with purified calpain showed that this enzyme can cleave beta 4 at two distinct sites in the cytoplasmic domain, generating truncated molecules of 165 and 130 kD. Immunoblotting experiments performed on cultured epithelial cells using an antibody to a peptide modeled after the COOH-terminus of the beta 4 subunit showed 70-kD fragments and several fragments of molecular masses between 185 and 115 kD. Similar fragments were detected in CHO cells transfected with the full-length beta 4 cDNA, but not in control transfected cells or in cells transfected with a mutant cDNA lacking the epitope of the cytoplasmic peptide antibody. The sizes of the fragments indicated that both the intracellular and extracellular domains of beta 4 are proteolytically processed. To examine the processing of the beta 4 subunit in epithelial tissues in vivo, human skin frozen sections were stained with antibodies to the ectodomain or the cytoplasmic domain of beta 4. The distinct staining patterns obtained with the two types of antibodies provided evidence that beta 4 is proteolytically processed in vivo in skin. Analogous experiments performed on sections of the cornea suggested that beta 4 is not proteolytically processed at a detectable level in this tissue. Thus, cleavage of the beta 4 subunit occurs in a tissue-specific fashion. These results suggest a potential mechanism of modulating the

  18. Nebivolol: the somewhat-different beta-adrenergic receptor blocker.

    PubMed

    Münzel, Thomas; Gori, Tommaso

    2009-10-13

    Although its clinical use in Europe dates almost 10 years, nebivolol is a beta-blocker that has been only recently introduced in the U.S. market. Like carvedilol, nebivolol belongs to the third generation of beta-blockers, which possess direct vasodilator properties in addition to their adrenergic blocking characteristics. Nebivolol has the highest beta(1)-receptor affinity among beta-blockers and, most interestingly, it substantially improves endothelial dysfunction via its strong stimulatory effects on the activity of the endothelial nitric oxide synthase and via its antioxidative properties. Because impaired endothelial activity is attributed a major causal role in the pathophysiology of hypertension, coronary artery disease, and congestive heart failure, the endothelium-agonistic properties of nebivolol suggest that this drug might provide additional benefit beyond beta-receptor blockade. Although lesser beta-blocker-related side effects have been reported in patients with chronic obstructive pulmonary disease or impotence taking nebivolol, side effects and contraindications overlap those of other beta-blockers. Clinically, this compound has been proven to have antihypertensive and anti-ischemic effects as well as beneficial effects on hemodynamics and prognosis in patients with chronic congestive heart failure. Further studies are now necessary to compare the benefit of nebivolol with that of other drugs in the same class and, most importantly, its prognostic impact in patients with hypertension.

  19. The effect of altered 5-hydroxytryptamine levels on beta-endorphin

    NASA Technical Reports Server (NTRS)

    Soliman, Karam F. A.; Mash, Deborah C.; Walker, Charles A.

    1986-01-01

    The purpose of the present study was to examine the effect of altering the concentration of 5-hydroxytryptamine (5-HT) on beta-endorphin (beta-Ep) content in the hypothalamus, thalamus, and periaqueductal gray (PAG)-rostral pons regions of the rat brain. The selective 5-HT reuptake inhibitor, fluoxetine (10 mg/kg), significantly lowered beta-Ep content in the hypothalamus and the PAG. Parachlorophenylalanine, which inhibits 5-HT synthesis, significantly elevated beta-Ep in all brain parts studied. Intracisternal injections of the neurotoxin 5-prime, 7-prime-dihydroxytryptamine with desmethylimipramine pretreatment significantly increased beta-Ep content in the hypothalamus and the PAG. In adrenalectomized rats, fluoxetine significantly decreased beta-Ep levels in the hypothalamus and increased the levels in the PAG. The results indicate that 5-HT may modulate the levels of brain beta-Ep.

  20. Evaluation of thrombogenicity of beta-propiolactone/ultraviolet (beta-PL/UV) treated PPSB in chimpanzees

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kotitschke, R.; Stephan, W.; Prince, A.M.

    1983-05-01

    The thrombogenicity of beta-PL/UV-treated PPSB (factor IX concentrate) was evaluated in chimpanzees. PPSB isolated from beta-propiolactone-treated and UV-irradiated plasma was injected into chimpanzees at a dose of approximately 100 units/kg body weight. An FDA licensed PPSB preparation served as the negative control, and a preparation containing activated as well as precursor clotting factors served as the positive control. 15 minutes, 1 h, 4 h, and 24 h after the PPSB application the following parameters were determined in the chimpanzee blood: factors II, VII, IX, X, VIII, fibrinogen, AT III, thrombin coagulase, Quick value, APTT and platelet count. Neither the untreatedmore » control preparation, nor the PPSB isolated from beta-propiolactone-treated and UV-irradiated plasma, showed signs of thrombogenicity in the chimpanzee model. The positive control indicated that the chimpanzee is a suitable model for the thrombogenicity testing of activated clotting factors.« less

  1. Use of beta-adrenoceptor blocking drugs in hyperthyroidism.

    PubMed

    Feely, J; Peden, N

    1984-05-01

    There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to

  2. Mesalamine inhibits epithelial beta-catenin activation in chronic ulcerative colitis.

    PubMed

    Brown, Jeffrey B; Lee, Goo; Managlia, Elizabeth; Grimm, Gery R; Dirisina, Ramanarao; Goretsky, Tatiana; Cheresh, Paul; Blatner, Nichole R; Khazaie, Khashayarsha; Yang, Guang-Yu; Li, Linheng; Barrett, Terrence A

    2010-02-01

    Mesalamine is a mainstay therapeutic agent in chronic ulcerative colitis (CUC) in which condition it reverses crypt architectural changes and reduces colitis-associated cancer (CAC). The present study addressed the possibility that mesalamine reduces beta-catenin-associated progenitor cell activation, Akt-phosphorylated beta-catenin(Ser552) (P-beta-catenin), and colitis-induced dysplasia (CID). Effects of mesalamine on P-beta-catenin staining and function were assessed by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in biopsy specimens of CUC in mild or "refractory" severe mucosal inflammation. Effects of mesalamine on epithelial proliferation and activation of Akt and beta-catenin were assessed in interleukin (IL)-10(-/-) colitis and CID by immunohistochemistry and Western blotting. Dysplasia was assessed by counting the number and lengths of lesions per colon. Data from IL-10(-/-) and human colitis samples show that mesalamine reduced Akt activation and P-beta-catenin levels in the middle and upper crypt. Reductions in P-beta-catenin in CUC biopsy specimens with severe inflammation suggested that mesalamine reduced P-beta-catenin levels in tissue refractory to mesalamine's anti-inflammatory effects. In IL-10(-/-) mice, mesalamine reduced CID concordant with inhibition of crypt Akt and beta-catenin signaling. The results are consistent with the model that mesalamine contributes to chemoprevention in CAC by reducing beta-catenin signaling within intestinal progenitors.

  3. Matching-adjusted comparisons demonstrate better clinical outcomes with SC peginterferon beta-1a every two weeks than with SC interferon beta-1a three times per week.

    PubMed

    Coyle, Patricia K; Shang, Shulian; Xiao, Zhen; Dong, Qunming; Castrillo-Viguera, Carmen

    2018-05-01

    Subcutaneous (SC) peginterferon beta-1a and SC interferon beta-1a (IFN beta-1a) have demonstrated efficacy in treating relapsing-remitting multiple sclerosis (RRMS) but have never been compared in direct head-to-head clinical trials, the gold-standard comparison. A well-balanced matching-adjusted comparison of weighted individual patient data on SC peginterferon beta-1a, and aggregate data from published phase 3 clinical trials of SC IFN beta-1a, was conducted to provide additional information on the comparative efficacy of these two agents. Individual patient data from a study of SC peginterferon beta-1a 125 mcg every two weeks (ADVANCE) and pooled summary data from four published studies of SC IFN beta-1a 44 mcg three times per week (OPERA I and II, CARE-MS I and II) with similar populations were utilized. A comparison was conducted by weighting individual peginterferon beta-1a-treated patients, using estimated propensity of enrolling in SC IFN beta-1a treatment to match multiple key aggregate baseline characteristics of SC IFN beta-1a-treated patients. After matching, weighted annualized relapse rate (ARR), 24-week confirmed disability worsening (CDW), and clinical no evidence of disease activity (clinical-NEDA) were calculated and compared for peginterferon beta-1a and SC IFN beta-1a. After matching, baseline characteristics were well balanced across treatment groups. At 2 years, ARR after matching was 0.256 for patients receiving peginterferon beta-1a (effective n = 376) and 0.335 for those receiving SC IFN beta-1a (n = 1218) (P = 0.0901). The percentage of patients who were relapse free over 2 years was significantly higher with peginterferon beta-1a than with SC IFN beta-1a (75.1% vs. 57.4% [after matching], P < 0.0001). The peginterferon beta-1a treatment group had a significantly lower proportion of patients with 24-week CDW compared with SC IFN beta-1a (after matching 6.5% vs. 13.2%; P = 0.0007). Clinical-NEDA occurred in a

  4. Venus gravity - Analysis of Beta Regio

    NASA Technical Reports Server (NTRS)

    Esposito, P. B.; Sjogren, W. L.; Mottinger, N. A.; Bills, B. G.; Abbott, E.

    1982-01-01

    Radio tracking data acquired over Beta Regio were analyzed to obtain a surface mass distribution from which a detailed vertical gravity field was derived. In addition, a corresponding vertical gravity field was evaluated solely from the topography of the Beta region. A comparison of these two maps confirms the strong correlation between gravity and topography which was previously seen in line-of-sight gravity maps. It also demonstrates that the observed gravity is a significant fraction of that predicted from the topography alone. The effective depth of complete isostatic compensation for the Beta region is estimated to be 330 km, which is somewhat deeper than that found for other areas of Venus.

  5. Chronology of endocrine differentiation and beta-cell neogenesis.

    PubMed

    Miyatsuka, Takeshi

    2016-01-01

    Diabetes is a chronic and incurable disease, which results from absolute or relative insulin insufficiency. Therefore, pancreatic beta cells, which are the only type of cell that expresses insulin, is considered to be a potential target for the cure of diabetes. Although the findings regarding beta-cell neogenesis during pancreas development have been exploited to induce insulin-producing cells from non-beta cells, there are still many hurdles towards generating fully functional beta cells that can produce high levels of insulin and respond to physiological signals. To overcome these problems, a solid understanding of pancreas development and beta-cell formation is required, and several mouse models have been developed to reveal the unique features of each endocrine cell type at distinct developmental time points. Here I review our understanding of pancreas development and endocrine differentiation focusing on recent progresses in improving temporal cell labeling in vivo.

  6. Top-Down Beta Enhances Bottom-Up Gamma

    PubMed Central

    Thompson, William H.

    2017-01-01

    Several recent studies have demonstrated that the bottom-up signaling of a visual stimulus is subserved by interareal gamma-band synchronization, whereas top-down influences are mediated by alpha-beta band synchronization. These processes may implement top-down control of stimulus processing if top-down and bottom-up mediating rhythms are coupled via cross-frequency interaction. To test this possibility, we investigated Granger-causal influences among awake macaque primary visual area V1, higher visual area V4, and parietal control area 7a during attentional task performance. Top-down 7a-to-V1 beta-band influences enhanced visually driven V1-to-V4 gamma-band influences. This enhancement was spatially specific and largest when beta-band activity preceded gamma-band activity by ∼0.1 s, suggesting a causal effect of top-down processes on bottom-up processes. We propose that this cross-frequency interaction mechanistically subserves the attentional control of stimulus selection. SIGNIFICANCE STATEMENT Contemporary research indicates that the alpha-beta frequency band underlies top-down control, whereas the gamma-band mediates bottom-up stimulus processing. This arrangement inspires an attractive hypothesis, which posits that top-down beta-band influences directly modulate bottom-up gamma band influences via cross-frequency interaction. We evaluate this hypothesis determining that beta-band top-down influences from parietal area 7a to visual area V1 are correlated with bottom-up gamma frequency influences from V1 to area V4, in a spatially specific manner, and that this correlation is maximal when top-down activity precedes bottom-up activity. These results show that for top-down processes such as spatial attention, elevated top-down beta-band influences directly enhance feedforward stimulus-induced gamma-band processing, leading to enhancement of the selected stimulus. PMID:28592697

  7. Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL-1alpha/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in turpentine-induced fever development and glucocorticoid secretion.

    PubMed

    Horai, R; Asano, M; Sudo, K; Kanuka, H; Suzuki, M; Nishihara, M; Takahashi, M; Iwakura, Y

    1998-05-04

    Interleukin (IL)-1 is a major mediator of inflammation and exerts pleiotropic effects on the neuro-immuno-endocrine system. To elucidate pathophysiological roles of IL-1, we have first produced IL-1alpha/beta doubly deficient (KO) mice together with mice deficient in either the IL-1alpha, IL-1beta, or IL-1 receptor antagonist (IL-1ra) genes. These mice were born healthy, and their growth was normal except for IL-1ra KO mice, which showed growth retardation after weaning. Fever development upon injection with turpentine was suppressed in IL-1beta as well as IL-1alpha/beta KO mice, but not in IL-1alpha KO mice, whereas IL-1ra KO mice showed an elevated response. At this time, expression of IL-1beta mRNA in the diencephalon decreased 1.5-fold in IL-1alpha KO mice, whereas expression of IL-1alpha mRNA decreased >30-fold in IL-1beta KO mice, suggesting mutual induction between IL-1alpha and IL-1beta. This mutual induction was also suggested in peritoneal macrophages stimulated with lipopolysaccharide in vitro. In IL-1beta KO mice treated with turpentine, the induction of cyclooxygenase-2 (EC 1.14.99.1) in the diencephalon was suppressed, whereas it was enhanced in IL-1ra KO mice. We also found that glucocorticoid induction 8 h after turpentine treatment was suppressed in IL-1beta but not IL-1alpha KO mice. These observations suggest that IL-1beta but not IL-1alpha is crucial in febrile and neuro-immuno-endocrine responses, and that this is because IL-1alpha expression in the brain is dependent on IL-1beta. The importance of IL-1ra both in normal physiology and under stress is also suggested.

  8. Enzymes oxidizing the azo dye 1-phenylazo-2-naphthol (Sudan I) and their contribution to its genotoxicity and carcinogenicity.

    PubMed

    Stiborova, Marie; Schmeiser, Heinz H; Frei, Eva; Hodek, Petr; Martinek, Vaclav

    2014-01-01

    Sudan I [1-(phenylazo)-2-naphthol, C.I. Solvent Yellow 14] is an industrial dye, which was found as a contaminant in numerous foods in several European countries. Because Sudan I has been assigned by the IARC as a Category 3 carcinogen, the European Union decreed that it cannot be utilized as food colorant in any European country. Sudan I induces the malignancies in liver and urinary bladder of rats and mice. This carcinogen has also been found to be a potent mutagen, contact allergen and sensitizer, and exhibits clastogenic properties. The oxidation of Sudan I increases its toxic effects and leads to covalent adducts in DNA. Identification of enzymatic systems that contribute to Sudan I oxidative metabolism to reactive intermediates generating such covalent DNA adducts on the one hand, and to the detoxification of this carcinogen on the other, is necessary to evaluate susceptibility to this toxicant. This review summarizes the identification of such enzymes and the molecular mechanisms of oxidation reactions elucidated to date. Human and animal cytochrome P450 (CYP) and peroxidases are capable of oxidizing Sudan I. Of the CYP enzymes, CYP1A1 is most important both in Sudan I detoxification and its bio-activation. Ring-hydroxylated metabolites and a dimer of this carcinogen were found as detoxification products of Sudan I generated with CYPs and peroxidases, respectively. Oxidative bio-activation of this azo dye catalyzed by CYPs and peroxidases leads to generation of proximate genotoxic metabolites (the CYP-catalyzed formation of the benzenediazonium cation and the peroxidase-mediated generation of one-electron oxidation products), which covalently modify DNA both in vitro and in vivo. The predominant DNA adduct generated with the benzenediazonium cation was characterized to be 8-(phenylazo)guanine. The Sudan I radical species mediated by peroxidases reacts with the -NH2 group in (deoxy)guanosine, generating the 4-[(deoxy)guanosin-N(2)-yl]Sudan I product. Sudan I

  9. [Beta-endorphin--physiologic role and menstrual cycle disorders].

    PubMed

    Meczekalski, B; Warenik-Szymankiewicz, A

    1995-10-01

    There are three classes of endogenous opioid peptides: endorphins, enkephalins, dynorphins. Beta-endorphin is the main representative of endogenous opioid peptides. Beta-endorphin plays a role in the regulation of the normal menstrual cycle and possibly in the onset of puberty. This peptide is also involved in the pathophysiology of such menstrual disorders as: exercise-associated amenorrhoea, stress-induced amenorrhoea, weight loss related amenorrhoea and premenstrual syndrome. Probable mechanism is that alterations in the levels of beta-endorphin may change the pulsatile release of GnRH. This article reviews contemporary views on the role of beta-endorphin in the physiology and disorders of the menstrual cycle.

  10. Pathogenesis of A-beta+ ketosis-prone diabetes

    USDA-ARS?s Scientific Manuscript database

    A-beta+ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible beta-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnit...

  11. Isoproterenol reduces ischemia-reperfusion lung injury despite beta-blockade.

    PubMed

    Takashima, Seiki; Schlidt, Scott A; Koukoulis, Giovanna; Sevala, Mayura; Egan, Thomas M

    2005-06-01

    If lungs could be retrieved from non-heart-beating donors (NHBDs), the shortage of lungs for transplantation could be alleviated. The use of lungs from NHBDs is associated with a mandatory warm ischemic interval, which results in ischemia-reperfusion injury upon reperfusion. In an earlier study, rat lungs retrieved 2-h postmortem from NHBDs had reduced capillary leak measured by filtration coefficient (Kfc) when reperfused with isoproterenol (iso), associated with an increase in lung tissue levels of cyclic AMP (cAMP). The objective was to determine if this decrease in Kfc was because of beta-stimulation, or would persist despite beta-blockade. Donor rats were treated intraperitoneally with beta-blockade (propranolol or pindolol) or carrier, sacrificed, and lungs were retrieved immediately or 2 h postmortem. The lungs were reperfused with or without iso and the beta-blockers in the reperfusate. Outcome measures were Kfc, wet:dry weight ratio (W/D), lung levels of adenine nucleotides and cAMP. Lungs retrieved immediately after death had normal Kfc and W/D. After 2 h of ischemia, Kfc and W/D were markedly elevated in controls (no drug) and lungs reperfused with beta-blockers alone. Isoproterenol-reperfusion decreased Kfc and W/D significantly (P < 0.01) even in the presence of beta-blockade. Lung cAMP levels were increased only with iso in the absence of beta-blockade. The attenuation of ischemia-reperfusion injury because of iso occurs even in the presence of beta-blockade, and may not be a result of beta-stimulated increased cAMP.

  12. Beta-delayed proton emission from 20Mg

    NASA Astrophysics Data System (ADS)

    Lund, M. V.; Andreyev, A.; Borge, M. J. G.; Cederkäll, J.; De Witte, H.; Fraile, L. M.; Fynbo, H. O. U.; Greenlees, P. T.; Harkness-Brennan, L. J.; Howard, A. M.; Huyse, M.; Jonson, B.; Judson, D. S.; Kirsebom, O. S.; Konki, J.; Kurcewicz, J.; Lazarus, I.; Lica, R.; Lindberg, S.; Madurga, M.; Marginean, N.; Marginean, R.; Marroquin, I.; Mihai, C.; Munch, M.; Nacher, E.; Negret, A.; Nilsson, T.; Page, R. D.; Pascu, S.; Perea, A.; Pucknell, V.; Rahkila, P.; Rapisarda, E.; Riisager, K.; Rotaru, F.; Sotty, C.; Stanoiu, M.; Tengblad, O.; Turturica, A.; Van Duppen, P.; Vedia, V.; Wadsworth, R.; Warr, N.

    2016-10-01

    Beta-delayed proton emission from 20 Mg has been measured at ISOLDE, CERN, with the ISOLDE Decay Station (IDS) setup including both charged-particle and gamma-ray detection capabilities. A total of 27 delayed proton branches were measured including seven so far unobserved. An updated decay scheme, including three new resonances above the proton separation energy in 20 Na and more precise resonance energies, is presented. Beta-decay feeding to two resonances above the Isobaric Analogue State (IAS) in 20 Na is observed. This may allow studies of the 4032.9(2.4)keV resonance in 19 Ne through the beta decay of 20 Mg, which is important for the astrophysically relevant reaction 15O( α, γ)19Ne . Beta-delayed protons were used to obtain a more precise value for the half-life of 20 Mg, 91.4(1.0)ms.

  13. An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth.

    PubMed

    Weihua, Zhang; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Ake

    2002-10-15

    Epithelial proliferation of the ventral prostate in rodents peaks between 2 and 4 weeks of age, and by week 8, proliferating cells are rare. We have used ERbeta(-/-) and CYP7B1(-/-) mice to investigate the role of ERbeta and one of its ligands, 5alpha-androstane-3beta,17beta-diol (3betaAdiol), in growth of the ventral prostate. Before puberty, ERbeta was found in quiescent but not in proliferating cells, and proliferating cells occurred more frequently in ventral prostates of ERbeta(-/-) mice than in wild-type littermates. Treatment with 3betaAdiol decreased proliferation in wild-type but not in ERbeta(-/-) mice. In rats, treatment with 3betaAdiol from postnatal day 2 to 28 resulted in reduction in growth of ventral prostates. The prostates of CYP7B1(-/-) mice were hypoproliferative before puberty and smaller than those of their wild-type littermates after puberty. Because CYP7B1 represents the major pathway for inactivating 3betaAdiol in the prostate, we suggest that ERbeta, 3betaAdiol, and CYP7B1 are the components of a pathway that regulates growth of the rodent ventral prostate. In this pathway, ERbeta is an antiproliferative receptor, 3betaAdiol is an ERbeta ligand, and CYP7B1 is the enzyme that regulates ERbeta function by regulating the level of 3betaAdiol.

  14. TEM study of {beta} Prime precipitate interaction mechanisms with dislocations and {beta} Prime interfaces with the aluminium matrix in Al-Mg-Si alloys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Teichmann, Katharina; Marioara, Calin D.; Andersen, Sigmund J.

