Activity of beta-lactam beta-lactamase inhibitor combinations against extended spectrum beta-lactamase producing enterobacteriaceae in urinary isolates

International Nuclear Information System (INIS)

Iqbal, F.I.; Farooqi, B.J.

2012-01-01

Objective: To determine the susceptibility pattern of beta-lactam beta-lactamase inhibitor combinations against extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae in urinary isolates. Study Design: Observational study. Place and Duration of Study: Ziauddin University Hospital, Karachi, from February to October 2008. Methodology: A total of 190 consecutive non-duplicate isolates of ESBL producing Enterobacteriaceae from urine samples of in-patients were included in the study. Urinary samples from out-patients, repeat samples and non-ESBL producing isolates were excluded. Detection of ESBL was carried out by double disk diffusion technique. Antimicrobial susceptibility testing was performed using modified Kirby Bauer's disk diffusion method according to CLSI guidelines. Statistical analysis was performed by SPSS version 10. Results: Of the 190 ESBL isolates tested, 88 cases (46.31%) were sensitive and 6 cases (3.15%) were resistant to all three combinations, the rest 96 cases (50.52%) were resistant to at least one of the combinations. Susceptibility pattern of cefoperazone/sulbactam, piperacillin/tazobactam, and amoxicillin/clavulanic acid was 95.26, 92.10, and 44.31 percent respectively. Conclusion: Cefoperazone/sulbactam exhibited the best activity against ESBL producing Enterobacteriaceae followed by piperacillin/tazobactam. Hospital antibiotic policies should be reviewed periodically to reduce the usage of extended spectrum cephalosporins and replace them with beta-lactam beta-lactamase inhibitor combinations agent for treating urinary tract infections. (author)

IFN-beta inhibits T cell activation capacity of central nervous system APCs

DEFF Research Database (Denmark)

Teige, Ingrid; Liu, Yawei; Issazadeh-Navikas, Shohreh

2006-01-01

We have previously investigated the physiological effects of IFN-beta on chronic CNS inflammation and shown that IFN-beta(-/-) mice develop a more severe experimental autoimmune encephalomyelitis than their IFN-beta(+/-) littermates. This result was shown to be associated with a higher activation...... state of the glial cells and a higher T cell cytokine production in the CNS. Because this state suggested a down-regulatory effect of IFN-beta on CNS-specific APCs, these results were investigated further. We report that IFN-beta pretreatment of astrocytes and microglia (glial cells) indeed down......-modulate their capacity to activate autoreactive Th1 cells. First, we investigated the intrinsic ability of glial cells as APCs and report that glial cells prevent autoreactive Th1 cells expansion while maintaining Ag-specific T cell effector functions. However, when the glial cells are treated with IFN-beta before...

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

Science.gov (United States)

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.

BETA digital beta radiometer

International Nuclear Information System (INIS)

Borovikov, N.V.; Kosinov, G.A.; Fedorov, Yu.N.

1989-01-01

Portable transportable digital beta radiometer providing for measuring beta-decay radionuclide specific activity in the range from 5x10 -9 up to 10 -6 Cu/kg (Cu/l) with error of ±25% is designed and introduced into commercial production for determination of volume and specific water and food radioactivity. The device specifications are given. Experience in the BETA radiometer application under conditions of the Chernobyl' NPP 30-km zone has shown that it is convenient for measuring specific activity of the order of 10 -8 Cu/kg, and application of a set of different beta detectors gives an opportunity to use it for surface contamination measurement in wide range of the measured value

Comparative analyses of two thermophilic enzymes exhibiting both beta-1,4 mannosidic and beta-1,4 glucosidic cleavage activities from Caldanaerobius polysaccharolyticus.

Science.gov (United States)

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.

Beta2- and beta3-adrenoceptors activate glucose uptake in chick astrocytes by distinct mechanisms: a mechanism for memory enhancement?

Science.gov (United States)

Hutchinson, Dana S; Summers, Roger J; Gibbs, Marie E

2007-11-01

Isoprenaline, acting at beta-adrenoceptors (ARs), enhances memory formation in single trial discriminated avoidance learning in day-old chicks by mechanisms involving alterations in glucose and glycogen metabolism. Earlier studies of memory consolidation in chicks indicated that beta3-ARs enhanced memory by increasing glucose uptake, whereas beta2-ARs enhance memory by increasing glycogenolysis. This study examines the ability of beta-ARs to increase glucose uptake in chick forebrain astrocytes. The beta-AR agonist isoprenaline increased glucose uptake in a concentration-dependent manner, as did insulin. Glucose uptake was increased by the beta2-AR agonist zinterol and the beta3-AR agonist CL316243, but not by the beta1-AR agonist RO363. In chick astrocytes, reverse transcription-polymerase chain reaction studies showed that beta1-, beta2-, and beta3-AR mRNA were present, whereas radioligand-binding studies showed the presence of only beta2- and beta3-ARs. beta-AR or insulin-mediated glucose uptake was inhibited by phosphatidylinositol-3 kinase and protein kinase C inhibitors, suggesting a possible interaction between the beta-AR and insulin pathways. However beta2- and beta3-ARs increase glucose uptake by two different mechanisms: beta2-ARs via a Gs-cAMP-protein kinase A-dependent pathway, while beta3-ARs via interactions with Gi. These results indicate that activation of beta2- and beta3-ARs causes glucose uptake in chick astrocytes by distinct mechanisms, which may be relevant for memory enhancement.

Persistent suppression of subthalamic beta-band activity during rhythmic finger tapping in Parkinson's disease.

Science.gov (United States)

Joundi, Raed A; Brittain, John-Stuart; Green, Alex L; Aziz, Tipu Z; Brown, Peter; Jenkinson, Ned

2013-03-01

The function of synchronous oscillatory activity at beta band (15-30Hz) frequencies within the basal ganglia is unclear. Here we sought support for the hypothesis that beta activity has a global function within the basal ganglia and is not directly involved in the coding of specific biomechanical parameters of movement. We recorded local field potential activity from the subthalamic nuclei of 11 patients with Parkinson's disease during a synchronized tapping task at three different externally cued rates. Beta activity was suppressed during tapping, reaching a minimum that differed little across the different tapping rates despite an increase in velocity of finger movements. Thus beta power suppression was independent of specific motor parameters. Moreover, although beta oscillations remained suppressed during all tapping rates, periods of resynchronization between taps were markedly attenuated during high rate tapping. As such, a beta rebound above baseline between taps at the lower rates was absent at the high rate. Our results demonstrate that beta desynchronization in the region of the subthalamic nucleus is independent of motor parameters and that the beta resynchronization is differentially modulated by rate of finger tapping, These findings implicate consistent beta suppression in the facilitation of continuous movement sequences. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Activation of Beta-Catenin Signaling in Androgen Receptor–Negative Prostate Cancer Cells

Science.gov (United States)

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

Polynucleotides encoding polypeptides having beta-glucosidase activity

Science.gov (United States)

Harris, Paul; Golightly, Elizabeth

2010-03-02

The present invention relates to isolated polypeptides having beta-glucosidase 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 for producing and using the polypeptides.

Overview of total beta activity index and beta rest in surface waters of the Spanish rivers; Vision general del indice de actividad beta total y beta resto en las aguas superficiales de los rios espanoles

Energy Technology Data Exchange (ETDEWEB)

Pujol, L.; Payeras, J.; Pablo, M. A. de

2013-07-01

This work aims to give an overview of the index of total beta activity and the activity index beta rest in surface waters of the main Spanish rivers. These indices are a parameter over water quality that CEDEX comes determined by order of the Ministry of Agriculture, Food and Environment, in water policy. (Author)

Chapter 4: Measurements of total beta-activity in the fallout

International Nuclear Information System (INIS)

Duggleby, J.C.; Johannessen, J.C.; Kotler, L.H.; Stewart, F.M.

1974-01-01

In order to provide information on fresh fission products in fallout reaching Australia from nuclear tests being conducted by France in Polynesia, measurements were made of total beta activity in daily fallout deposition of 25 Australian sampling stations covering a three month period from 25 July to 23 October 1973. The methods employed to measure the radioactivity of the samples are described and the data on total beta-activity, and the calculated external gamma radiation doses from fresh fallout are presented. (R.L.)

Identification of active anti-inflammatory principles of beta- beta ...

African Journals Online (AJOL)

chromatography. Components of the extracts were identified by thin layer chromatography (TLC) scanner and UV-visible spectroscopy, using scopoletin as standard. Results: ... basic coumarin skeleton ring structure reduce ... Figure 2: Thin-layer chromatogram: (1) Ethanol extract; (2) Dichloromethane fraction; (3) Beta-beta.

Gross beta activity of the Danube river samples in 2006

International Nuclear Information System (INIS)

Tanaskovic, I.; Pantelic, G.; Eremic-Savkovic, M.; Vuletic, V.; Javorina, Lj.; Tanaskovic, I.)

2007-01-01

Our paper presents the results of radioactivity control of the Danube samples on Serbian (Bezdan left coast) in 2006. The measurements were carried out by low-phone proportional gas alpha beta counter PIC-WPC-9550. Efficiency for activity was 47%. The results of measurements of gross beta activity (water, sediment, algae and fish) reveal that the values are at the same level as they were before the Paks Nuclear power plant started running. Our results of measurements correlate well with the results of Hungarian part. (author) [sr

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

Science.gov (United States)

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.

Glucose activates prenyltransferases in pancreatic islet {beta}-cells

Energy Technology Data Exchange (ETDEWEB)

Goalstone, Marc [Department of Medicine, University of Colorado, VA Medical Center, Denver, CO 80220 (United States); Kamath, Vasudeva [Department of Pharmaceutical Sciences, Wayne State University, VA Medical Center, Detroit, MI 48201 (United States); Kowluru, Anjaneyulu, E-mail: akowluru@med.wayne.edu [Department of Pharmaceutical Sciences, Wayne State University, VA Medical Center, Detroit, MI 48201 (United States)

2010-01-01

A growing body of evidence implicates small G-proteins [e.g., Cdc42 and Rac1] in glucose-stimulated insulin secretion [GSIS] in the islet {beta}-cell. These signaling proteins undergo post-translational modifications [e.g., prenylation] at their C-terminal cysteine residue and appear to be essential for the transport and fusion of insulin-containing secretory granules with the plasma membrane and the exocytotic secretion of insulin. However, potential regulation of the prenylating enzymes by physiological insulin secretogues [e.g., glucose] has not been investigated thus far. Herein, we report immunological localization, sub-cellular distribution and regulation of farnesyltransferases [FTases] and geranylgeranyltransferase [GGTase] by glucose in insulin-secreting INS 832/13 {beta}-cells and normal rat islets. Our findings suggest that an insulinotropic concentration of glucose [20 mM] markedly stimulated the expression of the {alpha}-subunits of FTase/GGTase-1, but not the {beta}-subunits of FTase or GGTase-1 without significantly affecting the predominantly cytosolic distribution of these holoenzymes in INS 832/13 cells and rodent islets. Under these conditions, glucose significantly stimulated [2.5- to 4.0-fold over basal] the activities of both FTase and GGTase-1 in both cell types. Together, these findings provide the first evidence to suggest that GSIS involves activation of the endogenous islet prenyltransferases by glucose, culminating in the activation of their respective G-protein substrates, which is necessary for cytoskeletal rearrangement, vesicular transport, fusion and secretion of insulin.

Production of beta-xylanase and beta-xylosidase by the extremely halophilic archaeon Halorhabdus utahensis

DEFF Research Database (Denmark)

Wainø, M.; Ingvorsen, K.

2003-01-01

-xylosidase stabilities, approximately 55% and 83% of the initial beta-xylanase and beta-xylosidase activities, respectively, remained after 24 h incubation at 20% NaCl. The enzymes were also shown to be slightly thermophilic: P-xylanase activity exhibiting two optima at 55degrees and 70degreesC, while beta......The extremely halophilic archaeon, Halorhabdus utahensis, isolated from the Great Salt Lake, Utah, produced beta-xylanase and beta-xylosidase activities. Both enzymes were active over a broad NaCl range from near zero to 30% NaCl when tested with culture broth. A broad NaCl optimum was observed...... for beta-xylanase activity between 5% and 15% NaCl, while beta-xylosidase activity was highest at 5% NaCl. Almost half of the maximum activities remained at 27%-30% NaCl for both enzyme activities. When dialyzed culture supernatant and culture broth were employed for determination of beta-xylanase and beta...

Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

Science.gov (United States)

Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

1993-04-01

The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene driven by the vitellogenin A2 ERE were transfected into estrogen-treated MCF-7 cells. RXR beta inhibited ERE-driven reporter activity in a dose-dependent and element-specific fashion. This inhibition occurred in the absence of the RXR ligand 9-cis retinoic acid. The RXR beta-induced inhibition was specific for estrogen receptor (ER)-mediated ERE activation because inhibition was observed in ER-negative MDA-MB-231 cells only following transfection of the estrogen-activated ER. No inhibition of the basal reporter activity was observed. The inhibition was not caused by simple competition of RXR beta with the ER for ERE binding, since deletion mutants retaining DNA binding activity but lacking the N-terminal or C-terminal domain failed to inhibit reporter activity. In addition, cross-linking studies indicated the presence of an auxiliary nuclear factor present in MCF-7 cells that contributed to RXR beta binding of the ERE. Studies using known heterodimerization partners of RXR beta confirmed that RXR beta/triiodothyronine receptor alpha heterodimers avidly bind the ERE but revealed the existence of another triiodothyronine-independent pathway of ERE inhibition. These results indicate that estrogen-responsive genes may be negatively regulated by RXR beta through two distinct pathways.

Immune activation in multiple sclerosis and interferon-beta therapy

DEFF Research Database (Denmark)

Krakauer, Martin

2007-01-01

The PhD dissertation emanated from the Danish MS Research Centre, Rigshosptalet, Copenhagen. Multiple sclerosis (MS) is an inflammatory disease of the CNS. Inflammatory responses by T helper (Th)-lymphocytes are characterised by distinct cytokine expression profiles. In MS, activated Th1...... of inflammation or secondary lymphatic organs. Chemokine receptors are differentially expressed in T cells in blood and cerebrospinal fluid, indicating their role for in T-cell-recruitment to the CNS. Interferon (IFN)-beta is a first-line treatment for MS. The mechanism of action is unclear, but probably includes...... changes in lymphocyte activation, cytokine secretion, and trafficking. The aim of the studies was to shed more light on T-cell immunology in MS and IFN-beta treatment, as well as identifying putative biomarkers of treatment response and/or disease activity. In one study we identified a Th-cell subset...

Biotransformation of isoimperatorin and imperatorin by Glomerella cingulata and beta-secretase inhibitory activity.

Science.gov (United States)

Marumoto, Shinsuke; Miyazawa, Mitsuo

2010-01-01

Biotransformation studies conducted on the furanocoumarins isoimperatorin (1) and imperatorin (3) have revealed that 1 was metabolized by Glomerella cingulata to give the corresponding reduced acid, 6,7-furano-5-prenyloxy hydrocoumaric acid (2), and 3 was transformed by G. cingulata to give the dealkylated metabolite, xanthotoxol (4) in high yields (83% and 81%), respectively. The structures of the new compound 2 have been established on the basis of spectral data. The metabolites 2 and 4 were tested for the beta-secretase (BACE1) inhibitory activity in vitro, and metabolite 2 slightly inhibited the beta-secretase activity with an IC(50) value of 185.6+/-6.8 microM. The metabolite 4 was less potent activity than compounds 1-3. In addition, methyl ester (2Me), methyl ether (2a) and methyl ester and ether (2aMe) of 2 were synthesized, and investigated for the ability to inhibit beta-secretase. Compound 2aMe exhibited the best beta-secretase inhibitory activity at the IC(50) value 16.2+/-1.2 microM and found to be the 2aMe showed competitive mode of inhibition against beta-secretase with K(i) value 11.3+/-2.8 microM. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity.

Science.gov (United States)

Tesco, Giuseppina; Koh, Young Ho; Kang, Eugene L; Cameron, Andrew N; Das, Shinjita; Sena-Esteves, Miguel; Hiltunen, Mikko; Yang, Shao-Hua; Zhong, Zhenyu; Shen, Yong; Simpkins, James W; Tanzi, Rudolph E

2007-06-07

Beta-site APP-cleaving enzyme (BACE) is required for production of the Alzheimer's disease (AD)-associated Abeta protein. BACE levels are elevated in AD brain, and increasing evidence reveals BACE as a stress-related protease that is upregulated following cerebral ischemia. However, the molecular mechanism responsible is unknown. We show that increases in BACE and beta-secretase activity are due to posttranslational stabilization following caspase activation. We also found that during cerebral ischemia, levels of GGA3, an adaptor protein involved in BACE trafficking, are reduced, while BACE levels are increased. RNAi silencing of GGA3 also elevated levels of BACE and Abeta. Finally, in AD brain samples, GGA3 protein levels were significantly decreased and inversely correlated with increased levels of BACE. In summary, we have elucidated a GGA3-dependent mechanism regulating BACE levels and beta-secretase activity. This mechanism may explain increased cerebral levels of BACE and Abeta following cerebral ischemia and existing in AD.

2-(2-Pyridyl) Benzimidazole Analogs and their beta-Glucuronidase Inhibitory Activity

International Nuclear Information System (INIS)

Kamil, A.; Noureen, S.

2015-01-01

Synthesis of 2-(2-Pyridyl) benzimidazole analogs 1-11 have been carried out and evaluated for in vitro beta-glucuronidase inhibitory potential. The compounds 4 (IC/sub 50/ = 4.06 ± 0.34 meuM), 5 (IC/sub 50/ = 09.63 ± 0.81 meuM), 1 (IC/sub 50/ = 19.66 ± 0.44 meuM), 7 (IC/sub 50/ = 24.75 ± 0.25 meuM), 6 (IC/sub 50/ = 26.30 ± 1.37 meuM), and 3 (IC/sub 50/ = 32.11 ± 0.89 meuM), showed beta-glucuronidase inhibitory activity superior to the standard D-saccharic acid 1,4-lactone, with (IC/sub 50/ = 48.4 ± 1.25 meuM). Based on structure-activity relationship, we discover a new class of potent beta-glucuronidase inhibitors. (author)

Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells

International Nuclear Information System (INIS)

Friesen, Claudia; Lubatschofski, Annelie; Debatin, Klaus-Michael; Kotzerke, Joerg; Buchmann, Inga; Reske, Sven N.

2003-01-01

Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-x L , a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies. (orig.)

Structural basis for substrate activation and regulation by cystathionine beta-synthase (CBS) domains in cystathionine [beta]-synthase

Energy Technology Data Exchange (ETDEWEB)

Koutmos, Markos; Kabil, Omer; Smith, Janet L.; Banerjee, Ruma (Michigan-Med)

2011-08-17

The catalytic potential for H{sub 2}S biogenesis and homocysteine clearance converge at the active site of cystathionine {beta}-synthase (CBS), a pyridoxal phosphate-dependent enzyme. CBS catalyzes {beta}-replacement reactions of either serine or cysteine by homocysteine to give cystathionine and water or H{sub 2}S, respectively. In this study, high-resolution structures of the full-length enzyme from Drosophila in which a carbanion (1.70 {angstrom}) and an aminoacrylate intermediate (1.55 {angstrom}) have been captured are reported. Electrostatic stabilization of the zwitterionic carbanion intermediate is afforded by the close positioning of an active site lysine residue that is initially used for Schiff base formation in the internal aldimine and later as a general base. Additional stabilizing interactions between active site residues and the catalytic intermediates are observed. Furthermore, the structure of the regulatory 'energy-sensing' CBS domains, named after this protein, suggests a mechanism for allosteric activation by S-adenosylmethionine.

Cross-sections for some millisecond beta activities. [14. 7 MeV

Energy Technology Data Exchange (ETDEWEB)

Garg, K C; Khurana, C S [Punjabi Univ., Patiala (India). Dept. of Physics

1979-06-01

An on-line irradiation system involving pulsed beam technique has been developed to handle the millisecond isomers produced in nuclear reactions with 14.7 MeV neutrons. The system originally used to measure the half-lives of a number of millisecond gamma-active isomers has been extended to handle the millisecond pure beta-activities produced in nuclear reactions. An end-window type GM counter has been employed to measure the produced beta activities of /sup 6/He and /sup 9/Li in /sup 7/ /sup 6/Li((n,d))/sup 6/He, /sup 9/Be(n,..cap alpha..)/sup 6/He and /sup 9/Be(n,p)/sup 9/Li reactions.

Homocysteine threshold value based on cystathionine beta synthase and paraoxonase 1 activities in mice.

Science.gov (United States)

Hamelet, J; Aït-Yahya-Graison, E; Matulewicz, E; Noll, C; Badel-Chagnon, A; Camproux, A-C; Demuth, K; Paul, J-L; Delabar, J M; Janel, N

2007-12-01

Hyperhomocysteinaemia is a metabolic disorder associated with the development of premature atherosclerosis. Among the determinants which predispose to premature thromboembolic and atherothrombotic events, serum activity of paraoxonase 1, mainly synthesized in the liver, has been shown to be a predictor of cardiovascular disease and to be negatively correlated with serum homocysteine levels in human. Even though treatments of hyperhomocysteinaemic patients ongoing cardiovascular complications are commonly used, it still remains unclear above which homocysteine level a preventive therapy should be started. In order to establish a threshold of plasma homocysteine concentration we have analyzed the hepatic cystathionine beta synthase and paraoxonase 1 activities in a moderate to intermediate murine model of hyperhomocysteinaemia. Using wild type and heterozygous cystathionine beta synthase deficient mice fed a methionine enriched diet or a control diet, we first studied the link between cystathionine beta synthase and paraoxonase 1 activities and plasma homocysteine concentration. Among the animals used in this study, we observed a negative correlation between plasma homocysteine level and cystathionine beta synthase activity (rho=-0.52, P=0.0008) or paraoxonase 1 activity (rho=-0.49, P=0.002). Starting from these results, a homocysteine cut-off value of 15 microm has been found for both cystathionine beta synthase (P=0.0003) and paraoxonase 1 (P=0.0007) activities. Our results suggest that both cystathionine beta synthase and paraoxonase 1 activities are significantly decreased in mice with a plasma homocysteine value greater than 15 microm. In an attempt to set up preventive treatment for cardiovascular disease our results indicate that treatments should be started from 15 microm of plasma homocysteine.

Discoidin domain receptor 1 is activated independently of beta(1) integrin

DEFF Research Database (Denmark)

Vogel, W; Brakebusch, C; Fässler, R

2000-01-01

independent of the epidermal growth factor (EGF) receptor. In cells that endogenously express both DDR1 and the EGF receptor, stimulation with EGF does not induce DDR activation. Third, we detected full DDR1 activation after collagen stimulation in cells that have been treated with blocking antibodies...... for alpha(2)beta(1) integrin or in cells with a targeted deletion of the beta(1) integrin gene. Finally, we show that overexpression of dominant negative DDR1 in the myoblast cell line C2C12 blocks cellular differentiation and the formation of myofibers....

17 beta-estradiol modifies nitric oxide-sensitive guanylyl cyclase expression and down-regulates its activity in rat anterior pituitary gland.

Science.gov (United States)

Cabilla, Jimena P; Díaz, María del Carmen; Machiavelli, Leticia I; Poliandri, Ariel H; Quinteros, Fernanda A; Lasaga, Mercedes; Duvilanski, Beatriz H

2006-09-01

Previous studies showed that 17 beta-estradiol (17 beta-E2) regulates the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP pathway in many tissues. Evidence from our laboratory indicates that 17 beta-E2 disrupts the inhibitory effect of NO on prolactin release, decreasing sGC activity and affecting the cGMP pathway in anterior pituitary gland of adult ovariectomized and estrogenized rats. To ascertain the mechanisms by which 17 beta-E2 affects sGC activity, we investigated the in vivo and in vitro effects of 17 beta-E2 on sGC protein and mRNA expression in anterior pituitary gland from immature female rats. In the present work, we showed that 17 beta-E2 acute treatment exerted opposite effects on the two sGC subunits, increasing alpha1 and decreasing beta1 subunit protein and mRNA expression. This action on sGC protein expression was maximal 6-9 h after 17 beta-E2 administration. 17beta-E2 also caused the same effect on mRNA expression at earlier times. Concomitantly, 17 beta-E2 dramatically decreased sGC activity 6 and 9 h after injection. These effects were specific of 17 beta-E2, because they were not observed with the administration of other steroids such as progesterone and 17 alpha-estradiol. This inhibitory action of 17beta-E2 on sGC also required the activation of estrogen receptor (ER), because treatment with the pure ER antagonist ICI 182,780 completely blocked 17 beta-E2 action. 17 beta-E2 acute treatment caused the same effects on pituitary cells in culture. These results suggest that 17 beta-E2 exerts an acute inhibitory effect on sGC in anterior pituitary gland by down-regulating sGC beta 1 subunit and sGC activity in a specific, ER-dependent manner.

Measurement of gross alpha and gross beta activity concentrations in human tooth

International Nuclear Information System (INIS)

Soeguet, Omer; Aydin, Mehmet Fatih; Kuecuekoender, Erdal; Zorer, Ozlem Selcuk; Dogru, Mahmut

2010-01-01

The gross alpha and gross beta activity concentrations were measured in human tooth taken from 3 to 6 age-groups to 40 and over ones. Accumulated teeth samples are investigated in two groups as under and above 18 years. The gross alpha and beta radioactivity of human tooth samples was measured by using a gas-flow proportional counter (PIC-MPC 9604-α/β counter). In tooth samples, for female age-groups, the obtained results show that the mean gross alpha and gross beta activity concentrations varied between 0.534-0.203 and 0.010-0.453 Bq g -1 and the same concentrations for male age-groups varied between 0.009-1.168 and 0.071-0.204 Bq g -1 , respectively.

New lupane triterpenoids from Solidago canadensis that inhibit the lyase activity of DNA polymerase beta.

Science.gov (United States)

Chaturvedula, V S Prakash; Zhou, Bing-Nan; Gao, Zhijie; Thomas, Shannon J; Hecht, Sidney M; Kingston, David G I

2004-12-01

Bioassay-directed fractionation of a methyl ethyl ketone extract of Solidago canadensis L. (Asteraceae), using an assay to detect the lyase activity of DNA polymerase beta, resulted in the isolation of the four new lupane triterpenoids 1-4 and the seven known compounds lupeol, lupeyl acetate, ursolic acid, cycloartenol, cycloartenyl palmitate, alpha-amyrin acetate, and stigmasterol. The structures of the new compounds were established as 3beta-(3R-acetoxyhexadecanoyloxy)-lup-20(29)-ene (1), 3beta-(3-ketohexadecanoyloxy)-lup-20(29)-ene (2), 3beta-(3R-acetoxyhexadecanoyloxy)-29-nor-lupan-20-one (3), and 3beta-(3-hetohexadecanoyloxy)-29-nor-lupan-20-one (4), respectively, on the basis of extensive 1D and 2D NMR spectroscopic interpretation and chemical modification studies. All 11 compounds were inhibitory to the lyase activity of DNA polymerase beta.

Complement activation by the amyloid proteins A beta peptide and beta 2-microglobulin

DEFF Research Database (Denmark)

Nybo, Mads; Nielsen, E H; Svehag, S E

1999-01-01

component nor heparan sulfate did significantly alter the A beta-induced CA. The results indicate that not only fibrillar A beta but also oligomers of, in particular, beta 2M from patients with dialysis-associated amyloidosis are capable of inducing CA at supra-physiological concentrations....

Resting-state beta and gamma activity in Internet addiction.

Science.gov (United States)

Choi, Jung-Seok; Park, Su Mi; Lee, Jaewon; Hwang, Jae Yeon; Jung, Hee Yeon; Choi, Sam-Wook; Kim, Dai Jin; Oh, Sohee; Lee, Jun-Young

2013-09-01

Internet addiction is the inability to control one's use of the Internet and is related to impulsivity. Although a few studies have examined neurophysiological activity as individuals with Internet addiction engage in cognitive processing, no information on spontaneous EEG activity in the eyes-closed resting-state is available. We investigated resting-state EEG activities in beta and gamma bands and examined their relationships with impulsivity among individuals with Internet addiction and healthy controls. Twenty-one drug-naïve patients with Internet addiction (age: 23.33 ± 3.50 years) and 20 age-, sex-, and IQ-matched healthy controls (age: 22.40 ± 2.33 years) were enrolled in this study. Severity of Internet addiction was identified by the total score on Young's Internet Addiction Test. Impulsivity was measured with the Barratt Impulsiveness Scale-11 and a stop-signal task. Resting-state EEG during eyes closed was recorded, and the absolute/relative power of beta and gamma bands was analyzed. The Internet addiction group showed high impulsivity and impaired inhibitory control. The generalized estimating equation showed that the Internet-addiction group showed lower absolute power on the beta band than did the control group (estimate = -3.370, p Internet-addiction group showed higher absolute power on the gamma band than did the control group (estimate = 0.434, p Internet addiction as well as with the extent of impulsivity. The present study suggests that resting-state fast-wave brain activity is related to the impulsivity characterizing Internet addiction. These differences may be neurobiological markers for the pathophysiology of Internet addiction. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of dietary fiber on the activity of intestinal and fecal beta-glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis.

Science.gov (United States)

Manoj, G; Thampi, B S; Leelamma, S; Menon, P V

2001-01-01

The effects of fiber isolated from black gram (Phaseolus mungo) and coconut (Cocos nucifera) kernel on the metabolic activity of intestinal and fecal beta glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis were studied. The results indicated that the inclusion of fiber from black gram and coconut kernel generally supported lower specific activities and less fecal output of beta-glucuronidase than did the fiber free diet. This study suggests that the fibers isolated from coconut or black gram may potentially play a role in preventing the formation of colon tumors induced by the carcinogen 1,2-dimethylhydrazine by reducing the activity of the intestinal as well as fecal beta-glucuronidase.

Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence.

Science.gov (United States)

Katiyar, S K; Gordon, V R; McLaughlin, G L; Edlind, T D

1994-01-01

Benzimidazoles have been widely used since the 1960s as anthelmintic agents in veterinary and human medicine and as antifungal agents in agriculture. More recently, selected benzimidazole derivatives were shown to be active in vitro against two protozoan parasites, Trichomonas vaginalis and Giardia lamblia, and clinical studies with AIDS patients have suggested that microsporidia are susceptible as well. Here, we first present in vitro susceptibility data for T. vaginalis and G. lamblia using an expanded set of benzimidazole derivatives. Both parasites were highly susceptible to four derivatives, including mebendazole, flubendazole, and fenbendazole (50% inhibitory concentrations of 0.005 to 0.16 microgram/ml). These derivatives also had lethal activity that was time dependent: 90% of T. vaginalis cells failed to recover following a 20-h exposure to mebendazole at 0.17 microgram/ml. G. lamblia, but not T. vaginalis, was highly susceptible to five additional derivatives. Next, we examined in vitro activity of benzimidazoles against additional protozoan parasites: little or no activity was observed against Entamoeba histolytica, Leishmania major, and Acanthamoeba polyphaga. Since the microtubule protein beta-tubulin has been identified as the benzimidazole target in helminths and fungi, potential correlations between benzimidazole activity and beta-tubulin sequence were examined. This analysis included partial sequences (residues 108 to 259) from the organisms mentioned above, as well as the microsporidia Encephalitozoon hellem and Encephalitozoon cuniculi and the sporozoan Cryptosporidium parvum. beta-tubulin residues Glu-198 and, in particular, Phe-200 are strong predictors of benzimidazole susceptibility; both are present in Encephalitozoon spp. but absent in C. parvum. PMID:7811023

Determination of gross gamma and gross beta activities in liquid effluent samples. Phase I

International Nuclear Information System (INIS)

Curtis, K.E.; Sood, S.P.

1985-08-01

Several inadequacies in the presently used procedures for gross gamma and gross beta measurements in aqueous wastes have been identified. Both the presence of suspended particulate activity and the use of cesium-137 as a calibration standard can cause gross gamma measurements to overestimate the actual activity in the sample. At the same time, sample preparation for the determination of gross beta activities causes large losses of radioiodine before the measurement step and the presence of solid material can cause a serious decrease in the beta counting efficiency. A combination of these errors could result in large discrepancies between the results obtained by the two measurement methods. Improved procedures are required to overcome these problems

Evaluation of the transforming growth factor-beta activity in normal and dry eye human tears by CCL-185 cell bioassay.

Science.gov (United States)

Zheng, Xiaofen; De Paiva, Cintia S; Rao, Kavita; Li, De-Quan; Farley, William J; Stern, Michael; Pflugfelder, Stephen C

2010-09-01

To develop a new bioassay method using human lung epithelial cells (CCL-185) to assess activity of transforming growth factor beta (TGF-beta) in human tear fluid from normal subjects and patients with dry eye. Two epithelial cell lines, mink lung cells (CCL-64) and human lung cells (CCL-185), were compared to detect the active form of TGF-beta by BrdU incorporation (quantitation of cell DNA synthesis) and WST assay (metabolic activity of viable cells). The effect of TGF-beta on the growth of CCL-185 cells was observed microscopically. Human tears from normal control subjects and patients with dry eye (DE) with and without Sjögren syndrome were evaluated for TGF-beta concentration by Luminex microbead assay, and TGF-beta activity by the CCL-185 cell growth inhibition bioassay. The metabolic activity of viable CCL-185 cells, measured by WST, was shown to be proportional to the TGF-beta1 concentration (R = 0.919) and confirmed by BrdU assay (R = 0.969). Compared with CCL-185, metabolic activity of viable cells and DNA synthesis, measured by WST and BrdU incorporation assays, were shown to be less proportional to the TGF-beta1 concentration in the CCL-64 line (R = 0.42 and 0.17, respectively). Coincubation with human anti-TGF-beta1 antibody (MAB-240) yielded a dose-dependent inhibition of TGF-beta1 (0.3 ng/mL) activity. CCL-185 cell growth observed microscopically was noted to decrease in response to increasing TGF-beta1 concentrations. Levels of immuodetectable TGF-beta1 and TGF-beta2 were similar in normal and DE tears. TGF-beta bioactivity in DE human tears measured by the CCL-185 cells assay was found to be higher (9777.5 +/- 10481.9 pg/mL) than those in normal controls (4129.3 +/- 1342.9 pg/mL) (P tears and 37.6% TGF-beta in normal tears were found to be biologically active. The CCL-185 cell assay was found to be a suitable tool for assessing TGF-beta activity in human tears. Tear TGF-beta bioactivity increases in DE, particularly in Sjögren syndrome, where

Latent transforming growth factor beta1 activation in situ: quantitative and functional evidence after low-dose gamma-irradiation

Science.gov (United States)

Ehrhart, E. J.; Segarini, P.; Tsang, M. L.; Carroll, A. G.; Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

1997-01-01

The biological activity of transforming growth factor beta1 (TGF-beta) is controlled by its secretion as a latent complex in which it is noncovalently associated with latency-associated peptide (LAP). Activation is the extracellular process in which TGF-beta is released from LAP, and is considered to be a primary regulatory control. We recently reported rapid and persistent changes in TGF-beta immunoreactivity in conjunction with extracellular matrix remodeling in gamma-irradiated mouse mammary gland. Our hypothesis is that these specific changes in immunoreactivity are indicative of latent TGF-beta activation. In the present study, we determined the radiation dose response and tested whether a functional relationship exists between radiation-induced TGF-beta and collagen type III remodeling. After radiation exposures as low as 0.1 Gy, we detected increased TGF-beta immunoreactivity in the mammary epithelium concomitant with decreased LAP immunostaining, which are events consistent with activation. Quantitative image analysis demonstrated a significant (P=0.0005) response at 0.1 Gy without an apparent threshold and a linear dose response to 5 Gy. However, in the adipose stroma, loss of LAP demonstrated a qualitative threshold at 0.5 Gy. Loss of LAP paralleled induction of collagen III immunoreactivity in this tissue compartment. We tested whether TGF-beta mediates collagen III expression by treating animals with TGF-beta panspecific monoclonal antibody, 1D11.16, administered i.p. shortly before irradiation. Radiation-induced collagen III staining in the adipose stroma was blocked in an antibody dose-dependent manner, which persisted through 7 days postirradiation. RNase protection assay revealed that radiation-induced elevation of total gland collagen III mRNA was also blocked by neutralizing antibody treatment. These data provide functional confirmation of the hypothesis that radiation exposure leads to latent TGF-beta activation, support our interpretation of the

Determination of total alpha and beta activities on vegetable samples by LSC

International Nuclear Information System (INIS)

Nogueira, Regina Apolinaria; Santos, Eliane Eugenia dos; Bakker, Alexandre Pereira; Vavassori, Giullia

2011-01-01

Gross alpha and beta analyses are screening techniques used for environmental radioactivity monitoring. The present study proposes to determine the gross alpha and beta activities in vegetable samples by using LSC - liquid scintillation spectrometry. The procedure was applied to vegetable foods. After ashing vegetable samples in a muffle furnace, 100 mg of ash were added to gel mixture of scintillation cocktails, Water - Instagel - Ultima Gold AB (6:10:4) ml, in polyethylene vial. Am-241 standard solution and a KCl (K-40) solution were used to determine the counting configuration, alpha/beta efficiencies and spillover

Adaptive grip force is modulated by subthalamic beta activity in Parkinson's disease patients

Directory of Open Access Journals (Sweden)

Lukas L. Imbach

2015-01-01

Conclusion: The time-locked suppression of beta oscillatory activity in the STN is in line with previous reports of beta ERD prior to voluntary movements. Our results show that the STN is involved in anticipatory grip force control in PD patients. The difference in the phasic beta ERD between the two tasks and the reduction of cortico-subthalamic synchronization suggests that qualitatively different neuronal network states are involved in different grip force control tasks.