    The interaction mechanisms between dislocations and semi-coherent, needle-shaped {beta} Prime precipitates in Al-Mg-Si alloys have been studied by High Resolution Transmission Electron Microscopy (HRTEM). Dislocation loops appearing as broad contrast rings around the precipitate cross-sections were identified in the Al matrix. A size dependency of the interaction mechanism was observed; the precipitates were sheared when the longest dimension of their cross-section was shorter than approximately 15 nm, and looped otherwise. A more narrow ring located between the Al matrix and bulk {beta} Prime indicates the presence of a transition interface layer. Together with the bulk {beta} Prime structure, this wasmore » further investigated by High Angle Annular Dark Field Scanning TEM (HAADF-STEM). In the bulk {beta} Prime a higher intensity could be correlated with a third of the Si-columns, as predicted from the published structure. The transition layer incorporates Si columns in the same arrangement as in bulk {beta} Prime , although it is structurally distinct from it. The Z-contrast information and arrangement of these Si-columns demonstrate that they are an extension of the Si-network known to structurally connect all the precipitate phases in the Al-Mg-Si(-Cu) system. The width of the interface layer was estimated to about 1 nm. - Highlights: Black-Right-Pointing-Pointer {beta} Prime is found to be looped at sizes larger than 15 nm (cross section diameter). Black-Right-Pointing-Pointer {beta} Prime is found to be sheared at sizes smaller than 15 nm (cross section diameter). Black-Right-Pointing-Pointer The recently determined crystal structure of {beta} Prime is confirmed by HAADF-STEM. Black-Right-Pointing-Pointer Between {beta} Prime and the Al-matrix a transition layer of about 1 nm is existent. Black-Right-Pointing-Pointer The {beta} Prime /matrix layer is structurally distinct from bulk {beta} Prime and the aluminium matrix.« less

  15. {beta}-Catenin stabilization imparts crypt progenitor phenotype to hyperproliferating colonic epithelia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sellin, Joseph H.; Wang Yu; Singh, Pomila

    2009-01-01

    Utilizing the Citrobacter rodentium (CR)-induced transmissible murine colonic hyperplasia (TMCH) model, we provide mechanistic basis of changes in {beta}-catenin/APC/CKI{epsilon} leading to progression and/or regression of hyperplasia in vivo. In response to CR-induced TMCH, crypt lengths increased significantly between days 6-27 post-infection, followed by a steep decline by day 34. {beta}-Cat{sup 45}/total {beta}-catenin were elevated on day 1 post-infection, preceding changes in crypt length, and persisted for 27 days before declining by day 34. Importantly, cellular CKI{epsilon} and {beta}-catenin co-immunoprecipitated and exhibited remarkable parallel changes in kinetics during hyperplasia/regression phases. {beta}-catenin, phosphorylated at Ser33,37 and Thr41 ({beta}-cat{sup 33,37/41}), was low tillmore » day 12, followed by gradual increase until day 27 before declining by day 34. GSK-3{beta} exhibited significant Ser{sup 9}-phosphorylation/inactivation at days 6-12 with partial recovery at days 27-34. Wild type (wt) APC (p312) levels increased at day 6 with transient proteolysis/truncation to p130 form between days 12 and 15; p312 reappeared by day 19 and returned to baseline by day 34. The kinetics of {beta}-Cat{sup 45}/{beta}-catenin nuclear accumulation and acetylation (Ac-{beta}-Cat{sup Lys49}) from days 6 to 27, followed by loss of phosphorylation/acetylation by day 34 was almost identical; Tcf-4 co-immunoprecipitated with {beta}-Cat{sup 45}/{beta}-catenin and localized immunohistochemically to {beta}-Cat{sup 41/45}-positive regions leading to elevated cyclin D1 expression, during the hyperproliferative, but not regression phases of TMCH. CKI{epsilon} mediated phosphorylation of {beta}-Cat{sup 45}, resulting in stabilization/nuclear translocation of {beta}-Cat{sup 45} may be critical for maintaining proliferation at days 6-27. Reversal of GSK-3{beta} phosphorylation and APC changes may be equally critical during the regression phase from days 27 to

  16. Natural triple beta-stranded fibrous folds.

    PubMed

    Mitraki, Anna; Papanikolopoulou, Katerina; Van Raaij, Mark J

    2006-01-01

    A distinctive family of beta-structured folds has recently been described for fibrous proteins from viruses. Virus fibers are usually involved in specific host-cell recognition. They are asymmetric homotrimeric proteins consisting of an N-terminal virus-binding tail, a central shaft or stalk domain, and a C-terminal globular receptor-binding domain. Often they are entirely or nearly entirely composed of beta-structure. Apart from their biological relevance and possible gene therapy applications, their shape, stability, and rigidity suggest they may be useful as blueprints for biomechanical design. Folding and unfolding studies suggest their globular C-terminal domain may fold first, followed by a "zipping-up" of the shaft domains. The C-terminal domains appear to be important for registration because peptides corresponding to shaft domains alone aggregate into nonnative fibers and/or amyloid structures. C-terminal domains can be exchanged between different fibers and the resulting chimeric proteins are useful as a way to solve structures of unknown parts of the shaft domains. The following natural triple beta-stranded fibrous folds have been discovered by X-ray crystallography: the triple beta-spiral, triple beta-helix, and T4 short tail fiber fold. All have a central longitudinal hydrophobic core and extensive intermonomer polar and nonpolar interactions. Now that a reasonable body of structural and folding knowledge has been assembled about these fibrous proteins, the next challenge and opportunity is to start using this information in medical and industrial applications such as gene therapy and nanotechnology.

  17. Uncertainties in nuclear transition matrix elements for neutrinoless {beta}{beta} decay

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rath, P. K.

    Uncertainties in nuclear transition matrix elements M{sup (0{nu})} and M{sub N}{sup (0{nu})} due to the exchange of light and heavy Majorana neutrinos, respectively have been estimated by calculating sets of twelve nuclear transition matrix elements for the neutrinoless {beta}{beta} decay of {sup 94,96}Zr, {sup 98,100}Mo, {sup 104}Ru, {sup 110}Pd, {sup 128,130}Te and {sup 150}Nd isotopes in the case of 0{sup +}{yields}0{sup +} transition by considering four different parameterizations of a Hamiltonian with pairing plus multipolar effective two-body interaction and three different parameterizations of Jastrow short range correlations. Exclusion of nuclear transition matrix elements calculated with the Miller-Spencer parametrization reduces themore » uncertainties by 10%-15%.« less

  18. Activation of the canonical beta-catenin pathway by histamine.

    PubMed

    Diks, Sander H; Hardwick, James C; Diab, Remco M; van Santen, Marije M; Versteeg, Henri H; van Deventer, Sander J H; Richel, Dick J; Peppelenbosch, Maikel P

    2003-12-26

    Histamine signaling is a principal regulator in a variety of pathophysiological processes including inflammation, gastric acid secretion, neurotransmission, and tumor growth. We report that histamine stimulation causes transactivation of a T cell factor/beta-catenin-responsive construct in HeLa cells and in the SW-480 colon cell line, whereas histamine did not effect transactivation of a construct containing the mutated response construct FOP. On the protein level, histamine treatment increases phosphorylation of glycogen synthase kinase 3-beta in HeLa cells, murine macrophages, and DLD-1, HT-29, and SW-480 colon cell lines. Furthermore, histamine also decreases the phosphorylated beta-catenin content in HeLa cells and murine macrophages. Finally, pharmacological inhibitors of the histamine H1 receptor counteracted histamine-induced T cell factor/beta-catenin-responsive construct transactivation and the dephosphorylation of beta-catenin in HeLa cells and in macrophages. We conclude that the canonical beta-catenin pathway acts downstream of the histamine receptor H1 in a variety of cell types. The observation that inflammatory molecules, like histamine, activate the beta-catenin pathway may provide a molecular explanation for a possible link between inflammation and cancer.

  19. Ultrasound-mediated interferon {beta} gene transfection inhibits growth of malignant melanoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yamaguchi, Kazuki; Department of Anatomy, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka City 814-0180; Feril, Loreto B., E-mail: ferilism@yahoo.com

    2011-07-22

    Highlights: {yields} Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-{beta} genes both in vitro and in vivo. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited proliferation of melanoma cells in vitro. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon {beta} (IFN-{beta}) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-{beta} in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-{beta} genes mixed with microbubbles. Successful sonotransfection with IFN-{beta} gene in vitro was confirmed by ELISA,more » which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-{beta} gene was significantly lower than the other experimental groups. These results may lead to a new method of treatment against melanoma and other hard-to-treat cancers.« less

  20. Polypeptides having beta-glucosidase activity and polynucleotides encoding same

    DOEpatents

    Morant, Marc

    2014-01-14

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase, or beta-glucosidase activity and isolated polynucleotides encoding polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  1. [beta]-Lactamases in the Biochemistry and Molecular Biology Laboratory

    ERIC Educational Resources Information Center

    Amador, Paula; Prudencio, Cristina; Vieira, Monica; Ferraz, Ricardo; Fonte, Rosalia; Silva, Nuno; Coelho, Pedro; Fernandes, Ruben

    2009-01-01

    [beta]-lactamases are hydrolytic enzymes that inactivate the [beta]-lactam ring of antibiotics such as penicillins and cephalosporins. The major diversity of studies carried out until now have mainly focused on the characterization of [beta]-lactamases recovered among clinical isolates of Gram-positive staphylococci and Gram-negative…

  2. Stereoselective synthesis of nicotinamide beta-riboside and nucleoside analogs.

    PubMed

    Franchetti, Palmarisa; Pasqualini, Michela; Petrelli, Riccardo; Ricciutelli, Massimo; Vita, Patrizia; Cappellacci, Loredana

    2004-09-20

    The beta-anomers of N-ribofuranosylnicotine-3-carboxamide (beta-NAR) and its nicotinic acid analog (beta-NaR) were obtained by stereoselective synthesis via glycosylation of the presilylated bases under Vorbruggen's protocol. A NAR analog, methylated in position 3 of the ribosylic moiety, is also reported.

  3. The role of estrogen receptor {beta} (ER{beta}) in malignant diseases-A new potential target for antiproliferative drugs in prevention and treatment of cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Warner, Margaret; Center for Nuclear Receptors and Cell Signaling, Department of Biochemistry and Cell Biology, University of Houston, Houston, TX; Gustafsson, Jan-Ake, E-mail: jan-ake.gustafsson@mednut.ki.se

    2010-05-21

    The discovery of ER{beta} in the middle of the 1990s represents a paradigm shift in our understanding of estrogen signaling. It has turned out that estrogen action is not mediated by one receptor, ER{alpha}, but by two balancing factors, ER{alpha} and ER{beta}, which are often antagonistic to one another. Excitingly, ER{beta} has been shown to be widespread in the body and to be involved in a multitude of physiological and pathophysiological events. This has led to a strong interest of the pharmaceutical industry to target ER{beta} by drugs against various diseases. In this review, focus is on the role ofmore » ER{beta} in malignant diseases where the anti proliferative activity of ER{beta} gives hope of new therapeutic approaches.« less

  4. Pain-Related Suppression of Beta Oscillations Facilitates Voluntary Movement

    PubMed Central

    Misra, Gaurav; Ofori, Edward; Chung, Jae Woo; Coombes, Stephen A.

    2017-01-01

    Abstract Increased beta oscillations over sensorimotor cortex are antikinetic. Motor- and pain-related processes separately suppress beta oscillations over sensorimotor cortex leading to the prediction that ongoing pain should facilitate movement. In the current study, we used a paradigm in which voluntary movements were executed during an ongoing pain-eliciting stimulus to test the hypothesis that a pain-related suppression of beta oscillations would facilitate the initiation of a subsequent voluntary movement. Using kinematic measures, electromyography, and high-density electroencephalography, we demonstrate that ongoing pain leads to shorter reaction times without affecting the kinematics or accuracy of movement. Reaction time was positively correlated with beta power prior to movement in contralateral premotor areas. Our findings corroborate the view that beta-band oscillations are antikinetic and provide new evidence that pain primes the motor system for action. Our observations provide the first evidence that a pain-related suppression of beta oscillations over contralateral premotor areas leads to shorter reaction times for voluntary movement. PMID:26965905

  5. Spectrofluorimetric determination of stoichiometry and association constants of the complexes of harmane and harmine with beta-cyclodextrin and chemically modified beta-cyclodextrins.

    PubMed

    Martín, L; León, A; Olives, A I; Del Castillo, B; Martín, M A

    2003-06-13

    The association characteristics of the inclusion complexes of the beta-carboline alkaloids harmane and harmine with beta-cyclodextrin (beta-CD) and chemically modified beta-cyclodextrins such as hydroxypropyl-beta-cyclodextrin (HPbeta-CD), 2,3-di-O-methyl-beta-cyclodextrin (DMbeta-CD) and 2,3,6-tri-O-methyl-beta-cyclodextrin (TMbeta-CD) are described. The association constants vary from 112 for harmine/DMbeta-CD to 418 for harmane/HPbeta-CD. The magnitude of the interactions between the host and the guest molecules depends on the chemical and geometrical characteristics of the guest molecules and therefore the association constants vary for the different cyclodextrin complexes. The steric hindrance is higher in the case of harmine due to the presence of methoxy group on the beta-carboline ring. The association obtained for the harmane complexes is stronger than the one observed for harmine complexes except in the case of harmine/TMbeta-CD. Important differences in the association constants were observed depending on the experimental variable used in the calculations (absolute value of fluorescence intensity or the ratio between the fluorescence intensities corresponding to the neutral and cationic forms). When fluorescence intensity values were considered, the association constants were higher than when the ratio of the emission intensity for the cationic and neutral species was used. These differences are a consequence of the co-existence of acid-base equilibria in the ground and in excited states together with the complexation equilibria. The existence of a proton transfer reaction in the excited states of harmane or harmine implies the need for the experimental dialysis procedure for separation of the complexes from free harmane or harmine. Such methodology allows quantitative results for stoichiometry determinations to be obtained, which show the existence of both 1:1 and 1:2 beta-carboline alkaloid:CD complexes with different solubility properties.

  6. Synthesis of plastic scintillation microspheres: alpha/beta discrimination.

    PubMed

    Santiago, L M; Bagán, H; Tarancón, A; Garcia, J F

    2014-11-01

    Plastic scintillation microspheres (PSm) have been developed as an alternative for liquid scintillation cocktails due to their ability to avoid the mixed waste, besides other strengths in which the possibility for alpha/beta discrimination is included. The aim of this work was to evaluate the capability of PSm containing two combinations of fluorescence solutes (PPO/POPOP and pT/Bis-MSB) and variable amounts of a second organic solvent (naphthalene) to enhance the alpha/beta discrimination. Two commercial detectors with different Pulse Shape Discrimination performances (Quantulus and Triathler) were used to evaluate the alpha/beta discrimination. An optimal discrimination of alpha/beta particles was reached, with very low misclassification values (2% for beta particles and 0.5% for alpha particles), when PSm containing PPO/POPOP and between 0.6 and 2.0 g of naphthalene were evaluated using Triathler and the appropriate programme for data processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Urinary and breast milk biomarkers to assess exposure to naphthalene in pregnant women: an investigation of personal and indoor air sources

    PubMed Central

    2014-01-01

    Background Naphthalene exposures for most non-occupationally exposed individuals occur primarily indoors at home. Residential indoor sources include pest control products (specifically moth balls), incomplete combustion such as cigarette smoke, woodstoves and cooking, some consumer and building products, and emissions from gasoline sources found in attached garages. The study aim was to assess naphthalene exposure in pregnant women from Canada, using air measurements and biomarkers of exposure. Methods Pregnant women residing in Ottawa, Ontario completed personal and indoor air sampling, and questionnaires. During pregnancy, pooled urine voids were collected over two 24-hour periods on a weekday and a weekend day. At 2–3 months post-birth, they provided a spot urine sample and a breast milk sample following the 24-hour air monitoring. Urines were analyzed for 1-naphthol and 2-naphthol and breast milk for naphthalene. Simple linear regression models examined associations between known naphthalene sources, air and biomarker samples. Results Study recruitment rate was 11.2% resulting in 80 eligible women being included. Weekday and weekend samples were highly correlated for both personal (r = 0.83, p < 0.0001) and indoor air naphthalene (r = 0.91, p < 0.0001). Urine specific gravity (SG)-adjusted 2-naphthol concentrations collected on weekdays and weekends (r = 0.78, p < 0.001), and between pregnancy and postpartum samples (r = 0.54, p < 0.001) were correlated. Indoor and personal air naphthalene concentrations were significantly higher post-birth than during pregnancy (p < 0.0001 for signed rank tests); concurrent urine samples were not significantly different. Naphthalene in breast milk was associated with urinary 1-naphthol: a 10% increase in 1-naphthol was associated with a 1.6% increase in breast milk naphthalene (95% CI: 0.2%-3.1%). No significant associations were observed between naphthalene sources reported in self

  8. A minimal peptide scaffold for beta-turn display: optimizing a strand position in disulfide-cyclized beta-hairpins.

    PubMed

    Cochran, A G; Tong, R T; Starovasnik, M A; Park, E J; McDowell, R S; Theaker, J E; Skelton, N J

    2001-01-31

    Phage display of peptide libraries has become a powerful tool for the evolution of novel ligands that bind virtually any protein target. However, the rules governing conformational preferences in natural peptides are poorly understood, and consequently, structure-activity relationships in these molecules can be difficult to define. In an effort to simplify this process, we have investigated the structural stability of 10-residue, disulfide-constrained beta-hairpins and assessed their suitability as scaffolds for beta-turn display. Using disulfide formation as a probe, relative free energies of folding were measured for 19 peptides that differ at a one strand position. A tryptophan substitution promotes folding to a remarkable degree. NMR analysis confirms that the measured energies correlate well with the degree of beta-hairpin structure in the disulfide-cyclized peptides. Reexamination of a subset of the strand substitutions in peptides with different turn sequences reveals linear free energy relationships, indicating that turns and strand-strand interactions make independent, additive contributions to hairpin stability. Significantly, the tryptophan strand substitution is highly stabilizing with all turns tested, and peptides that display model turns or the less stable C'-C' ' turn of CD4 on this tryptophan "stem" are highly structured beta-hairpins in water. Thus, we have developed a small, structured beta-turn scaffold, containing only natural L-amino acids, that may be used to display peptide libraries of limited conformational diversity on phage.

  9. Beta-cryptoxanthin: A vitamin A-forming carotenoid

    USDA-ARS?s Scientific Manuscript database

    Beta-cryptoxanthin is a common carotenoid. It is generally the fourth most abundant in human blood but can achieve high concentrations especially in Japanese and Spanish populations. Its richest food sources include mandarin oranges, persimmons, oranges, papayas, pumpkin, and red sweet peppers. Beta...

  10. Inhibition of glycogen synthase kinase 3beta during heart failure is protective.

    PubMed

    Hirotani, Shinichi; Zhai, Peiyong; Tomita, Hideharu; Galeotti, Jonathan; Marquez, Juan Pablo; Gao, Shumin; Hong, Chull; Yatani, Atsuko; Avila, Jesús; Sadoshima, Junichi

    2007-11-26

    Glycogen synthase kinase (GSK)-3, a negative regulator of cardiac hypertrophy, is inactivated in failing hearts. To examine the histopathological and functional consequence of the persistent inhibition of GSK-3beta in the heart in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative GSK-3beta (Tg-GSK-3beta-DN) and tetracycline-regulatable wild-type GSK-3beta. GSK-3beta-DN significantly reduced the kinase activity of endogenous GSK-3beta, inhibited phosphorylation of eukaryotic translation initiation factor 2B epsilon, and induced accumulation of beta-catenin and myeloid cell leukemia-1, confirming that GSK-3beta-DN acts as a dominant negative in vivo. Tg-GSK-3beta-DN exhibited concentric hypertrophy at baseline, accompanied by upregulation of the alpha-myosin heavy chain gene and increases in cardiac function, as evidenced by a significantly greater Emax after dobutamine infusion and percentage of contraction in isolated cardiac myocytes, indicating that inhibition of GSK-3beta induces well-compensated hypertrophy. Although transverse aortic constriction induced a similar increase in hypertrophy in both Tg-GSK-3beta-DN and nontransgenic mice, Tg-GSK-3beta-DN exhibited better left ventricular function and less fibrosis and apoptosis than nontransgenic mice. Induction of the GSK-3beta transgene in tetracycline-regulatable wild-type GSK-3beta mice induced left ventricular dysfunction and premature death, accompanied by increases in apoptosis and fibrosis. Overexpression of GSK-3beta-DN in cardiac myocytes inhibited tumor necrosis factor-alpha-induced apoptosis, and the antiapoptotic effect of GSK-3beta-DN was abrogated in the absence of myeloid cell leukemia-1. These results suggest that persistent inhibition of GSK-3beta induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility and that the antiapoptotic effect of GSK-3beta inhibition is mediated by myeloid cell leukemia-1. Thus

  11. Review of modern double beta decay experiments

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barabash, A. S., E-mail: barabash@itep.ru

    2015-10-28

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T{sub 1/2}(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino (〈m{sub ν}〉 < 0.46 eV) and a coupling constant of Majoron to neutrino (〈g{sub ee}〉 < 1.3 · 10{sup −5}) are obtained. Prospects of search for neutrinoless double beta decay inmore » new experiments with sensitivity to 〈m{sub ν}〉 at the level of ∼ 0.01-0.1 eV are discussed.« less

  12. Serum beta-2 microglobulin level in sympathetic ophthalmitis.

    PubMed

    Sen, D K; Sarin, G S; Mathur, M D

    1990-04-01

    Serum beta-2 microglobulin (beta 2-m) levels were measured in 12 patients with sympathetic ophthalmitis, 34 with neglected traumatic uveitis following penetrating injury and 36 healthy subjects by ELISA technique. There was no significant alteration of its level in patients with traumatic uveitis. However, its levels were significantly increased in patients with sympathetic ophthalmitis. They were high even in the early stage of the disease. Serum beta 2-m levels paralleled the severity of disease. It decreased significantly at the remission stage. Four patients came back with relapse of the condition and the level of serum beta 2-m was again found to be elevated in them. It is proposed that estimation of beta 2-m can be used as a diagnostic aid when the diagnosis of sympathetic ophthalmitis remains doubtful on clinical grounds. It is also suggested that a rise in serum beta 2-m in patients with traumatic uveitis following perforating injuries may point to the onset of sympathetic ophthalmitis. The extent of rise in its level may be considered a good parameter of the degree of severity of sympathetic ophthalmitis. It may also act as a useful tool to evaluate the drug efficacy in this disease and predict relapse.

  13. Beta-blocker use is associated with improved outcomes in adult trauma patients.

    PubMed

    Arbabi, Saman; Campion, Eric M; Hemmila, Mark R; Barker, Melissa; Dimo, Mary; Ahrns, Karla S; Niederbichler, Andreas D; Ipaktchi, Kyros; Wahl, Wendy L

    2007-01-01

    Beta-adrenoreceptor blocker (beta-blocker) therapy may improve outcomes in surgical patients by decreasing cardiac oxygen consumption and hypermetabolism. Because beta-blockers can lower the systemic blood pressure and cerebral perfusion pressure, there is concern regarding their use in patients with head injury. However, beta-blockers may protect beta-receptor rich brain cells by attenuating cerebral oxygen consumption and metabolism. We hypothesized that beta-blockers are safe in trauma patients, even if they have suffered a significant head injury. Using pharmacy and trauma registry data of a Level I trauma center, we identified a cohort of trauma patients who received beta-blockers during their hospital stay (beta-cohort). Trauma admissions who did not receive beta-blockers were in the control cohort. beta-blocker status, in combination with other variables associated with mortality, were placed in a stepwise multivariate logistic regression to identify independent predictors of fatal outcome. In all, 303 (7%) of 4,117 trauma patients received beta-blockers. In the beta-cohort, 45% of patients were on beta-blockers preinjury. The most common reason to initiate beta-blocker therapy was blood pressure (60%) and heart rate (20%) control. The overall mortality rate was 5.6% and head injury was considered to be the major cause of death. After adjusting for age, Injury Severity Scale score, blood pressure, Glasgow Coma Scale score, respiratory status, and mechanism of injury, the odds ratio for fatal outcome was 0.3 (p < 0.001) for beta-cohort as compared with control. Decreased risk of fatal outcome was more pronounced in patients with a significant head injury. beta-blocker therapy is safe and may be beneficial in selected trauma patients with or without head injury. Further studies looking at beta-blocker therapy in trauma patients and their effect on cerebral metabolism are warranted.

  14. Structural and sequence features of two residue turns in beta-hairpins.

    PubMed

    Madan, Bharat; Seo, Sung Yong; Lee, Sun-Gu

    2014-09-01

    Beta-turns in beta-hairpins have been implicated as important sites in protein folding. In particular, two residue β-turns, the most abundant connecting elements in beta-hairpins, have been a major target for engineering protein stability and folding. In this study, we attempted to investigate and update the structural and sequence properties of two residue turns in beta-hairpins with a large data set. For this, 3977 beta-turns were extracted from 2394 nonhomologous protein chains and analyzed. First, the distribution, dihedral angles and twists of two residue turn types were determined, and compared with previous data. The trend of turn type occurrence and most structural features of the turn types were similar to previous results, but for the first time Type II turns in beta-hairpins were identified. Second, sequence motifs for the turn types were devised based on amino acid positional potentials of two-residue turns, and their distributions were examined. From this study, we could identify code-like sequence motifs for the two residue beta-turn types. Finally, structural and sequence properties of beta-strands in the beta-hairpins were analyzed, which revealed that the beta-strands showed no specific sequence and structural patterns for turn types. The analytical results in this study are expected to be a reference in the engineering or design of beta-hairpin turn structures and sequences. © 2014 Wiley Periodicals, Inc.

  15. [Advances in research and application of beta-tricalcium phosphate, collagen and beta-tricalcium phosphate/collagen composite in bone tissue engineering].

    PubMed

    Han, Xiang-Yong; Fu, Yuan-Fei; Zhang, Fu-Qiang

    2007-02-01

    Bone defects in oral and maxillofacial region was a common problem. To repair the defect, bone grafts including autograft, allograft and artificial bone graft were used in clinic despite of their disadvantages. Nowadays, bone tissue engineering has become a commonly used method to repair bone defect. This paper reviewed the application of beta-TCP, collagen and beta-TCP/collagen composite in bone tissue engineering. It was concluded that beta-TCP/collagen composite was a promising materials in bone tissue engineering.

  16. Interleukin-1beta gene polymorphisms in Taiwanese patients with gout.

    PubMed

    Chen, Man-Ling; Huang, Chung-Ming; Tsai, Chang-Hai; Tsai, Fuu-Jen

    2005-04-01

    The purpose of this study was to examine whether interleukin-1 beta (IL-1beta) promoter and exon 5 gene polymorphisms are markers of susceptibility or clinical manifestations in Taiwanese patients with gout. The study included 196 patients in addition to 103 unrelated healthy control subjects living in central Taiwan. From genomic DNA, polymorphisms of the gene for IL-1beta promoter and IL-1beta exon 5 were typed. Allelic frequencies were compared between the two groups, and the relationship between allelic frequencies and clinical manifestations of gout was evaluated. No significant differences were observed in the allelic frequencies of the IL-1beta promoter between patients with gout and healthy control subjects. Additionally, we did not detect any association of the IL-1beta promoter genotype with the clinical and laboratory profiles of gout patients. However, there was a significant difference between the two groups in terms of hypertriglyceridemia (P=0.0004, chi(2)=12.52, OR 7.14, 95%CI 0.012-0.22). There was also a significant difference in the genotype of IL-1beta exon 5 polymorphism between patients with and without hypertriglyceridemia. Results of the present study suggest that polymorphisms of the IL-1beta promoter and IL-1beta exon 5 are not related to gout patients in central Taiwan.

  17. Role of beta-adrenergic receptor gene polymorphisms in the long-term effects of beta-blockade with carvedilol in patients with chronic heart failure.

    PubMed

    Metra, Marco; Covolo, Loredana; Pezzali, Natalia; Zacà, Valerio; Bugatti, Silvia; Lombardi, Carlo; Bettari, Luca; Romeo, Alessia; Gelatti, Umberto; Giubbini, Raffaele; Donato, Francesco; Dei Cas, Livio

    2010-02-01

    Beta-blockers are mainstay of current treatment of heart failure (HF). Beta-adrenergic receptors (AR) single nucleotide gene polymorphisms (SNPs) may influence the sensitivity and density of beta-AR. We assessed the relation between three common beta-AR SNPs and the response to carvedilol administration. We studied 183 consecutive patients with chronic HF due to ischemic or nonischemic cardiomyopathy, a LV ejection fraction (LVEF) < or = 0.35, not previously treated with beta-blockers. Each patient underwent gated-SPECT radionuclide ventriculography, cardiopulmonary exercise testing and invasive hemodynamic monitoring at baseline and after 12 months of carvedilol administration at maintenance dosages. The beta1-AR gene Arg389Gly and the beta2-AR gene Arg16Gly SNPs were not related to the response to carvedilol administration. Homozygotes for the Glu27Glu allele showed a greater increase in the LVEF, compared to the other patients (+13.0 +/- 12.2% versus +7.1 +/- 8.1% in the Gln27Gln homozygotes, and 8.3 +/- 11.4% units in the Gln27Glu heterozygotes; p = 0.022 by ANOVA). Glu27Glu homozygotes also showed a greater decline in the pulmonary wedge pressure both at rest and at peak exercise. Gln27Glu SNP was selected amongst the determinants of the LVEF response to carvedilol at multivariable analysis, in addition to the cause of cardiomyopathy, baseline systolic blood pressure and the dose of carvedilol administered. Beta1-AR Arg389Gly and beta2-AR Arg16Gly SNPs are not related to the response to carvedilol therapy. In contrast, the Gln27Glu SNP is a determinant of the LVEF response to this agent in patients with chronic HF.

  18. Deficiency of bone marrow beta3-integrin enhances non-functional neovascularization.

    PubMed

    Watson, Alan R; Pitchford, Simon C; Reynolds, Louise E; Direkze, Natalie; Brittan, Mairi; Alison, Malcolm R; Rankin, Sara; Wright, Nicholas A; Hodivala-Dilke, Kairbaan M

    2010-03-01

    beta3-Integrin is a cell surface adhesion and signalling molecule important in the regulation of tumour angiogenesis. Mice with a global deficiency in beta3-integrin show increased pathological angiogenesis, most likely due to increased vascular endothelial growth factor receptor 2 expression on beta3-null endothelial cells. Here we transplanted beta3-null bone marrow (BM) into wild-type (WT) mice to dissect the role of BM beta3-integrin deficiency in pathological angiogenesis. Mice transplanted with beta3-null bone marrow show significantly enhanced angiogenesis in subcutaneous B16F0 melanoma and Lewis lung carcinoma (LLC) cell models and in B16F0 melanoma lung metastasis when compared with tumours grown in mice transplanted with WT bone marrow. The effect of bone marrow beta3-integrin deficiency was also assessed in the RIPTAg mouse model of pancreatic tumour growth. Again, angiogenesis in mice lacking BM beta3-integrin was enhanced. However, tumour weight between the groups was not significantly altered, suggesting that the enhanced blood vessel density in the mice transplanted with beta3-null bone marrow was not functional. Indeed, we demonstrate that in mice transplanted with beta3-null bone marrow a significant proportion of tumour blood vessels are non-functional when compared with tumour blood vessels in WT-transplanted controls. Furthermore, beta3-null-transplanted mice showed an increased angiogenic response to VEGF in vivo when compared with WT-transplanted animals. BM beta3-integrin deficiency affects the mobilization of progenitor cells to the peripheral circulation. We show that VEGF-induced mobilization of endothelial progenitor cells is enhanced in mice transplanted with beta3-null bone marrow when compared with WT-transplanted controls, suggesting a possible mechanism underlying the increased blood vessel density seen in beta3-null-transplanted mice. In conclusion, although BM beta3-integrin is not required for pathological angiogenesis, our

  19. 17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes.

    PubMed

    Catanuto, Paola; Doublier, Sophie; Lupia, Enrico; Fornoni, Alessia; Berho, Mariana; Karl, Michael; Striker, Gary E; Xia, Xiaomei; Elliot, Sharon

    2009-06-01

    Diabetic nephropathy remains one of the most important causes of end-stage renal disease. This is particularly true for women from racial/ethnic minorities. Although administration of 17beta-estradiol to diabetic animals has been shown to reduce extracellular matrix deposition in glomeruli and mesangial cells, effects on podocytes are lacking. Given that podocyte injury has been implicated as a factor leading to the progression of proteinuria and diabetic nephropathy, we treated db/db mice, a model of type 2 diabetic glomerulosclerosis, with 17beta-estradiol or tamoxifen to determine whether these treatments reduce podocyte injury and decrease glomerulosclerosis. We found that albumin excretion, glomerular volume, and extracellular matrix accumulation were decreased in these mice compared to placebo treatment. Podocytes isolated from all treatment groups were immortalized and these cell lines were found to express the podocyte markers WT-1, nephrin, and the TRPC6 cation channel. Tamoxifen and 17beta-estradiol treatment decreased podocyte transforming growth factor-beta mRNA expression but increased that of the estrogen receptor subtype beta protein. 17beta-estradiol, but not tamoxifen, treatment decreased extracellular-regulated kinase phosphorylation. These data, combined with improved albumin excretion, reduced glomerular size, and decreased matrix accumulation, suggest that both 17beta-estradiol and tamoxifen may protect podocytes against injury and therefore ameliorate diabetic nephropathy.

  20. Increased T cell recruitment to the CNS after amyloid beta 1-42 immunization in Alzheimer's mice overproducing transforming growth factor-beta 1.

    PubMed

    Buckwalter, Marion S; Coleman, Bronwen S; Buttini, Manuel; Barbour, Robin; Schenk, Dale; Games, Dora; Seubert, Peter; Wyss-Coray, Tony

    2006-11-01

    Immunotherapy targeting the amyloid beta (Abeta) peptide is a novel therapy under investigation for the treatment of Alzheimer's disease (AD). A clinical trial using Abeta(1-42) (AN1792) as the immunogen was halted as a result of development of meningoencephalitis in a small number of patients. The cytokine TGF-beta1 is a key modulator of immune responses that is increased in the brain in AD. We show here that local overexpression of TGF-beta1 in the brain increases both meningeal and parenchymal T lymphocyte number. Furthermore, TGF-beta1 overexpression in a mouse model for AD [amyloid precursor protein (APP) mice] leads to development of additional T cell infiltrates when mice were immunized at a young but not old age with AN1792. Notably, only mice overproducing both Abeta (APP mice) and TGF-beta1 experienced a rise in T lymphocyte number after immunization. One-third of infiltrating T cells were CD4 positive. We did not observe significant differences in B lymphocyte numbers in any of the genotypes or treatment groups. These results demonstrate that TGF-beta1 overproduction in the brain can promote T cell infiltration, in particular after Abeta(1-42) immunization. Likewise, levels of TGF-beta1 or other immune factors in brains of AD patients may influence the response to Abeta(1-42) immunization.

  1. Streptococcal modulation of cellular invasion via TGF-beta1 signaling.

    PubMed

    Wang, Beinan; Li, Shaoying; Southern, Peter J; Cleary, Patrick P

    2006-02-14

    Group A Streptococcus (GAS) and other bacterial pathogens are known to interact with integrins as an initial step in a complex pathway of bacterial ingestion by host cells. Efficient GAS invasion depends on the interaction of bound fibronectin (Fn) with integrins and activation of integrin signaling. TGF-beta1 regulates expression of integrins, Fn, and other extracellular matrix proteins, and positively controls the integrin signaling pathway. Therefore, we postulated that TGF-beta1 levels could influence streptococcal invasion of mammalian cells. Pretreatment of HEp-2 cells with TGF-beta1 increased their capacity to ingest GAS when the bacteria expressed fibronectin-binding proteins (M1 or PrtF1). Western blots revealed significant induction of alpha5 integrin and Fn expression by HEp-2 cells in response to TGF-beta1. Increased ingestion of streptococci by these cells was blocked by a specific inhibitor of the TGF-beta1 receptor I and antibodies directed against alpha5 integrin and Fn, indicating that increased invasion depends on TGF-beta1 up-regulation of both the alpha5 integrin and Fn. The capacity of TGF-beta1 to up-regulate integrin expression and intracellular invasion by GAS was reproduced in primary human tonsil fibroblasts, which could be a source of TGF-beta1 in chronically infected tonsils. The relationship between TGF-beta1 and GAS invasion was strengthened by the observation that TGF-beta1 production was stimulated in GAS-infected primary human tonsil fibroblasts. These findings suggest a mechanism by which GAS induce a cascade of changes in mammalian tissue leading to elevated expression of the alpha5beta1 receptor, enhanced invasion, and increased opportunity for survival and persistence in their human host.

  2. 40 CFR 721.10239 - Trivalent chromium complexes of a substituted beta-naphthol amine azo dye (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Trivalent chromium complexes of a... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10239 Trivalent chromium complexes of... subject to reporting. (1) The chemical substance identified generically as trivalent chromium complexes of...

  3. 40 CFR 721.10239 - Trivalent chromium complexes of a substituted beta-naphthol amine azo dye (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Trivalent chromium complexes of a... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10239 Trivalent chromium complexes of... subject to reporting. (1) The chemical substance identified generically as trivalent chromium complexes of...

  4. 40 CFR 721.10239 - Trivalent chromium complexes of a substituted beta-naphthol amine azo dye (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Trivalent chromium complexes of a... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10239 Trivalent chromium complexes of... subject to reporting. (1) The chemical substance identified generically as trivalent chromium complexes of...

  5. Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein.

    PubMed

    Zhang, Can; Browne, Andrew; Child, Daniel; Tanzi, Rudolph E

    2010-09-10

    Alzheimer disease (AD) is a devastating neurodegenerative disease with no cure. The pathogenesis of AD is believed to be driven primarily by amyloid-beta (Abeta), the principal component of senile plaques. Abeta is an approximately 4-kDa peptide generated via cleavage of the amyloid-beta precursor protein (APP). Curcumin is a compound in the widely used culinary spice, turmeric, which possesses potent and broad biological activities, including anti-inflammatory and antioxidant activities, chemopreventative effects, and effects on protein trafficking. Recent in vivo studies indicate that curcumin is able to reduce Abeta-related pathology in transgenic AD mouse models via unknown molecular mechanisms. Here, we investigated the effects of curcumin on Abeta levels and APP processing in various cell lines and mouse primary cortical neurons. We show for the first time that curcumin potently lowers Abeta levels by attenuating the maturation of APP in the secretory pathway. These data provide a mechanism of action for the ability of curcumin to attenuate amyloid-beta pathology.

  6. Induction of TGF-beta1 and TGF-beta1-dependent predominant Th17 differentiation by group A streptococcal infection.

    PubMed

    Wang, Beinan; Dileepan, Thamotharampillai; Briscoe, Sarah; Hyland, Kendra A; Kang, Johnthomas; Khoruts, Alexander; Cleary, P Patrick

    2010-03-30

    Recurrent group A Streptococcus (GAS) tonsillitis and associated autoimmune diseases indicate that the immune response to this organism can be ineffective and pathological. TGF-beta1 is recognized as an essential signal for generation of regulatory T cells (Tregs) and T helper (Th) 17 cells. Here, the impact of TGF-beta1 induction on the T-cell response in mouse nasal-associated lymphoid tissue (NALT) following intranasal (i.n.) infections is investigated. ELISA and TGF-beta1-luciferase reporter assays indicated that persistent infection of mouse NALT with GAS sets the stage for TGF-beta1 and IL-6 production, signals required for promotion of a Th17 immune response. As predicted, IL-17, the Th17 signature cytokine, was induced in a TGF-beta1 signaling-dependent manner in single-cell suspensions of both human tonsils and NALT. Intracellular cytokine staining and flow cytometry demonstrated that CD4(+) IL-17(+) T cells are the dominant T cells induced in NALT by i.n. infections. Moreover, naive mice acquired the potential to clear GAS by adoptive transfer of CD4(+) T cells from immunized IL-17A(+)/(+) mice but not cells from IL-17A(-)/(-) mice. These experiments link specific induction of TGF-beta1 by a bacterial infection to an in vivo Th17 immune response and show that this cellular response is sufficient for protection against GAS. The association of a Th17 response with GAS infection reveals a potential mechanism for destructive autoimmune responses in humans.

  7. Method for treating beta-spodumene ceramics

    DOEpatents

    Day, J. Paul; Hickman, David L.

    1994-09-27

    A vapor-phase method for treating a beta-spodumene ceramic article to achieve a substitution of exchangeable hydrogen ions for the lithium present in the beta-spodumene crystals, wherein a barrier between the ceramic article and the source of exchangeable hydrogen ions is maintained in order to prevent lithium contamination of the hydrogen ion source and to generate highly recoverable lithium salts, is provided.

  8. Forbidden unique beta-decays and neutrino mass

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dvornický, Rastislav; Šimkovic, Fedor

    2013-12-30

    The measurement of the electron spectrum in beta-decays provides a robust direct determination of the values of neutrino masses. The planned rhenium beta-decay experiment, called the “Microcalorimeter Arrays for a Rhenium Experiment” (MARE), might probe the absolute mass scale of neutrinos with the same sensitivity as the Karlsruhe tritium neutrino mass (KATRIN) experiment, which is expected to collect data in a near future. In this contribution we discuss the spectrum of emitted electrons close to the end point in the case of the first unique forbidden beta-decay of {sup 79}Se, {sup 107}Pd and {sup 187}Re. It is found that themore » p{sub 3/2}-wave emission dominates over the s{sub 1/2}-wave. It is shown that the Kurie plot near the end point is within a good accuracy linear in the limit of massless neutrinos like the Kurie plot of the superallowed beta-decay of {sup 3}H.« less

  9. High-beta extended MHD simulations of stellarators

    NASA Astrophysics Data System (ADS)

    Bechtel, T. A.; Hegna, C. C.; Sovinec, C. R.; Roberds, N. A.

    2016-10-01

    The high beta properties of stellarator plasmas are studied using the nonlinear, extended MHD code NIMROD. In this work, we describe recent developments to the semi-implicit operator which allow the code to model 3D plasma evolution with better accuracy and efficiency. The configurations under investigation are an l=2, M=5 torsatron with geometry modeled after the Compact Toroidal Hybrid (CTH) experiment and an l=2, M=10 torsatron capable of having vacuum rotational transform profiles near unity. High-beta plasmas are created using a volumetric heating source and temperature dependent anisotropic thermal conduction and resistivity. To reduce computation expenses, simulations are initialized from stellarator symmetric pseudo-equilibria by turning on symmetry breaking modes at finite beta. The onset of MHD instabilities and nonlinear consequences are monitored as a function of beta as well as the fragility of the magnetic surfaces. Research supported by US DOE under Grant No. DE-FG02-99ER54546.

  10. Beta-blockers for the treatment of problematic hemangiomas

    PubMed Central

    Sharma, Vishal K; Fraulin, Frankie OG; Dumestre, Danielle O; Walker, Lori; Harrop, A Robertson

    2013-01-01

    OBJECTIVE: To examine treatment indications, efficacy and side effects of oral beta-blockers for the treatment of problematic hemangiomas. METHODS: A retrospective review of patients with hemangiomas presenting to the Alberta Children’s Hospital Vascular Birthmark Clinic (Calgary, Alberta) between 2009 and 2011 was conducted. The subset of patients treated with oral beta-blockers was further characterized, investigating indication for treatment, response to treatment, time to resolution of indication, duration of treatment, occurrence of rebound growth and side effects of therapy. RESULTS: Between 2009 and 2011, 311 new patients with hemangiomas were seen, of whom 105 were treated with oral beta-blockers. Forty-five patients completed beta-blocker treatment while the remainder continue to receive therapy. Indications for treatment were either functional concerns (68.6%) or disfigurement (31.4%). Functional concerns included ulceration (29.5%), periocular location with potential for visual interference (28.6%), airway interference (4.8%), PHACES syndrome (3.8%), auditory interference (0.95%) and visceral location with congestive heart failure (0.95%). The median age at beta-blocker initiation was 3.3 months; median duration of therapy was 10.6 months; and median maximal treatment dose was 1.5 mg/kg/day for propranolol and 1.6 mg/kg/day for atenolol. Ninety-nine patients (94.3%) responded to therapy with size reduction, colour changes, softened texture and/or healing of ulceration. Rebound growth requiring an additional course of therapy was observed in 23 patients. Side effects from beta-blockers included cool extremities (26.7%), irritability (17.1%), lower gastrointestinal upset (14.3%), emesis (11.4%), hypotension (10.5%), poor feeding (7.6%), lethargy (4.8%), bronchospasm (0.95%) and rash (0.95%). Side effects did not result in complete discontinuation of beta-blocker treatment in any case; however, they prompted a switch to a different beta

  11. Pain-Related Suppression of Beta Oscillations Facilitates Voluntary Movement.

    PubMed

    Misra, Gaurav; Ofori, Edward; Chung, Jae Woo; Coombes, Stephen A

    2017-04-01

    Increased beta oscillations over sensorimotor cortex are antikinetic. Motor- and pain-related processes separately suppress beta oscillations over sensorimotor cortex leading to the prediction that ongoing pain should facilitate movement. In the current study, we used a paradigm in which voluntary movements were executed during an ongoing pain-eliciting stimulus to test the hypothesis that a pain-related suppression of beta oscillations would facilitate the initiation of a subsequent voluntary movement. Using kinematic measures, electromyography, and high-density electroencephalography, we demonstrate that ongoing pain leads to shorter reaction times without affecting the kinematics or accuracy of movement. Reaction time was positively correlated with beta power prior to movement in contralateral premotor areas. Our findings corroborate the view that beta-band oscillations are antikinetic and provide new evidence that pain primes the motor system for action. Our observations provide the first evidence that a pain-related suppression of beta oscillations over contralateral premotor areas leads to shorter reaction times for voluntary movement. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. NMR study on (1alpha, 2beta, 4beta, 5alpha, 7beta)-7-[(hydroxydi-2-thienylacetyl) oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo [3.3.1.0(2,4)] nonane bromide monohydrate.