Mood states, sympathetic activity, and in vivo beta-adrenergic receptor function in a normal population.

Science.gov (United States)

Yu, Bum-Hee; Kang, Eun-Ho; Ziegler, Michael G; Mills, Paul J; Dimsdale, Joel E

2008-01-01

The purpose of this study was to examine the relationship between mood states and beta-adrenergic receptor function in a normal population. We also examined if sympathetic nervous system activity is related to mood states or beta-adrenergic receptor function. Sixty-two participants aged 25-50 years were enrolled in this study. Mood states were assessed using the Profile of Mood States (POMS). Beta-adrenergic receptor function was determined using the chronotropic 25 dose isoproterenol infusion test. Level of sympathetic nervous system activity was estimated from 24-hr urine norepinephrine excretion. Higher tension-anxiety, depression-dejection, and anger-hostility were related to decreased beta-adrenergic receptor sensitivity (i.e., higher chronotropic 25 dose values), but tension-anxiety was the only remaining independent predictor of beta-adrenergic receptor function after controlling for age, gender, ethnicity, and body mass index (BMI). Urinary norepinephrine excretion was unrelated to either mood states or beta-adrenergic receptor function. These findings replicate previous reports that anxiety is related to decreased (i.e., desensitized) beta-adrenergic receptor sensitivity, even after controlling for age, gender, ethnicity, and body mass index.

Polypeptides having beta-glucosidase activity and polynucleotides encoding same

Science.gov (United States)

Harris, Paul; Golightly, Elizabeth

2012-11-27

The present invention relates to isolated polypeptides having beta-glucosidase 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 for producing and using the polypeptides.

Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Dudas, Jozsef, E-mail: Jozsef.Dudas@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullar, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Bitsche, Mario, E-mail: Mario.Bitsche@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Schartinger, Volker, E-mail: Volker.Schartinger@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Sprinzl, Georg Mathias, E-mail: Georg.Sprinzl@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: Herbert.Riechelmann@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

2011-09-10

Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the

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

Science.gov (United States)

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.

Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

International Nuclear Information System (INIS)

Li, Jason Z.; Ke, Yuebin; Misra, Hara P.; Trush, Michael A.; Li, Y. Robert; Zhu, Hong; Jia, Zhenquan

2014-01-01

Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone, a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with

Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

Energy Technology Data Exchange (ETDEWEB)

Li, Jason Z. [Virginia Tech CRC, Blacksburg, VA (United States); Ke, Yuebin [Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Misra, Hara P. [Virginia Tech CRC, Blacksburg, VA (United States); Trush, Michael A. [Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (United States); Li, Y. Robert [Campbell University School of Osteopathic Medicine, Buies Creek, NC (United States); Virginia Tech-Wake Forest University SBES, Blacksburg, VA (United States); Department of Biology, University of North Carolina at Greensboro, NC (United States); Zhu, Hong, E-mail: zhu@campbell.edu [Campbell University School of Osteopathic Medicine, Buies Creek, NC (United States); Jia, Zhenquan, E-mail: z_jia@uncg.edu [Department of Biology, University of North Carolina at Greensboro, NC (United States)

2014-12-15

Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone, a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with

Labelling of. beta. -endorphin (. beta. -END) and. beta. -lipotropin (. beta. -LPH) by /sup 125/I

Energy Technology Data Exchange (ETDEWEB)

Deby-Dupont, G.; Joris, J.; Franchimont, P. (Universite de Liege (Belgique)); Reuter, A.M.; Vrindts-Gevaert, Y. (Institut des Radioelements, Fleurus (Belgique))

1983-01-01

5 ..mu..g of human ..beta..-endorphin were labelled with 2 mCi /sup 125/I by the chloramine T technique. After two gel filtrations on Sephadex G-15 and on Sephadex G-50 in phosphate buffer with EDTA, Trasylol and mercapto-ethanol, a pure tracer was obtained with a specific activity about 150 ..mu..Ci/..mu..g.Kept at + 4/sup 0/C, the tracer remained utilizable for 30 days without loss of immunoreactivity. The labelling with lactoperoxydase and the use of another gel filtration method (filtration on Aca 202) gave a /sup 125/I ..beta..-END tracer with the same immunoreactivity. The binding of this tracer to the antibody of an anti-..beta..-END antiserum diluted at 1/8000 was 32% with a non specific binding of 2%. 5 ..mu..g of human ..beta..-lipotropin were labelled with 0.5 mCi /sup 125/I by the lactoperoxydase method. After two gel filtrations on Sephadex G-25 and on Sephadex G-75 in phosphate buffer with EDTA, Trasylol and mercapto-ethanol, a pure tracer with a specific activity of 140 ..mu..Ci/..mu..g was obtained. It remained utilizable for 30 days when kept at + 4/sup 0/C. Gel filtration on Aca 202 did not give good purification, while gel filtration on Aca 54 was good but slower than on Sephadex G-75. The binding to antibody in absence of unlabelled ..beta..-LPH was 32% for an anti-..beta..-LPH antiserum diluted at 1/4000. The non specific binding was 2.5%.

Liver X receptor activation inhibits PC-3 prostate cancer cells via the beta-catenin pathway.

Science.gov (United States)

Youlin, Kuang; Li, Zhang; Weiyang, He; Jian, Kang; Siming, Liang; Xin, Gou

2017-03-01

Liver X receptors (LXRs) are nuclear receptors family of ligand-dependent transcription factors that play a crucial role in regulating cholesterol metabolism and inflammation. Recent studies show that LXR agonists exhibit anti-cancer activities in a variety of cancer cell lines including prostate. To further identify the potential mechanisms of LXRα activation on prostate cancer, we investigated the effect of LXR agonist T0901317 on PC3 prostate cancer cell and in which activity of beta-catenin pathway involved. Prostate cancer PC3 cells were transfected with LXR-a siRNA and treated with LXR activator T0901317. qRT-PCR and western blot were used to detect the LXR-a expression. beta-catenin, cyclin D1 and c-MYC were analyzed by western blot. Cell apoptosis was examined by flow cytometry and Cell proliferation was assessed by Cell Counting Kit-8 assay. Cell migration was detected by Transwell chambers. Data showed that T0901317 significantly inhibited PC3 cell proliferation as well as invasion and increased apoptosis in vitro. Furthermore, we found that LXRα activation induced the reduction of beta-catenin expression in PC3 cells, and this inhibitory effect could be totally abolished when cells were treated with LXRα. Meanwhile, the expression of beta-catenin target gene cyclin D1 and c-MYC were also decreased. This study provided additional evidence that LXR activation inhibited PC-3 prostate cancer cells via suppressing beta-catenin pathway. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

2010-11-19

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

Mechanism of activity, biosynthesis and identification of beta-lactam antimicrobial drugs

Directory of Open Access Journals (Sweden)

Marija Sedak

2011-01-01

Full Text Available Antimicrobal drugs are chemotherapeutics with a wide spectrum of use in human and veterinary medicine and livestock practice. Beta-lactams are the most widespread group of antimicrobal drugs and are most often used in human and veterinary medicine in the treatment of bacterial infections due to their powerful antimicrobial activity and very low toxicity. They are divided into the groups of penicillins, cefalosporins and monobactams. Penicillins are obtained from the filtrate of the mould cultures Penicillium notatum and Penicillium chrysogenum, while cefalosporins are obtained from the filtrate of the actinomycete cultures (Cephalosporium acremonium. Research has lead to the discovery of active groups of 6-amino-penicillin acids, whose isolation has made it possible to produce semi-synthetic penicillins that have surpassed the limitations of natural penicillin G. The physico-chemical properties of the beta-lactams can be altered by substituting hydrogen in the carboxyl group of penicillins, i.e. in modifying the side chain of cefalosporin. This increases the resistance to the activity of β-lactamase and expands the spectrum of activity. Beta-lactams, in therapy concentrations, act as a bacteriocide by inhibiting the synthesis of bacterial cell walls. Penicillins are important for antibacterial chemotherapy, often in combination with other antimicrobal drugs. Cefalosporins are usually used as a replacement for penicillin in treating infections caused by gram-negative bacteria and in prophylaxis for surgery. The use of beta-lactams in animals used for food can result in the residues of these drugs in meat and meat products or milk and eggs. The introduction of antimicrobal drugs in the human body via food is particularly dangerous due to their direct toxicity or carcinogenicity, influences on the composition of the intestinal microflora, possible allergic reactions in sensitive people, and the appearance of resistance of individual pathogenic

Lipidated alpha-Peptide/beta-Peptoid Hybrids with Potent Antiinflammatory Activity

DEFF Research Database (Denmark)

Skovbakke, Sarah L.; Larsen, Camilla J.; Heegaard, Peter M. H.

2015-01-01

is dependent on the length and position of the lipid element(s). The resulting lead compound, Pam-(Lys-beta NSpe)(6)-NH2, blocks LPS-induced cytokine secretion with a potency comparable to that of polymyxin B. The mode of action of this HDP mimic appears not to involve direct LPS interaction since it......, in contrast to polymyxin B, displayed only minor activity in the Limulus amebocyte lysate assay. Flow cytometry data showed specific interaction of a fluorophore-labeled lipidated a-peptide/beta-peptoid hybrid with monocytes and granulocytes indicating a cellular target expressed by these leukocyte subsets....

A simple method for determining the activity of large-area beta sources constructed from anodized aluminum foils

International Nuclear Information System (INIS)

Stanga, D.

2014-01-01

A simple method has been developed for determining the activity of large-area beta reference sources in anodized aluminum foils. It is based on the modeling of the transmission of beta rays through thin foils in planar geometry using Monte Carlo simulation. The method was checked experimentally and measurement results show that the activity of large-area beta reference sources in anodized aluminum foils can be measured with standard uncertainties smaller than the limit of 10% required by ISO 8769. - Highlights: • A method for determining the activity of large-area beta sources is presented. • The method is based on a model of electron transport in planar geometry. • The method makes use of linear programming for determining the activity. • The uncertainty of the method is smaller than 10%

Measurement of the activity of beta emitting gases using an ionisation chamber; Mesure de l'activite des gaz emetteurs beta au moyen d'une chambre d'ionisation

Energy Technology Data Exchange (ETDEWEB)

Lebouleux, P [Commissariat a l' Energie Atomique. Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France)

1962-07-01

An ionization chamber was developed for measuring directly the activity of a {beta}-emitting gas whatever the gas may be. The following two parameters are defined and determined: p, the average specific ionization produced by a {beta} disintegration, and i, the average {beta} path in the chamber. It was shown, during the determination of i, that the {beta} particles are reflected on the walls of the ionization chamber when the latter are made of a high atomic number material. It was possible to eliminate this effect by constructing an electrode chamber made of graphite. With this chamber a direct measurement can be made of the activity of a gaseous {beta} emitter with a precision of about {+-}10%. Some applications are given of the graphite electrode chamber (calibration of the chambers built industrially and determination of the activation cross section of a gaseous emitter). It was possible to determine the activation cross section of {sup 134}Xe; a value of 0.18 {+-} 0.03 barn was found. (author) [French] Le but de l'etude est de realiser une chambre d'ionisation permettant d'effectuer une mesure directe de l'activite d'un gaz emetteur {beta} quel que soit l'emetteur considere. On definit et l'on determine les deux parametres suivants: p: ionisation specifique moyenne produite par une desintegration {beta}. La determination est effectuee par une methode graphique, i: moyenne des parcours des {beta} dans la chambre. La determination est effectuee experimentalement par introduction dans la chambre d'un gaz radioactif dont on peut calculer l'activite. On a mis en evidence, au cours de la determination de i, la reflexion des particules {beta} sur les parois des chambres d'ionisation lorsque celles-ci sont constituees d'un materiau de numero atomique eleve. La construction d'une chambre a electrodes de graphite nous a permis d'eliminer ce phenomene. Avec cette chambre, on effectue une mesure directe de l'activite d'un emetteur {beta} gazeux avec une precision de l

A survey of gross alpha and gross beta activity in soil samples in Kinta District, Perak, Malaysia

International Nuclear Information System (INIS)

Lee, Siak Kuan; Wagiran, Husin; Ramli, Ahmad Termizi

2014-01-01

The objective of this study was to determine the gross alpha and gross beta activity concentrations from the different soil types found in the Kinta District, Perak, Malaysia. A total of 128 soil samples were collected and their dose rates were measured 1 m above the ground. Gross alpha and gross beta activity measurements were carried out using gas flow proportional counter, Tennelec Series 5 LB5500 Automatic Low Background Counting System. The alpha activity concentration ranged from 15 to 9634 Bq kg -1 with a mean value of 1558±121 Bq kg -1 . The beta activity concentration ranged from 142 to 6173 Bq kg -1 with a mean value of 1112±32 Bq kg -1 . High alpha and beta activity concentrations are from the same soil type. The results of the analysis show a strong correlation between the gross alpha activity concentration and dose rate (R = 0.92). The data obtained can be used as a database for each soil type. (authors)

Innovative procedure for the determination of gross-alpha/gross-beta activities in drinking water

International Nuclear Information System (INIS)

Wisser, S.; Frenzel, E.; Dittmer, M.

2006-01-01

An alternative sample preparation method for the determination of gross-alpha/beta activity concentrations in drinking water is introduced in this paper. After the freeze-drying of tap water samples, determination by liquid scintillation counting can be applied utilizing alpha/beta separation. It has been shown that there is no adsorption or loss of solid radionuclides during the freeze-drying procedure. However, the samples have to be measured quickly after the preparation since the ingrowth of daughter isotopes negatively effects the measurement. The limits of detection for gross-alpha and gross-beta activity are in the range 25-210 mBq/l, respectively, for a measurement time of only 8-9 h

Alkali pH directly activates ATP-sensitive K+ channels and inhibits insulin secretion in beta-cells.

Science.gov (United States)

Manning Fox, Jocelyn E; Karaman, Gunce; Wheeler, Michael B

2006-11-17

Glucose stimulation of pancreatic beta-cells is reported to lead to sustained alkalization, while extracellular application of weak bases is reported to inhibit electrical activity and decrease insulin secretion. We hypothesize that beta-cell K(ATP) channel activity is modulated by alkaline pH. Using the excised patch-clamp technique, we demonstrate a direct stimulatory action of alkali pH on recombinant SUR1/Kir6.2 channels due to increased open probability. Bath application of alkali pH similarly activates native islet beta-cell K(ATP) channels, leading to an inhibition of action potentials, and hyperpolarization of membrane potential. In situ pancreatic perfusion confirms that these cellular effects of alkali pH are observable at a functional level, resulting in decreases in both phase 1 and phase 2 glucose-stimulated insulin secretion. Our data are the first to report a stimulatory effect of a range of alkali pH on K(ATP) channel activity and link this to downstream effects on islet beta-cell function.

Rac1-NADPH oxidase signaling promotes CD36 activation under glucotoxic conditions in pancreatic beta cells.

Science.gov (United States)

Elumalai, Suma; Karunakaran, Udayakumar; Lee, In Kyu; Moon, Jun Sung; Won, Kyu Chang

2017-04-01

We recently reported that cluster determinant 36 (CD36), a fatty acid transporter, plays a pivotal role in glucotoxicity-induced β-cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression. Emerging evidence suggests that the small GTPase Rac1 is involved in the pathogenesis of beta cell dysfunction in type 2 diabetes (T2D). The primary objective of the current study was to determine the role of Rac1 in CD36 activation and its impact on β-cell dysfunction in diabetes mellitus. To address this question, we subjected INS-1 cells and human beta cells (1.1B4) to high glucose conditions (30mM) in the presence or absence of Rac1 inhibition either by NSC23766 (Rac1 GTPase inhibitor) or small interfering RNA. High glucose exposure in INS-1 and human beta cells (1.1b4) resulted in the activation of Rac1 and induced cell apoptosis. Rac1 activation mediates NADPH oxidase (NOX) activation leading to elevated ROS production in both cells. Activation of the Rac1-NOX complex by high glucose levels enhanced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. The inhibition of Rac1 by NSC23766 inhibited NADPH oxidase activity and ROS generation induced by high glucose concentrations in INS-1 & human 1.1b4 beta cells. Inhibition of Rac1-NOX complex activation by NSC23766 significantly reduced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. In addition, Rac1 inhibition by NSC23766 significantly reduced high glucose-induced mitochondrial dysfunction. Furthermore, NADPH oxidase inhibition by VAS2870 also attenuated high glucose-induced ROS generation and cell apoptosis. These results suggest that Rac1-NADPH oxidase dependent CD36 expression contributes to high glucose-induced beta cell dysfunction and cell death. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Concurrent Transient Activation of Wnt/{beta}-Catenin Pathway Prevents Radiation Damage to Salivary Glands

Energy Technology Data Exchange (ETDEWEB)

Hai Bo; Yang Zhenhua; Shangguan Lei; Zhao Yanqiu [Institute for Regenerative Medicine, Scott and White Hospital, Molecular and Cellular Medicine Department, Texas A and M Health Science Center, Temple, Texas (United States); Boyer, Arthur [Department of Radiology, Scott and White Hospital, Temple, Texas (United States); Liu, Fei, E-mail: fliu@medicine.tamhsc.edu [Institute for Regenerative Medicine, Scott and White Hospital, Molecular and Cellular Medicine Department, Texas A and M Health Science Center, Temple, Texas (United States)

2012-05-01

Purpose: Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explored the potential of transient activation of Wnt/{beta}-catenin signaling in preventing radiation damage to salivary glands in a preclinical model. Methods and Materials: Wnt reporter transgenic mice were exposed to 15 Gy single-dose radiation in the head and neck area to evaluate the effects of radiation on Wnt activity in salivary glands. Transient Wnt1 overexpression in basal epithelia was induced in inducible Wnt1 transgenic mice before together with, after, or without local radiation, and then saliva flow rate, histology, apoptosis, proliferation, stem cell activity, and mRNA expression were evaluated. Results: Radiation damage did not significantly affect activity of Wnt/{beta}-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated the Wnt/{beta}-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of the Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects, mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis, likely due to extensive induction of mitosis and up-regulation of proapoptosis gene PUMA while that after radiation might miss the critical treatment window. Conclusion: These results suggest that concurrent transient activation of the Wnt/{beta}-catenin pathway could prevent radiation-induced salivary gland dysfunction.

Regulation of glycogen synthase kinase-3{beta} (GSK-3{beta}) after ionizing radiation; Regulation der Glykogen Synthase Kinase-3{beta} (GSK-3{beta}) nach ionisierender Strahlung

Energy Technology Data Exchange (ETDEWEB)

Boehme, K.A.

2006-12-15

Glycogen Synthase Kinase-3{beta} (GSK-3{beta}) phosphorylates the Mdm2 protein in the central domain. This phosphorylation is absolutely required for p53 degradation. Ionizing radiation inactivates GSK-3{beta} by phosphorylation at serine 9 and in consequence prevents Mdm2 mediated p53 degradation. During the work for my PhD I identified Akt/PKB as the kinase that phosphorylates GSK-3{beta} at serine 9 after ionizing radiation. Ionizing radiation leads to phosphorylation of Akt/PKB at threonine 308 and serine 473. The PI3 Kinase inhibitor LY294002 completely abolished Akt/PKB serine 473 phosphorylation and prevented the induction of GSK-3{beta} serine 9 phosphorylation after ionizing radiation. Interestingly, the most significant activation of Akt/PKB after ionizing radiation occurred in the nucleus while cytoplasmic Akt/PKB was only weakly activated after radiation. By using siRNA, I showed that Akt1/PKBa, but not Akt2/PKB{beta}, is required for phosphorylation of GSK- 3{beta} at serine 9 after ionizing radiation. Phosphorylation and activation of Akt/PKB after ionizing radiation depends on the DNA dependent protein kinase (DNA-PK), a member of the PI3 Kinase family, that is activated by free DNA ends. Both, in cells from SCID mice and after knockdown of the catalytic subunit of DNA-PK by siRNA in osteosarcoma cells, phosphorylation of Akt/PKB at serine 473 and of GSK-3{beta} at serine 9 was completely abolished. Consistent with the principle that phosphorylation of GSK-3 at serine 9 contributes to p53 stabilization after radiation, the accumulation of p53 in response to ionizing radiation was largely prevented by downregulation of DNA-PK. From these results I conclude, that ionizing radiation induces a signaling cascade that leads to Akt1/PKBa activation mediated by DNA-PK dependent phosphorylation of serine 473. After activation Akt1/PKBa phosphorylates and inhibits GSK-3{beta} in the nucleus. The resulting hypophosphorylated form of Mdm2 protein is no longer

Frequency distribution analysis of the long-lived beta-activity of air dust

International Nuclear Information System (INIS)

Bunzl, K.; Hoetzl, H.; Winkler, R.

1977-01-01

In order to compare the average annual beta activities of air dust a frequency distribution analysis of data has been carried out in order to select a representative quantity for the average value of the data group. It was found that the data to be analysed were consistent with a log-normal frequency distribution and therefore calculations were made of, as the representative average, the median of the beta activity of each year as the antilog of the arithmetric mean of the logarithms, log x, of the analytical values x. The 95% confidence limits were also obtained. The quantities thus calculated are summarized in tabular form. (U.K.)

Polypeptides having beta-glucosidase activity and polynucleotides encoding the same

Science.gov (United States)

Brown, Kimberly; Harris, Paul

2013-12-17

The present invention relates to isolated polypeptides having beta-glucosidase 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.

Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.

Science.gov (United States)

Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T; Gage, Fred H; Evans, Ronald M; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active beta-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.

Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

OpenAIRE

Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

1993-01-01

The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene d...

Interleukin-1{beta} regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

Energy Technology Data Exchange (ETDEWEB)

Zitta, Karina; Brandt, Berenice [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Wuensch, Annegret [Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich (Germany); Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany)

2010-09-03

Research highlights: {yields} Levels of IL-1{beta} are increased in the pig myocardium after infarction. {yields} Cultured pig heart cells possess IL-1 receptors. {yields} IL-1{beta} increases cell proliferation of pig heart cells in-vitro. {yields} IL-1{beta} increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. {yields} IL-1{beta} may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1{beta} is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1{beta} on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1{beta}. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1{beta} resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1{beta} plays a major role in the events of tissue remodelling in the heart. Combined

Absolute measurement of {beta} activities and application to the determination of neutronic densities; Mesure absolue d'activites {beta} et application a la determination des densites neutronique

Energy Technology Data Exchange (ETDEWEB)

Cohen, R [Commissariat a l' Energie Atomique, Lab. du Fort de Chatillon, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1951-01-15

M. Berthelot, to my entrance to the ''Commissariat a l 'Energie Atomique'', proposed me to study the absolute measurement of neutron densities. Very quickly the problem of the absolute activity of {beta} sources became the central object of this work. In a first part, we will develop the methods of absolute determination for {beta} activities. The use of a 4{pi} counter permits to get the absolute activity of all beta radioactive source, susceptible to be put as thin leaf and of period superior than some minutes. The method is independent of the spectra of the measured radioelement. we will describe in the second part some applications which use neutron densities measurement, neutron sources intensities and ratio of cross sections of capture of thermal neutrons. (M.B.) [French] M. Berthelot, a mon entree au ''Commissariat a l 'Energie Atomique'', m'a propose d'etudier la mesure absolue des densites neutroniques. Tres rapidement le probleme de l'activite absolue des sources beta est devenu l'objet central de ce travail. Dans une premiere partie, on abordera les methodes de determination absolue des activites beta. L'utilisation d'un compteur 4{pi} permet d 'obtenir l'activite absolue de toute source radioactive beta, susceptible d'etre mise sous forme de feuille mince et de periode superieure a quelques minutes. La methode est independante du spectre du radioelement mesure. On decrira dans la seconde partie quelques applications a des mesures de densites neutroniques, d'intensites de sources de neutrons et de rapport de sections efficaces de capture de neutrons thermiques. (M.B.)

Elaboration of Co-60 sources on gilding vyns, with beta efficiencies 80 % or better and its activity measure by the coincidences method; Elaboracion de fuentes de Co-60 sobre vyns dorado, con eficiencias beta del 80 % o mejor y su medida de actividad por el metodo de coincidencias

Energy Technology Data Exchange (ETDEWEB)

Cortes P, A.; Tejera R, A.; Becerril V, A.; Ortiz C, A

1991-12-15

The measuring technique of radioactive activity by the coincidences method 4 {pi} {beta}{sup -} {gamma} it requires of the elaboration of radioactive sources on thin supports in order to flows the biggest percentage of beta particles, those of the order of the 80 % or but. In this work a procedure for the elaboration of this type of sources, with gilding Vyns is reported. (Author)

Antibodies against chromosomal beta-lactamase

DEFF Research Database (Denmark)

Giwercman, B; Rasmussen, J W; Ciofu, Oana

1994-01-01

A murine monoclonal anti-chromosomal beta-lactamase antibody was developed and an immunoblotting technique was used to study the presence of serum and sputum antibodies against Pseudomonas aeruginosa chromosomal group 1 beta-lactamase in patients with cystic fibrosis (CF). The serum antibody...... 1 cephalosporinase. We found a wide range of chromosomal beta-lactamase activity in the sputum samples, with no correlation with basal or induced activity of beta-lactamase expression. The presence of anti-beta-lactamase antibodies in endobronchial sputum could be an important factor in the defense...

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

Energy Technology Data Exchange (ETDEWEB)

Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: sungy2004@sohu.com [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: rtliu@tsinghua.edu.cn [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)

2009-12-25

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 phases 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.

Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 is not responsible for sodium retention in nephrotic rats

DEFF Research Database (Denmark)

Bistrup, C; Thiesson, H C; Jensen, B L

2005-01-01

AIM: In mineralocorticoid target cells 11-beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) converts glucocorticoids into non-active metabolites thereby protecting the mineralocorticoid receptor (MR) from stimulation by glucocorticoids. In nephrotic syndrome, a decreased activity of 11betaHSD2...... has been suggested to allow glucocorticoids to stimulate MR, thereby contributing to sodium retention. We tested this hypothesis in the puromycin aminonucleoside model of nephrotic syndrome in rats. METHODS: Complete sodium and potassium intakes and excretions (faeces and urine) were measured in rats......)] to suppress endogenous glucocorticoids in the proteinuric stage during active sodium retention. RESULTS: Nephrotic rats developed proteinuria, positive sodium balance, decreased plasma aldosterone concentration, and decreased urinary Na(+)/K(+) ratio. 11betaHSD2 mRNA expression was down-regulated but protein...

The Ewing sarcoma secretome and its response to activation of Wnt/beta-catenin signaling.

Science.gov (United States)

Hawkins, Allegra G; Basrur, Venkatesha; da Veiga Leprevost, Felipe; Pedersen, Elisabeth; Sperring, Colin; Nesvizhskii, Alexey I; Lawlor, Elizabeth R

2018-01-31

Tumor: tumor microenvironment (TME) interactions are critical for tumor progression and the composition and structure of the local extracellular matrix (ECM) are key determinants of tumor metastasis. We recently reported that activation of Wnt/beta-catenin signaling in Ewing sarcoma cells induces widespread transcriptional changes that are associated with acquisition of a metastatic tumor phenotype. Significantly, ECM protein-encoding genes were found to be enriched among Wnt/beta-catenin induced transcripts, leading us to hypothesize that activation of canonical Wnt signaling might induce changes in the Ewing sarcoma secretome. To address this hypothesis, conditioned media from Ewing sarcoma cell lines cultured in the presence or absence of Wnt3a was collected for proteomic analysis. Label-free mass spectrometry was used to identify and quantify differentially secreted proteins. We then used in silico databases to identify only proteins annotated as secreted. Comparison of the secretomes of two Ewing sarcoma cell lines revealed numerous shared proteins, as well as a degree of heterogeneity, in both basal and Wnt-stimulated conditions. Gene set enrichment analysis of secreted proteins revealed that Wnt stimulation reproducibly resulted in increased secretion of proteins involved in ECM organization, ECM receptor interactions, and collagen formation. In particular, Wnt-stimulated Ewing sarcoma cells upregulated secretion of structural collagens, as well as matricellular proteins, such as the metastasis-associated protein, tenascin C (TNC). Interrogation of published databases confirmed reproducible correlations between Wnt/beta-catenin activation and TNC and COL1A1 expression in patient tumors. In summary, this first study of the Ewing sarcoma secretome reveals that Wnt/beta-catenin activated tumor cells upregulate secretion of ECM proteins. Such Wnt/beta-catenin mediated changes are likely to impact on tumor: TME interactions that contribute to metastatic

Monitoring of gross alpha, gross beta and tritium activities in portuguese drinking waters

International Nuclear Information System (INIS)

Lopes, I.; Madruga, M.J.; Ferrador, G.O.; Sequeira, M.M.; Oliveira, E.J.; Gomes, A.R.; Rodrigues, F.D.; Carvalho, F.P.

2006-01-01

The gross beta and tritium activities in the forty Portuguese drinking waters analyzed using the ISO standard methods (Portuguese Guidelines) are below the guidance levels proposed in the Portuguese Drinking Water Quality Guidelines. In what concerns the gross alpha activity only 18% exceeded the recommended level. In general, it can be concluded that the ingestion of these drinking waters does not create a radiological hazard to the human consumption, however, more detailed analyses will be necessary mainly the determinations of the individual alpha emitters radionuclide concentrations. The minimum gross alpha and gross beta detectable activities by L.S.C. methodology are higher than for the proportional counting technique (ISO method). Higher concentration factors will be needed to reach lower required detection limits. (authors)

Safrole oxide induces neuronal apoptosis through inhibition of integrin beta4/SOD activity and elevation of ROS/NADPH oxidase activity.

Science.gov (United States)

Su, Le; Zhao, BaoXiang; Lv, Xin; Wang, Nan; Zhao, Jing; Zhang, ShangLi; Miao, JunYing

2007-02-20

Neuronal apoptosis is a very important event in the development of the central nervous system (CNS), but the underlying mechanisms remain to be elucidated. We have previously shown that safrole oxide, a small molecule, induces integrin beta4 expression and promotes apoptosis in vascular endothelial cells. In this study, the effects of safrole oxide on cell growth and apoptosis have been examined in primary cultures of mouse neurons. Safrole oxide was found to significantly inhibit neuronal cell growth and to induce apoptosis. The inhibitory and apoptotic activities of safrole oxide followed a dose- and time-dependent manner. Interestingly, the expression of integrin beta4 was significantly inhibited with safrole oxide treatment. Furthermore, safrole oxide dramatically increases the level of intracellular reactive oxygen species (ROS) and the activity of NADPH oxidase. Moreover, manganese-dependent superoxide dismutase (MnSOD) activity was decreased significantly with safrole oxide treatment. Our study thus demonstrates that safrole oxide induces neuronal apoptosis through integrin beta4, ROS, NADPH, and MnSOD.

Kinetics, improved activity and thermostability of endoglucanase and beta glucosidase from a mutant-derivative of aspergillus niger ms82

International Nuclear Information System (INIS)

Sohail, M.; Ahmad, A.; Khan, S.A.; Uddin, F.

2013-01-01

A mutant MS301 of Aspergillus niger MS82 showed 1.5 to 2.5-fold improved endoglucanase and beta-glucosidase activity when grown on crude lignocellulosic substrates under solid-state and submerged conditions. Indicators of thermal stability of enzymes (Tm and T1/2) showed that the wild type and mutant endoglucanase was more heat-resistant compared to beta-glucosidase. However, mutant and parent enzymes shared almost the same values for melting temperatures and half-lives. Endoglucanase and beta-glucosidase from both the strains showed optimum activity under acidic pH. Energy of activation (Ea) of mutant beta-glucosidase was substantially lower than the parent enzyme while Ea of mutant endoglucanase was slightly less than the parent. The lowered Ea values can be attributed to the improved beta-glucosidase activity of the mutant strain. Moreover, the MS301 enzymes were better in hydrolyzing purified and crude cellulosic materials than the parent MS82. (author)

Dimers of beta 2-glycoprotein I mimic the in vitro effects of beta 2-glycoprotein I-anti-beta 2-glycoprotein I antibody complexes

NARCIS (Netherlands)

Lutters, B. C.; Meijers, J. C.; Derksen, R. H.; Arnout, J.; de Groot, P. G.

2001-01-01

Anti-beta(2)-glycoprotein I antibodies are thought to cause lupus anticoagulant activity by forming bivalent complexes with beta(2)-glycoprotein I (beta(2)GPI). To test this hypothesis, chimeric fusion proteins were constructed of the dimerization domain (apple 4) of factor XI and beta(2)GPI. Both a

Gross alpha and beta activities in drinking water from Goias State, Brazil

Energy Technology Data Exchange (ETDEWEB)

Mingote, Raquel M. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN), Belo Horizonte, MG (Brazil); Nogueira, Regina A.; Costa, Heliana F. da, E-mail: raquel.mingote@cdtn.br, E-mail: rnogueira@cnen.gov.br, E-mail: heliana@cnen.gov.br [Centro Regional de Ciencias Nucleares do Centro-Oeste (CRCN-CO/CNEN), Abadia de Goias, GO (Brazil). Parque Estadual Telma Ortegal

2017-07-01

Detection of gross alpha and beta radioactivity is important for a quick surveying of both natural and anthropogenic radioactivity in water. Furthermore, gross alpha and gross beta parameters are included in Brazilian legislation on quality of drinking water. In this work, a low background liquid scintillation spectrometer was used to simultaneously determine gross alpha and gross beta in samples of the public water supplies in the state of Goias, Brazil, during 2010-2015. Sample preparation involved evaporation to concentrate the sample ten-fold. The results indicate that the water meets the radioactivity standards required by the regulations MS 2914/2011 of the Brazilian Department of Health. Concerning the high level of censored observations, a statistical treatment of data was conducted by using analysis methods of censored data to provide a reference value of the gross alpha and beta radioactivity in drinking water from the state of Goias. The estimated typical activities are very low, 0.030 Bq•L{sup -1} and 0.058 Bq•L{sup -1}, respectively. (author)

Beta-Adrenergic Receptor Activation during Distinct Patterns of Stimulation Critically Modulates the PKA-Dependence of LTP in the Mouse Hippocampus

Science.gov (United States)

Gelinas, Jennifer N.; Tenorio, Gustavo; Lemon, Neal; Abel, Ted; Nguyen, Peter V.

2008-01-01

Activation of Beta-adrenergic receptors (Beta-ARs) enhances hippocampal memory consolidation and long-term potentiation (LTP), a likely mechanism for memory storage. One signaling pathway linked to Beta-AR activation is the cAMP-PKA pathway. PKA is critical for the consolidation of hippocampal long-term memory and for the expression of some forms…

Increased expression of the auxiliary beta(2-subunit of ventricular L-type Ca(2+ channels leads to single-channel activity characteristic of heart failure.

Directory of Open Access Journals (Sweden)

Roger Hullin

2007-03-01

Full Text Available Increased activity of single ventricular L-type Ca(2+-channels (L-VDCC is a hallmark in human heart failure. Recent findings suggest differential modulation by several auxiliary beta-subunits as a possible explanation.By molecular and functional analyses of human and murine ventricles, we find that enhanced L-VDCC activity is accompanied by altered expression pattern of auxiliary L-VDCC beta-subunit gene products. In HEK293-cells we show differential modulation of single L-VDCC activity by coexpression of several human cardiac beta-subunits: Unlike beta(1 or beta(3 isoforms, beta(2a and beta(2b induce a high-activity channel behavior typical of failing myocytes. In accordance, beta(2-subunit mRNA and protein are up-regulated in failing human myocardium. In a model of heart failure we find that mice overexpressing the human cardiac Ca(V1.2 also reveal increased single-channel activity and sarcolemmal beta(2 expression when entering into the maladaptive stage of heart failure. Interestingly, these animals, when still young and non-failing ("Adaptive Phase", reveal the opposite phenotype, viz: reduced single-channel activity accompanied by lowered beta(2 expression. Additional evidence for the cause-effect relationship between beta(2-subunit expression and single L-VDCC activity is provided by newly engineered, double-transgenic mice bearing both constitutive Ca(V1.2 and inducible beta(2 cardiac overexpression. Here in non-failing hearts induction of beta(2-subunit overexpression mimicked the increase of single L-VDCC activity observed in murine and human chronic heart failure.Our study presents evidence of the pathobiochemical relevance of beta(2-subunits for the electrophysiological phenotype of cardiac L-VDCC and thus provides an explanation for the single L-VDCC gating observed in human and murine heart failure.

Metalo-beta-lactamases Metallo-beta-lactamases

Directory of Open Access Journals (Sweden)

Rodrigo Elisandro Mendes

2006-04-01

Full Text Available Nos últimos anos tem sido observada maior incidência de bacilos Gram-negativos resistentes a cefalosporinas de espectro ampliado no ambiente hospitalar, ocasionando, assim, maior uso de betalactâmicos mais potentes, como os carbapenens. A utilização de carbapenens exerce maior pressão seletiva sobre a microbiota hospitalar, o que pode ocasionar aumento da resistência a esses agentes. Entre os mecanismos de resistência a carbapenens mais comumente identificados estão a produção de betalactamases, como, por exemplo, as pertencentes à classe D de Ambler e as que pertencem à classe B de Ambler, ou metalo-beta-lactamases (MbetaL. Essas últimas hidrolisam todos betalactâmicos comercialmente disponíveis, sendo a única exceção o monobactam aztreonam. Desde o início da década de 1990, novos genes que codificam MbetaLs têm sido descritos em microrganismos clinicamente importantes, como Pseudomonas spp., Acinetobacter spp. e membros da família Enterobacteriaceae. O encontro desses microrganismos não-sensíveis a carbapenens pode ser submetido a metodologias fenotípicas para detecção da produção de MbetaL com o intuito de auxiliar a Comissão de Controle de Infecção Hospitalar (CCIH e prevenir a disseminação desses determinantes de resistência, uma vez que genes que codificam MbetaLs estão contidos em estruturas genéticas que propiciam sua mobilidade de forma muito efetiva, sendo então facilmente disseminados.Increase isolation of Gram-negative bacilli resistant to broad-spectrum cephalosporin has been observed during the last few years, thus determining the use of more potent beta-lactams, such as carbapenems. The use of these antimicrobial agents may lead to the emergence of carbapenem resistant Gram-negative bacilli in the nosocomial environment. Carbapenem resistance may be due to the production of Ambler class D beta-lactamase or Ambler class B beta-lactamase, also called metallo-beta-lactamase (MbetaL. Apart from

The biological activities of (1,3)-(1,6)-{beta}-d-glucan and porous electrospun PLGA membranes containing {beta}-glucan in human dermal fibroblasts and adipose tissue-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Woo, Yeon I; Park, Bong Joo; Kim, Hye-Lee; Lee, Mi Hee; Kim, Jungsung; Park, Jong-Chul [Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yang, Young-Il [Department of Pathology, School of Medicine, Paik Institute for Clinical Research, Inje University, 633-165 Gae-dong, Busan-jin-gu, Busan 614-735 (Korea, Republic of); Kim, Jung Koo [Department of Biomedical Engineering, College of Biomedical Science and Engineering, Inje University, Kimhae 621-749 (Korea, Republic of); Tsubaki, Kazufumi [R and D division, Asahi Denka Co. Ltd, 7-2-35 Higashi-ogu, Arakawa-ku, Tokyo 116-8554 (Japan); Han, Dong-Wook, E-mail: parkjc@yuhs.a [Department of Nanomedical Engineering, College of Nanoscience and Nanotechnology, Pusan National University, geumjeong-gu, Busan 609-735 (Korea, Republic of)

2010-08-01

In this study, we investigated the possible roles of (1,3)-(1,6)-{beta}-d-glucan ({beta}-glucan) and porous electrospun poly-lactide-co-glycolide (PLGA) membranes containing {beta}-glucan for skin wound healing, especially their effect on adult human dermal fibroblast (aHDF) and adipose tissue-derived stem cell (ADSC) activation, proliferation, migration, collagen gel contraction and biological safety tests of the prepared membrane. This study demonstrated that {beta}-glucan and porous PLGA membranes containing {beta}-glucan have enhanced the cellular responses, proliferation and migration, of aHDFs and ADSCs and the result of a collagen gel contraction assay also revealed that collagen gels contract strongly after 4 h post-gelation incubation with {beta}-glucan. Furthermore, we confirmed that porous PLGA membranes containing {beta}-glucan are biologically safe for wound healing study. These results indicate that the porous PLGA membranes containing {beta}-glucan interacted favorably with the membrane and the topical administration of {beta}-glucan was useful in promoting wound healing. Therefore, our study suggests that {beta}-glucan and porous PLGA membranes containing {beta}-glucan may be useful as a material for enhancing wound healing.

Gross beta activity and the concentration of sup(90)Sr in the vegetables of Daejeon area

Energy Technology Data Exchange (ETDEWEB)

Lee, J.Y.; Jun, J.S.; Oh, H.P. (Chungnam National Univ., Taejon (Republic of Korea))

1984-06-01

The measurement of gross beta activity and the concentration of sup(90)Sr in the vegetables such as Brassica Campestris, Raphanus Sativus and Lactuca Sativa grown in Daejeon area was carried out during the period of April through August 1983. The observed levels of gross beta activity and the concentration of sup(90)Sr in the levels of the vegetables were, on average, 189.2+-51.8pCi/g-ash (2372+-827pCi/kg-fresh) and 44.4+-11.5sup(90)Sr pCi/g-Ca(2.5+-0.5sup(90) pCi/g-ash or 31.6+-8.6 sup(90)Sr pCi/kg-fresh), respectively, while the mean level of the gross beta activity in roots was 158.6+-19.4pCi/g-ash(2121+-899pCi/kg-fresh). On the basis of the ICRP recommendations, an estimative evaluation was made for the concentration of sup(90)Sr in the vegetables, and it was turned out to be far below the permissible level. An attempt was also made to look for any existing difference in the gross beta, activities of the vegetables grown in vinyl house and in open field, taking seasonal variation of airborne radioactivity into account for normalizing the activity deposited during the course of discrepant farming period.

Absolute measurement of {beta} activities and application to the determination of neutronic densities; Mesure absolue d'activites {beta} et application a la determination des densites neutronique

Energy Technology Data Exchange (ETDEWEB)

Cohen, R. [Commissariat a l' Energie Atomique, Lab. du Fort de Chatillon, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1951-01-15

M. Berthelot, to my entrance to the ''Commissariat a l 'Energie Atomique'', proposed me to study the absolute measurement of neutron densities. Very quickly the problem of the absolute activity of {beta} sources became the central object of this work. In a first part, we will develop the methods of absolute determination for {beta} activities. The use of a 4{pi} counter permits to get the absolute activity of all beta radioactive source, susceptible to be put as thin leaf and of period superior than some minutes. The method is independent of the spectra of the measured radioelement. we will describe in the second part some applications which use neutron densities measurement, neutron sources intensities and ratio of cross sections of capture of thermal neutrons. (M.B.) [French] M. Berthelot, a mon entree au ''Commissariat a l 'Energie Atomique'', m'a propose d'etudier la mesure absolue des densites neutroniques. Tres rapidement le probleme de l'activite absolue des sources beta est devenu l'objet central de ce travail. Dans une premiere partie, on abordera les methodes de determination absolue des activites beta. L'utilisation d'un compteur 4{pi} permet d 'obtenir l'activite absolue de toute source radioactive beta, susceptible d'etre mise sous forme de feuille mince et de periode superieure a quelques minutes. La methode est independante du spectre du radioelement mesure. On decrira dans la seconde partie quelques applications a des mesures de densites neutroniques, d'intensites de sources de neutrons et de rapport de sections efficaces de capture de neutrons thermiques. (M.B.)

Bace1 activity impairs neuronal glucose metabolism: rescue by beta-hydroxybutyrate and lipoic acid

Directory of Open Access Journals (Sweden)

John A Findlay

2015-10-01

Full Text Available Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1, responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass

Directory of Open Access Journals (Sweden)

Vivas Yurena

2011-12-01

Full Text Available Abstract Background The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPARγ dependent transcriptional responses involved in the process of beta cell mass expansion Results Here we have investigated PPARγ dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob/ob, PPARγ2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance/activation of mechanisms essential for the continued function of the beta cell. Conclusions Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPARγ dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation.

Interleukin-1 beta activates specific populations of enteric neurons and enteric glia in the guinea pig ileum and colon

NARCIS (Netherlands)

Tjwa, ETTL; Bradley, JM; Keenan, CM; Kroese, ABA; Sharkey, KA

2003-01-01

Fos expression was used to assess whether the proinflammatory cytokine interleukin-1beta (IL-1beta) activated specific, chemically coded neuronal populations in isolated preparations of guinea pig ileum and colon. Whether the effects of IL-1beta were mediated through a prostaglandin pathway and

Cellular demise and inflammatory microglial activation during beta-amyloid toxicity are governed by Wnt1 and canonical signaling pathways.

Science.gov (United States)

Chong, Zhao Zhong; Li, Faqi; Maiese, Kenneth

2007-06-01

Initially described as a modulator of embryogenesis for a number of organ systems, Wnt1 has recently been linked to the development of several neurodegenerative disorders, none being of greater significance than Alzheimer's disease. We therefore examined the ability of Wnt1 to oversee vital pathways responsible for cell survival during beta-amyloid (Abeta1-42) exposure. Here we show that Wnt1 is critical for protection in the SH-SY5Y neuronal cell line against genomic DNA degradation, membrane phosphatidylserine (PS) exposure, and microglial activation, since these neuroprotective attributes of Wnt1 are lost during gene silencing of Wnt1 protein expression. Intimately tied to Wnt1 protection is the presence and activation of Akt1. Pharmacological inhibition of the PI 3-K pathway or gene silencing of Akt1 expression can abrogate the protective capacity of Wnt1. Closely aligned with Wnt1 and Akt1 are the integrated canonical pathways of synthase kinase-3beta (GSK-3beta) and beta-catenin. Through Akt1 dependent pathways, Wnt1 phosphorylates GSK-3beta and maintains beta-catenin integrity to insure its translocation from the cytoplasm to the nucleus to block apoptosis. Our work outlines a highly novel role for Wnt1 and its integration with Akt1, GSK-3beta, and beta-catenin to foster neuronal cell survival and repress inflammatory microglial activation that can identify new avenues of therapy against neurodegenerative disorders.

Methodology assessment of the total beta activity in tobacco and tobacco products and certain results

International Nuclear Information System (INIS)

Georgieva, A.; Srentz, A.

2016-01-01

The presence of alpha and beta radionuclides in tobacco and tobacco products is a frequently discussed issue. However, any information in publications about them and their presence in tobacco products is too scarce. World Health care Organization monitors the influence of tobacco smoking on human health. In 2003, a Framework Convention on Tobacco Control was accepted with the aim to protect human health, which was signed by 179 countries, including Bulgaria. The first debates on the presence of radionuclides in tobacco products are raised in Moscow in 2014. These were instigated by data on the findings of polonium-210, reported by USA and Russia. The aim of the report is to outline a methodology to detect the presence of beta-active radionuclides in tobacco and its products. Keywords: beta activity, geiger counter, samples with infinite thickness, tobacco samples

Calcium has a permissive role in interleukin-1beta-induced c-jun N-terminal kinase activation in insulin-secreting cells

DEFF Research Database (Denmark)

Størling, Joachim; Zaitsev, Sergei V; Kapelioukh, Iouri L

2005-01-01

The c-jun N-terminal kinase (JNK) signaling pathway mediates IL-1beta-induced apoptosis in insulin-secreting cells, a mechanism relevant to the destruction of pancreatic beta-cells in type 1 and 2 diabetes. However, the mechanisms that contribute to IL-1beta activation of JNK in beta-cells are la...

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.

Science.gov (United States)

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.

Monitoring gross alpha and beta activity in liquids by using ZnS(Ag) scintillation detectors

Energy Technology Data Exchange (ETDEWEB)

Stevanato, L.; Cester, D.; Filippi, D.; Lunardon, M.; Mistura, G.; Moretto, S.; Viesti, G. [Department of Physics and Astronomy ' Galileo Galilei' , University of Padova, (Italy); Badocco, D.; Pastore, P.; Romanini, F. [Department of Chemical Sciences, University of Padova, (Italy)

2015-07-01

In this work the possibility of monitoring gross alpha and beta activity in liquids using EJ-444 was investigated. Specific tests were carried out to determine the change of the detector properties in water tests. Possible protecting coating is also proposed and tested. Alpha/beta real-time monitoring in liquids is a goal of the EU project TAWARA{sub R}TM. (authors)

Genomic organization of the mouse peroxisome proliferator-activated receptor beta/delta gene

DEFF Research Database (Denmark)

Larsen, Leif K; Amri, Ez-Zoubir; Mandrup, Susanne

2002-01-01

Peroxisome proliferator-activated receptor (PPAR) beta/delta is ubiquitously expressed, but the level of expression differs markedly between different cell types. In order to determine the molecular mechanisms governing PPARbeta/delta gene expression, we have isolated and characterized the mouse...

Change in the aldolase activity in rats' hearts after irradiation with. gamma. and. beta. rays

Energy Technology Data Exchange (ETDEWEB)

Kukulyanskaya, M F; Borodina, G N

1973-01-01

The activity of aldolase fructoso-1-phosphate (I) and aldolase fructoso-1, 6-diphosphate (II) has been studied at various periods after total ..gamma.. and ..beta.. irradiation of rats at a dose of 42 rads. It has been shown that after ..gamma.. irradiation the activity of I increases in the supernatant liquid of the heart muscle homogenate, but drops sharply in the nuclei. In total, the activity of the homogenate did not change. The activity of II dropped for seven days, and after 1 hour and 30 days it was above the normal level. After ..beta.. radiation the activity of II is slowed down after 1, 7, and 15 days. These changes occur in all subcellular fractions. The authors note that the changes in the activity of aldolases are more sharply demarcated after ..gamma.. irradiation and are more substantial for II. (JPRS)

Phagocytosis of haemozoin (malarial pigment enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE

Directory of Open Access Journals (Sweden)

Giribaldi Giuliana

2008-08-01

Full Text Available Abstract Background It has been shown previously that human monocytes fed with haemozoin (HZ or trophozoite-parasitized RBCs displayed increased matrix metalloproteinase-9 (MMP-9 enzyme activity and protein/mRNA expression and increased TNF production, and showed higher matrix invasion ability. The present study utilized the same experimental model to analyse the effect of phagocytosis of: HZ, delipidized HZ, beta-haematin (lipid-free synthetic HZ and trophozoites on production of IL-1beta and MMP-9 activity and expression. The second aim was to find out which component of HZ was responsible for the effects. Methods Native HZ freshly isolated from Plasmodium falciparum (Palo Alto strain, Mycoplasma-free, delipidized HZ, beta-haematin (lipid-free synthetic HZ, trophozoites and control meals such as opsonized non-parasitized RBCs and inert latex particles, were fed to human monocytes. The production of IL-1beta by differently fed monocytes, in presence or absence of specific MMP-9 inhibitor or anti-hIL-1beta antibodies, was quantified in supernatants by ELISA. Expression of IL-1beta was analysed by quantitative real-time RT-PCR. MMP-9 activity and protein expression were quantified by gelatin zymography and Western blotting. Results Monocytes fed with HZ or trophozoite-parasitized RBCs generated increased amounts of IL-1beta and enhanced enzyme activity (in cell supernatants and protein/mRNA expression (in cell lysates of monocyte MMP-9. The latter appears to be causally related to enhanced IL-1beta production, as enhancement of both expression and enzyme activity were abrogated by anti-hIL-1beta Abs. Upregulation of IL-1beta and MMP-9 were absent in monocytes fed with beta-haematin or delipidized HZ, indicating a role for HZ-attached or HZ-generated lipid components. 15-HETE (15(S,R-hydroxy-6,8,11,13-eicosatetraenoic acid a potent lipoperoxidation derivative generated by HZ from arachidonic acid via haem-catalysis was identified as one mediator

GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells.

Science.gov (United States)

Tran, Dat Q; Andersson, John; Wang, Rui; Ramsey, Heather; Unutmaz, Derya; Shevach, Ethan M

2009-08-11

TGF-beta family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-beta is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFbeta-binding protein (LTBP) to produce a large latent form. Latent TGF-beta is also found on the surface of activated FOXP3(+) regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule of unknown function, is critical for tethering TGF-beta to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-beta and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-beta expression on activated Tregs and recombinant latent TGF-beta1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-beta on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism.

Activities of UDP-glucuronyltransferase, beta-glucuronidase and deiodinase types I and II in hyper- and hypothyroid rats

OpenAIRE

Heide, S.M. van der; Joosten, B.H.G.M.; Everts, M.E.; Klaren, P.H.M.

2004-01-01

We have investigated the hypothesis that uridine 5'-diphosphate (UDP)-glucuronyltransferases (UGTs) and beta-glucuronidase are jointly involved in a mechanism for the storage and mobilization of iodothyronine metabolites in liver, kidney, heart and brain. Specifically, we predicted UGT activities to decrease and increase respectively, and beta-glucuronidase activity to increase and decrease respectively in hypo- and hyperthyroidism. To this end we have studied the effects of thyroid status on...

The effect of TGF-beta2 on MMP-2 production and activity in highly metastatic human bladder carcinoma cell line 5637.

Science.gov (United States)

Dehnavi, Ehsan; Soheili, Zahra-Soheila; Samiei, Shahram; Ataei, Zahra; Aryan, Hajar

2009-06-01

Transforming growth factor-beta (TGF-beta) superfamily regulates matrix metalloproteinases (MMP), which intrinsically regulate various cell behaviors leading to metastasis. We investigated the effect of TGF-beta(2) on MMP-2 regulation in human bladder carcinoma cell line 5637. Zymography, ELISA, and real-time polymerase chain reaction revealed that TGF-beta(2) stimulated MMP-2 production, but the transcription of its gene remained unchanged. Wortmannin could not inhibit MMP-2 secretion and activity and conversely the amount of the protein and its enzymatic activity were increased. These data suggest that TGF-beta(2) increased MMP-2 at the posttranscriptional level and this upregulation was independent of phosphatidylinositol 3-kinase signaling pathway.

The gross beta activity and the concentration of sup(90)Sr in the vegetables of Daejeon area

International Nuclear Information System (INIS)

Lee, J.Y.; Jun, J.S.; Oh, H.P.

1984-01-01

The measurement of gross beta activity and the concentration of sup(90)Sr in the vegetables such as Brassica Campestris, Raphanus Sativus and Lactuca Sativa grown in Daejeon area was carried out during the period of April through August 1983. The observed levels of gross beta activity and the concentration of sup(90)Sr in the levels of the vegetables were, on average, 189.2+-51.8pCi/g-ash (2372+-827pCi/kg-fresh) and 44.4+-11.5sup(90)Sr pCi/g-Ca(2.5+-0.5sup(90) pCi/g-ash or 31.6+-8.6 sup(90)Sr pCi/kg-fresh), respectively, while the mean level of the gross beta activity in roots was 158.6+-19.4pCi/g-ash(2121+-899pCi/kg-fresh). On the basis of the ICRP recommendations, an estimative evaluation was made for the concentration of sup(90)Sr in the vegetables, and it was turned out to be far below the permissible level. An attempt was also made to look for any existing difference in the gross beta, activities of the vegetables grown in vinyl house and in open field, taking seasonal variation of airborne radioactivity into account for normalizing the activity deposited during the course of discrepant farming period. (Author)

IL-1beta signals through the EGF receptor and activates Egr-1 through MMP-ADAM.

Directory of Open Access Journals (Sweden)

Estella Sanchez-Guerrero

Full Text Available The immediate-early gene Egr-1 controls the inducible expression of many genes implicated in the pathogenesis of a range of vascular disorders, yet our understanding of the mechanisms controlling the rapid expression of this prototypic zinc finger transcription factor is poor. Here we show that Egr-1 expression induced by IL-1beta is dependent on metalloproteinases (MMP and a disintegrin and a metalloproteinase (ADAM. Pharmacologic MMP/ADAM inhibitors and siRNA knockdown prevent IL-1beta induction of Egr-1. Further, IL-1beta activates Egr-1 via the epidermal growth factor receptor (EGFR. This is blocked by EGFR tyrosine kinase inhibition and EGFR knockdown. IL-1beta induction of Egr-1 expression is reduced in murine embryonic fibroblasts (mEFs deficient in ADAM17 despite unbiased expression of EGFR and IL-1RI in ADAM17-deficient and wild-type mEFs. Finally, we show that IL-1beta-inducible wound repair after mechanical injury requires both EGFR and MMP/ADAM. This study reports for the first time that Egr-1 induction by IL-1beta involves EGFR and MMP/ADAM-dependent EGFR phosphorylation.

Designed beta-boomerang antiendotoxic and antimicrobial peptides: structures and activities in lipopolysaccharide.

Science.gov (United States)

Bhunia, Anirban; Mohanram, Harini; Domadia, Prerna N; Torres, Jaume; Bhattacharjya, Surajit

2009-08-14

Lipopolysaccharide (LPS), an integral part of the outer membrane of Gram-negative bacteria, is involved in a variety of biological processes including inflammation, septic shock, and resistance to host-defense molecules. LPS also provides an environment for folding of outer membrane proteins. In this work, we describe the structure-activity correlation of a series of 12-residue peptides in LPS. NMR structures of the peptides derived in complex with LPS reveal boomerang-like beta-strand conformations that are stabilized by intimate packing between the two aromatic residues located at the 4 and 9 positions. This structural feature renders these peptides with a high ability to neutralize endotoxicity, >80% at 10 nM concentration, of LPS. Replacements of these aromatic residues either with Ala or with Leu destabilizes the boomerang structure with the concomitant loss of antiendotoxic and antimicrobial activities. Furthermore, the aromatic packing stabilizing the beta-boomerang structure in LPS is found to be maintained even in a truncated octapeptide, defining a structured LPS binding motif. The mode of action of the active designed peptides correlates well with their ability to perturb LPS micelle structures. Fourier transform infrared spectroscopy studies of the peptides delineate beta-type conformations and immobilization of phosphate head groups of LPS. Trp fluorescence studies demonstrated selective interactions with LPS and the depth of insertion into the LPS bilayer. Our results demonstrate the requirement of LPS-specific structures of peptides for endotoxin neutralizations. In addition, we propose that structures of these peptides may be employed to design proteins for the outer membrane.

Non-linear Relationship between BOLD Activation and Amplitude of Beta Oscillations in the Supplementary Motor Area during Rhythmic Finger Tapping and Internal Timing

Science.gov (United States)

Gompf, Florian; Pflug, Anja; Laufs, Helmut; Kell, Christian A.

2017-01-01

Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region. PMID:29249950

Non-linear Relationship between BOLD Activation and Amplitude of Beta Oscillations in the Supplementary Motor Area during Rhythmic Finger Tapping and Internal Timing.

Science.gov (United States)

Gompf, Florian; Pflug, Anja; Laufs, Helmut; Kell, Christian A

2017-01-01

Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region.

[Antimicrobial activity of fosfomycin under various conditions against standard strains, beta-lactam resistant strains, and multidrug efflux system mutants].

Science.gov (United States)

Mikuniya, Takeshi; Hiraishi, Toru; Maebashi, Kazunori; Ida, Takashi; Takata, Toshihiko; Hikida, Muneo; Yamada, Sakuo; Gotoh, Naomasa; Nishino, Takeshi

2005-04-01

The purpose of this study was to evaluate the possible benefit of fosfomycin (FOM) as prophylactic antibiotic in terms of antimicrobial activity and the potential of inducibility of beta-lactamase, compared with cefazolin, cefotiam, cefmetazole, and piperacillin that are commonly used as perioperative agents. The in vitro activity of FOM against aerobic Gram-negative bacteria using Mueller-Hinton agar or nutrient agar supplemented with glucose-6-phosphate (G6P) as tested medium increased within a range from 2 to 256 times the activity in the medium without G6P. However, the susceptibility of Gram-positive bacteria to FOM remained largely unchanged with or without G6P. There was no aerobic- or anaerobic-bacteria which changed susceptibility against beta-lactam antibiotics under various tested medium conditions. FOM demonstrated strong bactericidal activity against Escherichia coli and Pseudomonas aeruginosa in a dose dependent manner, and decreased viable cell counts of Staphylococcus aureus. In the case of P. aeruginosa, transmission electron micrographs study revealed that numerous lysed cells were present 2 hours after treatment with FOM at four times the MIC. First and second generation cephalosporins induced AmpC-type beta-lactamase in a dose dependent manner among beta-lactamase inducible strains of P. aeruginosa and Enterobacter cloacae. On the other hand, inducible activity of FOM on beta-lactamase production was less than 1/25 to 1/65 compared with those of cephalosporins. In addition, FOM maintained strong antimicrobial activity for over then 20 years after marketing, because of the excellent stability against various types of beta-lactamase produced by plasmid-carrying bacteria and clinical isolates. FOM was not extruded by four types of efflux systems, such as MexAB-OprM, MexCD-OprJ, MexXY/ OprM and MexEF-OprN, however beta-lactam antibiotics were substrates of MexAB-OprM and MexCD-OprJ. In conclusion, FOM provides adequate coverage for both aerobic Gram

Expression profile of senescence-associated beta-galactosidase and activation of telomerase in human ovarian surface epithelial cells undergoing immortalization.

Science.gov (United States)

Litaker, J R; Pan, J; Cheung, Y; Zhang, D K; Liu, Y; Wong, S C; Wan, T S; Tsao, S W

1998-11-01

Senescence is a specific physiological stage of cells characterized by long population doubling time. It accounts for the inability of normal somatic cells to undergo indefinite cell division. As the number of population doublings increase, cell cycle regulatory mechanisms come into play and signal cells to exit the cell cycle and become senescent. Senescence has been implicated in the aging process and may function as a tumor suppressor mechanism in human cells. The ability to measure the degree of cellular senescence is important in understanding the biological processes regulating cell aging and immortalization. Senescent cells exhibit an enzyme termed senescence-associated histochemical staining. Cells immortalized by viral oncogenes often enter a stage of crisis at the early phase of immortalization. The cells at crisis have a long population doubling time. Cells at the crisis stage resemble senescent cells and the expression of SA- beta-Gal may be used to monitor the process of immortalization. In this study the expression profile of SA-beta-Gal was examined in human ovarian surface epithelial cells (HOSE 6-3) undergoing immortalization by the human papilloma viral oncogene E6 and E7 (HPV E6 and E7). Our results showed a low percentage (12.0%) of HOSE 6-3 cells expressing SA-beta-Gal activity at the pre-crisis stage. The percentage of HOSE 6-3 cells expressing SA-beta-Gal activity was highest (39.2%) at the crisis stage. When HOSE 6-3 cells achieved immortalized status there was a sharp decrease in cells (1. 3%) expressing SA-beta-Gal activity. In addition, an inverse relationship between the expression of SA-beta-Gal activity and telomerase activity was noted in cells undergoing immortalization. The results confirm that the SA-beta-Gal enzyme is a good marker for monitoring the population of cells undergoing senescence at different stages of immortalization and that telomerase activation is a characteristic feature of post-crisis cells.

Characterization of beta-adrenergic receptors and adenylate cyclase activity in rat brown fat

International Nuclear Information System (INIS)

Baresi, L.A.; Morley, J.E.; Scarpace, P.J.

1986-01-01

Catecholamines stimulate thermogenesis in rat brown fat through a mechanism which involves binding to the beta-adrenergic receptor (BAR), stimulation of adenylate cyclase (AC) and culminating with uncoupling of mitochondrial respiration from ATP synthesis. The authors characterized BAR, AC and cytochrome (cyt) c oxidase in CDF (F-344) interscapular brown fat. Scatchard analysis of [ 125 ]Iodopindolol binding yields a straight line consistent with a single class of antagonist binding sites with 41.8 +/- 12.0 fmol BAR/mg protein and a K/sub d/ of 118 +/- 15 pM. Binding was both specific and stereospecific. Competition with 1-propranolol (K/sub d/ = 6.7 nM) was 15 times more potent than d-propranolol (K/sub d/ = 103 nM). Competition with isoproterenol (K/sub d/ = 79 nM) was 10 times more potent than epinephrine (K/sub d/ = 820 nM) which was 35 times more potent than norepinephrine (K/sub d/ = 2.9 x 10 -5 M) suggesting predominate beta 2 -type BAR. Cyt c oxidase activity was assessed in brown fat mitochrondrial preparations. The ratio of BAR to cyt c activity was 959 +/- 275 nmol BAR/mol cyc c/min. Isoproterenol (0.1 mM) stimulated AC activity was 24 times GTP (0.1 mM) stimulated AC (98.5 vs 40.7 pmol cAMP/min/mg). NaF-stimulated AC was nine times basal activity (90.5 vs 11.3 pmol cAMP/min/mg). These data demonstrate the presence of a beta- 2 -type BAR coupled to adenylate cyclase in rat brown fat

Collateral sensitivity between aminoglycosides and beta-lactam antibiotics depends on active proton pumps.

Science.gov (United States)

Azimi, Leila; Rastegar Lari, Abdolaziz

2017-11-01

Selection inversion is the hypothesis for antibiotic resistant inhabitation in bacteria and collateral sensitivity is one of the proposed phenomena for achievement of this hypothesis. The presence of collateral sensitivity associated with the proton motivation pump between the aminoglycosides and beta-lactam group of antibiotics is one of the examples of collateral sensitivity in some studies. The aim of this study was to demonstrate that collateral sensitivity between aminoglycosides and beta-lactam antibiotics associated with proton motivation pump may not be true in all cases. In this study, 100 Pseudomonas aeruginosa were surveyed. Gentamicin and imipenem-resistant strains were confirmed by disc diffusion method and MIC. Active proton motivation pumps were screened by pumps inhibitor. Semi-quantitative Real-Time PCR assay was used to confirm gene overexpression. Seventy-six and 79 out of 100 strains were resistant to gentamicin and imipenem, respectively. Seventy-five strains were resistant to both gentamicin and imipenem. The results of proton pump inhibitor test showed the involvement of active proton motivation pump in 22 of 75 imipenem- and gentamicin-resistant strains. According to Real - Time PCR assay, mexX efflux gene was overexpressed in the majority of isolates tested. The collateral sensitivity effect cannot explain the involvement of active proton motivation pumps in both imipenem and gentamicin-resistant strains simultaneously. Active and/or inactive proton pump in gentamicin-sensitive and/or resistant strains cannot be a suitable example for explanation of collateral sensitivity between aminoglycosides and beta-lactam antibiotics. Copyright © 2017 Elsevier Ltd. All rights reserved.

The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.

Science.gov (United States)

Kanamori, Mutsumi; Sandy, Peter; Marzinotto, Stefania; Benetti, Roberta; Kai, Chikatoshi; Hayashizaki, Yoshihide; Schneider, Claudio; Suzuki, Harukazu

2003-10-03

Wnt signaling is essential during development while deregulation of this pathway frequently leads to the formation of various tumors including colorectal carcinomas. A key component of the pathway is beta-catenin that, in association with TCF-4, directly regulates the expression of Wnt-responsive genes. To identify novel binding partners of beta-catenin that may control its transcriptional activity, we performed a mammalian two-hybrid screen and isolated the Tax-interacting protein (TIP-1). The in vivo complex formation between beta-catenin and TIP-1 was verified by coimmunoprecipitation, and a direct physical association was revealed by glutathione S-transferase pull-down experiments in vitro. By using a panel of deletion mutants of both proteins, we demonstrate that the interaction is mediated by the PDZ (PSD-95/DLG/ZO-1 homology) domain of TIP-1 and requires primarily the last four amino acids of beta-catenin. TIP-1 overexpression resulted in a dose-dependent decrease in the transcriptional activity of beta-catenin when tested on the TOP/FOPFLASH reporter system. Conversely, siRNA-mediated knock-down of endogenous TIP-1 slightly increased endogenous beta-catenin transactivation function. Moreover, we show that overexpression of TIP-1 reduced the proliferation and anchorage-independent growth of colorectal cancer cells. These data suggest that TIP-1 may represent a novel regulatory element in the Wnt/beta-catenin signaling pathway.

Stimulation of Na{sup +}/K{sup +} ATPase activity and Na{sup +} coupled glucose transport by {beta}-catenin

Energy Technology Data Exchange (ETDEWEB)

Sopjani, Mentor [Department of Physiology, University of Tuebingen (Germany); Department of Chemistry, University of Prishtina, Kosovo (Country Unknown); Alesutan, Ioana; Wilmes, Jan [Department of Physiology, University of Tuebingen (Germany); Dermaku-Sopjani, Miribane [Department of Physiology, University of Tuebingen (Germany); Faculty of Medicine, University of Prishtina, Kosovo (Country Unknown); Lam, Rebecca S. [Department of Physiology, University of Tuebingen (Germany); Department of Molecular Neurogenetics, Max Planck Institute of Biophysics, Frankfurt/Main (Germany); Koutsouki, Evgenia [Department of Physiology, University of Tuebingen (Germany); Jakupi, Muharrem [Faculty of Medicine, University of Prishtina, Kosovo (Country Unknown); Foeller, Michael [Department of Physiology, University of Tuebingen (Germany); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology, University of Tuebingen (Germany)

2010-11-19

Research highlights: {yields} The oncogenic transcription factor {beta}-catenin stimulates the Na{sup +}/K{sup +}-ATPase. {yields} {beta}-Catenin stimulates SGLT1 dependent Na{sup +}, glucose cotransport. {yields} The effects are independent of transcription. {yields} {beta}-Catenin sensitive transport may contribute to properties of proliferating cells. -- Abstract: {beta}-Catenin is a multifunctional protein stimulating as oncogenic transcription factor several genes important for cell proliferation. {beta}-Catenin-regulated genes include the serum- and glucocorticoid-inducible kinase SGK1, which is known to stimulate a variety of transport systems. The present study explored the possibility that {beta}-catenin influences membrane transport. To this end, {beta}-catenin was expressed in Xenopus oocytes with or without SGLT1 and electrogenic transport determined by dual electrode voltage clamp. As a result, expression of {beta}-catenin significantly enhanced the ouabain-sensitive current of the endogeneous Na{sup +}/K{sup +}-ATPase. Inhibition of vesicle trafficking by brefeldin A revealed that the stimulatory effect of {beta}-catenin on the endogenous Na{sup +}/K{sup +}-ATPase was not due to enhanced stability of the pump protein in the cell membrane. Expression of {beta}-catenin further enhanced glucose-induced current (Ig) in SGLT1-expressing oocytes. In the absence of SGLT1 Ig was negligible irrespective of {beta}-catenin expression. The stimulating effect of {beta}-catenin on both Na{sup +}/K{sup +} ATPase and SGLT1 activity was observed even in the presence of actinomycin D, an inhibitor of transcription. The experiments disclose a completely novel function of {beta}-catenin, i.e. the regulation of transport.

sup. alpha. N-acetyl derivatives of. beta. -endorphin-(1-31) and -(1-27) regulate the supraspinal antinociceptive activity of different opioids in mice

Energy Technology Data Exchange (ETDEWEB)

Garzon, J.; Sanchez-Blazquez, P. (Cajal Institute, Madrid (Spain))

1991-01-01

{sup {alpha}}N-acetyl human {beta}-endorphin(1-31) injected icv to mice antagonized the analgesic activity of {beta}-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of {sup {alpha}}N-acetyl {beta}-endorphin-(1-31) was exhibited at remarkable low doses (fmols) reaching a maximum that persisted even though the dose was increased 100,000 times. The regulatory effect of a single dose of the acetylated neuropeptide lasted for 24h. The activity of {sup {alpha}}N-acetyl human {beta}-endorphin(1-31) was partially retained by the shorter peptide {sup {alpha}}N-acetyl human {beta}-endorphin-(1-27) and to a lesser extent by {beta}-endorphin-(1-27), {beta}-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated {beta}-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM ({sup 125}I)-Tyr{sup 27} human {beta}-endorphin-(1-31) specific binding, the first step was abolished with an apparent IC{sub 50} of 0.35 nM, and the rest with an IC{sub 50} of 200 nM. It is suggested that {sup {alpha}}N-acetyl {beta}-endorphin-(1-31) changed the efficiency of the opioid analgesics by acting upon a specific substrate that is functionally coupled to the opioid receptor, presumably the guanine nucleotide binding regulatory proteins G{sub i}/G{sub 0}.

Activity measurement of phosphorus-32 in the presence of pure beta-emitting impurities

CSIR Research Space (South Africa)

Simpson, B

2006-02-27

Full Text Available Activity measurements undertaken at the CSIR's National Metrology Laboratory (NML) on a solution of the pure beta-emitting radionuclide phosphorus-32, which formed part of an international key comparison, are described. Since exploratory source...

AMP-activated protein kinase (AMPK mediates nutrient regulation of thioredoxin-interacting protein (TXNIP in pancreatic beta-cells.

Directory of Open Access Journals (Sweden)

Maayan Shaked

Full Text Available Thioredoxin-interacting protein (TXNIP regulates critical biological processes including inflammation, stress and apoptosis. TXNIP is upregulated by glucose and is a critical mediator of hyperglycemia-induced beta-cell apoptosis in diabetes. In contrast, the saturated long-chain fatty acid palmitate, although toxic to the beta-cell, inhibits TXNIP expression. The mechanisms involved in the opposing effects of glucose and fatty acids on TXNIP expression are unknown. We found that both palmitate and oleate inhibited TXNIP in a rat beta-cell line and islets. Palmitate inhibition of TXNIP was independent of fatty acid beta-oxidation or esterification. AMP-activated protein kinase (AMPK has an important role in cellular energy sensing and control of metabolic homeostasis; therefore we investigated its involvement in nutrient regulation of TXNIP. As expected, glucose inhibited whereas palmitate stimulated AMPK. Pharmacologic activators of AMPK mimicked fatty acids by inhibiting TXNIP. AMPK knockdown increased TXNIP expression in presence of high glucose with and without palmitate, indicating that nutrient (glucose and fatty acids effects on TXNIP are mediated in part via modulation of AMPK activity. TXNIP is transcriptionally regulated by carbohydrate response element-binding protein (ChREBP. Palmitate inhibited glucose-stimulated ChREBP nuclear entry and recruitment to the Txnip promoter, thereby inhibiting Txnip transcription. We conclude that AMPK is an important regulator of Txnip transcription via modulation of ChREBP activity. The divergent effects of glucose and fatty acids on TXNIP expression result in part from their opposing effects on AMPK activity. In light of the important role of TXNIP in beta-cell apoptosis, its inhibition by fatty acids can be regarded as an adaptive/protective response to glucolipotoxicity. The finding that AMPK mediates nutrient regulation of TXNIP may have important implications for the pathophysiology and treatment

A proteomics strategy to discover beta-glucosidases from Aspergillus fumigatus with two-dimensional page in-gel activity assay and tandem mass spectrometry.