    PubMed

    Lin, Zhenguang; Mu, Yingdi; Liu, Yihui; Ren, Yeming; Lin, Jimao

    2010-03-01

    The structure of (1alpha, 2beta, 4beta, 5alpha, 7beta)-7-[(hydroxydi-2-thienylacetyl) oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo [3.3.1.0(2,4)] nonane bromide monohydrate was studied using 1D and 2D NMR techniques. Complete NMR assignments of the compound were obtained using DEPT, H-H COSY, as well as HMQC and HMBC heteronuclear correlation techniques. Copyright 2010 Elsevier B.V. All rights reserved.

  13. The J beta segment of the T cell receptor contributes to the V beta-specific T cell expansion caused by staphylococcal enterotoxin B and Urtica dioica superantigens.

    PubMed

    Musette, P; Galelli, A; Truffa-Bachi, P; Peumans, W; Kourilsky, P; Gachelin, G

    1996-03-01

    We have used a new polymerase chain reaction-based technique to analyze at the clonal level the CDR3 diversity and the J beta usage associated with the V beta-dependent T cell receptor (TCR) recognition of two superantigens: the staphylococcal enterotoxin B and the Urtica dioica agglutinin. Our results show that subset of J beta elements is preferentially expanded in a given V beta family, independently of the nature of the superantigen. By contrast, the CDR3 loop does not contribute significantly to the T cell expansion induced by the superantigens. We conclude that the J beta segment of the TCR beta chain, but not the CDR3 region, participates in superantigen binding, presumably by influencing the quaternary structure of the TCR beta chain.

  14. All-transglycolytic synthesis and characterization of sialyl(alpha2-3)galactosyl(beta1-4)xylosyl-p-nitrophenyl(beta1-), an oligosaccharide derivative related to glycosaminoglycan biosynthesis.

    PubMed

    Vetere, A; Ferro, S; Bosco, M; Cescutti, P; Paoletti, S

    1997-08-01

    Beta-D-Xylopyranosides, such as p-nitrophenyl-beta-D-xylopyranoside (Xyl-Np) or 4-methylumbelliferyl-beta-D-xylopyranoside (Xyl-MeUmb), when added to the culture medium of human skin fibroblasts have previously been shown to produce some Np- or MeUmb-oligosaccharides related to the regulation of glycosaminoglycan biosynthesis. Among these oligosaccharide derivatives, we synthesized the trisaccharide derivative NeuAc(alpha2-3)Gal(beta1-4)Xyl-Np(beta1- as a potential inhibitor of human skin fibroblast glycosaminoglycan biosynthesis. This synthesis was achieved by sequential use of transglycosylating activities of Escherichia coli beta-galactosidase and Trypanosoma cruzi trans-sialidase. The structure of the oligosaccharide obtained was determined by HPLC, ion-spray mass spectrometry, and NMR.

  15. Immunocytochemical localization of latent transforming growth factor-beta1 activation by stimulated macrophages

    NASA Technical Reports Server (NTRS)

    Chong, H.; Vodovotz, Y.; Cox, G. W.; Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1999-01-01

    Transforming growth factor-beta1 (TGF-beta) is secreted in a latent form consisting of mature TGF-beta noncovalently associated with its amino-terminal propeptide, which is called latency associated peptide (LAP). Biological activity depends upon the release of TGF-beta from the latent complex following extracellular activation, which appears to be the key regulatory mechanism controlling TGF-beta action. We have identified two events associated with latent TGF-beta (LTGF-beta) activation in vivo: increased immunoreactivity of certain antibodies that specifically detect TGF-beta concomitant with decreased immunoreactivity of antibodies to LAP. Macrophages stimulated in vitro with interferon-gamma and lipopolysaccharide reportedly activate LTGF-beta via cell membrane-bound protease activity. We show through dual immunostaining of paraformaldehyde-fixed macrophages that such physiological TGF-beta activation is accompanied by a loss of LAP immunoreactivity with concomitant revelation of TGF-beta epitopes. The induction of TGF-beta immunoreactivity colocalized with immunoreactive betaglycan/RIII in activated macrophages, suggesting that LTGF-beta activation occurs on the cell surface. Confocal microscopy of metabolically active macrophages incubated with antibodies to TGF-beta and betaglycan/RIII prior to fixation supported the localization of activation to the cell surface. The ability to specifically detect and localize LTGF-beta activation provides an important tool for studies of its regulation.

  16. Validation of the BetaStar® Advanced for Beta-lactams Test Kit for the Screening of Bulk Tank and Tanker Truck Milks for the Presence of Beta-lactam Drug Residues.

    PubMed

    Denhartigh, Andrew; Reynolds, Lindsay; Palmer, Katherine; Klein, Frank; Rice, Jennifer; Rejman, John J

    2018-05-18

    A validation study was conducted for an immunochromatographic method (BetaStar ® Advanced for Beta-lactams) for the detection of beta-lactam residues in raw, commingled bovine milk. The assay detected amoxicillin, ampicillin, cloxacillin, penicillin, cephapirin, and ceftiofur below the U.S. Food and Drug Administration tolerance levels but above the maximum sensitivity thresholds established by the National Conference on Interstate Milk Shipments. The results of internal and independent laboratory dose-response studies employing spiked samples were in agreement. The test detected all six drugs at the approximate 90/95% sensitivity levels in milk from cows treated with each drug. Selectivity of the assay was 100%, as no false-positive results were obtained in testing 1148 control milk samples. Testing the estimated 90/95% sensitivity level for amoxicillin (8.5 ppb), ampicillin (6.9 ppb), cloxacillin (8.9 ppb), penicillin (4.2 ppb), and cephapirin (17.6 ppb), and at 100 ppb for each antibiotic, resulted in 94-100% positive tests for each of the beta-lactam drugs. The results of ruggedness experiments established the operating parameter tolerances for the assay. Cross-reactivity testing established that the assay detects other certain beta-lactam drugs, but it does not cross-react with any of 30 drugs belonging to seven different drug classes. Abnormally high bacterial or somatic cell counts in raw milk produced no assay interference.

  17. Temporally variable environments maintain more beta-diversity in Mediterranean landscapes

    NASA Astrophysics Data System (ADS)

    Martin, Beatriz; Ferrer, Miguel

    2015-10-01

    We examined the relationships between different environmental factors and the alpha and beta-diversity of terrestrial vertebrates (birds, mammals, amphibians and reptiles) in a Mediterranean region at the landscape level. We investigated whether the mechanisms underlying alpha and beta-diversity patterns are influenced by energy availability, habitat heterogeneity and temporal variability and if the drivers of the diversity patterns differed between both components of diversity. We defined alpha-diversity as synonym of species richness whereas beta-diversity was measured as distinctiveness. We evaluated a total of 13 different predictors using generalized linear mixed model (GLMM) analysis. Habitat spatial heterogeneity increased alpha-diversity, but contrastingly, it did not significantly affect beta-diversity among sites. Disturbed landscapes may show higher habitat spatial variation and higher alpha-diversity due to the contribution of highly generalist species that are wide-distributed and do not differ in composition (beta-diversity) among different sites within the region. Contrastingly, higher beta-diversity levels were negatively related to more stable sites in terms of temporal environmental variation. This negative relationship between environmental stability and beta-diversity levels is explained in terms of species adaptation to the local environmental conditions. Our study highlights the importance of temporal environmental variability in maintaining beta-diversity patterns under highly variable environmental conditions.

  18. Pressure-induced subunit dissociation and unfolding of dimeric beta-lactoglobulin.

    PubMed Central

    Valente-Mesquita, V L; Botelho, M M; Ferreira, S T

    1998-01-01

    Effects of hydrostatic pressure on dimeric beta-lactoglobulin A (beta-Lg) were investigated. Application of pressures of up to 3.5 kbar induced a significant red shift ( approximately 11 nm) and a 60% increase in intrinsic fluorescence emission of beta-Lg. These changes were very similar to those induced by guanidine hydrochloride, which caused subunit dissociation and unfolding of beta-Lg. A large hysteresis in the recovery of fluorescence parameters was observed upon decompression of beta-Lg. Pressure-induced dissociation and unfolding were not fully reversible, because of the formation of a nonnative intersubunit disulfide bond that hampered correct refolding of the dimer. Comparison between pressure dissociation/unfolding at 3 degrees C and 23 degrees C revealed a marked destabilization of beta-Lg at low temperature. The stability of beta-Lg toward pressure was significantly enhanced by 1 M NaCl, but not by glycerol (up to 20% v/v). These observations suggest that salt stabilization was not related to a general cosolvent effect, but may reflect charge screening. Interestingly, pressure-induced dissociation/unfolding was completely independent of beta-Lg concentration, in apparent violation of the law of mass action. Possible causes for this anomalous behavior are discussed. PMID:9649408

  19. Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-{beta} estradiol and nonylphenol

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Soverchia, L.; Ruggeri, B.; Palermo, F.

    2005-12-15

    Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17{beta} and different concentrations (10{sup -6} and 10{sup -7} M) of 4-nonylphenol (4-NP) on the expression of liver ER{beta}-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17{beta}) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratusmore » is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good 'sentinel' species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10{sup -6} and 10{sup -7} M) of 4-nonylphenol (4-NP), or 10{sup -7} M of estradiol-17{beta}. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 deg. C; the gonads were fixed, then frozen and stored at -70 deg. C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 deg. C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17{beta} and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17{beta} plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ER{beta}-1 mRNA in the liver, demonstrating that both estradiol-17{beta} and 4-NP modulate the

  20. Rapid model building of beta-sheets in electron-density maps.

    PubMed

    Terwilliger, Thomas C

    2010-03-01

    A method for rapidly building beta-sheets into electron-density maps is presented. beta-Strands are identified as tubes of high density adjacent to and nearly parallel to other tubes of density. The alignment and direction of each strand are identified from the pattern of high density corresponding to carbonyl and C(beta) atoms along the strand averaged over all repeats present in the strand. The beta-strands obtained are then assembled into a single atomic model of the beta-sheet regions. The method was tested on a set of 42 experimental electron-density maps at resolutions ranging from 1.5 to 3.8 A. The beta-sheet regions were nearly completely built in all but two cases, the exceptions being one structure at 2.5 A resolution in which a third of the residues in beta-sheets were built and a structure at 3.8 A in which under 10% were built. The overall average r.m.s.d. of main-chain atoms in the residues built using this method compared with refined models of the structures was 1.5 A.

  1. Comparative analyses of two thermophilic enzymes exhibiting both beta-1,4 mannosidic and beta-1,4 glucosidic cleavage activities from Caldanaerobius polysaccharolyticus.

    PubMed

    Han, Yejun; Dodd, Dylan; Hespen, Charles W; Ohene-Adjei, Samuel; Schroeder, Charles M; Mackie, Roderick I; Cann, Isaac K O

    2010-08-01

    The hydrolysis of polysaccharides containing mannan requires endo-1,4-beta-mannanase and 1,4-beta-mannosidase activities. In the current report, the biochemical properties of two endo-beta-1,4-mannanases (Man5A and Man5B) from Caldanaerobius polysaccharolyticus were studied. Man5A is composed of an N-terminal signal peptide (SP), a catalytic domain, two carbohydrate-binding modules (CBMs), and three surface layer homology (SLH) repeats, whereas Man5B lacks the SP, CBMs, and SLH repeats. To gain insights into how the two glycoside hydrolase family 5 (GH5) enzymes may aid the bacterium in energy acquisition and also the potential application of the two enzymes in the biofuel industry, two derivatives of Man5A (Man5A-TM1 [TM1 stands for truncational mutant 1], which lacks the SP and SLH repeats, and Man5A-TM2, which lacks the SP, CBMs, and SLH repeats) and the wild-type Man5B were biochemically analyzed. The Man5A derivatives displayed endo-1,4-beta-mannanase and endo-1,4-beta-glucanase activities and hydrolyzed oligosaccharides with a degree of polymerization (DP) of 4 or higher. Man5B exhibited endo-1,4-beta-mannanase activity and little endo-1,4-beta-glucanase activity; however, this enzyme also exhibited 1,4-beta-mannosidase and cellodextrinase activities. Man5A-TM1, compared to either Man5A-TM2 or Man5B, had higher catalytic activity with soluble and insoluble polysaccharides, indicating that the CBMs enhance catalysis of Man5A. Furthermore, Man5A-TM1 acted synergistically with Man5B in the hydrolysis of beta-mannan and carboxymethyl cellulose. The versatility of the two enzymes, therefore, makes them a resource for depolymerization of mannan-containing polysaccharides in the biofuel industry. Furthermore, on the basis of the biochemical and genomic data, a molecular mechanism for utilization of mannan-containing nutrients by C. polysaccharolyticus is proposed.

  2. Continental rifting and the origin of Beta Regio, Venus

    NASA Technical Reports Server (NTRS)

    Mcgill, G. E.; Steenstrup, S. J.; Barton, C.; Ford, P. G.

    1981-01-01

    Topographic maps based on Pioneer Venus altimetry suggest that Beta Regio, an elevated feature centered at 27 deg N, 282 deg E, is analogous to domes associated with continental rift systems on earth. This interpretation is consistent with the commonly quoted analogy between the East African rift system and the topography of the region from Beta Regio southward to Phoebe Regio. If Beta Regio is a dome, major structural uplift of the crust of Venus is implied, suggesting a more dynamic upper mantle than would be the case if Beta Regio were simply a large volcanic construct.

  3. Difference between beta1-adrenoceptor autoantibodies of human and animal origin-Limitations detecting beta1-adrenoceptor autoantibodies using peptide based ELISA technology.

    PubMed

    Wenzel, Katrin; Schulze-Rothe, Sarah; Müller, Johannes; Wallukat, Gerd; Haberland, Annekathrin

    2018-01-01

    Cell-based analytics for the detection of the beta1-adrenoceptor autoantibody (beta1-AAB) are functional, yet difficult to handle, and should be replaced by easily applicable, routine lab methods. Endeavors to develop solid-phase-based assays such as ELISA to exploit epitope moieties for trapping autoantibodies are ongoing. These solid-phase-based assays, however, are often unreliable when used with human patient material, in contrast to animal derived autoantibodies. We therefore tested an immunogen peptide-based ELISA for the detection of beta1-AAB, and compared commercially available goat antibodies against the 2nd extracellular loop of human beta1-adrenoceptor (ADRB1-AB) to autoantibodies enriched from patient material. The functionality of these autoantibodies was tested in a cell based assay for comparison and their structural appearance was investigated using 2D gel electrophoresis. The ELISA showed a limit of detection for ADRB1-AB of about 1.5 nmol antibody/L when spiked in human control serum and only about 25 nmol/L when spiked in species identical (goat) matrix material. When applied to samples of human origin, the ELISA failed to identify the specific beta1-AABs. A low concentration of beta1-AAB, together with structural inconsistency of the patient originated samples as seen from the 2D Gel appearance, might contribute to the failure of the peptide based ELISA technology to detect human beta1-AABs.

  4. Effect of peptide aldehydes with IL-1 beta converting enzyme inhibitory properties on IL-1 alpha and IL-1 beta production in vitro.

    PubMed

    Németh, K; Patthy, M; Fauszt, I; Széll, E; Székely, J I; Bajusz, S

    1995-12-01

    Tripeptide and pentapeptide aldehydes as substrate-base inhibitors of cysteine proteases were designed in our laboratory for the inhibition of interleukin-1 beta converting enzyme (ICE), a recently described cysteine protease responsible for the processing of IL-1 beta. The biological effectivity of the peptide aldehydes was studied in THP-1 cells and human whole blood. The released and cell-associated IL-1 alpha and IL-1 beta levels were determined by ELISA from the supernatants and cell lysates, respectively. The total IL-1 like bioactivity was assayed by the D10 G4.1 cell proliferation method. The tripeptide aldehyde (Z-Val-His-Asp-H) and pentapeptide aldehyde (Eoc-Ala-Tyr-Val-Ala-Asp-H) significantly reduced IL-1 beta levels in the supernatants in relatively high concentrations (10-100 microM), but the IL-1 alpha release was unaffected by these peptides. However, a considerable decrease in the cell-associated IL-1 beta and IL-1 alpha levels was observed. N-terminal extension of the tripeptide aldehyde yielded even more potent inhibitors. Amino acid substitution at the P2 position did not cause considerable changes in the inhibitory activity. The peptide aldehydes suppressed the IL-1 beta production in a reversible manner, whereas dexamethasone, a glucocorticoid, had a prolonged inhibitory effect. The inhibitory effect of these peptides and that of dexamethasone appeared to be additive. These findings indicate that these peptide aldehydes might be used as IL-beta inhibitory agents in experimental models in which IL-1 beta is a key mediator or ICE is implicated.

  5. Activation of Beta-Catenin Signaling in Androgen Receptor–Negative Prostate Cancer Cells

    PubMed Central

    Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W.; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S.; Troncoso, Patricia; Maity, Sankar N.; Navone, Nora M.

    2012-01-01

    Purpose To study Wnt/beta-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the beta-catenin–androgen receptor (AR) interaction. Experimental Design We performed beta-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of beta-catenin–mediated transcription), and sequenced the beta-catenin gene in MDA PCa 118a, MDA PCa 118b, MDA PCa 2b, and PC-3 prostate cancer (PCa) cells. We knocked down beta-catenin in AR-negative MDA PCa 118b cells and performed comparative gene-array analysis. We also immunohistochemically analyzed beta-catenin and AR in 27 bone metastases of human CRPCs. Results Beta-catenin nuclear accumulation and TOP-flash reporter activity were high in MDA PCa 118b but not in MDA PCa 2b or PC-3 cells. MDA PCa 118a and 118b cells carry a mutated beta-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA PCa 118b cells with downregulated beta-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant beta-catenin. Finally, we found nuclear localization of beta-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher’s exact test), suggesting that reduced AR expression enables Wnt/beta-catenin signaling. Conclusion We identified a previously unknown downstream target of beta-catenin, HAS2, in PCa, and found that high beta-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone-metastatic PCa. These findings may guide physicians in managing these patients. PMID:22298898

  6. Primary structure of the hemoglobin beta-chain of rose-ringed parakeet (Psittacula krameri).

    PubMed

    Islam, A; Persson, B; Zaidi, Z H; Jörnvall, H

    1989-08-01

    The primary structure of Rose-ringed Parakeet hemoglobin beta-chain was established, completing the analysis of this hemoglobin. Comparison with other avian beta-chains show variations smaller than those for the corresponding alpha-chains. There are 11 amino acid exchanges in relationship to the only other characterized psittaciform beta-chain, and a total of 35 positions are affected by differences among all avian beta-chains analyzed (versus 61 for the alpha-chains). At three positions, the Psittacula beta-chain has residues unique to this species. Three alpha 1 beta 1 contacts are modified, by substitutions at positions beta 51, beta 116, and beta 125.

  7. Beta-Zone parapapillary atrophy and the velocity of glaucoma progression.

    PubMed

    Teng, Christopher C; De Moraes, Carlos Gustavo V; Prata, Tiago S; Tello, Celso; Ritch, Robert; Liebmann, Jeffrey M

    2010-05-01

    Beta-Zone parapapillary atrophy (PPA) occurs more commonly in eyes with glaucoma. Rates of glaucomatous visual field (VF) progression in eyes with and without beta-zone PPA at the time of baseline assessment were compared. Retrospective, comparative study. Two hundred forty-five patients from the New York Glaucoma Progression Study. Subjects with glaucomatous optic neuropathy and repeatable VF loss were assessed for eligibility. Eyes with a Heidelberg Retina Tomograph II (HRT) examination, at least 5 visual field tests after the HRT in either eye, optic disc photographs, and <6 diopters of myopia were enrolled. beta-Zone PPA was defined as a region of chorioretinal atrophy with visible sclera and choroidal vessels adjacent to the optic disc. Global rates of VF progression were determined by automated pointwise linear regression analysis. Univariate analysis included age, gender, ethnicity, central corneal thickness (CCT), refractive error, baseline mean deviation, baseline intraocular pressure (IOP), mean IOP, IOP fluctuation, disc area, rim area, rim area-to-disc area ratio, beta-zone PPA area, beta-zone PPA area-to-disc area ratio, and presence or absence of beta-zone PPA. The relationship between beta-zone PPA and the rate and risk of glaucoma progression. Two hundred forty-five eyes of 245 patients (mean age, 69.6+/-12.3 years) were enrolled. The mean follow-up was 4.9+/-1.4 years and the mean number of VFs after HRT was 9.3+/-2.7. beta-Zone PPA was present in 146 eyes (65%). Eyes with beta-zone PPA progressed more rapidly (-0.84+/-0.8 dB/year) than eyes without it (-0.51+/-0.6 dB/year; P<0.01). Multivariate regression showed significant influence of mean IOP (hazard ratio [HR], 1.11; P<0.01), IOP fluctuation (HR, 1.17; P = 0.02), and presence of beta-zone PPA (HR, 2.59; P<0.01) on VF progression. Moderate (0.5-1.5 dB/year; P = 0.01) and fast (>1.5 dB/year; P = 0.08) global rates of progression occurred more commonly in eyes with beta-zone PPA than in eyes

  8. Maternal breast milk transforming growth factor beta and feeding intolerance in preterm infants

    PubMed Central

    Frost, Brandy L.; Jilling, Tamas; Lapin, Brittany; Maheshwari, Akhil; Caplan, Michael S.