Science.gov (United States)

Kim, Kee-Hong; Brown, Kimberly M; Harris, Paul V; Langston, James A; Cherry, Joel R

2007-12-01

Economically competitive production of ethanol from lignocellulosic biomass by enzymatic hydrolysis and fermentation is currently limited, in part, by the relatively high cost and low efficiency of the enzymes required to hydrolyze cellulose to fermentable sugars. Discovery of novel cellulases with greater activity could be a critical step in overcoming this cost barrier. beta-Glucosidase catalyzes the final step in conversion of glucose polymers to glucose. Despite the importance, only a few beta-glucosidases are commercially available, and more efficient ones are clearly needed. We developed a proteomics strategy aiming to discover beta-glucosidases present in the secreted proteome of the cellulose-degrading fungus Aspergillus fumigatus. With the use of partial or complete protein denaturing conditions, the secretory proteome was fractionated in a 2DGE format and beta-glucosidase activity was detected in the gel after infusion with a substrate analogue that fluoresces upon hydrolysis. Fluorescing spots were subjected to tryptic-digestion, and identification as beta-glucosidases was confirmed by tandem mass spectrometry. Two novel beta-glucosidases of A. fumigatus were identified by this in situ activity staining method, and the gene coding for a novel beta-glucosidase ( EAL88289 ) was cloned and heterologously expressed. The expressed beta-glucosidase showed far superior heat stability to the previously characterized beta-glucosidases of Aspergillus niger and Aspergillus oryzae. Improved heat stability is important for development of the next generation of saccharifying enzymes capable of performing fast cellulose hydrolysis reactions at elevated temperatures, thereby lowering the cost of bioethanol production. The in situ activity staining approach described here would be a useful tool for cataloguing and assessing the efficiency of beta-glucosidases in a high throughput fashion.

Purification and properties of a beta-galactosidase from carambola fruit with significant activity towards cell wall polysaccharides.

Science.gov (United States)

Balasubramaniam, Sumathi; Lee, Heng Chin; Lazan, Hamid; Othman, Roohaida; Ali, Zainon Mohd

2005-01-01

beta-Galactosidase (EC. 3.2.1.23) from ripe carambola (Averrhoa carambola L. cv. B10) fruit was fractionated through a combination of ion exchange and gel filtration chromatography into four isoforms, viz. beta-galactosidase I, II, III and IV. This beta-galactosidases had apparent native molecular masses of 84, 77, 58 and 130 kDa, respectively. beta-Galactosidase I, the predominant isoform, was purified to electrophoretic homogeneity; analysis of the protein by SDS-PAGE revealed two subunits with molecular masses of 48 and 36 kDa. N-terminal amino acid sequence of the respective polypeptides shared high similarities albeit at different domains, with the deduced amino acid sequence of certain plant beta-galactosidases, thus, explaining the observed low similarity between the two subunits. beta-Galactosidase I was probably a heterodimer that have glycoprotein properties and a pI value of 7.2, with one of the potential glycosylation sites appeared to reside within the 48-kDa-polypeptide. The purified beta-galactosidase I was substantially active in hydrolyzing (1-->4)beta-linked spruce and a mixture of (1-->3)beta- and (1-->6)beta-linked gum arabic galactans. This isoform also had the capability to solubilize and depolymerize structurally intact pectins as well as to modify alkaline-soluble hemicelluloses, reflecting in part changes that occur during ripening.

Post-Movement Beta Activity in Sensorimotor Cortex Indexes Confidence in the Estimations from Internal Models.

Science.gov (United States)

Tan, Huiling; Wade, Cian; Brown, Peter

2016-02-03

Beta oscillations are a dominant feature of the sensorimotor system. A transient and prominent increase in beta oscillations is consistently observed across the sensorimotor cortical-basal ganglia network after cessation of voluntary movement: the post-movement beta synchronization (PMBS). Current theories about the function of the PMBS have been focused on either the closure of motor response or the processing of sensory afferance. Computational models of sensorimotor control have emphasized the importance of the integration between feedforward estimation and sensory feedback, and therefore the putative motor and sensory functions of beta oscillations may reciprocally interact with each other and in fact be indissociable. Here we show that the amplitude of sensorimotor PMBS is modulated by the history of visual feedback of task-relevant errors, and negatively correlated with the trial-to-trial exploratory adjustment in a sensorimotor adaptation task in young healthy human subjects. The PMBS also negatively correlated with the uncertainty associated with the feedforward estimation, which was recursively updated in light of new sensory feedback, as identified by a Bayesian learning model. These results reconcile the two opposing motor and sensory views of the function of PMBS, and suggest a unifying theory in which PMBS indexes the confidence in internal feedforward estimation in Bayesian sensorimotor integration. Its amplitude simultaneously reflects cortical sensory processing and signals the need for maintenance or adaptation of the motor output, and if necessary, exploration to identify an altered sensorimotor transformation. For optimal sensorimotor control, sensory feedback and feedforward estimation of a movement's sensory consequences should be weighted by the inverse of their corresponding uncertainties, which require recursive updating in a dynamic environment. We show that post-movement beta activity (13-30 Hz) over sensorimotor cortex in young healthy

A method for the determination of residual beta activity in drinking water samples

Energy Technology Data Exchange (ETDEWEB)

Idoeta, R. [Dpto. Ingenieria Nuclear y Mecanica de Fluidos, E. T. S. Ingenieria de Bilbao - Universidad del Pais Vasco (UPV/EHU), Alda. Urquijo s/n. 48013 Bilbao (Spain)], E-mail: raquel.idoeta@ehu.es; Herranz, M.; Abelairas, A.; Legarda, F. [Dpto. Ingenieria Nuclear y Mecanica de Fluidos, E. T. S. Ingenieria de Bilbao - Universidad del Pais Vasco (UPV/EHU), Alda. Urquijo s/n. 48013 Bilbao (Spain)

2007-09-15

The determination of residual beta activity in drinking water is usually needed in most monitoring programs. In this work a procedure for its determination is described and expressions for the calculations of detection limits and uncertainties are proposed.

A method for the determination of residual beta activity in drinking water samples

International Nuclear Information System (INIS)

Idoeta, R.; Herranz, M.; Abelairas, A.; Legarda, F.

2007-01-01

The determination of residual beta activity in drinking water is usually needed in most monitoring programs. In this work a procedure for its determination is described and expressions for the calculations of detection limits and uncertainties are proposed

Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11beta-HSD-2 activity

DEFF Research Database (Denmark)

Thiesson, Helle; Jensen, Boye L; Bistrup, Claus

2007-01-01

Downregulation of the renal glucocorticoid-metabolizing enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) during liver cirrhosis may allow activation of the mineralocorticoid receptor (MR) by glucocorticoids and contribute to sodium retention. We tested this hypothesis in male Wistar...... rats with decompensated liver cirrhosis and ascites 7 wk after bile duct ligation (BDL). Renal 11beta-HSD-2 mRNA, protein, and activity were significantly decreased in decompensated rats. The urinary Na(+)/K(+) ratio was reduced by 40%. Renal epithelial sodium channel (ENaC) mRNA and immunostaining...... were only slightly affected. Complete metabolic studies, including fecal excretion, showed that the BDL rats had avid renal sodium retention. Treatment of the BDL rats with dexamethasone suppressed endogenous glucocorticoid production, normalized total sodium balance and renal sodium excretion...

Human beta-glucuronidase. Measurement of its activity in gallbladder bile devoid of intrinsic interference.

Science.gov (United States)

Ho, Y C; Ho, K J

1988-04-01

Our purpose is to develop a standard method for preparing the bile for beta-glucuronidase determination by removal of bile acids and conjugated bilirubin which interfere with its activity. The bile acids and conjugated bilirubin in their purified solutions and in the diluted gallbladder biles could be extracted completely with cholestyramine in powder form or tetrahexylammonium chloride (THAC) in chloroform or ethyl acetate. The enzyme was, however, partially precipitated with cholestyramine and denatured by chloroform but not by ethyl acetate. A standard procedure, therefore, includes extraction of the diluted gallbladder bile with THAC in ethyl acetate, followed by determination of the maximal velocity (Vmax) of the enzyme by a kinetic method employing phenolphthalein glucuronide as the substrate. The average Vmax of beta-glucuronidase in the 20 normal gallbladder biles was 165 +/- 86 nmol/min/ml (mean +/- SD), a 23.5-fold increase over the activity before extraction. The measured activity represented the true activity of the enzyme in the bile for recovery of activity of the enzyme added to the bile was practically complete.

Liquid argon as active shielding and coolant for bare germanium detectors. A novel background suppression method for the GERDA 0{nu}{beta}{beta} experiment

Energy Technology Data Exchange (ETDEWEB)

Peiffer, J.P.

2007-07-25

Two of the most important open questions in particle physics are whether neutrinos are their own anti-particles (Majorana particles) as required by most extensions of the StandardModel and the absolute values of the neutrino masses. The neutrinoless double beta (0{nu}{beta}{beta}) decay, which can be investigated using {sup 76}Ge (a double beta isotope), is the most sensitive probe for these properties. There is a claim for an evidence for the 0{nu}{beta}{beta} decay in the Heidelberg-Moscow (HdM) {sup 76}Ge experiment by a part of the HdM collaboration. The new {sup 76}Ge experiment Gerda aims to check this claim within one year with 15 kg.y of statistics in Phase I at a background level of {<=}10{sup -2} events/(kg.keV.y) and to go to higher sensitivity with 100 kg.y of statistics in Phase II at a background level of {<=}10{sup -3} events/(kg.keV.y). In Gerda bare germanium semiconductor detectors (enriched in {sup 76}Ge) will be operated in liquid argon (LAr). LAr serves as cryogenic coolant and as high purity shielding against external background. To reach the background level for Phase II, new methods are required to suppress the cosmogenic background of the diodes. The background from cosmogenically produced {sup 60}Co is expected to be {proportional_to}2.5.10{sup -3} events/(kg.keV.y). LAr scintillates in UV ({lambda}=128 nm) and a novel concept is to use this scintillation light as anti-coincidence signal for background suppression. In this work the efficiency of such a LAr scintillation veto was investigated for the first time. In a setup with 19 kg active LAr mass a suppression of a factor 3 has been achieved for {sup 60}Co and a factor 17 for {sup 232}Th around Q{sub {beta}}{sub {beta}} = 2039 keV. This suppression will further increase for a one ton active volume (factor O(100) for {sup 232}Th and {sup 60}Co). LAr scintillation can also be used as a powerful tool for background diagnostics. For this purpose a new, very stable and robust wavelength

Activity measurement of phosphorus-32 in the presence of pure beta-emitting impurities

CSIR Research Space (South Africa)

Simpson, BRS

2006-01-01

Full Text Available Authors describe the activity measurements undertaken at the CSIR’s National Metrology Laboratory on a solution of the pure beta emitting Radio nuclide phosphorus-32 that formed part of an international key comparison. Depending on the production...

Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors.

Science.gov (United States)

Naujok, Ortwin; Lentes, Jana; Diekmann, Ulf; Davenport, Claudia; Lenzen, Sigurd

2014-04-29

Small membrane-permeable molecules are now widely used during maintenance and differentiation of embryonic stem cells of different species. In particular the glycogen synthase kinase 3 (GSK3) is an interesting target, since its chemical inhibition activates the Wnt/beta-catenin pathway. In the present comparative study four GSK3 inhibitors were characterized. Cytotoxicity and potential to activate the Wnt/beta-catenin pathway were tested using the commonly used GSK3 inhibitors BIO, SB-216763, CHIR-99021, and CHIR-98014. Wnt/beta-catenin-dependent target genes were measured by quantitative PCR to confirm the Wnt-reporter assay and finally EC50-values were calculated. CHIR-99021 and SB-216763 had the lowest toxicities in mouse embryonic stem cells and CHIR-98014 and BIO the highest toxicities. Only CHIR-99021 and CHIR-98014 lead to a strong induction of the Wnt/beta-catenin pathway, whereas BIO and SB-216763 showed a minor or no increase in activation of the Wnt/beta-catenin pathway over the natural ligand Wnt3a. The data from the Wnt-reporter assay were confirmed by gene expression analysis of the TCF/LEF regulated gene T. Out of the four tested GSK3 inhibitors, only CHIR-99021 and CHIR-98014 proved to be potent pharmacological activators of the Wnt/beta-catenin signaling pathway. But only in the case of CHIR-99021 high potency was combined with very low toxicity.

A monitor for beta activity in air

International Nuclear Information System (INIS)

Bansode, P.Y.; Karpagam, R.; Phatak, P.R.; Jakati, R.K.

2004-01-01

Radiation monitors using compensated ion chamber technique have been in use in nuclear power plants and facilities for measurement of beta activity in presence of gamma background. This paper describes a system based on auto-ranging electrometer with provision for selecting alarm-level and giving out measurement and status information on RS232 serial link for remote use such as PC or notebook computer via RadNet protocol. The over all system incorporates indigenously developed 40 litre ion-chamber reported in the literature and facility for circulating air through the chamber using pumping system. The setup is housed in standard racks with wheels for easy transport within the laboratory building. The data acquiring and I/O processing is carried out using Philips 80c552 micro-controller. (author)

Stabilization of beta-catenin induces pancreas tumor formation.

Science.gov (United States)

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.

Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

Energy Technology Data Exchange (ETDEWEB)

Xue, Deng; Tamai, Riyoko [Division of Oral Bacteriology, Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611 (Japan); Endo, Yasuo [Department of Molecular Regulation, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan); Kiyoura, Yusuke [Division of Oral Bacteriology, Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611 (Japan)

2009-02-15

Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1{beta}, but not TNF{alpha}, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1{beta} production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1{beta} production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1{beta} induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1{beta} release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs.

Beta cell proliferation and growth factors

DEFF Research Database (Denmark)

Nielsen, Jens Høiriis; Svensson, C; Møldrup, Annette

1999-01-01

Formation of new beta cells can take place by two pathways: replication of already differentiated beta cells or neogenesis from putative islet stem cells. Under physiological conditions both processes are most pronounced during the fetal and neonatal development of the pancreas. In adulthood little...... increase in the beta cell number seems to occur. In pregnancy, however, a marked hyperplasia of the beta cells is observed both in rodents and man. Increased mitotic activity has been seen both in vivo and in vitro in islets exposed to placental lactogen (PL), prolactin (PRL) and growth hormone (GH...... and activation of the tyrosine kinase JAK2 and the transcription factors STAT1 and 3. The activation of the insulin gene however also requires the distal part of the receptor and activation of calcium uptake and STAT5. In order to identify putative autocrine growth factors or targets for growth factors we have...

Vitamin A and beta-carotene concentrations in adults with HIV/AIDS on highly active antiretroviral therapy.

Science.gov (United States)

Kaio, Daniella Junko; Rondó, Patricia Helen Carvalho; Souza, José Maria Pacheco; Firmino, Aline Vale; Luzia, Liania Alves; Segurado, Aluisio Augusto

2013-01-01

Micronutrient deficiency is a common condition in HIV-infected individuals and may occur in all stages of the disease. The objective of this cross-sectional study was to compare the concentrations of vitamin A and beta-carotene, micronutrients related to immunity and oxidative stress, in 182 adults with HIV/AIDS, under different highly active antiretroviral therapy (HAART) regimens. Patients were divided into 3 groups according to their HAART regimen: combination of nucleoside analog reverse transcriptase inhibitors (NRTIs) and non-NRTIs; combination of NRTIs, protease inhibitors, and ritonavir; combination of NRTIs and other classes. Multiple linear regression analysis determined the effect of the treatment regimen, time of use, and compliance with the regimen, on vitamin A and beta-carotene concentrations, controlling for the following variables: gender, age, educational level, smoking, physical activity, body mass index, time of infection with HIV, presence of comorbidities, CD4(+) T lymphocyte count, total cholesterol and fractions, and triglyceride levels. There was no significant difference in vitamin A or beta-carotene concentrations in patients under the different HAART regimens. However, approximately 4% of the patients had deficient/low concentrations of vitamin A (<0.70 μmol/L), and 98% showed concentrations of beta-carotene <1.0 μmol/L. In conclusion, HIV/AIDS patients in this region will not benefit from vitamin A supplementation, independently of the HAART regimen utilized, but beta-carotene may be of importance, considering its antioxidant effect.

Plasma membrane recruitment of dephosphorylated beta-catenin upon activation of the Wnt pathway

NARCIS (Netherlands)

Hendriksen, Jolita; Jansen, Marnix; Brown, Carolyn M.; van der Velde, Hella; van Ham, Marco; Galjart, Niels; Offerhaus, G. Johan; Fagotto, Francois; Fornerod, Maarten

2008-01-01

The standard model of Wnt signaling specifies that after receipt of a Wnt ligand at the membranous receptor complex, downstream mediators inhibit a cytoplasmic destruction complex, allowing beta-catenin to accumulate in the cytosol and nucleus and co-activate Wnt target genes. Unexpectedly, shortly

Fibronectin regulates the activation of THP-1 cells by TGF-beta1.

Science.gov (United States)

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.

Impediments to Enhancement of CPT-11 Anticancer Activity by E. coli Directed Beta-Glucuronidase Therapy

Science.gov (United States)

Hsieh, Yuan-Ting; Chen, Kai-Chuan; Cheng, Chiu-Min; Cheng, Tian-Lu; Tao, Mi-Hua; Roffler, Steve R.

2015-01-01

CPT-11 is a camptothecin analog used for the clinical treatment of colorectal adenocarcinoma. CPT-11 is converted into the therapeutic anti-cancer agent SN-38 by liver enzymes and can be further metabolized to a non-toxic glucuronide SN-38G, resulting in low SN-38 but high SN-38G concentrations in the circulation. We previously demonstrated that adenoviral expression of membrane-anchored beta-glucuronidase could promote conversion of SN-38G to SN-38 in tumors and increase the anticancer activity of CPT-11. Here, we identified impediments to effective tumor therapy with E. coli that were engineered to constitutively express highly active E. coli beta-glucuronidase intracellularly to enhance the anticancer activity of CPT-11. The engineered bacteria, E. coli (lux/βG), could hydrolyze SN-38G to SN-38, increased the sensitivity of cultured tumor cells to SN-38G by about 100 fold and selectively accumulated in tumors. However, E. coli (lux/βG) did not more effectively increase CPT-11 anticancer activity in human tumor xenografts as compared to non-engineered E. coli. SN-38G conversion to SN-38 by E. coli (lux/βG) appeared to be limited by slow uptake into bacteria as well as by segregation of E. coli in necrotic regions of tumors that may be relatively inaccessible to systemically-administered drug molecules. Studies using a fluorescent glucuronide probe showed that significantly greater glucuronide hydrolysis could be achieved in mice pretreated with E. coli (lux/βG) by direct intratumoral injection of the glucuronide probe or by intratumoral lysis of bacteria to release intracellular beta-glucuronidase. Our study suggests that the distribution of beta-glucuronidase, and possibly other therapeutic proteins, in the tumor microenvironment might be an important barrier for effective bacterial-based tumor therapy. Expression of secreted therapeutic proteins or induction of therapeutic protein release from bacteria might therefore be a promising strategy to enhance anti

Follicle-stimulating hormone (FSH) activates extracellular signal-regulated kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH receptor internalization

Science.gov (United States)

Piketty, Vincent; Kara, Elodie; Guillou, Florian; Reiter, Eric; Crepieux, Pascale

2006-01-01

Background The follicle-stimulating hormone receptor (FSH-R) is a seven transmembrane spanning receptor (7TMR) which plays a crucial role in male and female reproduction. Upon FSH stimulation, the FSH-R activates the extracellular signal-regulated kinases (ERK). However, the mechanisms whereby the agonist-stimulated FSH-R activates ERK are poorly understood. In order to activate ERK, some 7 TMRs require beta-arrestin-and dynamin-dependent internalization to occur, whereas some others do not. In the present study, we examined the ability of the FSH-activated FSH-R to induce ERK phosphorylation, in conditions where its beta-arrestin- and dynamin-mediated internalization was impaired. Methods Human embryonic kidney (HEK) 293 cells were transiently transfected with the rat FSH-R. Internalization of the FSH-R was manipulated by co-expression of either a beta-arrestin (319–418) dominant negative peptide, either an inactive dynamin K44A mutant or of wild-type beta-arrestin 1 or 2. The outcomes on the FSH-R internalization were assayed by measuring 125I-FSH binding at the cell surface when compared to internalized 125I-FSH binding. The resulting ERK phosphorylation level was visualized by Western blot analysis. Results In HEK 293 cells, FSH stimulated ERK phosphorylation in a dose-dependent manner. Co-transfection of the beta- arrestin (319–418) construct, or of the dynamin K44A mutant reduced FSH-R internalization in response to FSH, without affecting ERK phosphorylation. Likewise, overexpression of wild-type beta-arrestin 1 or 2 significantly increased the FSH-R internalization level in response to FSH, without altering FSH-induced ERK phosphorylation. Conclusion From these results, we conclude that the FSH-R does not require beta-arrestin- nor dynamin-mediated internalization to initiate ERK phosphorylation in response to FSH. PMID:16787538

Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

Energy Technology Data Exchange (ETDEWEB)

Suarez, S.V.; Changeux, J.P.; Granon, S. [Unite de Neurobiologie Integrative du Systeme Cholinergique, URA CNRS 2182, Institut Pasteur, Departement de Neuroscience, 25 rue du Dr Roux, 75015 Paris (France); Amadon, A.; Giacomini, E.; Le Bihan, D. [Service Hospitalier Frederic Joliot, 4 place du general Leclerc, 91400 Orsay (France); Wiklund, A. [Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm (Sweden)

2009-07-01

Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity {beta}2-containing nicotinic receptors ({beta}2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the {beta}2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and {beta}2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, {beta}2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via {alpha}7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on {beta}2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

Dynamic returns of beta arbitrage

OpenAIRE

Nascimento, Mafalda

2017-01-01

This thesis studies the patterns of the abnormal returns of the beta strategy. The topic can be helpful for professional investors, who intend to achieve a better performance in their portfolios. Following the methodology of Lou, Polk, & Huang (2016), the COBAR measure is computed in order to determine the levels of beta arbitrage in the market in each point in time. It is argued that beta arbitrage activity can have impact on the returns of the beta strategy. In fact, it is demonstrated that...

Dietary (1-->3), (1-->4)-beta-D-glucans from oat activate nuclear factor-kappaB in intestinal leukocytes and enterocytes from mice

NARCIS (Netherlands)

Volman, Julia J.; Mensink, Ronald P.; Ramakers, Julian D.; de Winther, Menno P.; Carlsen, Harald; Blomhoff, Rune; Buurman, Wim A.; Plat, Jogchum

2010-01-01

Dietary components, like beta-glucans, can modulate the intestinal immune response. We previously showed that fecal water enriched with oat beta-glucan stimulated the cytokine-induced immune response of enterocytes. It is, however, unclear whether beta-glucans activate nuclear factor-kappaB

Stability of human interferon-beta 1: oligomeric human interferon-beta 1 is inactive but is reactivated by monomerization.

Science.gov (United States)

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.

Activation of the human beta interferon gene by the adenovirus type 12 E1B gene

International Nuclear Information System (INIS)

Shiroki, K.; Toth, M.

1988-01-01

The transcription of endogenous beta interferon mRNA was activated in human embryo kidney (HEK) cells infected with adenovirus 12 (Ad12) but was activated only inefficiently or not at all in HEK cells infected with Ad5 and rc-1 (Ad5 dl312 containing the Ad12 E1A region). The analysis with Ad12 mutants showed that Ad12 E1B products, especially the 19K protein, were important for the expression of the endogenous beta interferon gene and Ad12 E1A products were not involved in the expression. The expression of exogeneously transfected pIFN-CAT (a hybrid plasmid having the human beta interferon promoter fused with the CAT gene) was activated in HEK and chicken embryo fibroblast (CEF) cells infected with either Ad12 or Ad5. The analysis of cotransfection of CEF cells with pIFN-CAT and plasmids containing fragments of Ad12 or Ad5 DNA showed that Ad12 or Ad5 E1B (possibly the 19K protein) was and E1A was not involved in the expression of the exogenous pIFN-CAT

The Determination of Gross Alpha And Beta Activity of Drinking Water in Turkey

International Nuclear Information System (INIS)

Dilaver, A.T.; Cifter, C.; Altay, T.

2002-01-01

Man and his environment must be protected from the adverse effects of pesticides, radiation, noise and other forms of pollutions. Radioactive materials occur naturally in the environment (for example uranium, thorium and potassium). Same radioactive compounds arise from human activities (for example from medical or industrial uses of radioactivity). Drinking water should be safe to use and aesthetically pleasing. World Health Organisation (WHO) and Turkish Standards (TSE) have established maximum contaminant levels for gross alpha and gross beta. The purpose of these study is to determine the level of gross alpha and gross beta activities of samples collected from the different Regional Directories of The State Hydraulic Works (DSI)). After that compare the results versus permissible values of World Health Organisation and Turkish Standards. Collected samples from 14 Regional Directories of The State Hydraulic Works (DSI), have completed. All the analyses results suitable for WHO and TSE. We will give all the research our final report after completed the other Regional Directories' s analyses

Smart Beta or Smart Alpha

DEFF Research Database (Denmark)

Winther, Kenneth Lillelund; Steenstrup, Søren Resen

2016-01-01

that smart beta investing probably will do better than passive market capitalization investing over time, we believe many are coming to a conclusion too quickly regarding active managers. Institutional investors are able to guide managers through benchmarks and risk frameworks toward the same well......Smart beta has become the flavor of the decade in the investment world with its low fees, easy access to rewarded risk premiums, and appearance of providing good investment results relative to both traditional passive benchmarks and actively managed funds. Although we consider it well documented......-documented smart beta risk premiums and still motivate active managers to avoid value traps, too highly priced small caps, defensives, etc. By constructing the equity portfolios of active managers that resemble the most widely used risk premiums, we show that the returns and risk-adjusted returns measures...

Antimicrobial activity of beta-lactams against multiresistant micro-organisms from the family Enterobacteriaceae, and genus Pseudomonas.

Science.gov (United States)

Niebla, A; González, I; Vallín, C

1994-01-01

The antimicrobial activity of twenty beta-lactams was determined against multiresistant micro-organisms from the Enterobacteriaceae family (450) and the genus Pseudomonas (90). The antimicrobial susceptibility was assessed by the disk diffusion method. The most effective antibiotics were cephalosporins of the second and third generation, and non-classical beta-lactams (imipenem and moxalactam). A pronounced resistance was found to carbenicillin, ampicillin, cephalotin and cefazolin. These resistance patterns corresponded to a high consumption of these antibiotics.

Development of a gas-ionization {beta}-spectrometer; Etude et realisation d'un spectrometre {beta} a ionisation gazeuse

Energy Technology Data Exchange (ETDEWEB)

Le Du, R [Commissariat a l' Energie Atomique, Bruyeres-le-Chatel (France). Centre d' Etudes

1968-05-15

We intend to develop in our laboratory a {beta}-spectrometer. This apparatus will have two main objectives: 1 - the determination of the nature and the degree of purity of certain {beta}-emitting radioactive substances; 2 - the study of an activity calibration process for {beta}-emitting radioactive sources. (author) [French] Nous nous proposons d'etudier et de realiser dans notre laboratoire un spectrometre {beta}. Cet appareil aura deux buts principaux: 1 - determiner la nature et le degre de purete de certains corps radioactifs emetteurs {beta}; 2 - permettre l'etude d'un procede d'etalonnage en activite de sources radioactives emetteurs {beta}. (auteur)

Neurotensin receptor 1 gene activation by the Tcf/beta-catenin pathway is an early event in human colonic adenomas.

Science.gov (United States)

Souazé, Frédérique; Viardot-Foucault, Véronique; Roullet, Nicolas; Toy-Miou-Leong, Mireille; Gompel, Anne; Bruyneel, Erik; Comperat, Eva; Faux, Maree C; Mareel, Marc; Rostène, William; Fléjou, Jean-François; Gespach, Christian; Forgez, Patricia

2006-04-01

Alterations in the Wnt/APC (adenomatous polyposis coli) signalling pathway, resulting in beta-catenin/T cell factor (Tcf)-dependent transcriptional gene activation, are frequently detected in familial and sporadic colon cancers. The neuropeptide neurotensin (NT) is widely distributed in the gastrointestinal tract. Its proliferative and survival effects are mediated by a G-protein coupled receptor, the NT1 receptor. NT1 receptor is not expressed in normal colon epithelial cells, but is over expressed in a number of cancer cells and tissues suggesting a link to the outgrowth of human colon cancer. Our results demonstrate that the upregulation of NT1 receptor occurring in colon cancer is the result of Wnt/APC signalling pathway activation. We first established the functionality of the Tcf response element within the NT1 receptor promoter. Consequently, we observed the activation of NT1 receptor gene by agents causing beta-catenin cytosolic accumulation, as well as a strong decline of endogenous receptor when wt-APC was restored. At the cellular level, the re-establishment of wt-APC phenotype resulted in the impaired functionality of NT1 receptor, like the breakdown in NT-induced intracellular calcium mobilization and the loss of NT pro-invasive effect. We corroborated the Wnt/APC signalling pathway on the NT1 receptor promoter activation with human colon carcinogenesis, and showed that NT1 receptor gene activation was perfectly correlated with nuclear or cytoplasmic beta-catenin localization while NT1 receptor was absent when beta-catenin was localized at the cell-cell junction in early adenomas of patients with familial adenomatous polyposis, hereditary non-polyposis colorectal cancer and loss of heterozygosity tumours. In this report we establish a novel link in vitro between the Tcf/beta-catenin pathway and NT1 receptor promoter activation.

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

Science.gov (United States)

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.

Relation between the 2{nu}{beta}{beta} and 0{nu}{beta}{beta} nuclear matrix elements

Energy Technology Data Exchange (ETDEWEB)

Vogel, Petr [Kellogg Radiation Laboratory, Caltech, Pasadena, CA 91125 (United States); Simkovic, Fedor [Department of Nuclear Physics and Biophysics, Comenius University, Mlynska dolina F1, SK-84248 Bratislava (Slovakia)

2011-12-16

A formal relation between the GT part of the nuclear matrix elements M{sub GT}{sup 0{nu}} of 0{nu}{beta}{beta} decay and the closure matrix elements M{sub cl}{sup 2{nu}} of 2{nu}{beta}{beta} decay is established. This relation is based on the integral representation of these quantities in terms of their dependence on the distance r between the two nucleons undergoing transformation. We also discuss the difficulties in determining the correct values of the closure 2{nu}{beta}{beta} decay matrix elements.

Systemic lupus erythematosus activity and beta two microglobulin levels

Directory of Open Access Journals (Sweden)

Thelma Larocca Skare

Full Text Available CONTEXT AND OBJECTIVE: Systemic lupus erythematosus (SLE is an autoimmune disease with a cyclical clinical course. Evaluation of the clinical activity of this disease is important for choosing the correct treatment. The objective of this study was to analyze the value of beta-2 microglobulin (β2M serum levels in determining SLE clinical activity.DESIGN AND SETTING: Cross-sectional analytical study conducted at the rheumatology outpatient clinic of a private university hospital.METHODS: 129 SLE patients were studied regarding disease activity using SLEDAI (SLE Disease Activity Index and cumulative damage using SLICC ACR (SLE International Collaborating Clinics/American College of Rheumatology Damage Index for SLE. At the same time, the β2M serum level, ESR (erythrocyte sedimentation rate, anti-dsDNA (anti-double-stranded DNA and C3 and C4 complement fractions were determined.RESULTS: β2M levels correlated positively with SLEDAI (P = 0.02 and ESR (P = 0.0009 and negatively with C3 (P = 0.007. Patients who were positive for anti-dsDNA had higher β2M serum levels (P = 0.009.CONCLUSION: β2M levels are elevated in SLE patients with active disease.

Code Betal to calculation Alpha/Beta activities in environmental samples

International Nuclear Information System (INIS)

Romero, L.; Travesi, A.

1983-01-01

A codes, BETAL, was developed, written in FORTRAN IV, to automatize calculations and presentations of the result of the total alpha-beta activities measurements in environmental samples. This code performs the necessary calculations for transformation the activities measured in total counts, to pCi/1., bearing in mind the efficiency of the detector used and the other necessary parameters. Further more, it appraise the standard deviation of the result, and calculus the Lower limit of detection for each measurement. This code is written in iterative way by screen-operator dialogue, and asking the necessary data to perform the calculation of the activity in each case by a screen label. The code could be executed through any screen and keyboard terminal, (whose computer accepts Fortran IV) with a printer connected to the said computer. (Author) 5 refs

STAT5 activity in pancreatic beta-cells influences the severity of diabetes in animal models of type 1 and 2 diabetes

DEFF Research Database (Denmark)

Jackerott, Malene; Møldrup, Annette; Thams, Peter

2006-01-01

Pancreatic beta-cell growth and survival and insulin production are stimulated by growth hormone and prolactin through activation of the transcription factor signal transducer and activator of transcription (STAT)5. To assess the role of STAT5 activity in beta-cells in vivo, we generated transgen...... and type 2 diabetes....... reduced beta-cell proliferation at 6 months of age. The inhibitory effect of high-fat diet or leptin on insulin secretion was diminished in isolated islets from RIP-DNSTAT5 mice compared with wild-type islets. Upon multiple low-dose streptozotocin treatment, RIP-DNSTAT5 mice exhibited higher plasma...... of glucose tolerance, whereas RIP-CASTAT5 mice were more glucose tolerant and less hyperleptinemic than wild-type mice. Although the pancreatic insulin content and relative beta-cell area were increased in high-fat diet-fed RIP-DNSTAT5 mice compared with wild-type or RIP-CASTAT5 mice, RIP-DNSTAT5 mice showed...

Beta1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance

DEFF Research Database (Denmark)

Campos, Lia S; Leone, Dino P; Relvas, Joao B

2004-01-01

, signalling is required for neural stem cell maintenance, as assessed by neurosphere formation, and inhibition or genetic ablation of beta1 integrin using cre/lox technology reduces the level of MAPK activity. We conclude that integrins are therefore an important part of the signalling mechanisms that control......The emerging evidence that stem cells develop in specialised niches highlights the potential role of environmental factors in their regulation. Here we examine the role of beta1 integrin/extracellular matrix interactions in neural stem cells. We find high levels of beta1 integrin expression...... in the stem-cell containing regions of the embryonic CNS, with associated expression of the laminin alpha2 chain. Expression levels of laminin alpha2 are reduced in the postnatal CNS, but a population of cells expressing high levels of beta1 remains. Using neurospheres - aggregate cultures, derived from...

A comparison of the activities of three beta-galactosidases in aqueous-organic solvent mixtures

NARCIS (Netherlands)

Yoon, JH; Mckenzie, D

2005-01-01

The hydrolytic activities of beta-galactosidases from three different sources have been determined in various 50% (v/v) organic solvent-buffer mixtures with a view to finding solvent systems of reduced water content suitable for the synthesis of glycosides and oligosaccharides. K. fragilis

Purification and properties of beta-galactosidase from Aspergillus nidulans.

Science.gov (United States)

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).

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

Science.gov (United States)

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

Role of beta-adrenoceptors in memory consolidation: beta3-adrenoceptors act on glucose uptake and beta2-adrenoceptors on glycogenolysis.

Science.gov (United States)

Gibbs, Marie E; Hutchinson, Dana S; Summers, Roger J

2008-09-01

Noradrenaline, acting via beta(2)- and beta(3)-adrenoceptors (AR), enhances memory formation in single trial-discriminated avoidance learning in day-old chicks by mechanisms involving changes in metabolism of glucose and/or glycogen. Earlier studies of memory consolidation in chicks implicated beta(3)- rather than beta(2)-ARs in enhancement of memory consolidation by glucose, but did not elucidate whether stimulation of glucose uptake or of glycolysis was responsible. This study examines the role of glucose transport in memory formation using central injection of the nonselective facilitative glucose transporter (GLUT) inhibitor cytochalasin B, the endothelial/astrocytic GLUT-1 inhibitor phloretin and the Na(+)/energy-dependent endothelial glucose transporter (SGLT) inhibitor phlorizin. Cytochalasin B inhibited memory when injected into the mesopallium (avian cortex) either close to or between 25 and 45 min after training, whereas phloretin and phlorizin only inhibited memory at 30 min. This suggested that astrocytic/endothelial (GLUT-1) transport is critical at the time of consolidation, whereas a different transporter, probably the neuronal glucose transporter (GLUT-3), is important at the time of training. Inhibition of glucose transport by cytochalasin B, phloretin, or phlorizin also interfered with beta(3)-AR-mediated memory enhancement 20 min posttraining, whereas inhibition of glycogenolysis interfered with beta(2)-AR agonist enhancement of memory. We conclude that in astrocytes (1) activities of both GLUT-1 and SGLT are essential for memory consolidation 30 min posttraining; (2) neuronal GLUT-3 is essential at the time of training; and (3) beta(2)- and beta(3)-ARs consolidate memory by different mechanisms; beta(3)-ARs stimulate central glucose transport, whereas beta(2)-ARs stimulate central glycogenolysis.

beta-carotene does not change markers of enzymatic and nonenzymatic antioxidant activity in human blood

DEFF Research Database (Denmark)

Castenmiller, J.J.M.; Lauridsen, Søren T.; Dragsted, Lars O.

1999-01-01

and erythrocyte enzyme activities were assessed, and differences among experimental groups were tested. Consumption of spinach resulted in greater (P catalase activity and serum alpha-tocopherol concentration compared...... to an increased carotenoid (lutein and zeaxanthin) intake, but beta-carotene is unlikely to be a causative factor. Lower erythrocyte catalase activity after intervention with spinach products may be related to other constituents in spinach such as flavonoids....

Mutagenic activity of a fluorinated analog of the beta-adrenoceptor ligand carazolol in the Ames test

Energy Technology Data Exchange (ETDEWEB)

Doze, P. E-mail: P.Doze@pet.azg.nl; Elsinga, P.H.; Vries, E.F.J. de; Waarde, A. van; Vaalburg, W

2000-04-01

S-1'[{sup 18}F]-Fluorocarazolol (FCAR) is a fluorinated analog of the nonmutagenic beta-blocker carazolol (CAR). In former studies FCAR proved to be suitable for quantification of beta-adrenoceptors in vivo with positron emission tomography (PET). We report here that FCAR displays no acute toxicity in either rats or mice. However, FCAR induces a strong dose-related increase in the number of revertants in the Ames test. We conclude that FCAR yields mutagenic activity as measured by the Ames test.