    2015-01-01

    Background Feeding intolerance occurs commonly in the NICU. Breast milk contains a large pool of transforming growth factor-beta (TGF-beta). Few studies describe TGF-beta levels in preterm milk, and the relationship to feeding intolerance (FI) remains unexplored. We measured TGF-beta levels in preterm breast milk to investigate a correlation with FI in preterm infants. Methods Prospective observational trial of 100 mother-infant pairs, enrolling infants born below 32 weeks gestation and less than 1500 grams, and mothers who planned to provide breast milk. TGF-beta levels were measured using ELISA. Infant charts were reviewed for outcomes. Results TGF-beta declined postnatally, most elevated in colostrum (p<0.01). TGF-beta 2 levels were higher than TGF-beta 1 at all time points (p<0.01). Colostrum TGF-beta levels correlated inversely with birth weight (p<0.01) and gestational age (p<0.05). One week TGF-beta 2 levels were reduced in growth-restricted infants with FI (p<0.01). Of infants with NEC, TGF-beta 2 levels appeared low, but small sample size precluded meaningful statistical comparisons. Conclusions TGF-beta levels decline temporally in preterm milk. TGF-beta 1 colostrum levels correlate inversely with birth weight and gestational age. TGF-beta 2 may play a role in FI in growth-restricted infants. The relationship of TGF-beta 2 and NEC merits future investigation. PMID:24995914

  9. Fibronectin regulates the activation of THP-1 cells by TGF-beta1.

    PubMed

    Wang, A C; Fu, L

    2001-03-01

    To determine how fibronectin regulates the immunomodulatory effects of transforming growth factor (TGF)-beta on THP-1 cells. THP-1 monocytic cell line. THP-1 cells were primed for 48 h in the presence or absence of 250 pM TGF-beta1. Assays or assessments carried out, together with statistical test applied. We found that adherence to fibronectin dramatically modulates the effects of TGF-beta1 on the human monocytic cell line THP-1. TGF-beta did not significantly affect constitutive interleukin (IL)-8 secretion or IL-1beta-induced IL-8 secretion from suspended cells. In contrast, TGF-beta stimulated IL-8 secretion as well as augmented IL-1beta-induced IL-8 secretion from adherent cells. The differential effects of TGF-beta1 on IL-8 secretion from suspended and adherent cells could not be explained by differences in IL-1 receptor antagonist production. The effects of fibronectin on TGF-beta1 induced IL-8 secretion from THP-1 cells were mimicked by adhesion to immobilized anti-a4beta1 integrin antibody and to a fibronectin fragment containing the CS-1 domain. These results indicate that alpha4beta1-mediated adhesion to fibronectin may play a key role during inflammation by profoundly influencing the effects of TGF-beta1 on monocytes.

  10. Beta particle transport and its impact on betavoltaic battery modeling.

    PubMed

    Alam, Tariq R; Pierson, Mark A; Prelas, Mark A

    2017-12-01

    Simulation of beta particle transport from a Ni-63 radioisotope in silicon using the Monte Carlo N-Particle (MCNP) transport code for monoenergetic beta particle average energy, monoenergetic beta particle maximum energy, and the more precise full beta energy spectrum of Ni-63 were demonstrated. The beta particle penetration depth and the shape of the energy deposition varied significantly for different transport approaches. A penetration depth of 2.25±0.25µm with a peak in energy deposition was found when using a monoenergetic beta particle average energy and a depth of 14.25±0.25µm with an exponential decrease in energy deposition was found when using a full beta energy spectrum and a 0° angular variation. For a 90° angular variation, i.e. an isotropic source, the penetration depth was decreased to 12.75±0.25µm and the backscattering coefficient increased to 0.46 with 30.55% of the beta energy escaping when using a full beta energy spectrum. Similarly, for a 0° angular variation and an isotropic source, an overprediction in the short circuit current and open circuit voltage solved by a simplified drift-diffusion model was observed when compared to experimental results from the literature. A good agreement in the results was found when self-absorption and isotope dilution in the source was considered. The self-absorption effect was 15% for a Ni-63 source with an activity of 0.25mCi. This effect increased to about 28.5% for a higher source activity of 1mCi due to an increase in thickness of the Ni-63 source. Source thicknesses of approximately 0.1µm and 0.4µm for these Ni-63 activities predicted about 15% and 28.5% self-absorption in the source, respectively, using MCNP simulations with an isotropic source. The modeling assumptions with different beta particle energy inputs, junction depth of the semiconductor, backscattering of beta particles, an isotropic beta source, and self-absorption of the radioisotope have significant impacts in betavoltaic

  11. Determination of the efficiency of commercially available dose calibrators for beta-emitters.

    PubMed

    Valley, Jean-François; Bulling, Shelley; Leresche, Michel; Wastiel, Claude

    2003-03-01

    The goals of this investigation are to determine whether commercially available dose calibrators can be used to measure the activity of beta-emitting radionuclides used in pain palliation and to establish whether manufacturer-supplied calibration factors are appropriate for this purpose. Six types of commercially available dose calibrators were studied. Dose calibrator response was controlled for 5 gamma-emitters used for calibration or typically encountered in routine use. For the 4 most commonly used beta-emitters ((32)P, (90)Sr, (90)Y, and (169)Er) dose calibrator efficiency was determined in the syringe geometry used for clinical applications. Efficiency of the calibrators was also measured for (153)Sm and (186)Re, 2 beta-emitters with significant gamma-contributions. Source activities were traceable to national standards. All calibrators measured gamma-emitters with a precision of +/-10%, in compliance with Swiss regulatory requirements. For beta-emitters, dose calibrator intrinsic efficiency depends strongly on the maximal energy of the beta-spectrum and is notably low for (169)Er. Manufacturer-supplied calibration factors give accurate results for beta-emitters with maximal beta-energy in the middle-energy range (1 MeV) but are not appropriate for use with low-energy ((169)Er) or high-energy ((90)Y) beta-emitters. beta-emitters with significant gamma-contributions behave like gamma-emitters. Commercially available dose calibrators have an intrinsic efficiency that is sufficient for the measurement of beta-emitters, including beta-emitters with a low maximum beta-energy. Manufacturer-supplied calibration factors are reliable for gamma-emitters and beta-emitters in the middle-energy range. For low- and high-energy beta-emitters, the use of manufacturer-supplied calibration factors introduces significant measurement inaccuracy.

  12. beta-Arrestin 2: a Negative Regulator of Inflammatory Responses in Polymorphonuclear Leukocytes.

    PubMed

    Basher, Fahmin; Fan, Hongkuan; Zingarelli, Basilia; Borg, Keith T; Luttrell, Lou M; Tempel, George E; Halushka, Perry V; Cook, James A

    2008-01-01

    Heterotrimeric Gi proteins have been previously implicated in signaling leading to inflammatory mediator production induced by bacterial lipopolysaccharide (LPS). beta-arrestins are ubiquitously expressed proteins that alter G-protein-coupled receptors signaling. beta-arrestin 2 plays a multifaceted role as a scaffold protein in regulating cellular inflammatory responses. Polymorphonuclear leukocytes (PMNs) activated by LPS induce inflammatory responses resulting in organ injury during sepsis. We hypothesized that beta-arrestin 2 is a critical modulator of inflammatory responses in PMNs. To examine the potential role of beta-arrestin 2 in LPS-induced cellular activation, we studied homozygous beta-arrestin 2 (-/-), heterozygous (+/-), and wildtype (+/+) mice. PMNs were stimulated with LPS for 16h. There was increased basal TNFalpha and IL-6 production in the beta-arrestin 2 (-/-) compared to both beta-arrestin 2 (+/-) and (+/+) cells. LPS failed to stimulate TNFalpha production in the beta-arrestin 2 (-/-) PMNs. However, LPS stimulated IL-6 production was increased in the beta-arrestin 2 (-/-) cells compared to (+/+) cells. In subsequent studies, peritoneal PMN recruitment was increased 81% in the beta-arrestin 2 (-/-) mice compared to (+/+) mice (p<0.05). beta-arrestin 2 deficiency resulted in an augmented expression of CD18 and CD62L (p<0.05). In subsequent studies, beta-arrestin 2 (-/-) and (+/+) mice were subjected to cecal ligation and puncture (CLP) and lung was collected and analyzed for myeloperoxidase activity (MPO) as index of PMNs infiltrate. CLP-induced MPO activity was significantly increased (p<0.05) in the beta-arrestin 2 (-/-) compared to (+/+) mice. These studies demonstrate that beta-arrestin 2 is a negative regulator of PMN activation and pulmomary leukosequestration in response to polymicrobial sepsis.

  13. 18{beta}-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moon, Myung-Hee; Jeong, Jae-Kyo; Lee, You-Jin

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer 18{beta}-GA inhibits adipogenic differentiation in 3T3-L1 preadipocytes and stimulates lipolysis in differentiated adipocytes. Black-Right-Pointing-Pointer Anti-adipogenic effect of 18{beta}-GA is caused by down-regulation of PPAR{gamma} and inactivation of Akt signalling. Black-Right-Pointing-Pointer Lipolytic effect of 18{beta}-GA is mediated by up-regulation of HSL, ATGL and perilipin and activation of HSL. -- Abstract: 18{beta}-Glycyrrhetinic acid (18{beta}-GA) obtained from the herb liquorice has various pharmacological properties including anti-inflammatory and anti-bacterial activities. However, potential biological anti-obesity activities are unclear. In this study, novel biological activities of 18{beta}-GA in the adipogenesis of 3T3-L1 preadipocytes and in lipolysis of differentiated adipocytes were identified. Mouse 3T3-L1 cellsmore » were used as an in vitro model of adipogenesis and lipolysis, using a mixture of insulin/dexamethasone/3-isobutyl-1-methylxanthine (IBMX) to induce differentiation. The amount of lipid droplet accumulation was determined by an AdipoRed assay. The expression of several adipogenic transcription factors and enzymes was investigated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. 18{beta}-GA dose-dependently (1-40 {mu}M) significantly decreased lipid accumulation in maturing preadipocytes. In 3T3-L1 preadipocytes, 10 {mu}M of 18{beta}-GA down-regulated the transcriptional levels of the peroxisome proliferator-activated receptor {gamma}, CCAAT/enhancer-binding protein {alpha} and adiponectin, which are markers of adipogenic differentiation via Akt phosphorylation. Also, in differentiated adipocytes, 18{beta}-GA increased the level of glycerol release and up-regulated the mRNA of hormone-sensitive lipase, adipose TG lipase and perilipin, as well as the phosphorylation of hormone-sensitive lipase at Serine 563. The results indicate that 18

  14. Dopamine transporter-dependent and -independent actions of trace amine beta-phenylethylamine.

    PubMed

    Sotnikova, Tatyana D; Budygin, Evgeny A; Jones, Sara R; Dykstra, Linda A; Caron, Marc G; Gainetdinov, Raul R

    2004-10-01

    Beta-phenylethylamine (beta-PEA) is an endogenous amine that is found in trace amounts in the brain. It is believed that the locomotor-stimulating action of beta-PEA, much like amphetamine, depends on its ability to increase extracellular dopamine (DA) concentrations owing to reversal of the direction of dopamine transporter (DAT)-mediated DA transport. beta-PEA can also bind directly to the recently identified G protein-coupled receptors, but the physiological significance of this interaction is unclear. To assess the mechanism by which beta-PEA mediates its effects, we compared the neurochemical and behavioral effects of this amine in wild type (WT), heterozygous and 'null' DAT mutant mice. In microdialysis studies, beta-PEA, administered either systemically or locally via intrastriatal infusion, produced a pronounced outflow of striatal DA in WT mice whereas no increase was detected in mice lacking the DAT (DAT-KO mice). Similarly, in fast-scan voltammetry studies beta-PEA did not alter DA release and clearance rate in striatal slices from DAT-KO mice. In behavioral studies beta-PEA produced a robust but transient increase in locomotor activity in WT and heterozygous mice. In DAT-KO mice, whose locomotor activity and stereotypy are increased in a novel environment, beta-PEA (10-100 mg/kg) exerted a potent inhibitory action. At high doses, beta-PEA induced stereotypies in WT and heterozygous mice; some manifestations of stereotypy were also observed in the DAT-KO mice. These data demonstrate that the DAT is required for the striatal DA-releasing and hyperlocomotor actions of beta-PEA. The inhibitory action on hyperactivity and certain stereotypies induced by beta-PEA in DAT-KO mice indicate that targets other than the DAT are responsible for these effects.

  15. Transforming growth factor-beta and nitrates in epithelial ovarian cancer.

    PubMed

    Khalifa, A; Kassim, S K; Ahmed, M I; Fayed, S T

    1999-12-01

    The role of transforming growth factor-beta (TGF-beta) and nitric oxide (NO) in ovarian neoplasia is still not clear. We studied the expression of TGF-beta by enzyme immunoassay, and nitrates (as a stable end product of NO) in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant). Ploidy status and synthetic phase fraction (SPF) were also assessed by flow cytometry. Mean ranks of TGF-beta, nitrate, and SPF were significant among different groups (X2 = 12.01, P = 0.0025, X2 = 67.42, P = 0.000, X2 = 9.06, P = 0.011 respectively). Nitrate mean ranks were significant among different FIGO stages of the disease (X2 = 17.6, P = 0.000). A significant correlation was shown between TGF-beta, and nitrate levels in all tissues (r = 0.24, P = 0.01), as well as in malignant tissues (r = 0.3, P = 0.026). Cutoff values were determined for both TGF-beta (290 pg/mg protein), and nitrates (310 nmole/mg non protein nitrogenous substances). At these cut-offs, nitrates showed a sensitivity of 93% and 84% specificity for malignant versus normal cases, while TGF-beta had 76% sensitivity, and 82.4% specificity for poor versus good outcome. Patients with epithelial ovarian cancer were followed up for a total of 40 months. Survival analysis showed that patients with TGF-beta above the cut-off had worse prognosis (X2 = 12.69, P = 0.004). The present results suggest that malignant transformation of ovarian tissues is associated with increased TGF-beta and NO production. NO level is related to the development and progression of epithelial ovarian cancer, while high levels of TGF-beta could be of prognostic significance.

  16. A recipe for designing water-soluble, beta-sheet-forming peptides.

    PubMed Central

    Mayo, K. H.; Ilyina, E.; Park, H.

    1996-01-01

    Based on observations of solubility and folding properties of peptide 33-mers derived from the beta-sheet domains of platelet factor-4 (PF4), interleukin-8 (IL-8), and growth related protein (Gro-alpha), as well as other beta-sheet-forming peptides, general guidelines have been developed to aid in the design of water soluble, self-association-induced beta-sheet-forming peptides. CD, 1H-NMR, and pulsed field gradient NMR self-diffusion measurements have been used to assess the degree of folding and state of aggregation. PF4 peptide forms native-like beta-sheet tetramers and is sparingly soluble above pH 6. IL-8 peptide is insoluble between pH 4.5 and pH 7.5, yet forms stable, native-like beta-sheet dimers at higher pH. Gro-alpha peptide is soluble at all pH values, yet displays no discernable beta-sheet structure even when diffusion data indicate dimer-tetramer aggregation. A recipe used in the de novo design of water-soluble beta-sheet-forming peptides calls for the peptide to contain 40-50% hydrophobic residues, usually aliphatic ones (I, L, V, A, M) (appropriately paired and mostly but not always alternating with polar residues in the sheet sequence), a positively charged (K, R) to negatively charged (E, D) residue ratio between 4/2 and 6/2, and a noncharged polar residue (N, Q, T, S) composition of about 20% or less. Results on four de novo designed, 33-residue peptides are presented supporting this approach. Under near physiologic conditions, all four peptides are soluble, form beta-sheet structures to varying degrees, and self-associate. One peptide folds as a stable, compact beta-sheet tetramer, whereas the others are transient beta-sheet-containing aggregates. PMID:8819163

  17. Cross-talk of WNT and FGF signaling pathways at GSK3beta to regulate beta-catenin and SNAIL signaling cascades.

    PubMed

    Katoh, Masuko; Katoh, Masaru

    2006-09-01

    WNT and FGF signaling pathways cross-talk during a variety of cellular processes, such as human colorectal carcinogenesis, mouse mammary tumor virus (MMTV)-induced carcinogenesis, E2A-Pbx-induced leukemogenesis, early embryogenesis, body-axis formation, limb-bud formation, and neurogenesis. Canonical WNT signals are transduced through Frizzled receptor and LRP5/6 coreceptor to downregulate GSK3beta (GSK3B) activity not depending on Ser 9 phosphorylation. FGF signals are transduced through FGF receptor to the FRS2-GRB2-GAB1-PI3K-AKT signaling cascade to downregulate GSK3beta activity depending on Ser 9 phosphorylation. Because GSK3beta-dependent phosphorylation of beta-catenin and SNAIL leads to FBXW1 (betaTRCP)-mediated ubiquitination and degradation, GSK3beta downregulation results in the stabilization and the nuclear accumulation of beta-catenin and SNAIL. Nuclear beta-catenin is complexed with TCF/LEF, Legless (BCL9 or BCL9L) and PYGO (PYGO1 or PYGO2) to activate transcription of CCND1, MYC, FGF18 and FGF20 genes for the cell-fate determination. Nuclear SNAIL represses transcription of CDH1 gene, encoding E-cadherin, to induce the epithelial-mesenchymal transition (EMT). Mammary carcinogenesis in MMTV-Wnt1 transgenic mice is accelerated by MMTV infection due to MMTV integration around Fgf3-Fgf4 or Fgf8 loci, and mammary carcinogenesis in MMTV-Fgf3 transgenic mice due to MMTV integration around Wnt1-Wnt10b locus. Coactivation of WNT and FGF signaling pathways in tumors leads to more malignant phenotypes. Single nucleotide polymorphism (SNP) and copy number polymorphism (CNP) of WNT and FGF signaling molecules could be utilized as screening method of cancer predisposition. cDNA-PCR, microarray or ELISA reflecting aberrant activation of WNT and FGF signaling pathways could be developed as novel cancer-related biomarkers for diagnosis, prognosis, and therapy. Cocktail therapy using WNT and FGF inhibitors, such as small-molecule compounds and human neutralizing

  18. Cortisone Dissociates the Shaker Family K Channels from their Beta Subunit

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pan, Y.; Weng, J; Kabaleeswaran, V

    2008-01-01

    The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a wide variety of cells and are essential for cellular excitability. In humans, loss-of-function mutations of Kv1 channels lead to hyperexcitability and are directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels assemble with {Beta} subunits (Kv{Beta}s), and certain Kv{Beta}s, for example Kv{Beta}1, have an N-terminal segment that closes the channel by the N-type inactivation mechanism. In principle, dissociation of Kv{Beta}1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases rat Kv1 channel activity by binding to Kv{Beta}1. A crystal structuremore » of the K{Beta}v-cortisone complex was solved to 1.82-{angstrom}resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kv{Beta}. The new mode of channel modulation may be explored by native or synthetic ligands to fine-tune cellular excitability.« less

  19. Beta-Cryptoxanthin- and alpha-carotene-rich foods have greater apparent bioavailability than beta-carotene-rich foods in Western diets

    USDA-ARS?s Scientific Manuscript database

    Background: Beta-carotene (BC), beta-cryptoxanthin (CX) and alpha-carotene (AC) are common carotenoids that form vitamin A (VA). Conversion ratios for VA formation have been set at 12:1 for BC- and 24:1 for CX- and AC-rich foods, respectively. These conversion ratios are based on chemical structure...

  20. From the rat to the beta cell: a fast and effective technique of separation of Langerhans islets and direct purification of pancreatic beta cells.

    PubMed

    Tamagno, Gianluca; Vigolo, Simonetta; Olivieri, Massimiliano; Martini, Chiara; De Carlo, Eugenio

    2014-01-01

    Isolated Langerhans islets represent a useful model for the study of the endocrine pancreas. The possibility to purify pancreatic beta cells from a mixed Langerhans islet cell population may lead towards a dedicated focus on beta cell research. We describe an effective and rapid immunomagnetic technique for the direct purification of beta cells from isolated Langerhans islets of rat. After the sacrifice of the rat, the Langerhans islets were separated by ductal injection of the pancreas with collagenase, altered to a mixed Langerhans islet cell population and incubated with conditioned immunomagnetic beads targeted to the beta cell surface. The beads were previously coated with a specific antibody against the surface of the beta cell, namely K14D10. The suspension of mixed Langerhans islet cells and immunomagnetic K14D10-conditioned beads was pelleted by a magnetic particle concentrator to isolate the bead-bound cells, which were finally suspended in a culture medium. The purified cells were immunoreactive for insulin and no glucagon-positive cells were detected at immunocytochemistry. Real Time PCR confirmed the purification of the pancreatic beta cells. This immunomagnetic technique allows a rapid, effective and consistent purification of beta cells from isolated Langerhans islets in a direct manner by conditioning the immunomagnetic beads only. This technique is easy, fast and reproducible. It promises to be a reliable method for providing purified beta cells for in vitro research.

  1. Beta-endorphin. Synthesis and biological activity of analogs with disulfide bridges.

    PubMed

    Blake, J; Helmeste, D M; Li, C H

    1985-06-01

    Two analogs of human beta-endorphin (beta-EP) which contain cystine bridges, [Cys15-Cys26,Phe27,Gly31]-beta-EP (I) and [Cys16-Cys26,Phe27,Gly31]-beta-EP (II), were synthesized by the solid-phase method. Peptides I and II were shown to contain 2-2.5 times the opiate receptor binding activity of beta-endorphin. We also synthesized two analogs with reduced alkylated cysteine residues and these peptides, [Arg9,19,24,28,29 Cys(Cam)11,26,Phe27,Gly31] and [Arg9,19,24,28,29,Cys-(Cam)12,26,Phe27,Gly31], were shown to have approximately the same opiate receptor activity as beta-endorphin.

  2. Beta burst dynamics in Parkinson's disease OFF and ON dopaminergic medication.

    PubMed

    Tinkhauser, Gerd; Pogosyan, Alek; Tan, Huiling; Herz, Damian M; Kühn, Andrea A; Brown, Peter

    2017-11-01

    Exaggerated basal ganglia beta activity (13-35 Hz) is commonly found in patients with Parkinson's disease and can be suppressed by dopaminergic medication, with the degree of suppression being correlated with the improvement in motor symptoms. Importantly, beta activity is not continuously elevated, but fluctuates to give beta bursts. The percentage number of longer beta bursts in a given interval is positively correlated with clinical impairment in Parkinson's disease patients. Here we determine whether the characteristics of beta bursts are dependent on dopaminergic state. Local field potentials were recorded from the subthalamic nucleus of eight Parkinson's disease patients during temporary lead externalization during surgery for deep brain stimulation. The recordings took place with the patient quietly seated following overnight withdrawal of levodopa and after administration of levodopa. Beta bursts were defined by applying a common amplitude threshold and burst characteristics were compared between the two drug conditions. The amplitude of beta bursts, indicative of the degree of local neural synchronization, progressively increased with burst duration. Treatment with levodopa limited this evolution leading to a relative increase of shorter, lower amplitude bursts. Synchronization, however, was not limited to local neural populations during bursts, but also, when such bursts were cotemporaneous across the hemispheres, was evidenced by bilateral phase synchronization. The probability of beta bursts and the proportion of cotemporaneous bursts were reduced by levodopa. The percentage number of longer beta bursts in a given interval was positively related to motor impairment, while the opposite was true for the percentage number of short duration beta bursts. Importantly, the decrease in burst duration was also correlated with the motor improvement. In conclusion, we demonstrate that long duration beta bursts are associated with an increase in local and

  3. Antidiabetic and Beta Cell-Protection Activities of Purple Corn Anthocyanins

    PubMed Central

    Hong, Su Hee; Heo, Jee-In; Kim, Jeong-Hyeon; Kwon, Sang-Oh; Yeo, Kyung-Mok; Bakowska-Barczak, Anna M.; Kolodziejczyk, Paul; Ryu, Ok-Hyun; Choi, Moon-Ki; Kang, Young-Hee; Lim, Soon Sung; Suh, Hong-Won; Huh, Sung-Oh; Lee, Jae-Yong

    2013-01-01

    Antidiabetic and beta cell-protection activities of purple corn anthocyanins (PCA) were examined in pancreatic beta cell culture and db/db mice. Only PCA among several plant anthocyanins and polyphenols showed insulin secretion activity in culture of HIT-T15 cells. PCA had excellent antihyperglycemic activity (in terms of blood glucose level and OGTT) and HbA1c-decreasing activity when compared with glimepiride, a sulfonylurea in db/db mice. In addition, PCA showed efficient protection activity of pancreatic beta cell from cell death in HIT-T15 cell culture and db/db mice. The result showed that PCA had antidiabetic and beta cell-protection activities in pancreatic beta cell culture and db/db mice. PMID:24244813

  4. Extraction and characterization of beta-D-glucan from oat for industrial utilization.

    PubMed

    Ahmad, Asif; Anjum, Faqir Muhammad; Zahoor, Tahir; Nawaz, Haq; Ahmed, Zaheer

    2010-04-01

    Oat beta-D-glucan is a valuable functional ingredient having numerous industrial, nutritional and health benefits. Its extraction needs careful attention as extraction process may affect the physiochemical and functional properties of extracted beta-D-glucan. The present study aimed at analyzing the effect of extraction of beta-D-glucan gum pellets from oat cultivar followed by detailed chemical and functional analysis. Enzymatic extraction process resulted in highest yield and recovery. Chemical analysis revealed protein as a dominating impurity. The water binding capacity of the beta-D-glucan ranged between 3.14 and 4.52 g g(-1) of sample. beta-D-Glucan exhibited ideal foaming stability when appropriate extraction technique was used. The viscosity of beta-D-glucan gum ranged between 35.6 and 56.16 cp. The color analysis showed L* value of beta-D-glucan gum pellet ranged between 72.18 and 83.54. Phosphorus, potassium and calcium appeared as major minerals in beta-D-glucan gum whereas iron, manganese and copper appeared as minor minerals. FTIR spectroscopy also confirms the presence of beta-D-glucan, protein and other components in extracted beta-D-glucan gum pellets. Overall, extracted beta-D-glucan showed a good potential for industrial usage. Copyright 2010 Elsevier B.V. All rights reserved.

  5. 21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5630 Beta-2-microglobulin immunological test system. (a) Identification. A beta-2-microglobulin... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-2-microglobulin immunological test system...

  6. Beta-decay spectroscopy relevant to the r-process nucleosynthesis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nishimura, Shunji; Collaboration: RIBF Decay Collaboration

    2012-11-12

    A scientific program of beta-decay spectroscopy relevant to r-process nucleosynthesis has been started using high intensity U-beam at the RIBF. The first results of {beta}-decay half-lives of very neutron-rich Kr to Tc nuclides, all of which lie close to the r-process path, suggest a systematic enhancement of the the {beta}-decay rates of the Zr and Nb isotopes around A110 with respect to the predictions of the deformed quasiparticle-random-phase-approximation model (FRDM + QRPA). An impact of the results on the astrophysical r-process is discussed together with the future perspective of the {beta}-decay spectroscopy with the EURICA.

  7. Detection of alpha radiation in a beta radiation field

    DOEpatents

    Mohagheghi, Amir H.; Reese, Robert P.

    2001-01-01

    An apparatus and method for detecting alpha particles in the presence of high activities of beta particles utilizing an alpha spectrometer. The apparatus of the present invention utilizes a magnetic field applied around the sample in an alpha spectrometer to deflect the beta particles from the sample prior to reaching the detector, thus permitting detection of low concentrations of alpha particles. In the method of the invention, the strength of magnetic field required to adequately deflect the beta particles and permit alpha particle detection is given by an algorithm that controls the field strength as a function of sample beta energy and the distance of the sample to the detector.

  8. First demonstration of cerebrospinal fluid and plasma A beta lowering with oral administration of a beta-site amyloid precursor protein-cleaving enzyme 1 inhibitor in nonhuman primates.

    PubMed

    Sankaranarayanan, Sethu; Holahan, Marie A; Colussi, Dennis; Crouthamel, Ming-Chih; Devanarayan, Viswanath; Ellis, Joan; Espeseth, Amy; Gates, Adam T; Graham, Samuel L; Gregro, Allison R; Hazuda, Daria; Hochman, Jerome H; Holloway, Katharine; Jin, Lixia; Kahana, Jason; Lai, Ming-tain; Lineberger, Janet; McGaughey, Georgia; Moore, Keith P; Nantermet, Philippe; Pietrak, Beth; Price, Eric A; Rajapakse, Hemaka; Stauffer, Shaun; Steinbeiser, Melissa A; Seabrook, Guy; Selnick, Harold G; Shi, Xiao-Ping; Stanton, Matthew G; Swestock, John; Tugusheva, Katherine; Tyler, Keala X; Vacca, Joseph P; Wong, Jacky; Wu, Guoxin; Xu, Min; Cook, Jacquelynn J; Simon, Adam J

    2009-01-01

    beta-Site amyloid precursor protein (APP)-cleaving enzyme (BACE) 1 cleavage of amyloid precursor protein is an essential step in the generation of the potentially neurotoxic and amyloidogenic A beta 42 peptides in Alzheimer's disease. Although previous mouse studies have shown brain A beta lowering after BACE1 inhibition, extension of such studies to nonhuman primates or man was precluded by poor potency, brain penetration, and pharmacokinetics of available inhibitors. In this study, a novel tertiary carbinamine BACE1 inhibitor, tertiary carbinamine (TC)-1, was assessed in a unique cisterna magna ported rhesus monkey model, where the temporal dynamics of A beta in cerebrospinal fluid (CSF) and plasma could be evaluated. TC-1, a potent inhibitor (IC(50) approximately 0.4 nM), has excellent passive membrane permeability, low susceptibility to P-glycoprotein transport, and lowered brain A beta levels in a mouse model. Intravenous infusion of TC-1 led to a significant but transient lowering of CSF and plasma A beta levels in conscious rhesus monkeys because it underwent CYP3A4-mediated metabolism. Oral codosing of TC-1 with ritonavir, a potent CYP3A4 inhibitor, twice daily over 3.5 days in rhesus monkeys led to sustained plasma TC-1 exposure and a significant and sustained reduction in CSF sAPP beta, A beta 40, A beta 42, and plasma A beta 40 levels. CSF A beta 42 lowering showed an EC(50) of approximately 20 nM with respect to the CSF [TC-1] levels, demonstrating excellent concordance with its potency in a cell-based assay. These results demonstrate the first in vivo proof of concept of CSF A beta lowering after oral administration of a BACE1 inhibitor in a nonhuman primate.

  9. New developments and prospective applications for beta (1,3) glucans.

    PubMed

    Laroche, Celine; Michaud, Philippe

    2007-01-01

    Publications and patents relative to newly observed functions of beta-(1,3)-D-glucans have notably increased in the last few years with the exploitation of their biological activities. The term beta-(1,3)-D-glucans includes a very large number of polysaccharides from bacterial, fungal and vegetable sources. Their structures have a common backbone of beta-(1,3) linked glucopyranosyl residues but the polysaccharidic chain can be beta-(1,6) branched with glucose or integrate some beta-(1,4) linked glucopyranosyl residues in the main chain. Except for the curdlan, a bacterial linear beta-(1,3)-D-glucans, and for the scleroglucan produced by Sclerotium rolfsii, the main drawback limiting the development of these polysaccharides is the lack of efficient processes for their extraction and purification and their cost. However new applications in agronomy, foods, cosmetic and therapeutic could in a next future accentuate the effort of research for their development. So this review focuses on these beta-(1,3)-D-glucans with the objective to detail the strategies employed for their extraction and the relation structure-functions identified when they induce biological activities.

  10. Genetic basis of human complement C8[beta] deficiency

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kaufmann, T.; Rittner, C.; Schneider, P.M.

    1993-06-01

    The eighth component of human complement (c8) is a serum protein consisting of three chains ([alpha], [beta], and [gamma]) and encoded by three different genes, C8A, C8B, and C8G. C8A and C8B are closely linked on chromosome 1p, whereas C8G is located on chromosome 9q. In the serum the [beta] subunit is non-covalently bound to the disulfide-linked [alpha]-[gamma] subunit. Patients with C8[beta] deficiency suffer from recurrent neisserial infections such as meningitis. Exon-specific polymerase chain reaction (PCR) amplification with primer pairs from the flanking intron sequences was used to amplify all 12 C8B exons separately. No difference regarding the exon sizesmore » was observed in a C8[beta]-deficient patient compared with a normal person. Therefore, direct sequence analysis of all exon-specific PCR products from normal and C8[beta]-deficient individuals was carried out. As a cause for C8[beta] deficiency, we found a single C-T exchange in exon 9 leading to a stop codon. An allele-specific PCR system was designed to detect the normal and the deficiency allele simultaneously. Using this approach as well as PCR typing of the Taql polymorphism located in intron 11, five families with 7 C8[beta]-deficient members were investigated. The mutation was not found to be restricted to one of the two Taql RFLP alleles. The mutant allele was observed in all families investigated and can therefore be regarded as a major cause of C8[beta] deficiency in the Caucasian population. In addition, two C8[beta]-deficient patients were found to be heterozygous for the C-T exchange. The molecular basis of the alleles without this point mutation also causing deficiency has not yet been defined. 23 refs., 4 figs., 3 tabs.« less

  11. Beta oscillations reflect supramodal information during perceptual judgment.

    PubMed

    Haegens, Saskia; Vergara, José; Rossi-Pool, Román; Lemus, Luis; Romo, Ranulfo

    2017-12-26

    Previous work on perceptual decision making in the sensorimotor system has shown population dynamics in the beta band, corresponding to the encoding of stimulus properties and the final decision outcome. Here, we asked how oscillatory dynamics in the medial premotor cortex (MPC) contribute to supramodal perceptual decision making. We recorded local field potentials (LFPs) and spikes in two monkeys trained to perform a tactile-acoustic frequency discrimination task, including both unimodal and crossmodal conditions. We studied the role of oscillatory activity as a function of stimulus properties (frequency and sensory modality), as well as decision outcome. We found that beta-band power correlated with relevant stimulus properties: there was a significant modulation by stimulus frequency during the working-memory (WM) retention interval, as well as modulation by stimulus modality-the latter was observed only in the case of a purely unimodal task, where modality information was relevant to prepare for the upcoming second stimulus. Furthermore, we found a significant modulation of beta power during the comparison and decision period, which was predictive of decision outcome. Finally, beta-band spike-field coherence (SFC) matched these LFP observations. In conclusion, we demonstrate that beta power in MPC is reflective of stimulus features in a supramodal, context-dependent manner, and additionally reflects the decision outcome. We propose that these beta modulations are a signature of the recruitment of functional neuronal ensembles, which encode task-relevant information.

  12. Characterization of a Commercial Silicon Beta Cell

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Foxe, Michael P.; Hayes, James C.; Mayer, Michael F.

    Silicon detectors are of interest for the verification of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) due to their enhanced energy resolution compared to plastic scintillators beta cells. Previous work developing a figure-of-merit (FOM) for comparison of beta cells suggests that the minimum detectable activity (MDA) could be reduced by a factor of two to three with the use of silicon detectors. Silicon beta cells have been developed by CEA (France) and Lares Ltd. (Russia), with the PIPSBox developed by CEA being commercially available from Canberra for approximately $35k, but there is still uncertainty about the reproducibility of the capabilities in themore » field. PNNL is developing a high-resolution beta-gamma detector system in the shallow underground laboratory, which will utilize and characterize the operation of the PIPSBox detector. Throughout this report, we examine the capabilities of the PIPSBox as developed by CEA. The lessons learned through the testing and use of the PIPSBox will allow PNNL to strategically develop a silicon detector optimized to better suit the communities needs in the future.« less

  13. Double Charge Exchange Reactions and Double Beta Decay

    NASA Astrophysics Data System (ADS)

    Auerbach, N.

    2018-05-01

    The subject of this presentation is at the forefront of nuclear physics, namely double beta decay. In particular one is most interested in the neutrinoless process of double beta decay, when the decay proceeds without the emission of two neutrinos. The observation of such decay would mean that the lepton conservation symmetry is violated and that the neutrinos are of Majorana type, meaning that they are their own anti-particles. The life time of this process has two unknowns, the mass of the neutrino and the nuclear matrix element. Determining the nuclear matrix element and knowing the cross-section well will set limits on the neutrino mass. There is a concentrated effort among the nuclear physics community to calculate this matrix element. Usually these matrix elements are a very small part of the total strength of the transition operators involved in the process. There is no simple way to “calibrate” the nuclear double beta decay matrix element. The double beta decay is a double charge exchange process, therefore it is proposed that double charge exchange reactions using ion projectiles on nuclei that are candidates for double beta decay, will provide additional necessary information about the nuclear matrix elements.

  14. Beta ray flux measuring device

    DOEpatents

    Impink, Jr., Albert J.; Goldstein, Norman P.

    1990-01-01

    A beta ray flux measuring device in an activated member in-core instrumentation system for pressurized water reactors. The device includes collector rings positioned about an axis in the reactor's pressure boundary. Activated members such as hydroballs are positioned within respective ones of the collector rings. A response characteristic such as the current from or charge on a collector ring indicates the beta ray flux from the corresponding hydroball and is therefore a measure of the relative nuclear power level in the region of the reactor core corresponding to the specific exposed hydroball within the collector ring.

  15. HNF1(beta) is required for mesoderm induction in the Xenopus embryo.

    PubMed

    Vignali, R; Poggi, L; Madeddu, F; Barsacchi, G

    2000-04-01

    XHNF1(&bgr;) is a homeobox-containing gene initially expressed at the blastula stage in the vegetal part of the Xenopus embryo. We investigated its early role by functional ablation, through mRNA injection of an XHNF1(beta)/engrailed repressor fusion construct (XHNF1(beta)/EngR). Dorsal injections of XHNF1(beta)/EngR mRNA abolish dorsal mesoderm formation, leading to axial deficiencies; ventral injections disrupt ventral mesoderm formation without affecting axial development. XHNF1(beta)/EngR phenotypic effects specifically depend on the DNA-binding activity of its homeodomain and are fully rescued by coinjection of XHNF1(beta) mRNA. Vegetal injection of XHNF1(beta)/EngR mRNA blocks the mesoderm-inducing ability of vegetal explants. Both B-Vg1 and VegT maternal determinants trigger XHNF1(beta) expression in animal caps. XHNF1(beta)/EngR mRNA blocks B-Vg1-mediated, but not by eFGF-mediated, mesoderm induction in animals caps. However, wild-type XHNF1(beta) mRNA does not trigger Xbra expression in animal caps. We conclude that XHNF1(beta) function is essential, though not sufficient, for mesoderm induction in the Xenopus embryo.

  16. Presynaptic control of dopamine release by BETA-phenylethylamine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zharikova, A.D.; Godukhin, O.V.

    The authors study the effect of extracellular ions (Ca/sup 2 +/, Na/sup 2 +/) on the beta-phenylethylamine (beta-PEA) releasing effect, dependence of this effect on the membrane potential of dopaminergic endings, and the participation of dopamine presynaptic autoreceptors in the realization of the effects of beta-PEA on dopamine (DA) release. Experi ments were carried out on noninbred male albino rats. By means of a microsyringe, (/sup 3/H)-DA hydrochloride was injected. The significance of the difference in levels of (/sup 3/H)-DA release during analogous periods of perfusion in the groups of animals compared was estimated by Student's test. These experiments inmore » vivo thus demonstrated the ability of beta-PEA to regulate DA release in different directions depending on the functional state of the dopaminergic neuron.« less

  17. Preparation of powders suitable for conversion to useful .beta.-aluminas

    DOEpatents

    Morgan, Peter E. D.

    1982-01-01

    A process for forming a precursor powder which, when suitably pressed and sintered forms highly pure, densified .beta.- or .beta."-alumina, comprising the steps of: (1) forming a suspension (or slurry) of Bayer-derived Al(OH).sub.3 in a water-miscible solvent; (2) adding an aqueous solution of a Mg compound, a Li compound, a Na compound or mixtures thereof to the Bayer-derived Al(OH).sub.3 suspension while agitating the mixture formed thereby, to produce a gel; (3) drying the gel at a temperature above the normal boiling point of water to produce a powder material; (4) lightly ball milling and sieving said powder material; and (5) heating the ball-milled and sieved powder material at a temperature of between 350.degree. to 900.degree. C. to form the .beta.- or .beta."-alumina precursor powder. The precursor powder, thus formed, may be subsequently isopressed at a high pressure and sintered at an elevated temperature to produce .beta.- or .beta."-alumina. BACKGROUND OF THE INVENTION

  18. Beating the Heat - Fast Scanning Melts Silk Beta Sheet Crystals

    NASA Astrophysics Data System (ADS)

    Cebe, Peggy; Hu, Xiao; Kaplan, David L.; Zhuravlev, Evgeny; Wurm, Andreas; Arbeiter, Daniela; Schick, Christoph

    2013-01-01

    Beta-pleated-sheet crystals are among the most stable of protein secondary structures, and are responsible for the remarkable physical properties of many fibrous proteins, such as silk, or proteins forming plaques as in Alzheimer's disease. Previous thinking, and the accepted paradigm, was that beta-pleated-sheet crystals in the dry solid state were so stable they would not melt upon input of heat energy alone. Here we overturn that assumption and demonstrate that beta-pleated-sheet crystals melt directly from the solid state to become random coils, helices, and turns. We use fast scanning chip calorimetry at 2,000 K/s and report the first reversible thermal melting of protein beta-pleated-sheet crystals, exemplified by silk fibroin. The similarity between thermal melting behavior of lamellar crystals of synthetic polymers and beta-pleated-sheet crystals is confirmed. Significance for controlling beta-pleated-sheet content during thermal processing of biomaterials, as well as towards disease therapies, is envisioned based on these new findings.

  19. Serendipitous discovery of light-induced (In Situ) formation of an Azo-bridged dimeric sulfonated naphthol as a potent PTP1B inhibitor.

    PubMed

    Bongard, Robert D; Lepley, Michael; Thakur, Khushabu; Talipov, Marat R; Nayak, Jaladhi; Lipinski, Rachel A Jones; Bohl, Chris; Sweeney, Noreena; Ramchandran, Ramani; Rathore, Rajendra; Sem, Daniel S

    2017-05-31

    Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results. Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC 50 of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC 50 of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5. We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common

  20. Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein.

    PubMed

    Stroschein, S L; Wang, W; Zhou, S; Zhou, Q; Luo, K

    1999-10-22

    Smad proteins mediate transforming growth factor-beta (TGF-beta) signaling to regulate cell growth and differentiation. The SnoN oncoprotein was found to interact with Smad2 and Smad4 and to repress their abilities to activate transcription through recruitment of the transcriptional corepressor N-CoR. Immediately after TGF-beta stimulation, SnoN is rapidly degraded by the nuclear accumulation of Smad3, allowing the activation of TGF-beta target genes. By 2 hours, TGF-beta induces a marked increase in SnoN expression, resulting in termination of Smad-mediated transactivation. Thus, SnoN maintains the repressed state of TGF-beta-responsive genes in the absence of ligand and participates in negative feedback regulation of TGF-beta signaling.

  1. Polymerization of beta-amino acids in aqueous solution

    NASA Technical Reports Server (NTRS)

    Liu, R.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

    1998-01-01

    We have compared carbonyl diimidazole (CDI) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as activating agents for the oligomerization of negatively-charged alpha- and beta-amino acids in homogeneous aqueous solution. alpha-Amino acids can be oligomerized efficiently using CDI, but not by EDAC. beta-Amino acids can be oligomerized efficiently using EDAC, but not by CDI. Aspartic acid, an alpha- and beta-dicarboxylic acid is oligomerized efficiently by both reagents. These results are explained in terms of the mechanisms of the reactions, and their relevance to prebiotic chemistry is discussed.

  2. 15 beta-hydroxysteroids (Part IV). Steroids of the human perinatal period: the synthesis of 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one and its A/B-ring configurational isomers.

    PubMed

    Reeder, A Y; Joannou, G E

    1995-12-01

    In recent years several 15 beta-hydroxysteroids have emerged pathognomonic of adrenal disorders in human neonates of which 3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) was the first to be identified in the urine of newborn infants affected with congenital adrenal hyperplasia. In this investigation we report the synthesis of the three remaining 3 xi,5 xi-isomers, namely 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (3), 3 beta,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (7) and 3 beta,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (8) for their definitive identification in pathological conditions in human neonates. 3 beta,15 beta-Diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (11), a product of chemical synthesis was converted to the isomeric 3 and 7, while conversion of 15 beta,17 alpha-dihydroxy-4-pregnen-3,20-dione (4), a product of microbiological transformation, resulted in the preparation of 8. In brief, selective acetate hydrolysis of 11 gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5-pregnen-20-one (12) which on catalytic hydrogenation gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5 alpha-pregnan-20-one (13) a common intermediate for the synthesis of the 3 beta(and alpha),5 alpha-isomers. Hydrolysis of the 15 beta-acetate gave 7, whereas oxidation with pyridinium chlorochromate gave 15 beta-acetoxy-17 alpha-hydroxy-5 alpha-pregnan-3,20-dione (14) which on reduction with L-Selectride and hydrolysis of the 15 beta-acetate gave 3. Finally, hydrogenation of 4 gave 15 beta, 17 alpha-dihydroxy-5 beta-pregnan-3,20-dione (10) which on reduction with L-Selectride gave 8.