Hydrolyses of alpha-naphthyl acetate, beta-naphthyl acetate, and acetyl-DL-phenylalanine beta-naphthyl ester

DEFF Research Database (Denmark)

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...

El factor de crecimiento transformante beta como blanco terapéutico Transforming growth factor-beta as a therapeutic target

Directory of Open Access Journals (Sweden)

Francisco Javier Gálvez-Gastélum

2004-08-01

Full Text Available El factor de crecimiento transformante beta (TGF-beta es una familia de proteínas que incluye al TGF-beta, activinas y a la proteína morfogénica de hueso (BMP, por sus siglas en inglés, citocinas que son secretadas y se relacionan estructuralmente en diferentes especies de metazoarios. Los miembros de la familia del TGF-beta regulan diferentes funciones celulares como proliferación, apoptosis, diferenciación, migración, y tienen un papel clave en el desarrollo del organismo. El TGF-beta está implicado en varias patologías humanas, incluyendo desórdenes autoinmunes y vasculares, así como enfermedades fibróticas y cáncer. La activación del receptor del TGF-beta propicia su fosforilación en residuos de serina/treonina y dispara la fosforilación de proteínas efectoras intracelulares (smad, que una vez activas se translocan al núcleo para inducir la transcripción de genes blanco, y así regular procesos y funciones celulares. Se están desarrollando novedosas estrategias terapéuticas encaminadas a corregir las alteraciones presentes en patologías que involucran al TGF-beta como actor principal.Transforming growth factor-beta (TGF-beta family members include TGF-beta, activins, and bone morphogenetic proteins (BMP. These proteins are structurally related cytokines secreted in diverse Metazoans. TGF-beta family members regulate cellular functions such as proliferation, apoptosis, differentiation, and migration, and play an important role in organism development. Deregulated TGF-beta family signaling participates in various human pathologies including auto-immune diseases, vascular disorders, fibrotic disease, and cancer. Ligand-induced activation of TGF-beta family receptors with intrinsic serine/threonine kinase activity, triggers phosphorylation of the intracellular effectors of TGF-beta signaling, the Smads proteins. Once these proteins are activated they translocate into the nucleus, where they induce transcription of target

Mechanical unloading of the failing human heart fails to activate the protein kinase B/Akt/glycogen synthase kinase-3beta survival pathway.

Science.gov (United States)

Razeghi, Peter; Bruckner, Brian A; Sharma, Saumya; Youker, Keith A; Frazier, O H; Taegtmeyer, Heinrich

2003-01-01

Left ventricular assist device (LVAD) support of the failing human heart improves myocyte function and increases cell survival. One potential mechanism underlying this phenomenon is activation of the protein kinase B (PKB)/Akt/glycogen synthase kinase-3beta (GSK-3beta) survival pathway. Left ventricular tissue was obtained both at the time of implantation and explantation of the LVAD (n = 11). Six patients were diagnosed with idiopathic dilated cardiomyopathy, 4 patients with ischemic cardiomyopathy and 1 patient with peripartum cardiomyopathy. The mean duration of LVAD support was 205 +/- 35 days. Myocyte diameter and phosphorylation of ERK were used as indices for reverse remodeling. Transcript levels of genes required for the activation of PKB/Akt (insulin-like growth factor-1, insulin receptor substrate-1) were measured by quantitative RT-PCR. In addition, we measured the relative activity of PKB/Akt and GSK-3beta, and assayed for molecular and histological indices of PKB/Akt activation (cyclooxygenase mRNA levels and glycogen levels). Myocyte diameter and phosphorylation of ERK decreased with LVAD support. In contrast, none of the components of the PKB/Akt/GSK-3beta pathway changed significantly with mechanical unloading. The PKB/Akt/GSK-3beta pathway is not activated during LVAD support. Other signaling pathways must be responsible for the improvement of cellular function and cell survival during LVAD support. Copyright 2003 S. Karger AG, Basel

beta. -endorphin augments the cytolytic activity and interferon production of natural killer cells

Energy Technology Data Exchange (ETDEWEB)

Mandler, R.N.; Biddison, W.E.; Mandler, R.; Serrate, S.A.

1986-02-01

The in vitro effects of the neurohormone ..beta..-endorphin (b-end) on natural killer (NK) activity and interferon (IFN) production mediated by large granular lymphocytes (LGL) were investigated. LGL-enriched fractions from peripheral blood mononuclear cells (PBMC) from normal human volunteers were obtained by fractionation over discontinuous Percoll gradients. LGL were preincubated with or without various concentrations of b-end or the closely related peptides ..cap alpha..-endorphin (a-end), ..gamma..-endorphin (g-end), or D-ALA/sub 2/-..beta..-endorphin (D-ALA/sub 2/-b-end), a synthetic b-end analogue. NK activity was assayed on /sup 51/Cr-labeled K562 target cells. Preincubation of LGL effectors (but not K562 targets) for 2 to 18 hr with concentrations of b-end between 10/sup -7/ M and 10/sup -10/ M produced significant augmentation of NK cytolytic activity (mean percentage increase: 63%). The classic opiate antagonist naloxone blocked the enhancing effect when used at a 100-fold molar excess relative to b-end. These findings demonstrate that b-end enhances NK activity and IFN production of purified LGL, and suggests that b-end might bind to an opioid receptor on LGL that can be blocked by naloxone. These results lend support to the concepts of regulation of the immune response by neurohormones and the functional relationship between the nervous and immune systems.

17 beta-hydroxysteroid dehydrogenase activity in canine pancreas

International Nuclear Information System (INIS)

Mendoza-Hernandez, G.; Lopez-Solache, I.; Rendon, J.L.; Diaz-Sanchez, V.; Diaz-Zagoya, J.C.

1988-01-01

The mitochondrial fraction of the dog pancreas showed NAD(H)-dependent enzyme activity of 17 beta-hydroxysteroid dehydrogenase. The enzyme catalyzes oxidoreduction between androstenedione and testosterone. The apparent Km value of the enzyme for androstenedione was 9.5 +/- 0.9 microM, the apparent Vmax was determined as 0.4 nmol mg-1 min-1, and the optimal pH was 6.5. In phosphate buffer, pH 7.0, maximal rate of androstenedione reduction was observed at 37 degrees C. The oxidation of testosterone by the enzyme proceeded at the same rate as the reduction of the androstenedione at a pH of 6.8-7.0. The apparent Km value and the optimal pH of the enzyme for testosterone were 3.5 +/- 0.5 microM and 7.5, respectively

Interleukin-1 beta Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-beta 1

NARCIS (Netherlands)

Mia, Masum M.; Boersema, Miriam; Bank, Ruud A.

2014-01-01

One of the most potent pro-fibrotic cytokines is transforming growth factor (TGF beta). TGF beta is involved in the activation of fibroblasts into myofibroblasts, resulting in the hallmark of fibrosis: the pathological accumulation of collagen. Interleukin-1 beta (IL1 beta) can influence the

Association of. beta. -glucosidase with intact cells of thermoactinomyces

Energy Technology Data Exchange (ETDEWEB)

Haegerdal, B; Harris, H; Pye, E K

1979-03-01

The location of the ..beta..-glucosidase activity in a whole culture broth of the thermophilic organism Thermoactinomyces has been studied. Little ..beta..-glucosidase activity was found in the culture filtrate, while the culture solids contained the major part of the activity of the whole culture broth. The activity does not appear to be adsorbed to the culture solids; rather there is evidence that it is an intracellular soluble enzyme(s). The pH and temperature optima for a crude ..beta..-glucosidase preparation were determined to be pH 6.5 and 50 to 55/sup 0/C. Enzyme activity studies indicate that the same enzyme(s) accounts for the ..beta..-glucosidase and the cellobiase activities. The validity of using the filter paper activity of culture filtrates from Thermoactinomyces to predict the total saccharification of cellulosic materials to glucose is discussed.

Genetic analysis of beta1 integrin "activation motifs" in mice

DEFF Research Database (Denmark)

Czuchra, Aleksandra; Meyer, Hannelore; Legate, Kyle R

2006-01-01

-null phenotype in vivo. Surprisingly, neither the substitution of the tyrosines with phenylalanine nor the aspartic acid with alanine resulted in an obvious defect. These data suggest that the NPXY motifs of the beta1 integrin tail are essential for beta1 integrin function, whereas tyrosine phosphorylation...

Self-Absorption Studies with a 4 {pi} {beta}-Proportional Flow Counter; Etudes sur l'autoabsorption avec un compteur {beta} 4 {pi} proportionnel a courant; Izuchenie samopogloshcheniya pri pomoshchi {beta} proportsional'no-potochnogo 4 {pi} schetchika; Estudios sobre autoabsorcion con un contador de flujo proporcional {beta}4 {pi}

Energy Technology Data Exchange (ETDEWEB)

Yaffe, L; Fishman, J B [Radiochemistry Laboratory, Dept. of Chemistry, McGill University, Montreal, Quebec (Canada)

1960-06-15

entre 0,018 y 1,7 MeV) recogiendolos sobre finas peliculas de resina vinilica (VYNS) y han determinado las caracteristicas de autoabsorcion. Presentan una serie de curvas, obtenidas experimentalmente, que relacionan la E{sub max} el espesor de la fuente y la autoabsorcion. Les datos referentes a la autoabsorcion han sido sometidos a un analisis teorico, para contadores de angulo pequeno y 4 {pi}. Las curvas de autoabsorcion determinadas experimentalment e para contadores 4 {pi} estan comprendidas entre las curvas teoricas que corresponden a los angulos solidos pequenos y las curvas determinadas mediante contador de geometria 4 {pi}. (author) [Russian] Izuchenie samopogloshcheni {beta} izluchatelej provodilos' pri pomoshchi priemov, izlozhennykh Pejtom i YAffe v kanadskom khimicheskom zhurnale [Can. J. Chem. 34, 265 (1956]. Letuchie soedineniya H{sup 3}, S{sup 14}, So{sup 60}, Hg{sup 203}, As{sup 77} i P{sup 32} (E{sub max} ot 0,018 do 1,7 MeV) peregonyalis' na tonkie VYNS ustanovki i opredelyalas' kharakteristik a samopogloshcheniya . Privodyatsya serii s ehmpiri- cheskim opredeleniem krivykh, otnosyashchikhsya k E{sub max}, tolshchine istochnika i samopogloshchenie . Dannye samopogloshcheni ya podvergalis' teoreticheskom u analizu na schetchikakh s malym uglom i na 4 {pi} geometricheski kh schetchikakh. EHksperi- mental'no opredelennye krivye samopogloshcheni ya s pomoshch'yu 4 {pi} geometricheskikh schetchikov nakhodyatsya mezhdu krivymi, poluchennymi s pomoshch'yu schetchikov s teoreticheski malymi uglami i s pomoshch'yu 4 {pi} geometricheskikh schetchikov. (author)

Beta genus papillomaviruses and skin cancer.

Science.gov (United States)

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.

Endotoxin/lipopolysaccharide activates NF-kappa B and enhances tumor cell adhesion and invasion through a beta 1 integrin-dependent mechanism.

LENUS (Irish Health Repository)

Wang, Jiang Huai

2012-02-03

Beta(1) integrins play a crucial role in supporting tumor cell attachment to and invasion into the extracellular matrix. Endotoxin\\/LPS introduced by surgery has been shown to enhance tumor metastasis in a murine model. Here we show the direct effect of LPS on tumor cell adhesion and invasion in extracellular matrix proteins through a beta(1) integrin-dependent pathway. The human colorectal tumor cell lines SW480 and SW620 constitutively expressed high levels of the beta(1) subunit, whereas various low levels of alpha(1), alpha(2), alpha(4), and alpha(6) expression were detected. SW480 and SW620 did not express membrane-bound CD14; however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated beta(1) integrin expression; enhanced tumor cell attachment to fibronectin, collagen I, and laminin; and strongly promoted tumor cell invasion through the Matrigel. Anti-beta(1) blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14-induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with sCD14, resulted in NF-kappaB activation in both SW480 and SW620 cells. Inhibition of the NF-kappaB pathway significantly attenuated LPS-induced up-regulation of beta(1) integrin expression and prevented tumor cell adhesion and invasion. These results provide direct evidence that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-kappaB, up-regulate beta(1) integrin expression, and subsequently promote tumor cell adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and invasion through extracellular matrix proteins is beta(1) subunit-dependent.

Measurement of the absolute activity of alpha or beta emitters by measuring product nuclei (daughter) activity increase or by studing its radioactive decay

International Nuclear Information System (INIS)

Campos, L.C. de.

1981-01-01

A new method for determining absolute activity of alpha or beta emitters by measuring daughter product radioactive decay is presented. The separation method of UX from hexahydrated uranyl nitrate UO 2 (NO 3 ) 2 6H 2 O based on its dissolution in ethyl ether is described and the accuracy of this method is shown. The factors which accuate on total efficiency of a Geiger Mueller detector for beta particles are determined. The possibility to determine the mass of precursor element by daughter nuclei activity is shown. The results are compared with the one obtained by direct measurement of the mass (or number of atoms) of precursor radioactive substance and with theoretical values calculated for isotopes in secular equilibrium. (Author) [pt

Design of a Quality Control Program for the Measurement of Gross Alpha and Gross Beta Activities (LMPR-CIEMAT)

International Nuclear Information System (INIS)

Alvarez, A.; Yague, L.; Gasco, C.; Navarro, N.; Higueras, E.; Noguerales, C.

2010-01-01

In accordance with international standards, general requirements for testing laboratories have to include a quality system for planning, implementing, and assessing the work performed by the organization and for carrying out required quality assurance and quality control. The purpose of internal laboratory quality control is to monitor performance, identify problems, and initiate corrective actions. This report describes the internal quality control to monitor the gross alpha and beta activities determination. Identification of specific performance indicators, the principles that govern their use and statistical means of evaluation are explained. Finally, calculation of alpha and beta specific activities, uncertainties and detection limits are performed. (Author) 10 refs.

{beta}-adrenergic receptor density and adenylate cyclase activity in lead-exposed rat brain after cessation of lead exposure

Energy Technology Data Exchange (ETDEWEB)

Chang, Huoy-Rou [I-Shou University, Department of Biomedical Engineering, Dashu Shiang, Kaohsiung County (Taiwan); Tsao, Der-An [Fooyin University of Technology, Department of Medical Technology (Taiwan); Yu, Hsin-Su [Taiwan University, Department of Dermatology, College of Medicine (Taiwan); Ho, Chi-Kung [Kaohsiung Medical University, Occupational Medicine (Taiwan); Kaohsiung Medical University, Graduate Institute of Medicine, Research Center for Occupational Disease (Taiwan)

2005-01-01

To understanding the reversible or irreversible harm to the {beta}-adrenergic system in the brain of lead-exposed rats, this study sets up an animal model to estimate the change in the sympathetic nervous system of brain after lead exposure was withdrawn. We address the following topics in this study: (a) the relationship between withdrawal time of lead exposure and brain {beta}-adrenergic receptor, blood lead level, and brain lead level in lead-exposed rats after lead exposure was stopped; and (b) the relationship between lead level and {beta}-adrenergic receptor and cyclic AMP (c-AMP) in brain. Wistar rats were chronically fed with 2% lead acetate and water for 2 months. Radioligand binding was assayed by a method that fulfilled strict criteria of {beta}-adrenergic receptor using the ligand [{sup 125}I]iodocyanopindolol. The levels of lead were determined by electrothermal atomic absorption spectrometry. The c-AMP level was determined by radioimmunoassay. The results showed a close relationship between decreasing lead levels and increasing numbers of brain {beta}-adrenergic receptors and brain adenylate cyclase activity after lead exposure was withdrawn. The effect of lead exposure on the {beta}-adrenergic system of the brain is a partly reversible condition. (orig.)

Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin.

Directory of Open Access Journals (Sweden)

Patrick A M Jansen

Full Text Available BACKGROUND: Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2 is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis. METHODOLOGY/PRINCIPAL FINDINGS: We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects. CONCLUSIONS/SIGNIFICANCE: Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases.

LHCb: $2\\beta_s$ measurement at LHCb

CERN Multimedia

Conti, G

2009-01-01

A measurement of $2\\beta_s$, the phase of the $B_s-\\bar{B_s}$ oscillation amplitude with respect to that of the ${\\rm b} \\rightarrow {\\rm c^{+}}{\\rm W^{-}}$ tree decay amplitude, is one of the key goals of the LHCb experiment with first data. In the Standard Model (SM), $2\\beta_s$ is predicted to be $0.0360^{+0.0020}_{-0.0016} \\rm rad$. The current constraints from the Tevatron are: $2\\beta_{s}\\in[0.32 ; 2.82]$ at 68$\\%$CL from the CDF experiment and $2\\beta_{s}=0.57^{+0.24}_{-0.30}$ from the D$\\oslash$ experiment. Although the statistical uncertainties are large, these results hint at the possible contribution of New Physics in the $B_s-\\bar{B_s}$ box diagram. After one year of data taking at LHCb at an average luminosity of $\\mathcal{L}\\sim2\\cdot10^{32}\\rm cm^{-2} \\rm s^{-1}$ (integrated luminosity $\\mathcal{L}_{\\rm int}\\sim 2 \\rm fb^{-1}$), the expected statistical uncertainty on the measurement is $\\sigma(2\\beta_s)\\simeq 0.03$. This uncertainty is similar to the $2\\beta_s$ value predicted by the SM.

Top-Down Beta Enhances Bottom-Up Gamma.

Science.gov (United States)

Richter, Craig G; Thompson, William H; Bosman, Conrado A; Fries, Pascal

2017-07-12

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. Copyright © 2017 Richter, Thompson et al.

Activation of the Wnt/β-catenin pathway in pancreatic beta cells during the compensatory islet hyperplasia in prediabetic mice

International Nuclear Information System (INIS)

Maschio, D.A.; Oliveira, R.B.; Santos, M.R.; Carvalho, C.P.F.; Barbosa-Sampaio, H.C.L.; Collares-Buzato, C.B.

2016-01-01

The Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associated to the Wnt/β-catenin pathway. In the present study, we demonstrated that hyperplastic pancreatic islets from prediabetic mice fed a high-fat diet (HFD) for 60 d displayed nuclear translocation of active β-catenin associated with significant increases in protein content and gene expression of β-catenin as well as of cyclins D1, D2 and c-Myc (target genes of the Wnt pathway) but not of Tcf7l2 (the transcription factor). Meanwhile, these alterations were not observed in pancreatic islets from 30 d HFD-fed mice, that do not display significant beta cell hyperplasia. These data suggest that the Wnt/β-catenin pathway is activated in pancreatic islets during prediabetes and may play a role in the induction of the compensatory beta cell hyperplasia observed at early phase of T2DM. - Highlights: • Exposure to high-fat diet for 60 days induced prediabetes and beta cell mass expansion. • Hyperplastic pancreatic islets displayed nuclear translocation of active β-catenin. • Hyperplastic islets showed increased expression of target genes of the Wnt/β-catenin pathway. • Wnt/β-catenin pathway is activated during compensatory beta cell hyperplasia in mice.

Silencing of beta-carotene hydroxylase increases total carotenoid and beta-carotene levels in potato tubers

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Pizzichini Daniele

2007-03-01

Full Text Available Abstract Background Beta-carotene is the main dietary precursor of vitamin A. Potato tubers contain low levels of carotenoids, composed mainly of the xanthophylls lutein (in the beta-epsilon branch and violaxanthin (in the beta-beta branch. None of these carotenoids have provitamin A activity. We have previously shown that tuber-specific silencing of the first step in the epsilon-beta branch, LCY-e, redirects metabolic flux towards beta-beta carotenoids, increases total carotenoids up to 2.5-fold and beta-carotene up to 14-fold. Results In this work, we silenced the non-heme beta-carotene hydroxylases CHY1 and CHY2 in the tuber. Real Time RT-PCR measurements confirmed the tuber-specific silencing of both genes . CHY silenced tubers showed more dramatic changes in carotenoid content than LCY-e silenced tubers, with beta-carotene increasing up to 38-fold and total carotenoids up to 4.5-fold. These changes were accompanied by a decrease in the immediate product of beta-carotene hydroxylation, zeaxanthin, but not of the downstream xanthophylls, viola- and neoxanthin. Changes in endogenous gene expression were extensive and partially overlapping with those of LCY-e silenced tubers: CrtISO, LCY-b and ZEP were induced in both cases, indicating that they may respond to the balance between individual carotenoid species. Conclusion Together with epsilon-cyclization of lycopene, beta-carotene hydroxylation is another regulatory step in potato tuber carotenogenesis. The data are consistent with a prevalent role of CHY2, which is highly expressed in tubers, in the control of this step. Combination of different engineering strategies holds good promise for the manipulation of tuber carotenoid content.

Beta and gamma oscillatory activities associated with olfactory memory tasks: different rhythms for different functional networks?

Science.gov (United States)

Martin, Claire; Ravel, Nadine

2014-01-01

Olfactory processing in behaving animals, even at early stages, is inextricable from top down influences associated with odor perception. The anatomy of the olfactory network (olfactory bulb, piriform, and entorhinal cortices) and its unique direct access to the limbic system makes it particularly attractive to study how sensory processing could be modulated by learning and memory. Moreover, olfactory structures have been early reported to exhibit oscillatory population activities easy to capture through local field potential recordings. An attractive hypothesis is that neuronal oscillations would serve to "bind" distant structures to reach a unified and coherent perception. In relation to this hypothesis, we will assess the functional relevance of different types of oscillatory activity observed in the olfactory system of behaving animals. This review will focus primarily on two types of oscillatory activities: beta (15-40 Hz) and gamma (60-100 Hz). While gamma oscillations are dominant in the olfactory system in the absence of odorant, both beta and gamma rhythms have been reported to be modulated depending on the nature of the olfactory task. Studies from the authors of the present review and other groups brought evidence for a link between these oscillations and behavioral changes induced by olfactory learning. However, differences in studies led to divergent interpretations concerning the respective role of these oscillations in olfactory processing. Based on a critical reexamination of those data, we propose hypotheses on the functional involvement of beta and gamma oscillations for odor perception and memory.

Beta and gamma oscillatory activities associated with olfactory memory tasks: Different rhythms for different functional networks?

Directory of Open Access Journals (Sweden)

Claire eMartin

2014-06-01

Full Text Available Olfactory processing in behaving animals, even at early stages, is inextricable from top down influences associated with odor perception. The anatomy of the olfactory network (olfactory bulb, piriform and entorhinal cortices and its unique direct access to the limbic system makes it particularly attractive to study how sensory processing could be modulated by learning and memory. Moreover, olfactory structures have been early reported to exhibit oscillatory population activities easy to capture through local field potential recordings. An attractive hypothesis is that neuronal oscillations would serve to ‘bind’ distant structures to reach a unified and coherent perception. In relation to this hypothesis, we will assess the functional relevance of different types of oscillatory activity observed in the olfactory system of behaving animals. This review will focus primarily on two types of oscillatory activities: beta (15-40 Hz and gamma (60-100 Hz. While gamma oscillations are dominant in the olfactory system in the absence of odorant, both beta and gamma rhythms have been reported to be modulated depending on the nature of the olfactory task. Studies from the authors of the present review and other groups brought evidence for a link between these oscillations and behavioral changes induced by olfactory learning. However, differences in studies led to divergent interpretations concerning the respective role of these oscillations in olfactory processing. Based on a critical reexamination of those data, we propose hypotheses on the functional involvement of beta and gamma oscillations for odor perception and memory.

On the absolute measure of Beta activities

International Nuclear Information System (INIS)

Sanchez del Rio, C.; Jimenez Reynaldo, O.; Rodriguez Mayquez, E.

1956-01-01

A new method for absolute beta counting of solid samples is given. The mea surements is made with an inside Geiger-Muller tube of new construction. The backscattering correction when using an infinite thick mounting is discussed and results for different materials given. (Author)

C[sub 10]-O[sub eq]-N-(4-azido-5-[sup 125]iodo salicyloyl)-[beta]-alanyl-[beta] alanyl ryanodine (Az-[beta]AR), a novel photo-affinity ligand for the ryanodine binding site

Energy Technology Data Exchange (ETDEWEB)

Bidasee, K.R.; Besch, H.R. Jr.; Kwon, Sangyeol; Emmick, J.T.; Besch, K.T.; Gerzon, Koert; Humerickhouse, R.A. (Indiana Univ., Indianapolis, IN (United States). School of Medicine)

1994-01-01

A high affinity, photoactivatable, radio-iodinated ligand for the ryanodine binding site(s) of the sarcoplasmic reticulum calcium-release channel, C[sub 10]-O[sub e]-N-(4-azido-5-[sup 125]iodo salicyloyl)-[beta]-alanyl-[beta]-alanyl ryanodine (Az-[beta]AR), was synthesized at a specific activity of 1400mCi/mmol. (Author).

Lysosomal trafficking of {beta}-catenin induced by the tea polyphenol epigallocatechin-3-gallate

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Dashwood, Wan-Mohaiza [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Carter, Orianna [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Al-Fageeh, Mohamed [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Li, Qingjie [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Dashwood, Roderick H. [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States)]. E-mail: Rod.Dashwood@oregonstate.edu

2005-12-11

{beta}-Catenin is a cadherin-binding protein involved in cell-cell adhesion, which also functions as a transcriptional activator when complexed in the nucleus with members of the T-cell factor (TCF)/lymphoid enhancer factor (LEF) family of proteins. There is considerable interest in mechanisms that down-regulate {beta}-catenin, since this provides an avenue for the prevention of colorectal and other cancers in which {beta}-catenin is frequently over-expressed. We show here that physiologically relevant concentrations of the tea polyphenol epigallocatechin-3-gallate (EGCG) inhibited {beta}-catenin/TCF-dependent reporter activity in human embryonic kidney 293 cells transfected with wild type or mutant {beta}-catenins, and there was a corresponding decrease in {beta}-catenin protein levels in the nuclear, cytosolic and membrane-associated fractions. However, {beta}-catenin accumulated as punctate aggregates in response to EGCG treatment, including in human colon cancer cells over-expressing {beta}-catenin endogenously. Confocal microscopy studies revealed that the aggregated {beta}-catenin in HEK293 cells was extra-nuclear and co-localized with lysosomes, suggesting that EGCG activated a pathway involving lysosomal trafficking of {beta}-catenin. Lysosomal inhibitors leupeptin and transepoxysuccinyl-L-leucylamido(4-guanido)butane produced an increase in {beta}-catenin protein in total cell lysates, without a concomitant increase in {beta}-catenin transcriptional activity. These data provide the first evidence that EGCG facilitates the trafficking of {beta}-catenin into lysosomes, presumably as a mechanism for sequestering {beta}-catenin and circumventing further nuclear transport and activation of {beta}-catenin/TCF/LEF signaling.

Beta-adrenergic blockade for the treatment of hyperthyroidism.

Science.gov (United States)

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.

MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors.

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Brigitte Teissedre

Full Text Available Canonical Wnt/beta-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-DeltaN89beta-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin activate canonical Wnt signaling within distinct cell-types. DeltaN89beta-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18(+ER(-PR(-CD24(highCD49f(low profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14(+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14(+/p63(+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-DeltaN89beta-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand.

Interactions between two beta-sheets. Energetics of beta/beta packing in proteins.

Science.gov (United States)

Chou, K C; Némethy, G; Rumsey, S; Tuttle, R W; Scheraga, H A

1986-04-20

The analysis of the interactions between regularly folded segments of the polypeptide chain contributes to an understanding of the energetics of protein folding. Conformational energy-minimization calculations have been carried out to determine the favorable ways of packing two right-twisted beta-sheets. The packing of two five-stranded beta-sheets was investigated, with the strands having the composition CH3CO-(L-Ile)6-NHCH3 in one beta-sheet and CH3CO-(L-Val)6-NHCH3 in the other. Two distinct classes of low-energy packing arrangements were found. In the class with lowest energies, the strands of the two beta-sheets are aligned nearly parallel (or antiparallel) with each other, with a preference for a negative orientation angle, because this arrangement corresponds to the best complementary packing of the two twisted saddle-shaped beta-sheets. In the second class, with higher interaction energies, the strands of the two beta-sheets are oriented nearly perpendicular to each other. While the surfaces of the two beta-sheets are not complementary in this arrangement, there is good packing between the corner of one beta-sheet and the interior part of the surface of the other, resulting in a favorable energy of packing. Both classes correspond to frequently observed orientations of beta-sheets in proteins. In proteins, the second class of packing is usually observed when the two beta-sheets are covalently linked, i.e. when a polypeptide strand passes from one beta-sheet to the other, but we have shown here that a large contribution to the stabilization of this packing arrangement arises from noncovalent interactions.

Enhanced IL-1beta production in response to the activation of hippocampal glial cells impairs neurogenesis in aged mice.

Science.gov (United States)

Kuzumaki, Naoko; Ikegami, Daigo; Imai, Satoshi; Narita, Michiko; Tamura, Rie; Yajima, Marie; Suzuki, Atsuo; Miyashita, Kazuhiko; Niikura, Keiichi; Takeshima, Hideyuki; Ando, Takayuki; Ushijima, Toshikazu; Suzuki, Tsutomu; Narita, Minoru

2010-09-01

A variety of mechanisms that contribute to the accumulation of age-related damage and the resulting brain dysfunction have been identified. Recently, decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. However, the molecular mechanism of decreased neurogenesis with aging is still unclear. In the present study, we investigated whether aging decreases neurogenesis accompanied by the activation of microglia and astrocytes, which increases the expression of IL-1beta in the hippocampus, and whether in vitro treatment with IL-1beta in neural stem cells directly impairs neurogenesis. Ionized calcium-binding adaptor molecule 1 (Iba1)-positive microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes were increased in the dentate gyrus of the hippocampus of 28-month-old mice. Furthermore, the mRNA level of IL-1beta was significantly increased without related histone modifications. Moreover, a significant increase in lysine 9 on histone H3 (H3K9) trimethylation at the promoter of NeuroD (a neural progenitor cell marker) was observed in the hippocampus of aged mice. In vitro treatment with IL-1beta in neural stem cells prepared from whole brain of E14.5 mice significantly increased H3K9 trimethylation at the NeuroD promoter. These findings suggest that aging may decrease hippocampal neurogenesis via epigenetic modifications accompanied by the activation of microglia and astrocytes with the increased expression of IL-1beta in the hippocampus.

Purificação de três diferentes beta-galactosidades microbianas por partição em sistemas de duas fases aquosas Purification of three different microbial beta-galactosidases by partitioning in aqueous two-phase systems

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Maria Estela SILVA

1997-12-01

Full Text Available Este trabalho tratou da investigação do efeito do peso molecular de polietilenoglicol (PEG sobre a partição de enzimas beta-galactosidases de diferentes origens microbianas: Escherichia coli, Klueveromyces lactis e Aspergillus orizae em sistemas de duas fases aquosas (SDFA.Foi observado que os melhores sistemas para purificação da enzima de E. coli foram os formados por PEG 4000, 6000 e 8000/fosfato, fornecendo os mais elevados fatores de purificação da enzima. As enzimas de Klueveromyces lactis e Aspergillus orizae não foram eficientemente purificadas nestes sistemas sendo insensíveis à alterações do peso molecular do PEG. Portanto, um outro sistema de duas fases aquosas foi desenvolvido contendo um ligante específico, p-aminofenil 1-tio-beta-D-galactopiranosídeo (APGP, acoplado ao PEG para purificar a enzima de Klueveromyces lactis. Uma etapa simples de partição no SDFA formado por 6% APGP-PEG4000 + 12% dextrana T505.000 foi capaz de recuperar 83% da enzima na fase superior do sistema e de aumentar 1,6 vezes o fator de purificação.This work investigated the effect of the molecular weight of polyethyleneglycol (PEG upon the partition coefficient of beta-galactosidases from three different microorganisms: Escherichia coli, Klueveromyces lactis and Aspergillus orizae. It was found that PEG 6,000 and PEG 8,000/phosphate were the best systems for achieving the highest purification factors of E. coli beta-galactosidase. However, the other two yeast beta-galactosidases were not efficiently separated from their contaminants in any of the PEG/salt systems. In order to improve the separation of Klueveromyces lactis beta-galactosidase from the main protein contaminants, the biospecific ligand p-aminophenyl 1-thio-beta-D-galactopyranoside (APGP was attached to activated PEG 4000. The affinity PEG having APGP bound to its backbone was synthesized in two steps. The partitioning of Klueveromyces lactis beta-galactosidase in aqueous two

Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic {beta} cells

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Kumar, Divya P.; Rajagopal, Senthilkumar; Mahavadi, Sunila [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Mirshahi, Faridoddin [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Grider, John R. [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Murthy, Karnam S., E-mail: skarnam@vcu.edu [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Sanyal, Arun J., E-mail: asanyal@mcvh-vcu.edu [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States)

2012-10-26

Highlights: Black-Right-Pointing-Pointer G protein coupled receptor TGR5 is expressed in mouse and human islets. Black-Right-Pointing-Pointer TGR5 is coupled to activation of Gs and Ca{sup 2+} release via cAMP/Epac/PLC-{epsilon} pathway. Black-Right-Pointing-Pointer Activation of TGR5 by bile salts and selective ligands causes insulin secretion. Black-Right-Pointing-Pointer TGR5 could be a potential therapeutic target to treat diabetes. -- Abstract: Bile acids act as signaling molecules and stimulate the G protein coupled receptor, TGR5, in addition to nuclear farnesoid X receptor to regulate lipid, glucose and energy metabolism. Bile acid induced activation of TGR5 in the enteroendocrine cells promotes glucagon like peptide-1 (GLP-1) release, which has insulinotropic effect in the pancreatic {beta} cells. In the present study, we have identified the expression of TGR5 in pancreatic {beta} cell line MIN6 and also in mouse and human pancreatic islets. TGR5 selective ligands, oleanolic acid (OA) and INT-777 selectively activated G{alpha}{sub s} and caused an increase in intracellular cAMP and Ca{sup 2+}. OA and INT-777 also increased phosphoinositide (PI) hydrolysis and the increase was blocked by NF449 (a selective G{alpha}{sub s} inhibitor) or (U73122) (PI hydrolysis inhibitor). OA, INT-777 and lithocholic acid increased insulin release in MIN6 and human islets and the increase was inhibited by treatment with NF449, (U73122) or BAPTA-AM (chelator of calcium), but not with myristoylated PKI (PKA inhibitor), suggesting that the release is dependent on G{sub s}/cAMP/Ca{sup 2+} pathway. 8-pCPT-2 Prime -O-Me-cAMP, a cAMP analog, which activates Epac, but not PKA also stimulated PI hydrolysis. In conclusion, our study demonstrates that the TGR5 expressed in the pancreatic {beta} cells regulates insulin secretion and highlights the importance of ongoing therapeutic strategies targeting TGR5 in the control of glucose homeostasis.

18{beta}-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis

Energy Technology Data Exchange (ETDEWEB)

Moon, Myung-Hee; Jeong, Jae-Kyo; Lee, You-Jin; Seol, Jae-Won; Ahn, Dong-Choon; Kim, In-Shik [Center for Healthcare Technology Development, Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Park, Sang-Youel, E-mail: sypark@chonbuk.ac.kr [Center for Healthcare Technology Development, Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of)

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 cells 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{beta

TGF-beta1 expression in EL4 lymphoma cells overexpressing growth hormone.

Science.gov (United States)

Farmer, John T; Weigent, Douglas A

2006-03-01

Our previous studies show that growth hormone overexpression (GHo) upregulates the expression of the IGF-1R and IGF-2R resulting in the protection of the EL4 lymphoma cell line from apoptosis. In this study, we report that GHo also increases TGF-beta1 protein expression measured by luciferase promoter assay, Western analysis, and ELISA. Further, the data show that antibody to TGF-betaR2 decreases TGF-beta1 promoter activity to the level of vector alone control cells. GHo cells treated with (125)I-rh-latent TGF-beta1 showed increased activation of latent TGF-beta1 as measured by an increase in the active 24kDa, TGF-beta1 compared to vector alone control cells. The ability of endogenous GH to increase TGF-beta1 expression is blocked in EL4 cells by antisense but not sense oligodeoxynucleotides or in cells cultured with antibody to growth hormone (GH). The data suggest that endogenous GH may protect from apoptosis through the IGF-1R receptor while limiting cellular growth through increased expression and activation of TGF-beta1.

Effect of nipradilol, a beta-adrenergic blocker with vasodilating activity, on oxotremorine-induced tremor in mice.

Science.gov (United States)

Iwata, S; Nomoto, M; Fukuda, T

1996-10-01

The effect of nipradilol, a nonselective beta-adrenergic receptor blocker with nitroglycerin-like vasodilating activity, on oxotremorine-induced tremor was studied in mice. General tremor in mice was elicited by 0.5 mg/kg oxotremorine. The tremor was quantified using a capacitance transducer, then analyzed by a signal processor. The strength of the tremor was expressed in "points". The point values of the tremor (mean +/- SE) in control mice for 5 mg/kg (+/-)-propranolol, 2.5 mg/kg arotinolol, 0.5 mg/kg nipradilol, 1.0 mg/kg nipradilol and 2.5 mg/kg nipradilol were 87 +/- 16, 42 +/- 6, 38 +/- 6, 99 +/- 28, 28 +/- 6 and 31 +/- 7, respectively. The strength of the tremor was reduced by all beta-blockers. Although 1.0 mg/kg nipradilol significantly reduced the tremor, further inhibition of the tremor was not obtained with dosages up to 2.5 mg/kg of the drug. In conclusion, nipradilol was effective for suppressing oxotremorine-induced tremor, as were other beta-blockers.

Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

Science.gov (United States)

Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

2009-06-01

In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.

Defining carbohydrate specificity of Ricinus communis agglutinin as Gal beta 1-->4GlcNAc (II) > Gal beta 1-->3GlcNAc (I) > Gal alpha 1-->3Gal (B) > Gal beta 1-->3GalNAc (T).

Science.gov (United States)

Wu, J H; Herp, A; Wu, A M

1993-03-01

To define carbohydrate specificity of Ricinus communis agglutinin (RCA1), the combining site of RCA1 was further characterized by quantitative precipitin (QPA) and precipitin-inhibition assays (QPIA). Among the oligosaccharides tested for QPIA, Gal beta 1-->4GlcNAc (II, human blood group type II precursor sequence) was found to be 7.1 times more active than Gal beta 1-->3GalNAc (T, Thomsen-Friedenreich sequence) and about 1.7 times more active than the other three disaccharides tested--Gal beta 1-->4Man, Gal beta 1-->3DAra and Gal beta 1-->6GalNAc. Gal alpha 1-->4Gal, the receptor of the uropathogenic E. coli ligand was 3.6 times less active than the II sequence. These results indicate that the beta 1-->4 linkage of the terminal Gal to subterminal GlcNAc is important as this beta 1-->4GlcNAc sequence is at least 1.6 times more active than other types of disaccharides. Among the glycoproteins examined for QPA, native and desialized bovine submandibular glycoproteins, native and desialized human plasma alpha 1-acid glycoproteins, as well as crude hog stomach mucin and its three mild acid hydrolyzed products reacted well with the lectin. These glycoproteins precipitated over 75% of the lectin nitrogen added indicating that RCA1 has the ability to recognize Gal beta 1-->4/3GlcNAc and/or the related residues at the non-reducing ends and at positions in the interior of the chains. However, Tn (GalNAc alpha 1-->Ser/Thr sequence) rich glycoproteins such as desialized ovine submandibular glycoprotein and desialized armadillo salivary glycoprotein, in which over 90% of the carbohydrate side chains are Tn determinants with none or only a trace of I/II or T determinants, precipitated poorly with RCA1. From the present and previous results obtained, the carbohydrate specificity of RCA1 can be constructed and summarized in decreasing order by lectin determinants as follows: II (Gal beta 1-->4GlcNAc) > I (Gal beta 1-->3GlcNAc) > E (Gal alpha 1-->4Gal) and B (Gal alpha 1-->3Gal

Adrenergic receptors and gastric secretion in dogs. Is a "tonic balance" relationship between vagal and beta 2-adrenergic activity a possibility?

DEFF Research Database (Denmark)

Gottrup, F; Hovendal, C; Bech, K

1984-01-01

The relative influence of adrenergic receptors on gastric acid secretion in the dog stomach with different vagal activity or "tone" is almost unknown. beta-adrenoceptors seem to be most important for the direct effect of adrenergic stimulation on acid secretion. In this study the effects...... acid secretion was not influenced significantly by beta-blockade. Similar dose-response curves were found for non-vagotomized dogs with high beta 2-adrenergic tone and dogs with low vagal tone (vagotomy) after pentagastrin and histamine stimulated acid secretion. This study indicates...... that a counterbalance between beta 2-adrenergic and cholinergic vagal tone exists. A "tonic balance theory" is suggested and is probably involved in the resulting acid secretion after vagotomy....

E1A FUNCTIONS AS A COACTIVATOR OF RETINOIC ACID-DEPENDENT RETINOIC ACID RECEPTOR-BETA-2 PROMOTER ACTIVATION

NARCIS (Netherlands)

KRUYT, FAE; FOLKERS, GE; WALHOUT, AJM; VANDERLEEDE, BM; VANDERSAAG, PT; Kruyt, Frank

The retinoic acid (RA) receptor (RAR) beta2 promoter is strongly activated by RA in embryonal carcinoma (EC) cells. We examined this activation in the P19 EC-derived END-2 cell line and in E1A-expressing counterparts and found strong RA-dependent RARbeta2 promoter activation in the E1A-expressing

EX4 stabilizes and activates Nrf2 via PKCδ, contributing to the prevention of oxidative stress-induced pancreatic beta cell damage

Energy Technology Data Exchange (ETDEWEB)

Kim, Mi-Hwi; Kim, Eung-Hwi [College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Jung, Hye Seung [Department of Internal Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Yang, Dongki [Department of Physiology, Gachon University College of Medicine, Incheon (Korea, Republic of); Park, Eun-Young, E-mail: parkey@mokpo.ac.kr [College of Pharmacy, Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam (Korea, Republic of); Jun, Hee-Sook, E-mail: hsjun@gachon.ac.kr [College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, Incheon (Korea, Republic of)

2017-01-15

Oxidative stress in pancreatic beta cells can inhibit insulin secretion and promote apoptotic cell death. Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, can suppress beta cell apoptosis, improve beta cell function and protect against oxidative damage. In this study, we investigated the molecular mechanisms for antioxidative effects of EX4 in pancreatic beta cells. INS-1 cells, a rat insulinoma cell line, were pretreated with EX4 and exposed to palmitate or H{sub 2}O{sub 2}. Reactive oxygen species (ROS) production, and glutathione and insulin secretion were measured. The mRNA and protein expression levels of antioxidant genes were examined. The level of nuclear factor erythroid 2-related factor 2 (Nrf2), its binding to antioxidant response element (ARE), and its ubiquination in the presence of EX4 were determined. The Nrf2 signaling pathway was determined using rottlerin (protein kinase [PK]Cδ inhibitor), H89 (PKA inhibitor) and LY294002 (phosphatidylinositide 3-kinase [PI3K] inhibitor). EX4 treatment decreased ROS production, recovered cellular glutathione levels and insulin secretion in the presence of oxidative stress in INS-1 cells. The expression levels of glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 were increased by EX4 treatment. EX4 promoted Nrf2 translocation, ARE binding activity and enhanced stabilization of Nrf2 by inhibition of ubiquitination. Knockdown of Nrf2 abolished the effect of EX4 on increased insulin secretion. Inhibition of PKCδ attenuated Nrf2 translocation and antioxidative gene expression by EX4 treatment. We suggest that EX4 activates and stabilizes Nrf2 through PKCδ activation, contributing to the increase of antioxidant gene expression and consequently improving beta cell function in the presence of oxidative stress. - Highlights: • EX4 protects against oxidative stress-induced pancreatic beta cell dysfunction. • EX4 increases antioxidant gene expression. • Antioxidative effect of EX4 is

EX4 stabilizes and activates Nrf2 via PKCδ, contributing to the prevention of oxidative stress-induced pancreatic beta cell damage

International Nuclear Information System (INIS)

Kim, Mi-Hwi; Kim, Eung-Hwi; Jung, Hye Seung; Yang, Dongki; Park, Eun-Young; Jun, Hee-Sook

2017-01-01

Oxidative stress in pancreatic beta cells can inhibit insulin secretion and promote apoptotic cell death. Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, can suppress beta cell apoptosis, improve beta cell function and protect against oxidative damage. In this study, we investigated the molecular mechanisms for antioxidative effects of EX4 in pancreatic beta cells. INS-1 cells, a rat insulinoma cell line, were pretreated with EX4 and exposed to palmitate or H 2 O 2 . Reactive oxygen species (ROS) production, and glutathione and insulin secretion were measured. The mRNA and protein expression levels of antioxidant genes were examined. The level of nuclear factor erythroid 2-related factor 2 (Nrf2), its binding to antioxidant response element (ARE), and its ubiquination in the presence of EX4 were determined. The Nrf2 signaling pathway was determined using rottlerin (protein kinase [PK]Cδ inhibitor), H89 (PKA inhibitor) and LY294002 (phosphatidylinositide 3-kinase [PI3K] inhibitor). EX4 treatment decreased ROS production, recovered cellular glutathione levels and insulin secretion in the presence of oxidative stress in INS-1 cells. The expression levels of glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 were increased by EX4 treatment. EX4 promoted Nrf2 translocation, ARE binding activity and enhanced stabilization of Nrf2 by inhibition of ubiquitination. Knockdown of Nrf2 abolished the effect of EX4 on increased insulin secretion. Inhibition of PKCδ attenuated Nrf2 translocation and antioxidative gene expression by EX4 treatment. We suggest that EX4 activates and stabilizes Nrf2 through PKCδ activation, contributing to the increase of antioxidant gene expression and consequently improving beta cell function in the presence of oxidative stress. - Highlights: • EX4 protects against oxidative stress-induced pancreatic beta cell dysfunction. • EX4 increases antioxidant gene expression. • Antioxidative effect of EX4 is mediated by

Functional analysis of the active site of the maize beta-glucosidase Zm-p60.1

Czech Academy of Sciences Publication Activity Database

Fohlerová, Radka; Mazura, Pavel; Janda, L.; Chaloupková, R.; Jeřábek, P.; Damborský, J.; Brzobohatý, Břetislav

2005-01-01

Roč. 409, - (2005), S3 [2nd International Symposium Auxins and Cytokinins in Plant Development, 07.07.2005-12.07.2005] R&D Projects: GA ČR(CZ) GA203/02/0865 Institutional research plan: CEZ:AV0Z50040507 Keywords : beta-glucosidase * active site Subject RIV: BO - Biophysics

Mitogen-Activated Protein Kinases Promote WNT/beta-Catenin Signaling via Phosphorylation of LRP6

Czech Academy of Sciences Publication Activity Database

Červenka, I.; Wolf, J.; Mašek, J.; Krejčí, Pavel; Wilcox, W. R.; Kozubík, Alois; Schulte, G.; Gutkind, J.S.; Bryja, Vítězslav

2011-01-01

Roč. 31, č. 1 (2011), s. 179-189 ISSN 0270-7306 R&D Projects: GA ČR(CZ) GC204/09/J030 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : WNT RECEPTOR ACTIVATION * BETA-CATENIN * CORECEPTOR LRP6 Subject RIV: BO - Biophysics Impact factor: 5.527, year: 2011

Un aporte al debate sobre la convergencia en Argentina: la importancia de los cambios estructurales

Directory of Open Access Journals (Sweden)

Alberto José Figueras

2014-09-01

Full Text Available El análisis del crecimiento económico de las provincias argentinas, signado por su comportamiento idiosincrático, es un valioso aporte a los estudios de convergencia regional. En el presente trabajo, se propone un análisis de Convergencia Beta y Sigma de las provincias argentinas para el periodo 1970-2007, con variables que aproximan el capital humano, las economías de escala, la inversión y la política fiscal. Adicionalmente, se intenta aislar el efecto de shocks sobre el crecimiento económico de provincias con diferentes estructuras productivas, y sus consecuencias sobre la convergencia/divergencia regional en Argentina.******Since Argentinian provinces’ economic growth is determined by idiosyncratic behaviour, its analysis is a valuable contribution to the studies on regional convergence. This paper takes on an analysis of Sigma and Beta convergence in Argentinian provinces for the 1970 -2007 period, with variables that include human capital, economies of scale, investment and fiscal policy. It also focuses on the effect structural changes exert upon provinces’ economic growth -with their different productive structures- and its impact on the regional convergence/divergence in Argentina.

Activation of the transcription factor carbohydrate-responsive element-binding protein by glucose leads to increased pancreatic beta cell differentiation in rats.

Science.gov (United States)

Soggia, A; Flosseau, K; Ravassard, P; Szinnai, G; Scharfmann, R; Guillemain, G

2012-10-01

Pancreatic cell development is a tightly controlled process. Although information is available regarding the mesodermal signals that control pancreatic development, little is known about the role of environmental factors such as nutrients, including glucose, on pancreatic development. We previously showed that glucose and its metabolism through the hexosamine biosynthesis pathway (HBP) promote pancreatic endocrine cell differentiation. Here, we analysed the role of the transcription factor carbohydrate-responsive element-binding protein (ChREBP) in this process. This transcription factor is activated by glucose, and has been recently described as a target of the HBP. We used an in vitro bioassay in which pancreatic endocrine and exocrine cells develop from rat embryonic pancreas in a way that mimics in vivo pancreatic development. Using this model, gain-of-function and loss-of-function experiments were undertaken. ChREBP was produced in the endocrine lineage during pancreatic development, its abundance increasing with differentiation. When rat embryonic pancreases were cultured in the presence of glucose or xylitol, the production of ChREBP targets was induced. Concomitantly, beta cell differentiation was enhanced. On the other hand, when embryonic pancreases were cultured with inhibitors decreasing ChREBP activity or an adenovirus producing a dominant-negative ChREBP, beta cell differentiation was reduced, indicating that ChREBP activity was necessary for proper beta cell differentiation. Interestingly, adenovirus producing a dominant-negative ChREBP also reduced the positive effect of N-acetylglucosamine, a substrate of the HBP acting on beta cell differentiation. Our work supports the idea that glucose, through the transcription factor ChREBP, controls beta cell differentiation from pancreatic progenitors.

Design of a Quality Control Program for the Measurement of Gross Alpha and Gross Beta Activities (LMPR-CIEMAT); Diseno del Control de Calidad de las Medidas de Actividad Alfa-Beta Total (LMPR-CIEMAT)

Energy Technology Data Exchange (ETDEWEB)

Alvarez, A.; Yague, L.; Gasco, C.; Navarro, N.; Higueras, E.; Noguerales, C.

2010-10-21

In accordance with international standards, general requirements for testing laboratories have to include a quality system for planning, implementing, and assessing the work performed by the organization and for carrying out required quality assurance and quality control. The purpose of internal laboratory quality control is to monitor performance, identify problems, and initiate corrective actions. This report describes the internal quality control to monitor the gross alpha and beta activities determination. Identification of specific performance indicators, the principles that govern their use and statistical means of evaluation are explained. Finally, calculation of alpha and beta specific activities, uncertainties and detection limits are performed. (Author) 10 refs.

Milk Intolerance, Beta-Casein and Lactose.

Science.gov (United States)

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.

Milk Intolerance, Beta-Casein and Lactose

Directory of Open Access Journals (Sweden)

Sebely Pal

2015-08-01

Full Text Available 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.

Abstraction Mechanisms in the BETA Programming Language

DEFF Research Database (Denmark)

Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger

1983-01-01

. It is then necessary that the abstraction mechanisms are powerful in order to define more specialized constructs. BETA is an object oriented language like SIMULA 67 ([SIMULA]) and SMALLTALK ([SMALLTALK]). By this is meant that a construct like the SIMULA class/subclass mechanism is fundamental in BETA. In contrast......]) --- covering both data, procedural and control abstractions, substituting constructs like class, procedure, function and type. Correspondingly objects, procedure activation records and variables are all regarded as special cases of the basic building block of program executions: the entity. A pattern thus......The BETA programming language is developed as part of the BETA project. The purpose of this project is to develop concepts, constructs and tools in the field of programming and programming languages. BETA has been developed from 1975 on and the various stages of the language are documented in [BETA...

Effects of hydration and oxygen vacancy on CO2 adsorption and activation on beta-Ga2O3(100).

Science.gov (United States)

Pan, Yun-xiang; Liu, Chang-jun; Mei, Donghai; Ge, Qingfeng

2010-04-20

The effects of hydration and oxygen vacancy on CO(2) adsorption on the beta-Ga(2)O(3)(100) surface have been studied using density functional theory slab calculations. Adsorbed CO(2) is activated on the dry perfect beta-Ga(2)O(3)(100) surface, resulting in a carbonate species. This adsorption is slightly endothermic, with an adsorption energy of 0.07 eV. Water is preferably adsorbed molecularly on the dry perfect beta-Ga(2)O(3)(100) surface with an adsorption energy of -0.56 eV, producing a hydrated perfect beta-Ga(2)O(3)(100) surface. Adsorption of CO(2) on the hydrated surface as a carbonate species is also endothermic, with an adsorption energy of 0.14 eV, indicating a slightly repulsive interaction when H(2)O and CO(2) are coadsorbed. The carbonate species on the hydrated perfect surface can be protonated by the coadsorbed H(2)O to a bicarbonate species, making the CO(2) adsorption exothermic, with an adsorption energy of -0.13 eV. The effect of defects on CO(2) adsorption and activation has been examined by creating an oxygen vacancy on the dry beta-Ga(2)O(3)(100) surface. The formation of an oxygen vacancy is endothermic, by 0.34 eV, with respect to a free O(2) molecule in the gas phase. Presence of the oxygen vacancy promoted the adsorption and activation of CO(2). In the most stable CO(2) adsorption configuration on the dry defective beta-Ga(2)O(3)(100) surface with an oxygen vacancy, one of the oxygen atoms of the adsorbed CO(2) occupies the oxygen vacancy site, and the CO(2) adsorption energy is -0.31 eV. Water favors dissociative adsorption at the oxygen vacancy site on the defective surface. This process is spontaneous, with a reaction energy of -0.62 eV. These results indicate that, when water and CO(2) are present in the adsorption system simultaneously, water will compete with CO(2) for the oxygen vacancy sites and impact CO(2) adsorption and conversion negatively.

Beta/alpha continuous air monitor

Science.gov (United States)

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.

Serum TGF-beta2 and TGF-beta3 are increased and positively correlated to pain, functionality, and radiographic staging in osteoarthritis.

Science.gov (United States)

Kapetanakis, Stilianos; Drygiannakis, Ioannis; Kazakos, Kostantinos; Papanas, Nikolaos; Kolios, George; Kouroumalis, Elias; Verettas, Dionysios-Alexandros

2010-08-11

The goal of this study was to verify or reject the hypothesis that systematic differences exist in various profibrotic or antifibrotic factors between osteoarthritic patients and controls, as well as between different stages of osteoarthritis. The study group comprised 63 patients with knee osteoarthritis and 18 controls. Transforming growth factor-beta (TGF-beta)1, -2, -3; tissue inhibitor of metalloproteinase (TIMP)-1 protein levels; and gelatinolytic activity of matrix metalloproteinase (MMP)-1, -2, -3, -9 activities were measured by enzyme-linked immunosorbent assay and gelatin zymography, respectively. Visual analog scale scores, Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Lequesne clinical osteoarthritis scales, and Kellgren-Lawrence radiographic grading were recorded for each patient.Transforming growth factor-beta2 and -3 (in contrast to TGF-beta1 and TIMP-1) serum protein levels were significantly higher in osteoarthritic patients compared to controls (210%+/-14% [P<.001] and 232%+/-7% [P<10(-7)], respectively). Additionally, TGF-beta2 and -3 were strongly positively correlated to Kellgren-Lawrence radiographic grading of the disease (P<10(-5) and P<10(-7), respectively). Moreover, TGF-beta2 correlated positively with the WOMAC scale (P=.007). However, TIMP-1 decreased as osteoarthritis progressed clinically, but remained irrelevant to radiographic staging. Furthermore, activities of MMP-2 and -9, but not MMP-1+/-3, were lower in patients with osteoarthritis. Copyright 2010, SLACK Incorporated.

Interaction of Protease-Activated Receptor 2 with G Proteins and Beta-Arrestin 1 Studied by Bioluminescence Resonance Energy Transfer

Directory of Open Access Journals (Sweden)

Mohammed Akli eAyoub

2013-12-01

Full Text Available G protein-coupled receptors (GPCRs are well recognized as being able to activate several signaling pathways through the activation of different G proteins as well as other signaling proteins such as beta-arrestins. Therefore, understanding how such multiple GPCR-mediated signaling can be integrated constitute an important aspect. Here, we applied bioluminescence resonance energy transfer (BRET to shed more light on the G protein coupling profile of trypsin receptor, or protease-activated receptor 2 (PAR2, and its interaction with beta-arrestin1. Using YFP and Rluc fusion constructs expressed in COS-7 cells, BRET data revealed a pre-assembly of PAR2 with both Galphai1 and Galphao and a rapid and transient activation of these G proteins upon receptor activation. In contrast, no preassembly of PAR2 with Galpha12 could be detected and their physical association can be measured with a very slow and sustained kinetics similar to that of beta-arrestin1 recruitment. These data demonstrate the coupling of PAR2 with Galphai1, Galphao and Galpha12 in COS-7 cells with differences in the kinetics of GPCR-G protein coupling, a parameter that very likely influences the cellular response. Moreover, this further illustrates that preassembly or agonist-induced G protein interaction depends on receptor-G protein pairs indicating another level of complexity and regulation of the signaling of GPCR-G protein complexes and its multiplicity.

Phosphorylation prevents C/EBP{beta} from the calpain-dependent degradation

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yuan-yuan; Li, Shu-fen; Qian, Shu-wen; Zhang, You-you; Liu, Yuan; Tang, Qi-Qun; Li, Xi, E-mail: lixi@shmu.edu.cn

2012-03-16

Highlights: Black-Right-Pointing-Pointer Phosphorylation protected C/EBP{beta} from {mu}-calpain-mediated proteolysis in vitro. Black-Right-Pointing-Pointer Phosphorylation mimic C/EBP{beta} was insensitive to calpain accelerator and inhibitor. Black-Right-Pointing-Pointer Phosphorylation on Thr{sub 188} contributed more to the stabilization of C/EBP{beta}. -- Abstract: CCAAT/enhancer-binding protein (C/EBP) {beta} plays an important role in proliferation and differentiation of 3T3-L1 preadipocytes. C/EBP{beta} is sequentially phosphorylated during the 3T3-L1 adipocyte differentiation program, first by MAPK/Cyclin A/cdk2 on Thr{sub 188} and subsequently by GSK3{beta} on Ser{sub 184} or Thr{sub 179}. Dual phosphorylation is critical for the gain of DNA binding activity of C/EBP{beta}. In this manuscript, we found that phosphorylation also contributed to the stability of C/EBP{beta}. Both ex vivo and in vitro experiments showed that phosphorylation by MAPK/Cyclin A/cdk2 and GSK3{beta} protected C/EBP{beta} from {mu}-calpain-mediated proteolysis, while phosphorylation on Thr{sub 188} by MAPK/Cyclin A/cdk2 contributed more to the stabilization of C/EBP{beta}, Further studies indicated that phosphorylation mimic C/EBP{beta} was insensitive to both calpain accelerator and calpain inhibitor. Thus, phosphorylation might contribute to the stability as well as the gain of DNA binding activity of C/EBP{beta}.

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

Science.gov (United States)

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.

Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

The BETA ® nursing measure: Calibrating construct validity with ...

African Journals Online (AJOL)

Background: The BETA nursing measure has been introduced as a tool to routinely measure and monitor the outcomes of patients' activities of daily living in a restorative nursing care context. Objectives: To investigate the BETA's construct validity using the Rasch model with specific reference to the BETA's potential to be ...

Glycogen synthase kinase-3beta and the p25 activator of cyclin dependent kinase 5 increase pausing of mitochondria in neurons.

Science.gov (United States)

Morel, M; Authelet, M; Dedecker, R; Brion, J P

2010-06-02

The complex bi-directional axoplasmic transport of mitochondria is essential for proper metabolic functioning of neurons and is controlled by phosphorylation. We have investigated by time-lapse imaging the effects of increased expression of glycogen synthase kinase-3beta (GSK-3beta) and of the p25 activator of cyclin dependent kinase 5 on mitochondria movements in mammalian cortical neurons and in PC12 cells. Both GSK-3beta and p25 increased the stationary behaviour of mitochondria in PC12 and in neurons, decreased their anterograde transport but did not affect the intrinsic velocities of mitochondria. The microtubule-associated tau proteins were more phosphorylated in GSK-3beta and p25 transfected neurons, but ultrastructural observation showed that these cells still contained microtubules and nocodazole treatment further reduced residual mitochondria movements in GSK-3beta or p25 transfected neurons, indicating that microtubule disruption was not the primary cause of increased mitochondrial stationary behaviour in GSK-3beta or p25 transfected neurons. Our results suggest that increased expression of GSK-3beta and p25 acted rather by decreasing the frequency of mitochondrial movements driven by molecular motors and that GSK-3beta and p25 might regulate these transports by controlling the time that mitochondria spend pausing, rather than their velocities. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Activities of UDP-glucuronyltransferase, beta-glucuronidase and deiodinase types I and II in hyper- and hypothyroid rats

NARCIS (Netherlands)

Heide, S.M. van der; Joosten, B.H.G.M.; Everts, M.E.; Klaren, P.H.M.

2004-01-01

We have investigated the hypothesis that uridine 5'-diphosphate (UDP)-glucuronyltransferases (UGTs) and beta-glucuronidase are jointly involved in a mechanism for the storage and mobilization of iodothyronine metabolites in liver, kidney, heart and brain. Specifically, we predicted UGT activities to

Coevolving residues of (beta/alpha)(8)-barrel proteins play roles in stabilizing active site architecture and coordinating protein dynamics.

Science.gov (United States)

Shen, Hongbo; Xu, Feng; Hu, Hairong; Wang, Feifei; Wu, Qi; Huang, Qiang; Wang, Honghai

2008-12-01

Indole-3-glycerol phosphate synthase (IGPS) is a representative of (beta/alpha)(8)-barrel proteins-the most common enzyme fold in nature. To better understand how the constituent amino-acids work together to define the structure and to facilitate the function, we investigated the evolutionary and dynamical coupling of IGPS residues by combining statistical coupling analysis (SCA) and molecular dynamics (MD) simulations. The coevolving residues identified by the SCA were found to form a network which encloses the active site completely. The MD simulations showed that these coevolving residues are involved in the correlated and anti-correlated motions. The correlated residues are within van der Waals contact and appear to maintain the active site architecture; the anti-correlated residues are mainly distributed on opposite sides of the catalytic cavity and coordinate the motions likely required for the substrate entry and product release. Our findings might have broad implications for proteins with the highly conserved (betaalpha)(8)-barrel in assessing the roles of amino-acids that are moderately conserved and not directly involved in the active site of the (beta/alpha)(8)-barrel. The results of this study could also provide useful information for further exploring the specific residue motions for the catalysis and protein design based on the (beta/alpha)(8)-barrel scaffold.

Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines

DEFF Research Database (Denmark)

Damstrup, L; Rygaard, K; Spang-Thomsen, M

1993-01-01

A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis......(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell...... lines express TGF beta-receptors and also produce TGF beta mRNAs....

Murrayafoline A attenuates the Wnt/{beta}-catenin pathway by promoting the degradation of intracellular {beta}-catenin proteins

Energy Technology Data Exchange (ETDEWEB)

Choi, Hyuk; Gwak, Jungsug; Cho, Munju; Ryu, Min-Jung [PharmacoGenomics Research Center, Inje University, Busan 614-735 (Korea, Republic of); Lee, Jee-Hyun; Kim, Sang Kyum; Kim, Young Ho [College of Pharmacy, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Lee, Gye Won [Department of Pharmaceutical Engineering, Konyang University, Nonsan 320-711 (Korea, Republic of); Yun, Mi-Young [Department of Beauty Health Care, Daejeon University, Daejeon 305-764 (Korea, Republic of); Cuong, Nguyen Manh [Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Hanoi (Viet Nam); Shin, Jae-Gook [PharmacoGenomics Research Center, Inje University, Busan 614-735 (Korea, Republic of); Song, Gyu-Yong, E-mail: gysong@cnu.ac.kr [College of Pharmacy, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Oh, Sangtaek, E-mail: ohsa@inje.ac.kr [PharmacoGenomics Research Center, Inje University, Busan 614-735 (Korea, Republic of)

2010-01-01

Molecular lesions in Wnt/{beta}-catenin signaling and subsequent up-regulation of {beta}-catenin response transcription (CRT) occur frequently during the development of colon cancer. To identify small molecules that suppress CRT, we screened natural compounds in a cell-based assay for detection of TOPFalsh reporter activity. Murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa, antagonized CRT that was stimulated by Wnt3a-conditioned medium (Wnt3a-CM) or LiCl, an inhibitor of glycogen synthase kinase-3{beta} (GSK-3{beta}), and promoted the degradation of intracellular {beta}-catenin without altering its N-terminal phosphorylation at the Ser33/37 residues, marking it for proteasomal degradation, or the expression of Siah-1, an E3 ubiquitin ligase. Murrayafoline A repressed the expression of cyclin D1 and c-myc, which is known {beta}-catenin/T cell factor (TCF)-dependent genes and thus inhibited the proliferation of various colon cancer cells. These findings indicate that murrayafoline A may be a potential chemotherapeutic agent for use in the treatment of colon cancer.

The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

DEFF Research Database (Denmark)

Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen

2012-01-01

A gene-drug interaction has been indicated between beta-1 selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). We studied the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR) and the genotype...

High beta-Lactamase Levels Change the Pharmacodynamics of beta-Lactam Antibiotics in Pseudomonas aeruginosa Biofilms

DEFF Research Database (Denmark)

Wang, Hengzhuang; Ciofu, Oana; Yang, Liang

2013-01-01

the role of beta-lactamase in the pharmacokinetics (PK) and pharmacodynamics (PD) of ceftazidime and imipenem on P. aeruginosa biofilms. P. aeruginosa PAO1 and its corresponding beta-lactamase-overproducing mutant, PA Delta DDh2Dh3, were used in this study. Biofilms of these two strains in flow chambers......, microtiter plates, and on alginate beads were treated with different concentrations of ceftazidime and imipenem. The kinetics of antibiotics on the biofilms was investigated in vitro by time-kill methods. Time-dependent killing of ceftazidime was observed in PAO1 biofilms, but concentration-dependent killing...... activity of ceftazidime was observed for beta-lactamase-overproducing biofilms of P. aeruginosa in all three models. Ceftazidime showed time-dependent killing on planktonic PAO1 and PA Delta DDh2Dh3. This difference is probably due to the special distribution and accumulation in the biofilm matrix of beta...

Study of collagen metabolism and regulation after {beta} radiation injury

Energy Technology Data Exchange (ETDEWEB)

Yinghui, Zhou; Lan, Xu; Shiliang, Wu; Hao, Qiu; Zhi, Jiang; Youbin, Tu; Xueguang, Zhang [Suzhou Medical College (China)

2001-04-01

The animal model of {beta} radiation injury was established by the {beta} radiation produced by the linear accelerator; and irradiated NIH 3T3 cells were studied. In the experiment the contents of total collagen, collagen type I and type III were measured. The activity of MMPs-1 were tested. The contents of TGF-{beta}{sub 1}, IL-6 were also detected. The results showed that after exposure to {beta} radiation, little change was found in the content of total collagen, but the content of collagen I decreased and the content of collagen III, MMPs-1 activity increased; the expression of TGF-{beta}{sub 1}, IL-6 increased. The results suggest that changes in the metabolism of collagen play an important role in the irradiated injury of the skin; TGF-{beta}{sub 1}, IL-6 may be essential in the regulation of the collagen metabolism.

How Should Beta-Diversity Inform Biodiversity Conservation?

Science.gov (United States)

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.

Reactivation of the chloroplast CF1-ATPase beta subunit by trace amounts of the CF1 alpha subunit suggests a chaperonin-like activity for CF1 alpha.

Science.gov (United States)

Avni, A; Avital, S; Gromet-Elhanan, Z

1991-04-25

Incubation of tobacco and lettuce thylakoids with 2 M LiCl in the presence of MgATP removes the beta subunit from their CF1-ATPase (CF1 beta) together with varying amounts of the CF1 alpha subunit (CF1 alpha). These 2 M LiCl extracts, as with the one obtained from spinach thylakoids (Avital, S., and Gromet-Elhanan, Z. (1991) J. Biol. Chem. 266, 7067-7072), could form active hybrid ATPases when reconstituted into inactive beta-less Rhodospirillum rubrum chromatophores. Pure CF1 beta fractions that have been isolated from these extracts could not form such active hybrids by themselves, but could do so when supplemented with trace amounts (less than 5%) of CF1 alpha. A mitochondrial F1-ATPase alpha subunit was recently reported to be a heat-shock protein, having two amino acid sequences that show a highly conserved identity with sequences found in molecular chaperones (Luis, A. M., Alconada, A., and Cuezva, J. M. (1990) J. Biol. Chem. 265, 7713-7716). These sequences are also conserved in CF1 alpha isolated from various plants, but not in F1 beta subunits. The above described reactivation of CF1 beta by trace amounts of CF1 alpha could thus be due to a chaperonin-like function of CF1 alpha, which involves the correct, active folding of isolated pure CF1 beta.

Orientation of the calcium channel beta relative to the alpha(12.2 subunit is critical for its regulation of channel activity.

Directory of Open Access Journals (Sweden)

Iuliia Vitko

Full Text Available BACKGROUND: The Ca(vbeta subunits of high voltage-activated Ca(2+ channels control the trafficking and biophysical properties of the alpha(1 subunit. The Ca(vbeta-alpha(1 interaction site has been mapped by crystallographic studies. Nevertheless, how this interaction leads to channel regulation has not been determined. One hypothesis is that betas regulate channel gating by modulating movements of IS6. A key requirement for this direct-coupling model is that the linker connecting IS6 to the alpha-interaction domain (AID be a rigid structure. METHODOLOGY/PRINCIPAL FINDINGS: The present study tests this hypothesis by altering the flexibility and orientation of this region in alpha(12.2, then testing for Ca(vbeta regulation using whole cell patch clamp electrophysiology. Flexibility was induced by replacement of the middle six amino acids of the IS6-AID linker with glycine (PG6. This mutation abolished beta2a and beta3 subunits ability to shift the voltage dependence of activation and inactivation, and the ability of beta2a to produce non-inactivating currents. Orientation of Ca(vbeta with respect to alpha(12.2 was altered by deletion of 1, 2, or 3 amino acids from the IS6-AID linker (Bdel1, Bdel2, Bdel3, respectively. Again, the ability of Ca(vbeta subunits to regulate these biophysical properties were totally abolished in the Bdel1 and Bdel3 mutants. Functional regulation by Ca(vbeta subunits was rescued in the Bdel2 mutant, indicating that this part of the linker forms beta-sheet. The orientation of beta with respect to alpha was confirmed by the bimolecular fluorescence complementation assay. CONCLUSIONS/SIGNIFICANCE: These results show that the orientation of the Ca(vbeta subunit relative to the alpha(12.2 subunit is critical, and suggests additional points of contact between these subunits are required for Ca(vbeta to regulate channel activity.

Severity of murine collagen-induced arthritis correlates with increased CYP7B activity: enhancement of dehydroepiandrosterone metabolism by interleukin-1beta.

Science.gov (United States)

Dulos, John; Verbraak, Evert; Bagchus, Wilma M; Boots, Annemieke M H; Kaptein, Allard

2004-10-01

The endogenous steroid dehydroepiandrosterone (DHEA) has been reported to play a role in rheumatoid arthritis (RA). DHEA is metabolized by the P450 enzyme CYP7B into 7alpha-OH-DHEA, which has immunostimulating properties. This study was undertaken to investigate the putative role of CYP7B in arthritis using murine collagen-induced arthritis (CIA), an interleukin-1beta (IL-1beta)-dependent model. DBA/1J mice were immunized and administered a booster with type II collagen. The presence of 7alpha-OH-DHEA was determined in both arthritic and nonarthritic joints and the serum of CIA mice by radioimmunoassay. CYP7B messenger RNA (mRNA) expression was analyzed in synovial biopsy samples, and in fibroblast-like synoviocytes (FLS) isolated from these synovial biopsy samples, by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, the regulatory role of IL-1beta on CYP7B activity in FLS was determined using RT-PCR, Western blotting, and high-performance liquid chromatography. In knee joint synovial biopsy samples from arthritic mice, 7alpha-OH-DHEA levels were 5-fold higher than in nonarthritic mice. Elevated levels of 7alpha-OH-DHEA were accompanied by an increase in CYP7B mRNA expression and were positively correlated with disease severity. In serum, no differences in 7alpha-OH-DHEA levels were observed between arthritic and nonarthritic mice. Incubation of FLS with IL-1beta resulted in a dose-dependent increase in 7alpha-OH-DHEA formation. In addition, IL-1beta enhanced CYP7B mRNA and CYP7B protein levels in FLS. Disease progression in CIA is correlated with enhanced CYP7B activity, which leads to locally enhanced 7alpha-OH-DHEA levels. Elevated IL-1beta levels within the arthritic joint may regulate this increase in CYP7B activity. Copyright 2004 American College of Rheumatology

Beta-energy averaging and beta spectra

International Nuclear Information System (INIS)

Stamatelatos, M.G.; England, T.R.

1976-07-01

A simple yet highly accurate method for approximately calculating spectrum-averaged beta energies and beta spectra for radioactive nuclei is presented. This method should prove useful for users who wish to obtain accurate answers without complicated calculations of Fermi functions, complex gamma functions, and time-consuming numerical integrations as required by the more exact theoretical expressions. Therefore, this method should be a good time-saving alternative for investigators who need to make calculations involving large numbers of nuclei (e.g., fission products) as well as for occasional users interested in restricted number of nuclides. The average beta-energy values calculated by this method differ from those calculated by ''exact'' methods by no more than 1 percent for nuclides with atomic numbers in the 20 to 100 range and which emit betas of energies up to approximately 8 MeV. These include all fission products and the actinides. The beta-energy spectra calculated by the present method are also of the same quality

Formulary considerations in selection of beta-blockers.