  3. Trichoderma .beta.-glucosidase

    DOEpatents

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian

    2006-01-03

    The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl3, and the corresponding BGL3 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL3, recombinant BGL3 proteins and methods for producing the same.

  4. Pharmacotoxicological screening on new derivatives of beta-phenylethylamine, potential agonists of beta3-adrenergic receptors.

    PubMed

    Negreş, Simona; Zanfirescu, Anca; Ionică, Floriana Elvira; Moroşan, Elena; Velescu, Bruno Ştefan; Şeremet, Oana Cristina; Zbârcea, Cristina Elena; Ştefănescu, Emil; Militaru, Manuella; Arsene, Andreea LetiŢia; Margină, Denisa Marilena; Uncu, Livia; Scutari, Corina; ChiriŢă, Cornel

    2016-01-01

    Beta3-adrenergic receptors (beta3-ARs) have been initially characterized in 1989. Afterwards, their tissue distribution was established: white and brown adipose tissue, central nervous system, myocardium (atrial and ventricular), blood vessels, smooth gastrointestinal muscles (stomach, small intestine, colon), gallbladder, urinary bladder, prostate, skeletal muscles. Non-clinical trials have demonstrated the major implication of beta3-ARs in glucose metabolism, implicitly, in insulin release, and also in obesity. Therefore, new compounds were synthesized starting from beta-phenylethylamine nucleus and substituted in various positions, for possible antidiabetic and÷or antiobesity action. In the present research, the antidiabetic action of newly synthesized compounds was investigated on an experimental model of alloxan-induced diabetes, administered in dose of 130 mg÷kg body weight (bw), intraperitoneally (i.p.). After 14 days of treatment, glycemia and enzymes involved in homeostasis of glucose metabolism, glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase (G6Pase) and hexokinase were determined. Animals were then euthanized and histopathology examinations were performed on harvested liver, kidney, spleen and brain in order to document pathological changes induced by alloxan-induced diabetes and÷or by tested compounds. Glycemia in animals treated with the tested compounds decreased statistically significant for groups C2 and C3 (-42.13% and -37.2%, respectively), compared to diabetic control group. C2 was also the compound to favorably modify the dynamics of determined enzymes, together with the display of very good safety profile supported by minor, non-significant, histopathological changes.

  5. Phosphorylation of PPP(S/T)P motif of the free LRP6 intracellular domain is not required to activate the Wnt/beta-catenin pathway and attenuate GSK3beta activity.

    PubMed

    Beagle, Brandon; Mi, Kaihong; Johnson, Gail V W

    2009-11-01

    The canonical Wnt/beta-catenin signaling pathway plays a critical role in numerous physiological and pathological processes. LRP6 is an essential co-receptor for Wnt/beta-catenin signaling; as transduction of the Wnt signal is strongly dependent upon GSK3beta-mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane-anchored LRP6 intracellular domain. Previously, we showed that the free LRP6 intracellular domain (LRP6-ICD) can activate the Wnt/beta-catenin pathway in a beta-catenin and TCF/LEF-1 dependent manner, as well as interact with and attenuate GSK3beta activity. However, it is unknown if the ability of LRP6-ICD to attenuate GSK3beta activity and modulate activation of the Wnt/beta-catenin pathway requires phosphorylation of the LRP6-ICD PPP(S/T)P motifs, in a manner similar to the membrane-anchored LRP6 intracellular domain. Here we provide evidence that the LRP6-ICD does not have to be phosphorylated at its PPP(S/T)P motif by GSK3beta to stabilize endogenous cytosolic beta-catenin resulting in activation of TCF/LEF-1 and the Wnt/beta-catenin pathway. LRP6-ICD and a mutant in which all 5 PPP(S/T)P motifs were changed to PPP(A)P motifs equivalently interacted with and attenuated GSK3beta activity in vitro, and both constructs inhibited the in situ GSK3beta-mediated phosphorylation of beta-catenin and tau to the same extent. These data indicate that the LRP6-ICD attenuates GSK3beta activity similar to other GSK3beta binding proteins, and is not a result of it being a GSK3beta substrate. Our findings suggest the functional and regulatory mechanisms governing the free LRP6-ICD may be distinct from membrane-anchored LRP6, and that release of the LRP6-ICD may provide a complimentary signaling cascade capable of modulating Wnt-dependent gene expression. (c) 2009 Wiley-Liss, Inc.

  6. Beta-catenin regulates vitamin C biosynthesis and cell survival in murine liver.

    PubMed

    Nejak-Bowen, Kari N; Zeng, Gang; Tan, Xinping; Cieply, Benjamin; Monga, Satdarshan P

    2009-10-09

    Because the Wnt/beta-catenin pathway plays multiple roles in liver pathobiology, it is critical to identify gene targets that mediate such diverse effects. Here we report a novel role of beta-catenin in controlling ascorbic acid biosynthesis in murine liver through regulation of expression of regucalcin or senescence marker protein 30 and L-gulonolactone oxidase. Reverse transcription-PCR, Western blotting, and immunohistochemistry demonstrate decreased regucalcin expression in beta-catenin-null livers and greater expression in beta-catenin overexpressing transgenic livers, HepG2 hepatoma cells (contain constitutively active beta-catenin), regenerating livers, and in hepatocellular cancer tissues that exhibit beta-catenin activation. Interestingly, coprecipitation and immunofluorescence studies also demonstrate an association of beta-catenin and regucalcin. Luciferase reporter and chromatin immunoprecipitation assays verified a functional TCF-4-binding site located between -163 and -157 (CTTTGCA) on the regucalcin promoter to be critical for regulation by beta-catenin. Significantly lower serum ascorbate levels were observed in beta-catenin knock-out mice secondary to decreased expression of regucalcin and also of L-gulonolactone oxidase, the penultimate and last (also rate-limiting) steps in the synthesis of ascorbic acid, respectively. These mice also show enhanced basal hepatocyte apoptosis. To test if ascorbate deficiency secondary to beta-catenin loss and regucalcin decrease was contributing to apoptosis, beta-catenin-null hepatocytes or regucalcin small interfering RNA-transfected HepG2 cells were cultured, which exhibited significant apoptosis that was alleviated by the addition of ascorbic acid. Thus, through regucalcin and L-gulonolactone oxidase expression, beta-catenin regulates vitamin C biosynthesis in murine liver, which in turn may be one of the mechanisms contributing to the role of beta-catenin in cell survival.

  7. Topological side-chain classification of beta-turns: ideal motifs for peptidomimetic development.

    PubMed

    Tran, Tran Trung; McKie, Jim; Meutermans, Wim D F; Bourne, Gregory T; Andrews, Peter R; Smythe, Mark L

    2005-08-01

    Beta-turns are important topological motifs for biological recognition of proteins and peptides. Organic molecules that sample the side chain positions of beta-turns have shown broad binding capacity to multiple different receptors, for example benzodiazepines. Beta-turns have traditionally been classified into various types based on the backbone dihedral angles (phi2, psi2, phi3 and psi3). Indeed, 57-68% of beta-turns are currently classified into 8 different backbone families (Type I, Type II, Type I', Type II', Type VIII, Type VIa1, Type VIa2 and Type VIb and Type IV which represents unclassified beta-turns). Although this classification of beta-turns has been useful, the resulting beta-turn types are not ideal for the design of beta-turn mimetics as they do not reflect topological features of the recognition elements, the side chains. To overcome this, we have extracted beta-turns from a data set of non-homologous and high-resolution protein crystal structures. The side chain positions, as defined by C(alpha)-C(beta) vectors, of these turns have been clustered using the kth nearest neighbor clustering and filtered nearest centroid sorting algorithms. Nine clusters were obtained that cluster 90% of the data, and the average intra-cluster RMSD of the four C(alpha)-C(beta) vectors is 0.36. The nine clusters therefore represent the topology of the side chain scaffold architecture of the vast majority of beta-turns. The mean structures of the nine clusters are useful for the development of beta-turn mimetics and as biological descriptors for focusing combinatorial chemistry towards biologically relevant topological space.

  8. 21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5160 Beta-globulin immunolog-ical test system. (a) Identification. A beta-globulin immunological test system is a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-globulin immunolog-ical test system. 866.5160...

  9. Effect of beta-carotene-rich tomato lycopene beta-cyclase ( tlcy-b) on cell growth inhibition in HT-29 colon adenocarcinoma cells.

    PubMed

    Palozza, Paola; Bellovino, Diana; Simone, Rossella; Boninsegna, Alma; Cellini, Francesco; Monastra, Giovanni; Gaetani, Sancia

    2009-07-01

    Lycopene beta-cyclase (tlcy-b) tomatoes, obtained by modulating carotenogenesis via genetic engineering, contain a large amount of beta-carotene, as clearly visible by their intense orange colour. In the present study we have subjected tlcy-b tomatoes to an in vitro simulated digestion and analysed the effects of digestate on cell proliferation. To this aim we used HT-29 human colon adenocarcinoma cells, grown in monolayers, as a model. Digested tomatoes were diluted (20 ml, 50 ml and 100 ml/l) in culture medium and added to the cells for different incubation times (24 h, 48 h and 72 h). Inhibition of cell growth by tomato digestate was dose-dependent and resulted from an arrest of cell cycle progression at the G0/G1 and G2/M phase and by apoptosis induction. A down-regulation of cyclin D1, Bcl-2 and Bcl-xl expression was observed. We also found that heat treatment of samples before digestion enhanced beta-carotene release and therefore cell growth inhibition. To induce with purified beta-carotene solubilised in tetrahydrofuran the same cell growth inhibition obtained with the tomato digestate, a higher amount of the carotenoid was necessary, suggesting that beta-carotene micellarised during digestion is utilised more efficiently by the cells, but also that other tomato molecules, reasonably made available during digestion, may be present and cooperate with beta-carotene in promoting cell growth arrest.

  10. Dysfunctional C8 beta chain in patients with C8 deficiency.

    PubMed

    Tschopp, J; Penea, F; Schifferli, J; Späth, P

    1986-12-01

    Two sera from unrelated individuals, each lacking C8 activity, were examined by Western blot analysis. Using antisera raised against whole C8, the two sera are shown to lack the C8 beta chain, indicating a C8 beta deficiency, which is frequently observed in cases of dysfunctional C8. In contrast, by means of a specific anti-C8-beta antiserum, a C8 beta-like polypeptide chain of apparently identical molecular weight compared to normal C8 beta was detected. Digestion of normal and dysfunctional C8 beta with Staphylococcus aureus V8 protease revealed distinct differences in the enzymatic digestion pattern. We conclude that the dysfunction in the C8 protein in these two patients resides in the dysfunctional C8 beta chain, and that this form of C8 deficiency is distinct from C8 deficiencies previously reported, in which one or both C8 subunits are lacking.

  11. Effect of citric pectin on beta-carotene bioavailability in rats.

    PubMed

    Zanutto, Márcia E; Jordão Júnior, Alceu A; Meirelles, Mônica S S; Fávaro, Rosa M D; Vannucchi, Hélio

    2002-07-01

    The effect of citric pectin on the bioavailability of synthetic beta-carotene was studied. Thirty Wistar rats were used, ten animals were sacrificed at the beginning of the experiment and remaining animals were divided into two groups and received the following diets for 30 days: control group (CG)--24 micrograms beta-carotene/g diet + 0% citric pectin; experimental group (EG)--24 micrograms beta-carotene/g diet + 7% citric pectin. Plasma and liver beta-carotene, vitamin A, and retinyl palmitate concentrations were determined by high-performance liquid chromatography (HPLC). Plasma retinol concentration was 1.42 +/- 0.36 mumol/L for CG and 1.10 +/- 0.24 mumol/L for EG (p = 0.1), and plasma beta-carotene concentration was 0.20 +/- 2.51 mumol/L for CG and 0.07 +/- 0.04 mumol/L for EG (p = 0.01). Only traces of retinyl palmitate were detected in CG and none in EG. Retinol did not differ significantly between groups CG and EG, while a significantly higher beta-carotene concentration was observed for CG. Liver concentrations of retinol (CG: 4.90 +/- 2.51 micrograms/g; EG: 2.68 +/- 1.12 micrograms/g), beta-carotene (CG: 0.98 +/- 0.28 microgram/g; EG: 0.11 +/- 0.06 microgram/g), and retinyl palmitate (CG: 95.47 +/- 45.13 micrograms/g, EG: 37.01 +/- 17.20 micrograms/g) differed significantly between groups (p < 0.05), with a lower concentration being observed for EG. We conclude that 7% citric pectin in the rat diet decreases the bioavailability of synthetic beta-carotene, reducing the liver reserves of vitamin A and beta-carotene.

  12. Multiperiodicity in the Light Variations of the Beta Cephei Star Beta Crucis

    NASA Technical Reports Server (NTRS)

    Cuypers, J.; Aerts, C.; Buzasi, D.; Catanzarite, J.; Conrow, T.; Laher, R.

    2002-01-01

    High-resolution spectroscopic observations have led recently to the discovery that the beta Cephei star beta Crucis (Mimosa) is multiperiodic with at least three non-radial pulsation modes. Data obtained by the star tracker of the WIRE satellite have now allowed us to confirm this multiperiodicity in the light variations. A total of 5 million observations covering 17 days was analyzed and the three main periods we find in this work are in perfect agreement with the results derived from the line profile variations. The photometric amplitudes are small (3, 2.7 and 0.6 millimag for the dominant modes), but this is not surprising in view of the mode identifications derived earlier from the line profiles. Additional periods of low-amplitude modes (between 0.2-0.3 mmag) are also derived, including one suggested earlier by the radial velocity data.

  13. Solute effects on deformation and fracture of beta brass

    NASA Technical Reports Server (NTRS)

    Shea, M. M.; Stoloff, N. S.

    1973-01-01

    It is shown that the ductility of several ternary beta brass alloys in air and in several liquid metals can be related to the operative slip and grain boundary relaxation processes. Nickel and manganese were chosen as alloying elements because they are expected to respectively enhance and suppress cross slip in beta brass. Single-phase binary and ternary beta brass alloys were used in both polycrystalline and single crystal form.

  14. Isolation of beta-mannanase from Cocos nucifera Linn haustorium and its application in the depolymerization of beta-(1,4)-linked D-mannans.

    PubMed

    Soumya, Rema S; Abraham, Emilia T

    2010-05-01

    Beta-mannanase was extracted from coconut (Cocos nucifera Linn) haustorium and purified through ammonium sulfate precipitation and sepharose 6B-lectin affinity chromatography. Coconut beta-mannanase is an acidic protein with a pI of 3.75. The molecular mass of coconut beta-mannanase (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) was found to be 44 kDa and was confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The optimum temperature and pH for enzyme activity was 70 degrees C and 5.2. The enzyme was used for the preparation of neutraceutical dietary supplement from galactomannans of guar gum and tender coconut kernel having a beta-(1,4)-linked D-mannose backbone. Depolymerized guar gum has 92% of oligosaccharides with a degree of polymerization of 3 and 7. Tender coconut kernel has a degree of polymerization of 9-39 oligosaccharides along with disaccharides and trisaccharides. Hence this mannanase will be useful to depolymerize beta-(1,4)-linked D-mannose polysaccharides from most plant sources to produce prebiotics in a cost-effective technique.

  15. Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics.

    PubMed

    Majiduddin, Fahd K; Palzkill, Timothy

    2003-03-01

    Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring beta-lactamases and extended-spectrum beta-lactamases. Four enzymes from the class A group of beta-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these beta-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of beta-lactam antibiotics.

  16. Different susceptibility of rat pancreatic alpha and beta cells to hypoxia.

    PubMed

    Bloch, Konstantin; Vennäng, Julia; Lazard, Daniel; Vardi, Pnina

    2012-06-01

    Insulin-producing beta cells are known to be highly susceptible to hypoxia, which is a major factor in their destruction after pancreatic islet transplantation. However, whether the glucagon-producing pancreatic islet alpha cells are sensitive to hypoxia is not known. Our objective was to compare the sensitivity of alpha and beta cells to hypoxia. Isolated rat pancreatic islets were exposed to hypoxia (1% oxygen, 94% N(2), 5% CO(2)) for 3 days. The viability of the alpha and beta cells, as well as the stimulus-specific secretion of glucagon and insulin, was evaluated. A quantitative analysis of the proportion of beta to alpha cells indicated that, under normoxic conditions, islet cells were composed mainly of beta cells (87 ± 3%) with only 13 ± 3% alpha cells. Instead, hypoxia treatment significantly increased the proportion of alpha cells (40 ± 13%) and decreased the proportion of beta cells to 60 ± 13%. Using the fluorescent TUNEL assay we found that only a few percent of beta cells and alpha cells were apoptotic in normoxia. In contrast, hypoxia induced an abundance of apoptotic beta cells (61 ± 22%) and had no effect on the level of apoptosis in alpha cells. In conclusion, this study demonstrates that hypoxia results in severe functional abnormality in both beta and alpha cells while alpha cells display significantly decreased rate of apoptosis compared to intensive apoptotic injury of beta cells. These findings have implications for the understanding of the possible role of hypoxia in the pathophysiology of diabetes.

  17. A kinetic comparison of the processing and secretion of the alpha beta dimer and the uncombined alpha and beta subunits of chorionic gonadotropin synthesized by human choriocarcinoma cells.

    PubMed

    Peters, B P; Krzesicki, R F; Hartle, R J; Perini, F; Ruddon, R W

    1984-12-25

    Human choriocarcinoma cells (JAR) synthesize the alpha and beta subunits of the glycoprotein hormone chorionic gonadotropin (hCG) (R.W. Ruddon, C.A. Hanson, A. H. Bryan, G.J. Putterman, E.L. White, F. Perini, K. S. Meade, and P.H. Aldenderfer (1980) J. Biol. Chem. 255, 1000-1007). In addition to the hCG dimer (alpha beta), JAR cells secrete uncombined alpha and beta subunits into the culture medium (L.A. Cole, R.J. Hartle, J.A. Laferla, and R.W. Ruddon (1983) Endocrinology 113, 1176-1178). Pulse-chase studies with [35S]methionine or [3H]mannose were carried out in order to compare free alpha, free beta, and the alpha beta dimer with regard to the kinetics of synthesis, N-linked oligosaccharide processing, and secretion and to determine the kinetics of alpha-beta subunit combination. A panel of three antisera was used to immunoprecipitate directly the free subunits and the alpha beta dimer sequentially from the same cell lysates and culture media. The alpha subunit of hCG was synthesized in a slight molar excess (1.2-1.5-fold) over the beta subunit, and alpha beta dimer was rapidly formed by combination of the intracellular alpha and beta precursors. Dimer formation was already apparent in JAR cells following a 10-min biosynthetic labeling incubation with [35S]methionine. The combination of subunits ceased by 30 min of chase even though 51% of alpha and 44% of beta remained free within the cells. Combination of the alpha and beta precursors had occurred before their N-linked oligosaccharides were processed beyond the Man8GlcNAc2 structure. The initial trimming of glucosyl and mannosyl units from the high-mannose oligosaccharides of the hCG precursors occurred more rapidly for free alpha and CG-alpha than for free beta and CG-beta. JAR cells accumulated alpha precursors bearing mostly Man8GlcNAc2 units and beta precursors bearing Man8GlcNAc2 units that represent the substrates of the rate-limiting step in the secretory pathway. In spite of the fact that their N

  18. beta-Endorphin: synthesis of analogs modified at the carboxyl terminus with increased activites.

    PubMed Central

    Li, C H; Yamashiro, D; Tseng, L F; Chang, W C; Ferrara, P

    1979-01-01

    Three analogs of human beta-endorphin (beta h-EP) have been synthesized: [Gly31]beta h-EP, [Gly31]beta h-endorphinamide, and [Gly31]beta h-endorphinylglycine. All are more active than beta h-EP in both the guinea pig ileum bioassay and the opiate receptor binding assay. The last two analogs are about twice as active as beta h-EP in an assay for analgesia. Modification at position 31 and extension at the COOH terminus may afford a route toward analogs with even greater biological activity. PMID:226965

  19. beta-Endorphin: synthesis of analogs modified at the carboxyl terminus with increased activites.

    PubMed

    Li, C H; Yamashiro, D; Tseng, L F; Chang, W C; Ferrara, P

    1979-07-01

    Three analogs of human beta-endorphin (beta h-EP) have been synthesized: [Gly31]beta h-EP, [Gly31]beta h-endorphinamide, and [Gly31]beta h-endorphinylglycine. All are more active than beta h-EP in both the guinea pig ileum bioassay and the opiate receptor binding assay. The last two analogs are about twice as active as beta h-EP in an assay for analgesia. Modification at position 31 and extension at the COOH terminus may afford a route toward analogs with even greater biological activity.

  20. Pin1 promotes transforming growth factor-beta-induced migration and invasion.

    PubMed

    Matsuura, Isao; Chiang, Keng-Nan; Lai, Chen-Yu; He, Dongming; Wang, Guannan; Ramkumar, Romila; Uchida, Takafumi; Ryo, Akihide; Lu, Kunping; Liu, Fang

    2010-01-15

    Transforming growth factor-beta (TGF-beta) regulates a wide variety of biological activities. It induces potent growth-inhibitory responses in normal cells but promotes migration and invasion of cancer cells. Smads mediate the TGF-beta responses. TGF-beta binding to the cell surface receptors leads to the phosphorylation of Smad2/3 in their C terminus as well as in the proline-rich linker region. The serine/threonine phosphorylation sites in the linker region are followed by the proline residue. Pin1, a peptidyl-prolyl cis/trans isomerase, recognizes phosphorylated serine/threonine-proline motifs. Here we show that Smad2/3 interacts with Pin1 in a TGF-beta-dependent manner. We further show that the phosphorylated threonine 179-proline motif in the Smad3 linker region is the major binding site for Pin1. Although epidermal growth factor also induces phosphorylation of threonine 179 and other residues in the Smad3 linker region the same as TGF-beta, Pin1 is unable to bind to the epidermal growth factor-stimulated Smad3. Further analysis suggests that phosphorylation of Smad3 in the C terminus is necessary for the interaction with Pin1. Depletion of Pin1 by small hairpin RNA does not significantly affect TGF-beta-induced growth-inhibitory responses and a number of TGF-beta/Smad target genes analyzed. In contrast, knockdown of Pin1 in human PC3 prostate cancer cells strongly inhibited TGF-beta-mediated migration and invasion. Accordingly, TGF-beta induction of N-cadherin, which plays an important role in migration and invasion, is markedly reduced when Pin1 is depleted in PC3 cells. Because Pin1 is overexpressed in many cancers, our findings highlight the importance of Pin1 in TGF-beta-induced migration and invasion of cancer cells.

  1. beta-Adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses.