Science.gov (United States)

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

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

Energy Technology Data Exchange (ETDEWEB)

Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of); Chun, Ji Na; Jung, Sun-Ah [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Cho, Jin Won [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lee, Joon H., E-mail: joonhlee@konyang.ac.kr [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)

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 in 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 information

The antibacterial activity of peptides derived from human beta-2 glycoprotein I is inhibited by protein H and M1 protein from Streptococcus pyogenes

NARCIS (Netherlands)

Nilsson, Maria; Wasylik, Sylwia; Mörgelin, Matthias; Olin, Anders I.; Meijers, Joost C. M.; Derksen, Ronald H. W. M.; de Groot, Philip G.; Herwald, Heiko

2008-01-01

During the last years, the importance of antibacterial peptides has attracted considerable attention. We report here that peptides derived from the fifth domain of beta-2 glycoprotein I (beta(2)GPI), a human heparin binding plasma protein, have antibacterial activities against Gram-positive and

Biochemical and catalytic properties of two intracellular beta-glucosidases from the fungus Penicillium decumbens active on flavonoid glucosides

DEFF Research Database (Denmark)

Mamma, D.; Hatzinikolaou, D.G.; Christakopoulos, Paul

2004-01-01

,6)-beta-glucosides as well as aryl beta-glucosides. Determination of k(cat)/K-m revealed that G(II) hydrolyzed 3-8 times more efficiently the above-mentioned substrates. The ability of G(I) and G(II) to deglycosylate various flavonoid glycosides was also investigated. Both enzymes were active against...... flavonoids glycosylated at the 7 position but G(II) hydrolyzed them 5 times more efficiently than G(I). Of the flavanols tested, both enzymes were incapable of hydrolyzing quercetrin and kaempferol-3-glucoside. The main difference between G(I) and G(II) as far as the hydrolysis of flavanols is concerned...

Casein kinase 2 down-regulation and activation by polybasic peptides are mediated by acidic residues in the 55-64 region of the beta-subunit. A study with calmodulin as phosphorylatable substrate

DEFF Research Database (Denmark)

Meggio, F; Boldyreff, B; Issinger, O G

1994-01-01

to substitute for wild-type beta-subunit as a suppressor of activity toward calmodulin. The only mutations that reduced the ability of the beta-subunit to suppress calmodulin phosphorylation activity, though being compatible with normal reconstitution of CK2 holoenzyme, were those affecting Asp55, Glu57...... are conversely ineffective. The latent "calmodulin kinase" activity of CK2 can also be specifically unmasked by a peptide (alpha[66-86]) reproducing a basic insert of the catalytic subunit. This effect is reversed by equimolar addition of a peptide (beta[55-71]) including the 55-64 acidic stretch of the beta......-subunit. Comparable polylysine stimulation was observed with the holoenzymes reconstituted with either beta wt or the beta mutants capable of assembling with the alpha-subunit, with the notable exception of those bearing Ala substitutions for acidic residues at positions 55, 57, and 59-61. These were nearly...

Atividades de quitinase e beta-1,3-glucanase após eliciação das defesas do tomateiro contra a mancha-bacteriana Chitinase and beta-1,3-glucanase activities after the elicitation of tomato defenses against bacterial spot

Directory of Open Access Journals (Sweden)

Fábio Rossi Cavalcanti

2006-12-01

Full Text Available O objetivo deste trabalho foi avaliar a influência de eliciadores biológicos e químicos sobre as atividades de duas proteínas relacionadas à patogênese (PR, quitinase e beta-1,3-glucanase, em folhas de tomateiro, e avaliar o potencial desses eliciadores na redução do progresso da mancha-foliar causada por Xanthomonas campestris pv. vesicatoria. Plantas de tomateiro da cultivar Santa Cruz Kada foram pulverizadas com: acibenzolar-S-metil (ASM; 0,2 g L-1; formulação biológica proveniente de biomassa cítrica, denominada Ecolife (5 mL L-1; suspensão de quitosana (MCp; 200 g L-1, proveniente de micélio de Crinipellis perniciosa; extrato aquoso de ramos de lobeira (Solanum lycocarpum infectados por C. perniciosa (VLA; 300 g L-1. As plantas foram desafiadas com um isolado virulento da bactéria, quatro dias depois das pulverizações. Plantas pulverizadas com extratos biológicos mostraram redução da mancha-bacteriana. ASM proporcionou 49,3% de proteção, e foi igual à MCp e Ecolife e superior ao VLA. Este último não diferiu significativamente de MCp e Ecolife. Observou-se maior atividade das duas enzimas nas plantas tratadas, principalmente nas primeiras horas após as pulverizações.The objective of this work was to assess the influence of foliar application of resistance inducers and the activation of plant pathogenesis-related (PR proteins, chitinases and beta-1,3-glucanases, against Xanthomonas campestris pv. vesicatoria, and evaluate the potential of these elicitors on the reduction of bacterial leaf spot. Tomato plants of the cultivar Santa Cruz Kada were sprayed with: acibenzolar-S-methyl (0.2 g L-1 ASM; Ecolife, a biological formulation based on citric biomass (5 mL L-1; chitosan suspension from Crinipellis perniciosa mycelium (MCp; 200 g L-1; an aqueous extract from branches of lobeira (Solanum lycocarpum infected with C. perniciosa (VLA; 300 g L-1. Plants were challenged with a virulent bacterial strain four days after

Speculative Betas

OpenAIRE

Harrison Hong; David Sraer

2012-01-01

We provide a model for why high beta assets are more prone to speculative overpricing than low beta ones. When investors disagree about the common factor of cash-flows, high beta assets are more sensitive to this macro-disagreement and experience a greater divergence-of-opinion about their payoffs. Short-sales constraints for some investors such as retail mutual funds result in high beta assets being over-priced. When aggregate disagreement is low, expected return increases with beta due to r...

Development of the 'Beta-Boy' radiation counter for public acceptance activities

International Nuclear Information System (INIS)

Tanabe, Hiroshi; Kitada, Hiroshi

1993-01-01

Japan Nuclear Fuel Ltd., which was established on July 1st, 1992 largely financed by Japan's electric power companies is presently developing four projects in the village of Rokkasho, Aomori Prefecture, roughly 700 km north of Tokyo: a uranium enrichment plant, which began operation in March, 1992; a reprocessing plant to begin construction in March, 1993; a high level radioactive waste storage facility for waste returned from overseas reprocessing, construction of which began in May, 1992; and a low level radioactive waste disposal center for waste generated in nuclear power plants, which began operation in December, 1992. Approval for the location of these facilities was obtained from the authorities in Aomori Prefecture and Rokkasho Village in 1985. However, following the Chernobyl accident in 1986, the nuclear fuel cycle project in Rokkasho as well as other nuclear facilities throughout the country were faced with very active opposition from the antinuclear movement. Through our efforts to obtain public acceptance by arranging site tours, lectures, public debates and so on, we realized that many of the people of Aomori Prefecture had doubts about the nuclear fuel cycle, and that more than 80% of those people held concerns about radiation. We also found that through the demonstration of measuring atmospheric radiation levels using a large conventional portable GM survey meter of the type used in nuclear facilities, we were able to obtain considerable understanding of the nature of radiation at our lectures. Realizing therefore the need to increase this effect, we decided to develop a simple radiation counter, which all the participants at our lectures could operate themselves to measure radiation. I will now explain the characteristics of 'Beta-Boy', new radiation counter, and the method to explain radiation by using 'Beta-Boy' in our public acceptance activities

Enhanced basal contractility but reduced excitation-contraction coupling efficiency and beta-adrenergic reserve of hearts with increased Cav1.2 activity.

Science.gov (United States)

Tang, Mingxin; Zhang, Xiaoying; Li, Yingxin; Guan, Yinzheng; Ai, Xiaojie; Szeto, Christopher; Nakayama, Hiroyuki; Zhang, Hongyu; Ge, Shuping; Molkentin, Jeffery D; Houser, Steven R; Chen, Xiongwen

2010-08-01

Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca(2+) channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the beta-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) mouse model overexpressing the Cavbeta2a subunit in a cardiac-specific and inducible manner was established. We studied cardiac (in vivo) and myocyte (in vitro) contractility at baseline and upon beta-adrenergic stimulation. E-C coupling efficiency was evaluated in isolated myocytes as well. The following results were found: 1) in DTG myocytes, L-type Ca(2+) current (I(Ca,L)) density, myocyte fractional shortening (FS), peak Ca(2+) transients, and sarcoplasmic reticulum (SR) Ca(2+) content (caffeine-induced Ca(2+) transient peak) were significantly increased (by 100.8%, 48.8%, 49.8%, and 46.8%, respectively); and 2) cardiac contractility evaluated with echocardiography [ejection fraction (EF) and (FS)] and invasive intra-left ventricular pressure (maximum dP/dt and -dP/dt) measurements were significantly greater in DTG mice than in control mice. However, 1) the cardiac contractility (EF, FS, dP/dt, and -dP/dt)-enhancing effect of the beta-adrenergic agonist isoproterenol (2 microg/g body wt ip) was significantly reduced in DTG mice, which could be attributed to the loss of beta-adrenergic stimulation on contraction, Ca(2+) transients, I(Ca,L), and SR Ca(2+) content in DTG myocytes; and 2) E-C couplng efficiency was significantly lower in DTG myocytes. In conclusion, increasing Cav1.2 activity by promoting its high-activity mode enhances cardiac contractility but decreases E-C coupling efficiency and the adrenergic reserve of the heart.

Methods and results of reconstruction of 131I concentration in milk from total beta-activity measurements in Belarus after Chernobyl

International Nuclear Information System (INIS)

Savkin, Mikhail; Shinkarev, Sergey; Titov, Alexey

2008-01-01

Full text: During the first few weeks following the Chernobyl accident a large scale monitoring of radioactive contamination of foodstuffs locally produced was carried out in the most contaminated areas of Belarus. Due to a lack of spectrometric instruments, radiometric devices (DP-100) were used for beta activity measurements mostly of milk and milk products. Because the intake of 131 I with milk was the main contributor of the thyroid dose for the Belarus population, it is very important to reconstruct levels of 131 I in milk for Belarus settlements. The purpose of the paper is to present the methods and results of assessing the 13I concentration in milk based on historical records of total-beta activity measurements carried out in April-June 1986 in Belarus. The results of reconstruction of the 131 I concentration in milk will be used in on-going epidemiologic studies of a cohort of Belarus children. About 20,000 total-beta activity measurements were used in the analysis; for about 50% of those, the measurement result exceeded the minimum detectable activity. Estimates of 131 I concentration in milk at the date of sampling and of time-integrated milk concentrations were reconstructed for 482 settlements in Gomel Oblast and for 100 settlements in Mogilev Oblast, the most contaminated areas in Belarus, where at least one milk measurement was available. The assessment of the 131 I concentrations in milk involved: 1) An analysis of the calibration coefficients of the detectors for radionuclides available in milk (the main radionuclides were 131 I, 132 4Cs, 137 Cs, 89 Sr, 90 Sr); and 2) An assessment of the relative activity distribution of those radionuclides in milk. Only measurements made before 21 May 1986 were considered to be reliable, as the measurements conducted late May and in June were found to be unreliable because of the decrease in 131 I concentrations and the growing influence of other radionuclides with longer half-lives. Analysis of multiple

Effect of beta-agonists on LAM progression and treatment.

Science.gov (United States)

Le, Kang; Steagall, Wendy K; Stylianou, Mario; Pacheco-Rodriguez, Gustavo; Darling, Thomas N; Vaughan, Martha; Moss, Joel

2018-01-30

Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s over time in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Because beta-agonists increase cAMP and PKA activity, we investigated effects of PKA activation on the mTOR pathway. Human skin TSC2 +/- fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth. Cells incubated long-term with isoproterenol, which may lead to beta-adrenergic receptor desensitization, did not show increased S6 phosphorylation. Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus, activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an effect abrogated by beta-agonist-driven receptor desensitization. In agreement, retrospective clinical data from patients with LAM suggested that a combination of bronchodilators in conjunction with sirolimus may be preferable to sirolimus alone for stabilization of pulmonary function.

Cytokines interleukin-1beta and tumor necrosis factor-alpha regulate different transcriptional and alternative splicing networks in primary beta-cells

DEFF Research Database (Denmark)

Ortis, Fernanda; Naamane, Najib; Flamez, Daisy

2010-01-01

by the cytokines interleukin (IL)-1beta + interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha + IFN-gamma in primary rat beta-cells. RESEARCH DESIGN AND METHODS: Fluorescence-activated cell sorter-purified rat beta-cells were exposed to IL-1beta + IFN-gamma or TNF-alpha + IFN-gamma for 6 or 24 h......-cells, with temporal differences in the number of genes modulated by IL-1beta + IFNgamma or TNF-alpha + IFN-gamma. These cytokine combinations induced differential expression of inflammatory response genes, which is related to differential induction of IFN regulatory factor-7. Both treatments decreased the expression...... of genes involved in the maintenance of beta-cell phenotype and growth/regeneration. Cytokines induced hypoxia-inducible factor-alpha, which in this context has a proapoptotic role. Cytokines also modified the expression of >20 genes involved in RNA splicing, and exon array analysis showed cytokine...

Standardization and estimation of gross alpha and beta activities for potable water samples in presence of TDS using TDCR based LSA (Hidex 300SL)

International Nuclear Information System (INIS)

Gupta, Anil; Lenka, P.; Sahoo, S.K.; Patra, A.C.; Jha, S.K.; Tripathi, R.M.

2018-01-01

Quality of water is important in environmental studies because of its daily use for human consumption and an important route of intake for various elements and radionuclides. Therefore radiological quality of drinking water must be ensured. The screening parameter to evaluate the radiological safety of potable water is by estimating gross alpha and gross beta activities with a limit of 0.5 Bq/l and 1 Bq/l respectively. These have been traditionally being done by radiochemical co-precipitation of alpha and beta emitters followed by counting by ZnS(Ag) counter for alpha and gas flow proportional counter for beta. Gross alpha estimation in water samples with high TDS by ZnS(Ag) is difficult and often leads to underestimation of result due to self-absorption of alpha within the residue. This study was carried out to standardize a method to provide rapid results by simultaneously estimating both gross alpha and gross beta activity in the presence of TDS with adequate sensitivity, minimum sample processing

The Fas pathway is involved in pancreatic beta cell secretory function

DEFF Research Database (Denmark)

Schumann, Desiree M; Maedler, Kathrin; Franklin, Isobel

2007-01-01

Pancreatic beta cell mass and function increase in conditions of enhanced insulin demand such as obesity. Failure to adapt leads to diabetes. The molecular mechanisms controlling this adaptive process are unclear. Fas is a death receptor involved in beta cell apoptosis or proliferation, depending...... on the activity of the caspase-8 inhibitor FLIP. Here we show that the Fas pathway also regulates beta cell secretory function. We observed impaired glucose tolerance in Fas-deficient mice due to a delayed and decreased insulin secretory pattern. Expression of PDX-1, a beta cell-specific transcription factor...... regulating insulin gene expression and mitochondrial metabolism, was decreased in Fas-deficient beta cells. As a consequence, insulin and ATP production were severely reduced and only partly compensated for by increased beta cell mass. Up-regulation of FLIP enhanced NF-kappaB activity via NF...

Highly Potent, Water Soluble Benzimidazole Antagonist for Activated (alpha)4(beta)1 Integrin

Energy Technology Data Exchange (ETDEWEB)

Carpenter, R D; Andrei, M; Lau, E Y; Lightstone, F C; Liu, R; Lam, K S; Kurth, M J

2007-08-29

The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC{sub 50} = 305 pM]. With exceptional solubility, this finding has potential for improving PK to help diagnose and treat lymphomas.

Endothelial-monocyte activating polypeptide II alters fibronectin based endothelial cell adhesion and matrix assembly via alpha5 beta1 integrin

International Nuclear Information System (INIS)

Schwarz, Margaret A.; Zheng, Hiahua; Liu, Jie; Corbett, Siobhan; Schwarz, Roderich E.

2005-01-01

Mature Endothelial-Monocyte Activating Polypeptide (mEMAP) II functions as a potent antiangiogenic peptide. Although the anti-tumor effect of mEMAP II has been described, little is known regarding its mechanism of action. Observations that mEMAP II induced apoptosis only in a subset of migrating and proliferating endothelial cells (EC) suggests a targeted effect on cells engaged in angiogenic activities which are known to rely upon cell adhesion and migration. Indeed, we demonstrate that mEMAP II inhibited fibronectin (FN) dependent microvascular EC (MEC) adhesion and spreading and we show that this depends upon the alpha5 beta1 integrin. Immunofluorescence analysis demonstrated that mEMAP II-dependent blockade of FN-alpha5 beta1 interactions was associated with disassembly of both actin stress fiber networks and FN matrix. These findings suggest that mEMAP II blocks MEC adhesion and spreading on fibronectin, via a direct interaction with the integrin alpha5 beta1, thus implicating that alpha5 integrin may be a mediator of mEMAP II's antiangiogenic function

The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo.

Science.gov (United States)

Xie, Zhongcong; Culley, Deborah J; Dong, Yuanlin; Zhang, Guohua; Zhang, Bin; Moir, Robert D; Frosch, Matthew P; Crosby, Gregory; Tanzi, Rudolph E

2008-12-01

An estimated 200 million patients worldwide have surgery each year. Anesthesia and surgery have been reported to facilitate emergence of Alzheimer's disease. The commonly used inhalation anesthetic isoflurane has previously been reported to induce apoptosis, and to increase levels and aggregation of Alzheimer's disease-associated amyloid beta-protein (Abeta) in cultured cells. However, the in vivo relevance has not been addressed. We therefore set out to determine effects of isoflurane on caspase activation and levels of beta-site amyloid precursor protein-cleaving enzyme (BACE) and Abeta in naive mice, using Western blot, immunohistochemistry, and reverse transcriptase polymerase chain reaction. Here we show for the first time that a clinically relevant isoflurane anesthesia (1.4% isoflurane for 2 hours) leads to caspase activation and modest increases in levels of BACE 6 hours after anesthesia in mouse brain. Isoflurane anesthesia induces caspase activation, and increases levels of BACE and Abeta up to 24 hours after anesthesia. Isoflurane may increase BACE levels by reducing BACE degradation. Moreover, the Abeta aggregation inhibitor, clioquinol, was able to attenuate isoflurane-induced caspase-3 activation in vivo. Given that transient insults to brain may lead to long-term brain damage, these findings suggest that isoflurane may promote Alzheimer's disease neuropathogenesis and, as such, have implications for use of isoflurane in humans, pending human study confirmation.

Activity of beta-glucosidase and levels of isoflavone glucosides in soybean cultivars affected by the environment Atividade de beta-glicosidase e níveis de isoflavonóides glicosídios em cultivares de soja, influenciadas pelo ambiente

Directory of Open Access Journals (Sweden)

MERCEDES CONCÓRDIA CARRÃO-PANIZZI

2000-05-01

Full Text Available The enzyme beta-glucosidase hydrolyses the isoflavone glucosides developing aglycones, which are compounds with anticancer effects, that are also related with the astringency observed in soybean flavor. Due to the importance of this enzyme, a study was carried out to determine beta-glucosidase activity in soybean (Glycine max (L. Merrill cultivars with different contents of isoflavone glucosides (enzyme substrate. The enzyme activity was determined in 51 soybean cultivars sowed in Londrina (latitude 23ºS, in Paraná State, Brazil, and in the cultivar IAS 5 from soybean production regions of different Brazilian states. Among the cultivars, a range of variability of 176.1 to 96.3 units of enzyme activity (cultivars IAC-2 and Embrapa 2, respectively was observed. A significant variability among cultivars could suggest genetic differences. In the states of Rio Grande do Sul, Paraná and Mato Grosso do Sul, the cultivar IAS 5 presented similar average of beta-glucosidase activity: 132.1, 131.9 and 132.5 units, respectively. Among locations in the states, the cultivar IAS 5 presented a variability for enzyme activity from 138.8 to 124.8 units, which were statistically different. In spite of statistics, the numerical values were not too different to assume that environmental conditions affected enzyme activity. A non-significative correlation for isoflavone glucoside concentrations and enzyme activity was observed among cultivars.

The islet beta-cell: fuel responsive and vulnerable.

Science.gov (United States)

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.

Biologic activities of recombinant human-beta-defensin-4 toward cultured human cancer cells.

Science.gov (United States)

Gerashchenko, O L; Zhuravel, E V; Skachkova, O V; Khranovska, N N; Filonenko, V V; Pogrebnoy, P V; Soldatkina, M A

2013-06-01

The aim of the study was in vitro analysis of biological activity of recombinant human beta-defensin-4 (rec-hBD-4). hBD-4 cDNA was cloned into pGEX-2T vector, and recombinant plasmid was transformed into E. coli BL21(DE3) cells. To purify soluble fusion GST-hBD-4 protein, affinity chromatography was applied. Rec-hBD-4 was cleaved from the fusion protein with thrombin, and purified by reverse phase chromatography on Sep-Pack C18. Effects of rec-hBD-4 on proliferation, viability, cell cycle distribution, substrate-independent growth, and mobility of cultured human cancer cells of A431, A549, and TPC-1 lines were analyzed by direct cell counting technique, MTT assay, flow cytofluorometry, colony forming assay in semi-soft medium, and wound healing assay. Rec-hBD-4 was expressed in bacterial cells as GST-hBD-4 fusion protein, and purified by routine 3-step procedure (affine chromatography on glutathione-agarose, cleavage of fusion protein by thrombin, and reverse phase chromatography). Analysis of in vitro activity of rec-hBD-4 toward three human cancer cell lines has demonstrated that the defensin is capable to affect cell behaviour in concentration-dependent manner. In 1-100 nM concentrations rec-hBD-4 significantly stimulates cancer cell proliferation and viability, and promotes cell cycle progression through G2/M checkpoint, greatly enhances colony-forming activity and mobility of the cells. Treatment of the cells with 500 nM of rec-hBD-4 resulted in opposite effects: significant suppression of cell proliferation and viability, blockage of cell cycle in G1/S checkpoint, significant inhibition of cell migration and colony forming activity. Recombinant human beta-defensin-4 is biologically active peptide capable to cause oppositely directed effects toward biologic features of cancer cells in vitro dependent on its concentration.

Proteolytically modified human beta 2-microglobulin augments the specific cytotoxic activity in murine mixed lymphocyte culture

DEFF Research Database (Denmark)

Nissen, Mogens Holst; Claësson, M H

1987-01-01

the endogenous production of interleukin 2 in the MLC culture; monoclonal antibody which reacts with both the native beta 2-m and M-beta 2-m molecule blocks the augmentation of cytotoxic T lymphocyte production induced by M-beta 2-m; murine as well as human MLC responder cells can proteolytically modify native......A proteolytically modified form of beta 2-microglobulin (beta 2-m) present in the serum of patients suffering from autoimmune, immunodeficient diseases and cancer has been reported in the literature. In the present study we show that human beta 2-m as well as the proteolytically modified human form...... (M-beta 2-m) bind to murine lymphocytes expressing H-2 class I antigens; M-beta 2-m, when added at day 0 and 1 of culture in nanomolar concentrations to a one-way murine allogeneic mixed lymphocyte culture (MLC) augments the generation of specific cytotoxic T lymphocytes; M-beta 2-m increases...

Plasmid-mediated AmpC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam.

Science.gov (United States)

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

The effects of beta-adrenoceptor activation on contraction in isolated fast- and slow-twitch skeletal muscle fibres of the rat.

OpenAIRE

Cairns, S. P.; Dulhunty, A. F.

1993-01-01

1. The aim of the experiments was to examined the effects of beta-adrenoceptor activation on twitch and tetanic contractions in fast- and slow-twitch mammalian skeletal muscle fibres. Isometric force was recorded from bundles of intact fibres isolated from the normal and denervated slow-twitch soleus and normal fast-twitch sternomastoid muscles of the rat. 2. Terbutaline (10 microM), a beta 2-adrenoceptor agonist, induced an average 15% potentiation of peak twitch and peak tetanic force in no...

Glucose, other secretagogues, and nerve growth factor stimulate mitogen-activated protein kinase in the insulin-secreting beta-cell line, INS-1

DEFF Research Database (Denmark)

Frödin, M; Sekine, N; Roche, E

1995-01-01

The signaling pathways whereby glucose and hormonal secretagogues regulate insulin-secretory function, gene transcription, and proliferation of pancreatic beta-cells are not well defined. We show that in the glucose-responsive beta-cell line INS-1, major secretagogue-stimulated signaling pathways...... converge to activate 44-kDa mitogen-activated protein (MAP) kinase. Thus, glucose-induced insulin secretion was found to be associated with a small stimulatory effect on 44-kDa MAP kinase, which was synergistically enhanced by increased levels of intracellular cAMP and by the hormonal secretagogues......-1. Phorbol ester, an activator of protein kinase C, stimulated 44-kDa MAP kinase by both Ca(2+)-dependent and -independent pathways. Nerve growth factor, independently of changes in cytosolic Ca2+, efficiently stimulated 44-kDa MAP kinase without causing insulin release, indicating that activation...

Biodegradable films containing {alpha}-tocopherol/{beta}-cyclodextrin complex; Filmes biodegradaveis contendo {alpha}-tocoferol complexado em {beta}-ciclodextrina

Energy Technology Data Exchange (ETDEWEB)

Motta, Caroline; Martelli, Silvia M.; Soldi, Valdir, E-mail: vsoldi@qmc.ufsc.br [Lab. de Materiais Polimericos (POLIMAT), Dept. de Quimica, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Barreto, Pedro L.M. [Lab. de Reologia (REOLAB), Dept. de Ciencia e Tecnologia de Alimentos, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil)

2011-07-01

The growing environmental concern about pollution and the need to reduce dependence of plastic industry in relation to non-renewable resources has increased the interest of both researchers and industry in the use of biopolymers. In this work {beta}-cyclodextrin/{alpha}-tocopherol complexes were prepared and characterized. In order to obtain polymeric active biofilms, the {beta}-cyclodextrin/{alpha}-tocopherol complex was incorporated into a polymeric matrix of carboxymethylcellulose. The {beta}-cyclodextrin/{alpha}-tocopherol complex was characterized through of X-ray diffraction and thermogravimetric analysis. The physicochemical properties of the films incorporated with the complex were evaluated through mechanical and colorimetric analysis and moisture sorption isotherm. (author)

Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice.

Science.gov (United States)

Liu, Karen J; Arron, Joseph R; Stankunas, Kryn; Crabtree, Gerald R; Longaker, Michael T

2007-03-01

Glycogen synthase kinase-3beta (GSK-3beta) has integral roles in a variety of biological processes, including development, diabetes, and the progression of Alzheimer's disease. As such, a thorough understanding of GSK-3beta function will have a broad impact on human biology and therapeutics. Because GSK-3beta interacts with many different pathways, its specific developmental roles remain unclear. We have discovered a genetic requirement for GSK-3beta in midline development. Homozygous null mice display cleft palate, incomplete fusion of the ribs at the midline and bifid sternum as well as delayed sternal ossification. Using a chemically regulated allele of GSK-3beta (ref. 6), we have defined requirements for GSK-3beta activity during discrete temporal windows in palatogenesis and skeletogenesis. The rapamycin-dependent allele of GSK-3beta produces GSK-3beta fused to a tag, FRB* (FKBP/rapamycin binding), resulting in a rapidly destabilized chimaeric protein. In the absence of drug, GSK-3beta(FRB)*(/FRB)* mutants appear phenotypically identical to GSK-3beta-/- mutants. In the presence of drug, GSK-3betaFRB* is rapidly stabilized, restoring protein levels and activity. Using this system, mutant phenotypes were rescued by restoring endogenous GSK-3beta activity during two distinct periods in gestation. This technology provides a powerful tool for defining windows of protein function during development.

Beta burst dynamics in Parkinson's disease OFF and ON dopaminergic medication.

Science.gov (United States)

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

Imaging the Beta-cell mass: why and how

DEFF Research Database (Denmark)

Saudek, Frantisek; Brogren, Carl-Henrik; Manohar, Srirang

2008-01-01

is called dihydrotetrabenazine (DTBZ), antibodies to zinc transporter (ZnT-8) and the monoclonal antibody IC2. While DTBZ and antibodies to ZnT-8 showed binding activities to more than beta-cells, the anti-IC2 monoclonal antibody showed binding properties exclusively to insulin-producing beta...

Developmental changes of beta-adrenergic receptor-linked adenylate cyclase of rat liver

International Nuclear Information System (INIS)

Katz, M.S.; Boland, S.R.; Schmidt, S.J.

1985-01-01

beta-Adrenergic agonist-sensitive adenylate cyclase activity and binding of the beta-adrenergic antagonist(-)-[ 125 I]iodopindolol were studied in rat liver during development of male Fischer 344 rats ages 6-60 days. In liver homogenates maximum adenylate cyclase response to beta-adrenergic agonist (10(-5) M isoproterenol or epinephrine) decreased by 73% (P less than 0.01) between 6 and 60 days, with most of the decrease (56%; P less than 0.01) occurring by 20 days. beta-adrenergic receptor density (Bmax) showed a corresponding decrease of 66% (P less than 0.01) by 20 days without subsequent change. Binding characteristics of stereospecificity, pharmacological specificity, saturability with time, and reversibility were unchanged with age. GTP-, fluoride-, forskolin-, and Mn2+-stimulated adenylate cyclase activities also decreased during development, suggesting a decrease of activity of the catalytic component and/or guanine nucleotide regulatory component of adenylate cyclase. These results indicate that the developmental decrease of beta-adrenergic agonist-sensitive adenylate cyclase activity may result from decreased numbers of beta-adrenergic receptors. Developmental alterations of nonreceptor components of the enzyme may also contribute to changes of catecholamine-sensitive adenylate cyclase

Is an absolute level of cortical beta suppression required for proper movement? Magnetoencephalographic evidence from healthy aging.

Science.gov (United States)

Heinrichs-Graham, Elizabeth; Wilson, Tony W

2016-07-01

Previous research has connected a specific pattern of beta oscillatory activity to proper motor execution, but no study to date has directly examined how resting beta levels affect motor-related beta oscillatory activity in the motor cortex. Understanding this relationship is imperative to determining the basic mechanisms of motor control, as well as the impact of pathological beta oscillations on movement execution. In the current study, we used magnetoencephalography (MEG) and a complex movement paradigm to quantify resting beta activity and movement-related beta oscillations in the context of healthy aging. We chose healthy aging as a model because preliminary evidence suggests that beta activity is elevated in older adults, and thus by examining older and younger adults we were able to naturally vary resting beta levels. To this end, healthy younger and older participants were recorded during motor performance and at rest. Using beamforming, we imaged the peri-movement beta event-related desynchronization (ERD) and extracted virtual sensors from the peak voxels, which enabled absolute and relative beta power to be assessed. Interestingly, absolute beta power during the pre-movement baseline was much stronger in older relative to younger adults, and older adults also exhibited proportionally large beta desynchronization (ERD) responses during motor planning and execution compared to younger adults. Crucially, we found a significant relationship between spontaneous (resting) beta power and beta ERD magnitude in both primary motor cortices, above and beyond the effects of age. A similar link was found between beta ERD magnitude and movement duration. These findings suggest a direct linkage between beta reduction during movement and spontaneous activity in the motor cortex, such that as spontaneous beta power increases, a greater reduction in beta activity is required to execute movement. We propose that, on an individual level, the primary motor cortices have an

On the coherent behavior of pancreatic beta cell clusters

Energy Technology Data Exchange (ETDEWEB)

Loppini, Alessandro, E-mail: a.loppini@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); Capolupo, Antonio, E-mail: capolupo@sa.infn.it [Physics Department, University of Salerno, Fisciano, 84084 (Italy); Cherubini, Christian, E-mail: c.cherubini@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); International Center for Relativistic Astrophysics, University Campus Bio-Medico, Via A. del Portillo 21, I-00128, Rome (Italy); Gizzi, Alessio, E-mail: a.gizzi@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); Bertolaso, Marta, E-mail: m.bertolaso@unicampus.it [Faculty of Engineering and Institute of Philosophy of Scientific and Technological Practice, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); Filippi, Simonetta, E-mail: s.filippi@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); International Center for Relativistic Astrophysics, University Campus Bio-Medico, Via A. del Portillo 21, I-00128, Rome (Italy); Vitiello, Giuseppe, E-mail: vitiello@sa.infn.it [Physics Department, University of Salerno, Fisciano, 84084 (Italy)

2014-09-12

Beta cells in pancreas represent an example of coupled biological oscillators which via communication pathways, are able to synchronize their electrical activity, giving rise to pulsatile insulin release. In this work we numerically analyze scale free self-similarity features of membrane voltage signal power density spectrum, through a stochastic dynamical model for beta cells in the islets of Langerhans fine tuned on mouse experimental data. Adopting the algebraic approach of coherent state formalism, we show how coherent molecular domains can arise from proper functional conditions leading to a parallelism with “phase transition” phenomena of field theory. - Highlights: • Beta cells in pancreas are coupled oscillators able to synchronize their activity. • We analyze scale free self-similarity features for beta cells. • We adopt the algebraic approach of coherent state formalism. • We show that coherent molecular domains arise from functional conditions.

Regulation of 11 beta-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol.

Science.gov (United States)

Gomez-Sanchez, Elise P; Ganjam, Venkataseshu; Chen, Yuan Jian; Liu, Ying; Zhou, Ming Yi; Toroslu, Cigdem; Romero, Damian G; Hughson, Michael D; de Rodriguez, Angela; Gomez-Sanchez, Celso E

2003-08-01

The 11beta-hydroxysteroid dehydrogenase (11betaHSD) type 1 (11betaHSD1) enzyme is an NADP+-dependent oxidoreductase, usually reductase, of major glucocorticoids. The NAD+-dependent type 2 (11betaHSD2) enzyme is an oxidase that inactivates cortisol and corticosterone, conferring extrinsic specificity of the mineralocorticoid receptor for aldosterone. We reported that addition of a reducing agent to renal homogenates results in the monomerization of 11betaHSD2 dimers and a significant increase in NAD+-dependent corticosterone conversion. Estrogenic effects on expression, dimerization, and activity of the kidney 11betaHSD1 and -2 enzymes are described herein. Renal 11betaHSD1 mRNA and protein expressions were decreased to very low levels by estradiol (E2) treatment of both intact and castrated male rats; testosterone had no effect. NADP+-dependent enzymatic activity of renal homogenates from E2-treated rats measured under nonreducing conditions was less than that of homogenates from intact animals. Addition of 10 mM DTT to aliquots from these same homogenates abrogated the difference in NADP+-dependent activity between E2-treated and control rats. In contrast, 11betaHSD2 mRNA and protein expressions were significantly increased by E2 treatment. There was a marked increase in the number of juxtamedullary proximal tubules stained by the antibody against 11betaHSD2 after the administration of E2. Notwithstanding, neither the total corticosterone and 11-dehydrocorticosterone excreted in the urine nor their ratio differed between E2- and vehicle-treated rats. NAD+-dependent enzymatic activity in the absence or presence of a reducing agent demonstrated that the increase in 11betaHSD2 protein was not associated with an increase in in vitro activity unless the dimers were reduced to monomers.

Alpha- and Beta-Cyclodextrin Inclusion Complexes with 5-Fluorouracil: Characterization and Cytotoxic Activity Evaluation

Directory of Open Access Journals (Sweden)

Cristina Di Donato

2016-12-01

Full Text Available Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in the treatment of the colon, liver, and stomac cancers, the drug was complexed with alpha- and beta-cyclodextrin. The inclusion complexes were prepared in the solid state by kneading method and characterized by Fourier transform-infrared (FT-IR spectroscopy and X-ray powder diffractometry. In solution, the 1:1 stoichiometry for all the inclusion complexes was established by the Job plot method and the binding constants were determined at different pHs by UV-VIS titration. Furthermore, the cytotoxic activity of 5-fluorouracil and its complexation products were evaluated using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay on MCF-7 (breast cancer cell line, Hep G2 (hepatocyte carcinoma cell line, Caco-2 (colon adenocarcinoma cell line, and A-549 (alveolar basal epithelial carcinoma cell line. The results showed that both inclusion complexes increased the 5-fluorouracil capability of inhibiting cell growth. In particular, 5-fluorouracil complexed with beta-cyclodextrin had the highest cytotoxic activity on MCF-7; with alpha-cyclodextrin the highest cytotoxic activity was observed on A-549. The IC50 values were equal to 31 and 73 µM at 72 h, respectively. Our results underline the possibility of using these inclusion complexes in pharmaceutical formulations for improving 5-fluorouracil therapeutic efficacy.

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways

DEFF Research Database (Denmark)

Karlsen, Allan Ertman; Heding, P E; Frobøse, H

2004-01-01

The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback reg...... regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown....

Activation of PPAR{delta} up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic {beta}-cells

Energy Technology Data Exchange (ETDEWEB)

Wan, Jun; Jiang, Li; Lue, Qingguo; Ke, Linqiu [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China); Li, Xiaoyu [State Key Laboratory of Oral Diseases, Sichuan University, No. 14, 3rd Section, Renmin South Road, Chengdu, Sichuan 610041 (China); Tong, Nanwei, E-mail: buddyjun@hotmail.com [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China)

2010-01-15

Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor {delta} (PPAR{delta}) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic {beta}-cells. After HIT-T15 cells (a {beta}-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPAR{delta}), we found that administration of GW increased the expression of PPAR{delta} mRNA. GW-induced activation of PPAR{delta} up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPAR{delta} plays an important role in protecting pancreatic {beta}-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.

Human interleukin 1. beta. stimulates islet insulin release by a mechanism not dependent on changes in phospholipase C and protein kinase C activities or Ca sup 2+ handling

Energy Technology Data Exchange (ETDEWEB)

Welsh, N.; Nilsson, T.; Hallberg, A.; Arkhammar, P.; Berggren, P.-O.; Sandler, S.