    PubMed Central

    Cowen, P. J.; Grahame-Smith, D. G.; Green, A. R.; Heal, D. J.

    1982-01-01

    The beta-adrenoceptor agonists, salbutamol, terbutaline and clenbuterol, were investigated for their effect on 5-hydroxytryptamine-mediated (5-HT) hyperactivity. 2 The lipophilic beta-adrenoceptor agonist, clenbuterol (5 mg/kg) enhanced the behaviours induced by quipazine (25 mg/kg), including headweaving, forepaw treading and hind-limb abduction and thus increased automated activity recording. Clenbuterol (5 mg/kg) also enhanced the hyperactivity syndrome produced by the 5-HT agonist, 5-methoxy N,N-dimethyltryptamine (2 mg/kg) and the combination of tranylcypromine (10 mg/kg) and L-tryptophan (50 mg/kg). Salbutamol and terbutaline potentiated quipazine-induced hyperactivity only when given at the higher dose of 20 mg/kg. 3 The effect of clenbuterol in enhancing quipazine hyperactivity was blocked by the centrally acting beta 1-adrenoceptor antagonist, metoprolol (5 mg/kg), but not by the beta 2-adrenoceptor antagonist, butoxamine (5 mg/kg) or the peripherally acting beta 1-adrenoceptor antagonist, atenolol (5 mg/kg). 4 Clenbuterol (5 mg/kg) did not enhance the circling responses produced by methamphetamine (0.5 mg/kg) in unilateral nigrostriatal-lesioned rats. 5 The results suggest that beta-adrenoceptor agonists in common with some established antidepressant treatments produce enhancement of 5-HT-mediated behavioural responses. PMID:6124294

  2. Immunohistochemical detection of active transforming growth factor-beta in situ using engineered tissue

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Ehrhart, E. J.; Kalia, M.; Jirtle, R.; Flanders, K.; Tsang, M. L.; Chatterjee, A. (Principal Investigator)

    1995-01-01

    The biological activity of transforming growth factor-beta 1 (TGF-beta) is governed by dissociation from its latent complex. Immunohistochemical discrimination of active and latent TGF-beta could provide insight into TGF-beta activation in physiological and pathological processes. However, evaluation of immunoreactivity specificity in situ has been hindered by the lack of tissue in which TGF-beta status is known. To provide in situ analysis of antibodies to differentiate between these functional forms, we used xenografts of human tumor cells modified by transfection to overexpress latent TGF-beta or constitutively active TGF-beta. This comparison revealed that, whereas most antibodies did not differentiate between TGF-beta activation status, the immunoreactivity of some antibodies was activation dependent. Two widely used peptide antibodies to the amino-terminus of TGF-beta, LC(1-30) and CC(1-30) showed marked preferential immunoreactivity with active TGF-beta versus latent TGF-beta in cryosections. However, in formalin-fixed, paraffin-embedded tissue, discrimination of active TGF-beta by CC(1-30) was lost and immunoreactivity was distinctly extracellular, as previously reported for this antibody. Similar processing-dependent extracellular localization was found with a neutralizing antibody raised to recombinant TGF-beta. Antigen retrieval recovered cell-associated immunoreactivity of both antibodies. Two antibodies to peptides 78-109 showed mild to moderate preferential immunoreactivity with active TGF-beta only in paraffin sections. LC(1-30) was the only antibody tested that discriminated active from latent TGF-beta in both frozen and paraffin-embedded tissue. Thus, in situ discrimination of active versus latent TGF-beta depends on both the antibody and tissue preparation. We propose that tissues engineered to express a specific form of a given protein provide a physiological setting in which to evaluate antibody reactivity with specific functional forms of a

  3. Corrections for Exchange and Screening Effects in Low-energy Beta Decays

    NASA Astrophysics Data System (ADS)

    Mougeot, X.; Bé, M.-M.; Bisch, C.; Loidl, M.

    2014-06-01

    The beta spectra of 241Pu and 63Ni have been recently measured using metallic magnetic calorimeters. This powerful experimental technique allows theoretical beta spectra calculations to be tested at low energy with an accuracy never before achievable. Their comparison with classical beta calculations exhibits a significant deviation below 4 keV for 241Pu and 8 keV for 63Ni. The atomic exchange effect explains the main part of this deviation in the 63Ni beta spectrum. This effect has a significant contribution, equivalent to the magnitude of the screening, in the 241Pu beta spectrum.

  4. Plasmid-mediated AmpC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam.

    PubMed Central

    Horii, T; Arakawa, Y; Ohta, M; Ichiyama, S; Wacharotayankun, R; Kato, N

    1993-01-01

    Klebsiella pneumoniae NU2936 was isolated from a patient and was found to produce a plasmid-encoded beta-lactamase (MOX-1) which conferred resistance to broad spectrum beta-lactams, including moxalactam, flomoxef, ceftizoxime, cefotaxime, and ceftazidime. Resistance could be transferred from K. pneumoniae NU2936 to Escherichia coli CSH2 by conjugation with a transfer frequency of 5 x 10(-7). The structural gene of MOX-1 (blaMOX-1) was cloned and expressed in E. coli HB101. The MIC of moxalactam for E. coli HB101 producing MOX-1 was > 512 micrograms/ml. The apparent molecular mass and pI of this enzyme were calculated to be 38 kDa and 8.9, respectively. Hg2+ and Cu2+ failed to block enzyme activity, and the presence of EDTA in the reaction buffer did not reduce the enzyme activity. However, clavulanate and cloxacillin, serine beta-lactamase inhibitors, inhibited the enzyme activity competitively (Kis = 5.60 and 0.35 microM, respectively). The kinetic study of MOX-1 suggested that it effectively hydrolyzed broad-spectrum beta-lactams. A hybridization study confirmed that blaMOX-1 is encoded on a large resident plasmid (pRMOX1; 180 kb) of strain NU2936. By deletion analysis, the functional region was localized within a 1.2-kb region of the plasmid. By amino acid sequencing, 18 of 33 amino acid residues at the N terminus of MOX-1 were found to be identical to those of Pseudomonas aeruginosa AmpC. These findings suggest that MOX-1 is a plasmid-mediated AmpC-type beta-lactamase that provides enteric bacteria resistance to broad-spectrum beta-lactams, including moxalactam. Images PMID:8517725

  5. 21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... beta-2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement of beta-2... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Beta-2-microglobulin immunological test system. 866.5630 Section 866.5630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  6. 21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... beta-2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement of beta-2... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Beta-2-microglobulin immunological test system. 866.5630 Section 866.5630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  7. 21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... beta-2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement of beta-2... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Beta-2-microglobulin immunological test system. 866.5630 Section 866.5630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  8. 21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... beta-2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement of beta-2... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Beta-2-microglobulin immunological test system. 866.5630 Section 866.5630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  9. Local Interstellar Medium Properties and Deuterium Abundances for the Lines of Sight Toward HR 1099, 31 Comae, beta Ceti, and beta Cassiopeiae

    NASA Technical Reports Server (NTRS)

    Piskunov, Nikolai; Wood, Brian E.; Linsky, Jeffrey L.; Dempsey, Robert C.; Ayres, Thomas R.

    1997-01-01

    We analyze Goddard High-Resolution Spectrograph data to infer the properties of local interstellar gas and the Deuterium/Hydrogen (D/H) ratio for lines of sight toward four nearby late-type stars-HR 1099, 31 Comae, beta Ceti, and beta Cassiopeiae. The data consist of spectra of the hydrogen and deuterium Lyman-(alpha) lines, and echelle spectra of the Mg IIh and k lines toward all stars except beta Cas. Spectra of the RS CVn-type spectroscopic binary system HR 1099 were obtained near opposite quadratures to determine the intrinsic stellar emission line profile and the interstellar absorption separately. Multiple-velocity components were found toward HR 1099 and beta Cet. The spectra of 31 Com and beta Cet are particularly interesting because they sample lines of sight toward the north and south Galactic poles, respectively, for which H I and D I column densities were not previously available. The north Galactic pole appears to be a region of low hydrogen density like the 'interstellar tunnel' toward epsilon CMa. The temperature and turbulent velocities of the Local InterStellar Medium (LISM) that we measure for the lines of sight toward HR 1099, 31 Com, beta Cet, and beta Cas are similar to previously measured values (T approx.7000 K and xi = 1.0-1.6 km/s). The deuterium/hydrogen ratios found for these lines of sight are also consistent with previous measurements of other short lines of sight, which suggest D/H approx. 1.6 x 10(sup -5). In contrast, the Mg abundance measured for the beta Cet line of sight (implying a logarithmic depletion of D(Mg) = +0.30 +/- 0.15) is about 5 times larger than the Mg abundance previously observed toward alpha Cen, and about 20 times larger than all other previous measurements for the LISM. These results demonstrate that metal abundances in the LISM vary greatly over distances of only a few parsecs.

  10. Receptor-binding region in human choriogonadotropin/lutropin. beta. subunit

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Keutmann, H.T.; Charlesworth, M.C.; Mason, K.A.

    1987-04-01

    Synthetic fragments have not been widely used thus far to evaluate structure-activity relations in the glycoprotein hormones. The authors prepared a series of peptides representing the intercysteine loop sequence (residues 38-57) in human choriogonadotropin (hCG) and lutropin (hLH) ..beta.. subunits, anticipating that it might be oriented toward the surface and accessible to receptors. The peptides were characterized chemically and tested for bioactivity by binding to rat ovarian membrane receptor and stimulation of Leydig cell testosterone production. The hCG..beta..-(38-57) and hLH..beta..-(38-57) peptides inhibited binding of /sup 125/I-labeled hCG half-maximally at 1.51 x 10/sup -4/ and 2.03 x 10/sup -5/ M, respectively,more » while other peptide hormones and fragments from elsewhere in the ..beta.. subunit were inactive. Both peptides stimulated testosterone production, with half-maximal responses at 3.55 x 10/sup -5/ M (hCG) and 2.18 x 10/sup -5/ M (hLH). By radioimmunoassay with an antibody to thyroglobulin-conjugated hCG..beta..-(38-57) peptide, native hCG and ..beta.. subunit were highly reactive, as were the reduced and carboxymethylated subunit and peptide. These results indicate that the 38-57 region of ..beta.. subunit is exposed on the surface and constitutes a component in the receptor-binding domain for hCG and hLH. A region of amphipathic-helical structure in the 38-57 sequence may promote hormone-receptor interactions in a manner proposed for several other peptide hormones.« less

  11. Low-Temperature Forming of Beta Titanium Alloys

    NASA Technical Reports Server (NTRS)

    Kaneko, R. S.; Woods, C. A.

    1983-01-01

    Low cost methods for titanium structural fabrication using advanced cold-formable beta alloys were investigated for application in a Mach 2.7 supersonic cruise vehicle. This work focuses on improving processing and structural efficiencies as compared with standard hot formed and riveted construction of alpha-beta alloy sheet structure. Mechanical property data and manufacturing parameters were developed for cold forming, brazing, welding, and processing Ti-15V-3Cr-3Sn-3Al sheet, and Ti-3Al-8V-6Cr-4Zr on a more limited basis. Cost and structural benefits were assessed through the fabrication and evaluation of large structural panels. The feasibility of increasing structural efficiency of beta titanium structure by selective reinforcement with metal matrix composite was also explored.

  12. Crystal Structures of T Cell Receptor (Beta) Chains Related to Rheumatoid Arthritis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li,H.; van Vranken, S.; Zhao, Y.

    The crystal structures of the V{beta}17+ {beta} chains of two human T cell receptors (TCRs), originally derived from the synovial fluid (SF4) and tissue (C5-1) of a patient with rheumatoid arthritis (RA), have been determined in native (SF4) and mutant (C5-1{sub F104{yields}Y/C187{yields}S}) forms, respectively. These TCR {beta} chains form homo-dimers in solution and in crystals. Structural comparison reveals that the main-chain conformations in the CDR regions of the C5-1 and SF4 V{beta}17 closely resemble those of a V{beta}17 JM22 in a bound form; however, the CDR3 region shows different conformations among these three V{beta}17 structures. At the side-chain level, conformationalmore » differences were observed at the CDR2 regions between our two ligand-free forms and the bound JM22 form. Other significant differences were observed at the V{beta} regions 8-12, 40-44, and 82-88 between C5-1/SF4 and JM22 V{beta}17, implying that there is considerable variability in the structures of very similar {beta} chains. Structural alignments also reveal a considerable variation in the V{beta}-C{beta} associations, and this may affect ligand recognition. The crystal structures also provide insights into the structure basis of T cell recognition of Mycoplasma arthritidis mitogen (MAM), a superantigen that may be implicated in the development of human RA. Structural comparisons of the V{beta} domains of known TCR structures indicate that there are significant similarities among V{beta} regions that are MAM-reactive, whereas there appear to be significant structural differences among those V{beta} regions that lack MAM-reactivity. It further reveals that CDR2 and framework region (FR) 3 are likely to account for the binding of TCR to MAM.« less

  13. Development of a new family of conformationally restricted peptides as potent nucleators of beta-turns. Design, synthesis, structure, and biological evaluation of a beta-lactam peptide analogue of melanostatin.

    PubMed

    Palomo, Claudio; Aizpurua, Jesus M; Benito, Ana; Miranda, José Ignacio; Fratila, Raluca M; Matute, Carlos; Domercq, Maria; Gago, Federico; Martin-Santamaria, Sonsoles; Linden, Anthony

    2003-12-31

    Novel enantiopure (i)-(beta-lactam)-(Gly)-(i+3) peptide models, defined by the presence of a central alpha-alkyl-alpha-amino-beta-lactam ring placed as the (i+1) residue, have been synthesized in a totally stereocontrolled way by alpha-alkylation of suitable N-[bis(trimethylsilyl)methyl]-beta-lactams. The structural properties of these beta-lactam pseudopeptides have been studied by X-ray crystallography, Molecular Dynamics simulation, and NOESY-restrained NMR simulated annealing techniques, showing a strong tendency to form stable type II or type II' beta-turns either in the solid state or in highly coordinating DMSO solutions. Tetrapeptide models containing syn- or anti-alpha,beta-dialkyl-alpha-amino-beta-lactam rings have also been synthesized and their conformations analyzed, revealing that alpha-alkyl substitution is essential for beta-turn stabilization. A beta-lactam analogue of melanostatin (PLG amide) has also been prepared, characterized as a type-II beta-turn in DMSO-d6 solution, and tested by competitive binding assay as a dopaminergic D2 modulator in rat neuron cultured cells, displaying moderate agonist activity in the micromolar concentration range. On the basis of these results, a novel peptidomimetic design concept, based on the separation of constraint and recognition elements, is proposed.

  14. New precision measurements of free neutron beta decay with cold neutrons

    DOE PAGES

    Baeßler, Stefan; Bowman, James David; Penttilä, Seppo I.; ...

    2014-10-14

    Precision measurements in free neutron beta decay serve to determine the coupling constants of beta decay, and offer several stringent tests of the standard model. This study describes the free neutron beta decay program planned for the Fundamental Physics Beamline at the Spallation Neutron Source at Oak Ridge National Laboratory, and finally puts it into the context of other recent and planned measurements of neutron beta decay observables.

  15. Development of an alpha/beta/gamma detector for radiation monitoring

    NASA Astrophysics Data System (ADS)

    Yamamoto, Seiichi; Hatazawa, Jun

    2011-11-01

    For radiation monitoring at the site of nuclear power plant accidents such as Fukushima Daiichi, radiation detectors not only for gamma photons but also for alpha and beta particles are needed because some nuclear fission products emit beta particles and gamma photons and some nuclear fuels contain plutonium that emits alpha particles. We developed a radiation detector that can simultaneously monitor alpha and beta particles and gamma photons for radiation monitoring. The detector consists of three-layered scintillators optically coupled to each other and coupled to a photomultiplier tube. The first layer, which is made of a thin plastic scintillator (decay time: 2.4 ns), detects alpha particles. The second layer, which is made of a thin Gd2SiO5 (GSO) scintillator with 1.5 mol.% Ce (decay time: 35 ns), detects beta particles. The third layer made of a thin GSO scintillator with 0.4 mol.% Ce (decay time: 70 ns) detects gamma photons. By using pulse shape discrimination, the count rates of these layers can be separated. With individual irradiation of alpha and beta particles and gamma photons, the count rate of the first layer represented the alpha particles, the second layer represented the beta particles, and the third layer represented the gamma photons. Even with simultaneous irradiation of the alpha and beta particles and the gamma photons, these three types of radiation can be individually monitored using correction for the gamma detection efficiency of the second and third layers. Our developed alpha, beta, and gamma detector is simple and will be useful for radiation monitoring, especially at nuclear power plant accident sites or other applications where the simultaneous measurements of alpha and beta particles and gamma photons are required.

  16. [Isolation, purification and primary culture of rat pancreatic beta-cells].

    PubMed

    Liu, Yu-Pu; Lü, Qing-Guo; Tong, Nan-Wei

    2009-01-01

    To isolate and purify rat pancreatic beta-cells and to explore the best conditions for the primary culture of the pancreatic beta-cells in vitro. The pancreas of Norman Wistar rats were digested by collagenase V. The islets were purified by mesh sieve. The activity of the islets was stimulated by different concentrations of glucose and detected by dithizone dye. The purified islets were put into RPMI-1640 nutritive medium for culture overnight. The cultured islets were digested again with trypsin and DNAase to obtain the suspension containing single pancreatic cells. The beta-cells were separated and purified in a fluorescence-activated cell sorter (FACS) in the medium containing 2.8 mmol/L glucose. The purified beta-cells were identified by immunohistochemistry and glucose stimulating test. Ham's F-10 with different concentrations of glucose and 3-Isobutyl-1-methylxanthine (IBMX) were used as nutritive medium for the primary cell culture for 24 hours. The best conditions for the culture were identified. An average of 550 +/- 90 islets with fine activities were obtained per rat. The purification with FACS obtained about 5688 beta-cells per rat, with a recovery rate of (93.69 +/- 1.26)% and a purity of (85.5 +/- 1.24)%. A concentration of 10.0 mmol/L and 16.0 mmol/L glucose in primary culture for 24 hours produced the highest survival rates of beta-cells, but IBMX did not increase the survival rates of beta-cells. FACS is effective in purifying pancreatic beta-cells from the suspension with a medium containing 2.8 mmol/L glucose. Pancreatic beta-cells maintain relatively high activities in Ham's F-10 medium containing 10.0-16.0 mmol/L glucose in primary culture.

  17. Development of an alpha/beta/gamma detector for radiation monitoring.

    PubMed

    Yamamoto, Seiichi; Hatazawa, Jun

    2011-11-01

    For radiation monitoring at the site of nuclear power plant accidents such as Fukushima Daiichi, radiation detectors not only for gamma photons but also for alpha and beta particles are needed because some nuclear fission products emit beta particles and gamma photons and some nuclear fuels contain plutonium that emits alpha particles. We developed a radiation detector that can simultaneously monitor alpha and beta particles and gamma photons for radiation monitoring. The detector consists of three-layered scintillators optically coupled to each other and coupled to a photomultiplier tube. The first layer, which is made of a thin plastic scintillator (decay time: 2.4 ns), detects alpha particles. The second layer, which is made of a thin Gd(2)SiO(5) (GSO) scintillator with 1.5 mol.% Ce (decay time: 35 ns), detects beta particles. The third layer made of a thin GSO scintillator with 0.4 mol.% Ce (decay time: 70 ns) detects gamma photons. By using pulse shape discrimination, the count rates of these layers can be separated. With individual irradiation of alpha and beta particles and gamma photons, the count rate of the first layer represented the alpha particles, the second layer represented the beta particles, and the third layer represented the gamma photons. Even with simultaneous irradiation of the alpha and beta particles and the gamma photons, these three types of radiation can be individually monitored using correction for the gamma detection efficiency of the second and third layers. Our developed alpha, beta, and gamma detector is simple and will be useful for radiation monitoring, especially at nuclear power plant accident sites or other applications where the simultaneous measurements of alpha and beta particles and gamma photons are required. © 2011 American Institute of Physics

  18. Role of ROS-mediated TGF beta activation in laser photobiomodulation

    NASA Astrophysics Data System (ADS)

    Arany, Praveen R.; Chen, Aaron Chih-Hao; Hunt, Tristan; Mooney, David J.; Hamblin, Michael

    2009-02-01

    The ability of laser light to modulate specific biological processes has been well documented but the precise mechanism mediating these photobiological interactions remains an area of intense investigation. We recently published the results of our clinical trial with 30 patients in an oral tooth-extraction wound healing model using a 904nm GaAs laser (Oralaser 1010, Oralia, Konstnaz, Germany), assessing healing parameters using routine histopathology and immunostaining (Arany et al Wound Rep Regen 2007, 15, 866). We observed a better organized healing response in laser irradiated oral tissues that correlated with an increased expression of TGF-beta1 immediately post laser irradiation. Our data suggested the source of latent TGF-beta1 might be from the degranulating platelets in the serum, an abundant source of in vivo latent TGF-beta, in the freshly wounded tissues. Further, we also demonstrated the ability of the low power near-infrared laser irradiation to activate the latent TGF-beta complexes in vitro at varying fluences from 10sec (0.1 J/cm2) to 600secs (6 J/cm2). Using serum we observed two isoforms, namely TGF-beta1 and TGF-beta3, were capable of being activated by laser irradiation using an isoform-specific ELISA and a reporter based (p3TP) assay system. We are presently pursuing the precise photomolecular mechanisms focusing on potential chromophores, wavelength and fluence parameters affecting the Latent TGF-beta activation process in serum. As ROS mediated TGF-beta activation has been previously demonstrated and we are also exploring the role of Laser generated-ROS in this activation process. In summary, we present evidence of a potential molecular mechanism for laser photobiomodulation in its ability to activate latent TGF-beta complexes.

  19. TGF-.beta. antagonists as mitigators of radiation-induced tissue damage

    DOEpatents

    Barcellos-Hoff, Mary H.

    1997-01-01

    A method for treating tissue damage caused by radiation is described by use of a TGF-.beta. antagonist, such as an anti-TGF-.beta. antibody or a TGF-.beta. latency associated protein. It is administered not more than a week after exposure, and is particularly useful in mitigating the side effects of breast cancer therapy.

  20. TGF-{beta} antagonists as mitigators of radiation-induced tissue damage

    DOEpatents

    Barcellos-Hoff, M.H.

    1997-04-01

    A method for treating tissue damage caused by radiation is described by use of a TGF-{beta} antagonist, such as an anti-TGF-{beta} antibody or a TGF-{beta} latency associated protein. It is administered not more than a week after exposure, and is particularly useful in mitigating the side effects of breast cancer therapy.