1989-01-01

Isolated islets from adult rats or obese hyperglycemic (ob/ob) mice were incubated with human recombinant interleukin 1{beta} in order to study whether the acute effects of the cytokine on islet insulin release are associated with changes in islet phospholipase C activity, Ca{sup 2+} handling or protein phosphorylation. The cytokine stimulated insulin release both at low and high glucose concentrations during one hour incubations. In shortterm incubations (<1 min) interleukin 1{beta} did not affect the production of inositoltrisphosphate. Addition of interleukin 1{beta} affected neither the cytoplasmic free Ca{sup 2+} concentration at rest nor that observed subsequent to stimulation with a high concentration of glucose. Furthermore, the endogenous protein kinase C activity, as visualized by immunoprecipitation of a {sup 32}P-labelled substrate for this enzyme, was not altered by interleukin 1{beta}. Separation of {sup 32}P-labelled proteins by means of 2-dimensional gel electrophoresis failed to reveal any specific effects of the cytokine on the total protein phosphorylation activity. These results suggest that the stimulatory effects on insulin release exerted by interleukin 1{beta} are not caused by acute activation of phospholipase C and protein kinase C or by an alternation of islet Ca{sup 2+} handling of the B-cells. (author).

Dopaminergic and beta-adrenergic effects on gastric antral motility

DEFF Research Database (Denmark)

Bech, K; Hovendal, C P; Gottrup, F

1984-01-01

of bethanechol or pentagastrin inducing motor activity patterns as in the phase III of the MMC and the digestive state respectively. The stimulated antral motility was dose-dependently inhibited by dopamine. The effect was significantly blocked by specifically acting dopaminergic blockers, while alpha- and beta......-adrenergic blockers were without any significant effects. Dose-response experiments with bethanechol and dopamine showed inhibition of a non-competitive type. Isoprenaline was used alone and in conjunction with selective blockade of beta 1- and beta 2-receptors during infusion of bethanechol which induces a pattern...... similar to phase III in the migrating myoelectric complex. The stimulated antral motility was dose-dependently inhibited by isoprenaline. The effect could be significantly blocked by propranolol (beta 1 + beta 2-adrenoceptor blocker) and by using in conjunction the beta 1-adrenoceptor blocker practolol...

Assessment of affinities of beta-CIT, beta-CIT-FE, and beta-CIT-FP for monoamine transporters permanently expressed in cell lines

International Nuclear Information System (INIS)

Okada, Tomoya; Fujita, Masahiro; Shimada, Shoichi; Sato, Kohji; Schloss, Patrick; Watanabe, Yoshiyuki; Itoh, Yasushi; Tohyama, Masaya; Nishimura, Tsunehiko

1998-01-01

We investigated the effects of three cocaine analogs, beta-CIT (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane), beta-CIT-FE (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(2-fluoroethyl)-nortropane), and beta-CIT-FP (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane), on the uptake of [ 3 H]dopamine(DA), serotonin(5-HT), and 1-norepinephrine (NE) using cell lines permanently expressing DA, 5-HT, and NE transporters, respectively, to determine their affinities for these three transporters. We generated cell lines stably expressing DA, 5-HT, and NE transporters, respectively, by the Chen-Okayama method, and then tested the abilities of (-)cocaine, beta-CIT, beta-CIT-FE, beta-CIT-FP, and clomipramine to inhibit the uptake of [ 3 H]DA, 5-HT, and 1-NE. Ki values of beta-CIT, beta-CIT-FE, and beta-CIT-FP for [ 3 H]DA, 5-HT, 1-NE uptake were 6, 29, and 33 nM, 91, 133, and 130 nM, and 28, 113 and 70 nM, respectively, whereas those of cocaine and clomipramine were 316, 581, and 176 nM and > 10,000, 437, and 851 nM, respectively. Beta-CIT, beta-CIT-FE, and beta-CIT-FP were shown to be potent DA, 5-HT, and NE uptake inhibitors. Beta-CIT and beta-CIT-FP were highly potent and selective dopamine uptake inhibitors, and therefore might be useful for imaging of DA transporter with single photon emission computed tomography (SPECT) or positron emission tomography (PET)

Expression and characterization of recombinant single-chain salmon class I MHC fused with beta2-microglobulin with biological activity

DEFF Research Database (Denmark)

Zhao, Heng; Stet, René J M; Skjødt, Karsten

2008-01-01

Heterodimeric class I major histocompatibility complex (MHC) molecules consist of a putative 45-kDa heavy chain and a 12-kDa beta2-microglobulin (beta2m) light chain. The knowledge about MHC genes in Atlantic salmon accumulated during the last decade has allowed us to generate soluble and stable ...... MHC class I molecules with biological activity. We report here the use of a bacterial expression system to produce the recombinant single-chain MHC molecules based on a specific allele Sasa-UBA*0301. This particular allele was selected because previous work has shown its association...... antibodies were successfully produced against both the MHC class I heavy chain and beta(2)m, and showed binding to the recombinant molecule. The recombinant complex Sasabeta2mUBA*0301 was expressed and isolated; the production was scaled up by adjusting to its optimal conditions. Subsequently......, the recombinant proteins were purified by affinity chromatography using mAb against beta2m and alpha3. Eluates were analyzed by Western blot and refolded by the removal of denaturant. The correct folding was confirmed by measuring its binding capacity against mAb produced to recognize the native form of MHC...

The AMP-activated protein kinase beta 1 subunit modulates erythrocyte integrity.

Science.gov (United States)

Cambridge, Emma L; McIntyre, Zoe; Clare, Simon; Arends, Mark J; Goulding, David; Isherwood, Christopher; Caetano, Susana S; Reviriego, Carmen Ballesteros; Swiatkowska, Agnieszka; Kane, Leanne; Harcourt, Katherine; Adams, David J; White, Jacqueline K; Speak, Anneliese O

2017-01-01

Failure to maintain a normal in vivo erythrocyte half-life results in the development of hemolytic anemia. Half-life is affected by numerous factors, including energy balance, electrolyte gradients, reactive oxygen species, and membrane plasticity. The heterotrimeric AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that acts as a critical regulator of cellular energy balance. Previous roles for the alpha 1 and gamma 1 subunits in the control of erythrocyte survival have been reported. In the work described here, we studied the role of the beta 1 subunit in erythrocytes and observed microcytic anemia with compensatory extramedullary hematopoiesis together with splenomegaly and increased osmotic resistance. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Measuring phospholipase D activity in insulin-secreting pancreatic beta-cells and insulin-responsive muscle cells and adipocytes.

Science.gov (United States)

Cazzolli, Rosanna; Huang, Ping; Teng, Shuzhi; Hughes, William E

2009-01-01

Phospholipase D (PLD) is an enzyme producing phosphatidic acid and choline through hydrolysis of phosphatidylcholine. The enzyme has been identified as a member of a variety of signal transduction cascades and as a key regulator of numerous intracellular vesicle trafficking processes. A role for PLD in regulating glucose homeostasis is emerging as the enzyme has recently been identified in events regulating exocytosis of insulin from pancreatic beta-cells and also in insulin-stimulated glucose uptake through controlling GLUT4 vesicle exocytosis in muscle and adipose tissue. We present methodologies for assessing cellular PLD activity in secretagogue-stimulated insulin-secreting pancreatic beta-cells and also insulin-stimulated adipocyte and muscle cells, two of the principal insulin-responsive cell types controlling blood glucose levels.

Insulin-like growth factor I enhances proenkephalin synthesis and dopamine. beta. -hydroxylase activity in adrenal chromaffin cells

Energy Technology Data Exchange (ETDEWEB)

Wilson, S.P. (Univ. of South Carolina School of Medicine, Columbia (USA))

1991-01-01

Insulin-like growth factor I (IGF-I) increased both the contents of proenkephalin derived enkephalin-containing peptides and the activity of dopamine {beta}-hydroxylase in bovine adrenal chromaffin cells. These increases in dopamine {beta}-hydroxylase and enkephalin-containing peptides continued for at least 8 days. The half-maximal IGF-I concentration for these effects was {approximately} 1 nM, with maximal effects observed at 10-30 nM. In contrast, insulin was 1,000-fold less potent. Pretreatment of chromaffin cells with IGF-I increased the rate of ({sup 35}S)proenkephalin synthesis 4-fold compared to untreated cells. Total protein synthesis increased only 1.5-fold under these conditions. These results suggest that IGF-I may be a normal regulator of chromaffin cell function.

Transforming growth factor-beta messenger RNA and protein in murine colitis

DEFF Research Database (Denmark)

Whiting, C V; Williams, A M; Claesson, Mogens Helweg

2001-01-01

Using a CD4+ T-cell-transplanted SCID mouse model of colitis, we have analyzed TGF-beta transcription and translation in advanced disease. By in situ hybridization, the epithelium of both control and inflamed tissues transcribed TGF-beta1 and TGF-beta3 mRNAs, but both were expressed significantly...... farther along the crypt axis in disease. Control lamina propria cells transcribed little TGF-beta1 or TGF-beta3 mRNA, but in inflamed tissues many cells expressed mRNA for both isoforms. No TGF-beta2 message was detected in either control or inflamed tissues. Immunohistochemistry for latent and active TGF...

Pancreatic beta-cell lipotoxicity induced by overexpression of hormone-sensitive lipase

DEFF Research Database (Denmark)

Winzell, Maria Sörhede; Svensson, Håkan; Enerbäck, Sven

2003-01-01

Lipid perturbations associated with triglyceride overstorage in beta-cells impair insulin secretion, a process termed lipotoxicity. To assess the role of hormone-sensitive lipase, which is expressed and enzymatically active in beta-cells, in the development of lipotoxicity, we generated transgenic...... mice overexpressing hormone-sensitive lipase specifically in beta-cells. Transgenic mice developed glucose intolerance and severely blunted glucose-stimulated insulin secretion when challenged with a high-fat diet. As expected, both lipase activity and forskolin-stimulated lipolysis was increased...

GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines.

Science.gov (United States)

Panka, David J; Cho, Daniel C; Atkins, Michael B; Mier, James W

2008-01-11

Glycogen synthase kinase-3beta (GSK-3beta) can participate in the induction of apoptosis or, alternatively, provide a survival signal that minimizes cellular injury. We previously demonstrated that the multikinase inhibitor sorafenib induces apoptosis in melanoma cell lines. In this report, we show that sorafenib activates GSK-3beta in multiple subcellular compartments and that this activation undermines the lethality of the drug. Pharmacologic inhibition and/or down-modulation of the kinase enhances sorafenib-induced apoptosis as determined by propidium iodide staining and by assessing the mitochondrial release of apoptosis-inducing factor and Smac/DIABLO. Conversely, the forced expression of a constitutively active form of the enzyme (GSK-3beta(S9A)) protects the cells from the apoptotic effects of the drug. This protective effect is associated with a marked increase in basal levels of Bcl-2, Bcl-x(L), and survivin and a diminution in the degree to which these anti-apoptotic proteins are down-modulated by sorafenib exposure. Sorafenib down-modulates the pro-apoptotic Bcl-2 family member Noxa in cells with high constitutive GSK-3beta activity. Pharmacologic inhibition of GSK-3beta prevents the disappearance of Noxa induced by sorafenib and enhances the down-modulation of Mcl-1. Down-modulation of Noxa largely eliminates the enhancing effect of GSK-3 inhibition on sorafenib-induced apoptosis. These data provide a strong rationale for the use of GSK-3beta inhibitors as adjuncts to sorafenib treatment and suggest that preservation of Noxa may contribute to their efficacy.

Measurement of low-level beta activity of samples in liquid state using plastic scintillator vials

International Nuclear Information System (INIS)

Wezranowski, E.; Panczyk, E.; Radwan, M.

1977-01-01

Plastic scintillation vials having walls from a plastic scintillator and the bottom from perspex were used. Wall thickness was 0.8 to 3 mm. The solution radioactivity was measured by a scintillation beta spectrometer. The total measurement errors were found for the following radionuclides: 14 C +-3.7%; 204 Tl +-3%; 32 P +-2.8%; 137 Cs +-2%, and 72 Ga +-5%. Detection efficiency was found to decrease rapidly with the solution layer thickness. For a solution thickness of 0.2 mm the highest detection efficiency was observed with the 4% measurement error. Linear dependence was found of detection efficiency on beta energy. For a solution layer thickness of 0.2 mm the minimum measurable activities were determined to be 30.3 pCi for 14 C and 2.12 pCi for 32 P. The use of the above vials permits quick and simple measurement without sample chemical preparation. (J.P.)

Few active mechanisms of the neutrinoless double beta-decay and effective mass of Majorana neutrinos

CERN Document Server

Simkovic, Fedor; Faessler, Amand

2010-01-01

It is well known that there exist many mechanisms that may contribute to neutrinoless double beta decay (0nbb-decay). By exploiting the fact that the associated nuclear matrix elements are target dependent we show that, given definite experimental results on a sufficient number of targets, one can determine or sufficiently constrain all lepton violating parameters including the mass term. As a specific example we show that, assuming the observation of the 0nbb-decay in three different nuclei, e.g., 76Ge, 100Mo and 130Te, and just three lepton number violating mechanisms (light and heavy neutrino mass mechanisms as well as R-parity breaking SUSY mechanism) being active, there are only four different solutions for the lepton violating parameters, provided that they are relatively real. In particular, assuming evidence of the 0nbb-decay of 76Ge, the effective neutrino Majorana mass |m_bb| can be almost uniquely extracted by utilizing other existing constraints (cosmological observations and tritium beta-decay ex...

Non-fusion and fusion expression of beta-galactosidase from Lactobacillus bulgaricus in Lactococcus lactis.

Science.gov (United States)

Wang, Chuan; Zhang, Chao-Wu; Liu, Heng-Chuan; Yu, Qian; Pei, Xiao-Fang

2008-10-01

To construct four recombinant Lactococcus lactis strains exhibiting high beta-galactosidase activity in fusion or non-fusion ways, and to study the influence factors for their protein expression and secretion. The gene fragments encoding beta-galactosidase from two strains of Lactobacillus bulgaricus, wch9901 isolated from yogurt and 1.1480 purchased from the Chinese Academy of Sciences, were amplified and inserted into lactococcal expression vector pMG36e. For fusion expression, the open reading frame of the beta-galactosidase gene was amplified, while for non-fusion expression, the open reading frame of the beta-galactosidase gene was amplified with its native Shine-Dalgarno sequence upstream. The start codon of the beta-galactosidase gene partially overlapped with the stop codon of vector origin open reading frame. Then, the recombinant plasmids were transformed into Escherichia coli DH5 alpha and Lactococcus lactis subsp. lactis MG1363 and confirmed by determining beta-galactosidase activities. The non-fusion expression plasmids showed a significantly higher beta-galactosidase activity in transformed strains than the fusion expression plasmids. The highest enzyme activity was observed in Lactococcus lactis transformed with the non-fusion expression plasmids which were inserted into the beta-galactosidase gene from Lactobacillus bulgaricus wch9901. The beta-galactosidase activity was 2.75 times as high as that of the native counterpart. In addition, beta-galactosidase expressed by recombinant plasmids in Lactococcus lactis could be secreted into the culture medium. The highest secretion rate (27.1%) was observed when the culture medium contained 20 g/L of lactose. Different properties of the native bacteria may have some effects on the protein expression of recombinant plasmids. Non-fusion expression shows a higher enzyme activity in host bacteria. There may be a host-related weak secretion signal peptide gene within the structure gene of Lb. bulgaricus beta

Beta Beams for Precision Measurements of Neutrino Oscillation Parameters

CERN Document Server

Wildner, E; Hansen, C; De Melo Mendonca, T; Stora, T; Damjanovic, S; Payet, J; Chancé, A; Zorin, V; Izotov, I; Rasin, S; Sidorov, A; Skalyga, V; De Angelis, G; Prete, G; Cinausero, M; Kravchuk, V; Gramegna, F; Marchi, T; Collazuol, G; Mezzetto, M; Delbar, T; Loiselet, M; Keutgen, T; Mitrofanov, S; Burt, G; Dexter, A; Lamy, T; Latrasse, L; Marie-Jeanne, M; Sortais, P; Thuillier, T; Debray, F; Trophime, C; Hass, M; Hirsh, T; Berkovits, D; Stahl, A; Vardaci, E; Di Nitto, A; Brondi, A; La Rana, G; Moro, R; De Rosa, G; Palladino, V

2012-01-01

Neutrino oscillations have implications for the Standard Model of particle physics. The CERN Beta Beam has outstanding capabilities to contribute to precision measurements of the parameters governing neutrino oscillations. The FP7 collaboration EUROnu (2008-2012) is a design study that will review three facilities (Super-Beams, Beta Beams and Neutrino Factories) and perform a cost assessment that, coupled with the physics performance, will give means to the European research authorities to make decisions on future European neutrino oscillation facilities. ”Beta Beams” produce collimated pure electron (anti)neutrinos by accelerating beta active ions to high energies and having them decay in a storage ring. Using existing machines and infrastructure is an advantage for the cost evaluation; however, this choice is also constraining the Beta Beams. Recent work to make the Beta Beam facility a solid option will be described: production of Beta Beam isotopes, the 60 GHz pulsed ECR source development, integratio...

Activation of the Wnt/{beta}-catenin signaling pathway is associated with glial proliferation in the adult spinal cord of ALS transgenic mice

Energy Technology Data Exchange (ETDEWEB)

Chen, Yanchun [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong (China); Guan, Yingjun, E-mail: guanyj@wfmc.edu.cn [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong (China); Liu, Huancai [Department of Orthopedic, Affiliated Hospital, Weifang Medical University, Weifang, Shandong (China); Wu, Xin; Yu, Li; Wang, Shanshan; Zhao, Chunyan; Du, Hongmei [Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong (China); Wang, Xin, E-mail: xwang@rics.bwh.harvard.edu [Department of Neurosurgery, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States)

2012-04-06

Highlights: Black-Right-Pointing-Pointer Wnt3a and Cyclin D1 were upregulated in the spinal cord of the ALS mice. Black-Right-Pointing-Pointer {beta}-catenin translocated from the cell membrane to the nucleus in the ALS mice. Black-Right-Pointing-Pointer Wnt3a, {beta}-catenin and Cyclin D1 co-localized for astrocytes were all increased. Black-Right-Pointing-Pointer BrdU/Cyclin D1 double-positive cells were increased in the spinal cord of ALS mice. Black-Right-Pointing-Pointer BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. -- Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and fatal loss of motor neurons. In ALS, there is a significant cell proliferation in response to neurodegeneration; however, the exact molecular mechanisms of cell proliferation and differentiation are unclear. The Wnt signaling pathway has been shown to be involved in neurodegenerative processes. Wnt3a, {beta}-catenin, and Cyclin D1 are three key signaling molecules of the Wnt/{beta}-catenin signaling pathway. We determined the expression of Wnt3a, {beta}-catenin, and Cyclin D1 in the adult spinal cord of SOD1{sup G93A} ALS transgenic mice at different stages by RT-PCR, Western blot, and immunofluorescence labeling techniques. We found that the mRNA and protein of Wnt3a and Cyclin D1 in the spinal cord of the ALS mice were upregulated compared to those in wild-type mice. In addition, {beta}-catenin translocated from the cell membrane to the nucleus and subsequently activated transcription of the target gene, Cyclin D1. BrdU and Cyclin D1 double-positive cells were increased in the spinal cord of these mice. Moreover, Wnt3a, {beta}-catenin, and Cyclin D1 were also expressed in both neurons and astrocytes. The expression of Wnt3a, {beta}-catenin or Cyclin D1 in mature GFAP{sup +} astrocytes increased. Moreover, BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. Our findings suggest that

Modifications of the alpha,beta-double bond in chalcones only marginally affect the antiprotozoal activities

DEFF Research Database (Denmark)

Nielsen, S F; Kharazmi, A; Christensen, S B

1998-01-01

Methods for selective alkylation of chalcones in the alpha- or beta-position and for selective reduction of the alpha,beta-double bond have been developed. The antiparasitic potencies of the alpha,beta-double bond modified chalcones only differ marginally from the potencies of the parent chalcones...

Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women.

Directory of Open Access Journals (Sweden)

Therése Andersson

Full Text Available With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1 which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05, indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05. Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion, suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

Oscillatory activity in the human basal ganglia: more than just beta, more than just Parkinson's disease.

Science.gov (United States)

Alegre, Manuel; Valencia, Miguel

2013-10-01

The implantation of deep brain stimulators in different structures of the basal ganglia to treat neurological and psychiatric diseases has allowed the recording of local field potential activity in these structures. The analysis of these signals has helped our understanding of basal ganglia physiology in health and disease. However, there remain some major challenges and questions for the future. In a recent work, Tan et al. (Tan, H., Pogosyan, A., Anam, A., Foltynie, T., Limousin, P., Zrinzo, L., et al. 2013. Frequency specific activity in subthalamic nucleus correlates with hand bradykinesia in Parkinson's disease. Exp. Neurol. 240,122-129) take profit of these recordings to study the changes in subthalamic oscillatory activity during the hold and release phases of a grasping paradigm, and correlate the changes in different frequency bands with performance parameters. They found that beta activity was related to the release phase, while force maintenance related most to theta and gamma/HFO activity. There was no significant effect of the motor state of the patient on this latter association. These findings suggest that the alterations in the oscillatory activity of the basal ganglia in Parkinson's disease are not limited to the beta band, and they involve aspects different from movement preparation and initiation. Additionally, these results highlight the usefulness of the combination of well-designed paradigms with recordings in off and on motor states (in Parkinson's disease), or in different pathologies, in order to understand not only the pathophysiology of the diseases affecting the patients, but also the normal physiology of the basal ganglia. Copyright © 2013 Elsevier Inc. All rights reserved.

Biosynthesis and release of beta-endorphin-, N-acetyl beta-endorphin-, beta-endorphin-(1-27)-, and N-acetyl beta-endorphin-(1-27)-like peptides by rat pituitary neurointermediate lobe: beta-endorphin is not further processed by anterior lobe

International Nuclear Information System (INIS)

Liotta, A.S.; Yamaguchi, H.; Krieger, D.T.

1981-01-01

Continuous labeling and pulse-chase techniques were employed to study the synthesis and secretion of multiple forms of immunoreactive beta-endorphin by cultured dispersed rat anterior lobe cells and intact neurointermediate pituitary lobe. Intact neurointermediate lobes incorporated radiolabeled amino acids into four to six forms of immunoreactive beta-endorphin. Four of these forms were physicochemically similar to authentic beta-endorphin, N-acetylated beta-endorphin, beta-endorphin-(1-27), and N-acetylated beta-endorphin-(1-27). Pulse-chase studies indicated that a beta-lipotropin-like molecule served as a metabolic intermediate for a beta-endorphin-like molecule. As beta-endorphin-like material accumulated in the cell, some of it was N-acetylated (approximately 18% at 2 hr chase and approximately 65% at 18 hr chase). At later chase times, beta-endorphin-(1-27)- and N-acetylated beta-endorphin-(1-27)-like peptides were the predominant molecular species detected. All endorphin forms were detected in unlabeled tissue maintained in culture or tissue continuously labeled for 72 hr and were released into the medium under basal, stimulatory (10(-8) M norepinephrine), or inhibitory (10(-7) M dopamine) incubation conditions. In all cases, beta-endorphin-(1-27)-like species were the predominant forms (more than 70% of total) present in the cells and released into the medium. In contrast, approximately 90% of radiolabeled immunoreactive beta-endorphin extracted from anterior lobe cells and medium similarly incubated appeared to represent the authentic beta-endorphin molecule. Continuous labeling (72 hr) revealed the beta-lipotropin/beta-endorphin molar ratio to be approximately 4. We conclude that, in anterior lobe, most of the beta-endorphin is not processed further and is released intact, while in neurointermediate lobe, it serves as a biosynthetic intermediate

A MONOCLONAL ANTIBODY-BETA-GLUCURONIDASE CONJUGATE AS ACTIVATOR OF THE PRODRUG EPIRUBICIN-GLUCURONIDE FOR SPECIFIC TREATMENT OF CANCER

NARCIS (Netherlands)

Haisma, Hidde; BOVEN, E; VANMUIJEN, M; DEJONG, J; VANDERVIJGH, WJF; PINEDO, HM

The anti-pan carcinoma monoclonal antibody (MAb) 323/A3, linked to E. coli-derived beta-glucuronidase (GUS) was used to study the tumour-site-selective activation of the prodrug Epirubicin-glucuronide (Epi-glu). Epi-glu was isolated from the urine of patients treated with Epirubicin (Epi) by

Activated endothelial interleukin-1beta, -6, and -8 concentrations and intercellular adhesion molecule-1 expression are attenuated by lidocaine.

LENUS (Irish Health Repository)

Lan, Wei

2012-02-03

Endothelial cells play a key role in ischemia reperfusion injury. We investigated the effects of lidocaine on activated human umbilical vein endothelial cell (HUVEC) interleukin (IL)-1beta, IL-6, and IL-8 concentrations and intercellular adhesion molecule-1 (ICAM-1) expression. HUVECs were pretreated with different concentrations of lidocaine (0 to 0.5 mg\\/mL) for 60 min, thereafter tumor necrosis factor-alpha was added at a concentration of 2.5 ng\\/mL and the cells incubated for 4 h. Supernatants were harvested, and cytokine concentrations were analyzed by enzyme-linked immunosorbent assay. Endothelial ICAM-1 expression was analyzed by using flow cytometry. Differences were assessed using analysis of variance and post hoc unpaired Student\\'s t-test where appropriate. Lidocaine (0.5 mg\\/mL) decreased IL-1beta (1.89 +\\/- 0.11 versus 4.16 +\\/- 1.27 pg\\/mL; P = 0.009), IL-6 (65.5 +\\/- 5.14 versus 162 +\\/- 11.5 pg\\/mL; P < 0.001), and IL-8 (3869 +\\/- 785 versus 14,961 +\\/- 406 pg\\/mL; P < 0.001) concentrations compared with the control. IL-1beta, IL-6, and IL-8 concentrations in HUVECs treated with clinically relevant plasma concentrations of lidocaine (0.005 mg\\/mL) were similar to control. ICAM-1 expression on lidocaine-treated (0.05 mg\\/mL) HUVECs was less than on controls (198 +\\/- 52.7 versus 298 +\\/- 50.3; Mean Channel Fluorescence; P < 0.001). Activated endothelial IL-1beta, IL-6, and IL-8 concentrations and ICAM-1 expression are attenuated only by lidocaine at concentrations larger than clinically relevant concentrations.

Inhibition of. beta. -bungarotoxin binding to brain membranes by mast cell degranulating peptide, toxin I, and ethylene glycol bis(. beta. -aminoethyl ether)-N,N,N',N'-tetraacetic acid

Energy Technology Data Exchange (ETDEWEB)

Schmidt, R.R.; Betz, H.; Rehm, H.

1988-02-09

The presynaptically active snake venom neurotoxin ..beta..-bungarotoxin (..beta..-Butx) is known to affect neurotransmitter release by binding to a subtype of voltage-activated K/sup +/ channels. Here the authors show that mast cell degranulating (MCD) peptide from bee venom inhibits the binding of /sup 125/I-labeled ..beta..-Butx to chick and rat brain membranes with apparent K/sub i/ values of 180 nM and 1100 nM, respectively. The mechanisms of inhibition of MCD peptide is noncompetitive, as is inhibition of /sup 125/I-..beta..-Butx binding by the protease inhibitor homologue from mamba venom, toxin I. ..beta..-Butx and its binding antagonists thus bind to different sites of the same membrane protein. Removal of Ca/sup 2 +/ by ethylene glycol bis(..beta..-aminoethyl ether)-N,N,N',N'-tetraacetic acid inhibits the binding of /sup 125/I-..beta..-Butx by lowering its affinity to brain membranes.

Elaboration of supports for beta emitting sources (with vyns); Elaboracion de soportes para fuentes emisoras beta (con vyns)

Energy Technology Data Exchange (ETDEWEB)

Cortes P, A.; Torre O, J. De la; Tejera R, A.; Becerril V, A.; Bribiesca S, L

1990-04-15

The Laboratory of Radioactive patterns account with a 4 {pi}{beta}-{gamma} coincidence system of recent acquisition with which absolute measures of radioactive activity with uncertainties of the order of 0.1% can be made. Since the coincidence method for the activity measure consists on detecting to the particle and the photon corresponding to oneself nuclear disintegration, it is necessary to elaborate special radioactive sources on thin supports, in order to allowing the maximum possible fluence of {beta} particles ({approx} 100%). This work a technique for the elaboration of these sources and for the measure of the thickness of the walls of the support is presented. (Author)

Glycogen synthase kinase 3 beta alters anxiety-, depression-, and addiction-related behaviors and neuronal activity in the nucleus accumbens shell

Science.gov (United States)

Crofton, Elizabeth J.; Nenov, Miroslav N.; Zhang, Yafang; Scala, Federico; Page, Sean A.; McCue, David L.; Li, Dingge; Hommel, Jonathan D.; Laezza, Fernanda; Green, Thomas A.

2017-01-01

Psychiatric disorders such as anxiety, depression and addiction are often comorbid brain pathologies thought to share common mechanistic biology. As part of the cortico-limbic circuit, the nucleus accumbens shell (NAcSh) plays a fundamental role in integrating information in the circuit, such that modulation of NAcSh circuitry alters anxiety, depression, and addiction-related behaviors. Intracellular kinase cascades in the NAcSh have proven important mediators of behavior. To investigate glycogen-synthase kinase 3 (GSK3) beta signaling in the NAcSh in vivo we knocked down GSK3beta expression with a novel adeno-associated viral vector (AAV2) and assessed changes in anxiety- and depression-like behavior and cocaine self-administration in GSK3beta knockdown rats. GSK3beta knockdown reduced anxiety-like behavior while increasing depression-like behavior and cocaine self-administration. Correlative electrophysiological recordings in acute brain slices were used to assess the effect of AAV-shGSK3beta on spontaneous firing and intrinsic excitability of tonically active interneurons (TANs), cells required for input and output signal integration in the NAcSh and for processing reward-related behaviors. Loose-patch recordings showed that TANs transduced by AAV-shGSK3beta exhibited reduction in tonic firing and increased spike half width. When assessed by whole-cell patch clamp recordings these changes were mirrored by reduction in action potential firing and accompanied by decreased hyperpolarization-induced depolarizing sag potentials, increased action potential current threshold, and decreased maximum rise time. These results suggest that silencing of GSK3beta in the NAcSh increases depression- and addiction-related behavior, possibly by decreasing intrinsic excitability of TANs. However, this study does not rule out contributions from other neuronal sub-types. PMID:28126496

Biosynthesis of beta-glucosidase by Aspergillus niger a-5

Energy Technology Data Exchange (ETDEWEB)

Atev, A.; Panayotov, C.; Bubareva, L.; Benadova, R.; Kolev, E.

1984-01-01

Aspergillus niger A-5 produced beta-glucosidase, exocellobihydrolase (C1 enzyme) and endo-1, 4-beta-glucanase (Cx enzyme) in a culture medium containing farm residues of plant origin: wheat straw, ground maize stalks, wheat bran, and micricell as substrates. Maize stalk and wheat bran were the best inducers of the cellulase complex. Intensive aeration stimulated growth and enzyme synthesis. The highest beta-glucosidase activity (54 units/mL) was observed after 96 h of cultivation.

NMR study of the preparation of 6 {alpha}, 7 {beta}-dihydroxyvouacapan-17 beta-oic acid mannich base derivatives

Energy Technology Data Exchange (ETDEWEB)

Santos, Flavio Jose Leite dos; Pilo-Veloso, Dorila [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Inst. de Ciencias Exatas. Dept. Quimica]. E-mail: dorila@zeus.qui.ufmg.br; Ferreira-Alves, Dalton L. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Inst. de Ciencias Biologicas. Dept. de Farmacologia

2007-07-01

This work presents four new Mannich base compounds obtained by the Mannich reaction of a {delta}-keto-lactone derivative of 6{alpha}, 7{beta}-dihydroxyvouacapan- 17{beta}-oic acid, a furano diterpene isolated from the hexane extract of Pterodon polygalaeflorus Benth fruits, which shows anti-inflammatory and analgesic activities. The use of 1D and 2D NMR (COSY, DEPT-135, HMBC, HMQC) spectroscopy made it possible to characterize the new compounds. (author)

Interactions between beta subunits of the KCNMB family and Slo3: beta4 selectively modulates Slo3 expression and function.

Directory of Open Access Journals (Sweden)

Cheng-Tao Yang

2009-07-01

Full Text Available The pH and voltage-regulated Slo3 K(+ channel, a homologue of the Ca(2+- and voltage-regulated Slo1 K(+ channel, is thought to be primarily expressed in sperm, but the properties of Slo3 studied in heterologous systems differ somewhat from the native sperm KSper pH-regulated current. There is the possibility that critical partners that regulate Slo3 function remain unidentified. The extensive amino acid identity between Slo3 and Slo1 suggests that auxiliary beta subunits regulating Slo1 channels might coassemble with and modulate Slo3 channels. Four distinct beta subunits composing the KCNMB family are known to regulate the function and expression of Slo1 Channels.To examine the ability of the KCNMB family of auxiliary beta subunits to regulate Slo3 function, we co-expressed Slo3 and each beta subunit in heterologous expression systems and investigated the functional consequences by electrophysiological and biochemical analyses. The beta4 subunit produced an 8-10 fold enhancement of Slo3 current expression in Xenopus oocytes and a similar enhancement of Slo3 surface expression as monitored by YFP-tagged Slo3 or biotin labeled Slo3. Neither beta1, beta2, nor beta3 mimicked the ability of beta4 to increase surface expression, although biochemical tests suggested that all four beta subunits are competent to coassemble with Slo3. Fluorescence microscopy from beta4 KO mice, in which an eGFP tag replaced the deleted exon, revealed that beta4 gene promoter is active in spermatocytes. Furthermore, quantitative RT-PCR demonstrated that beta4 and Slo3 exhibit comparable mRNA abundance in both testes and sperm.These results argue that, for native mouse Slo3 channels, the beta4 subunit must be considered as a potential interaction partner and, furthermore, that KCNMB subunits may have functions unrelated to regulation of the Slo1 alpha subunit.

86Rb(K) influx and [3H]ouabain binding by human platelets: Evidence for beta-adrenergic stimulation of Na-K ATPase activity

International Nuclear Information System (INIS)

Turaihi, K.; Khokher, M.A.; Barradas, M.A.; Mikhailidis, D.P.; Dandona, P.

1989-01-01

Although active transport of potassium into human platelets has been demonstrated previously, there is hitherto no evidence that human platelets have an ouabain-inhibitable Na-K ATPase in their membrane. The present study demonstrates active rubidium (used as an index of potassium influx), 86 Rb(K), influx into platelets, inhibitable by ouabain, and also demonstrates the presence of specific [ 3 H]ouabain binding by the human platelet. This 86 Rb(K) influx was stimulated by adrenaline, isoprenaline, and salbutamol, but noradrenaline caused a mild inhibition. Active 86 Rb(K) influx by platelets was inhibited markedly by timolol, mildly by atenolol, but not by phentolamine. Therefore, active 86 Rb(K) influx in human platelets is enhanced by stimulation of beta adrenoceptors of the beta 2 subtype. The platelet may therefore replace the leukocyte in future studies of Na-K ATPase activity. This would be a considerable advantage in view of the ease and rapidity of preparation of platelets

Immunochemical studies on the N-acetyllactosamine beta-(1----6)-linked trisaccharide specificity of Ricinus communis agglutinin.

Science.gov (United States)

Wu, A M; Sugii, S; Gruezo, F G; Kabat, E A

1988-07-15

The combining site of Ricinus communis agglutinin (RCA1) was studied by quantitative precipitin and precipitin inhibition assays. Of 31 complex carbohydrates tested, all except active and inactive antifreeze glycoproteins, Streptococcus group C polysaccharide, and native rat salivary glycoprotein, reacted strongly, and 22 completely precipitated the lectin, indicating that RCA1 has both a broad range of affinity and a low solubility of its carbohydrate-bound complex. Of the monosaccharides and glycosides tested for inhibition of precipitation, p-nitrophenyl beta-D-galactopyranoside was the best. It was about 6.4 times better than methyl beta-D-galactopyranoside. The beta anomer of glycosides of D-galactose was much more potent than the corresponding alpha anomer. Among the oligosaccharides tested, beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----6)-D-Gal was the best inhibitor, which was approximately 2/3 as active as p-nitrophenyl beta-D-galactopyranoside. It was approximately 1.4 times as active as beta-D-Gal-(1----4)-D-GlcNAc (N-acetyllactosamine), twice as active as beta-D-Gal-(1----3)-D-GlcNAc, and 4.5 times more active than lacto-N-tetraose. From the results, it can be concluded that; (a) hydrophobic interaction is important for binding; (b) the combining site of this lectin is at least as large as a trisaccharide; and (c) of the compounds studied, the trisaccharide beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----6)-D-Gal was the most complementary to the human blood group I Ma determinant beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----6)-D-Gal.

Crystal Structure of Full-length Mycobacterium tuberculosis H37Rv Glycogen Branching Enzyme; Insights of N-Terminal [beta]-Sandwich in Sustrate Specifity and Enzymatic Activity

Energy Technology Data Exchange (ETDEWEB)

Pal, Kuntal; Kumar, Shiva; Sharma, Shikha; Garg, Saurabh Kumar; Alam, Mohammad Suhail; Xu, H. Eric; Agrawal, Pushpa; Swaminathan, Kunchithapadam (NU Sinapore); (Van Andel); (IMT-India)

2010-07-13

The open reading frame Rv1326c of Mycobacterium tuberculosis (Mtb) H37Rv encodes for an {alpha}-1,4-glucan branching enzyme (MtbGlgB, EC 2.4.1.18, Uniprot entry Q10625). This enzyme belongs to glycoside hydrolase (GH) family 13 and catalyzes the branching of a linear glucose chain during glycogenesis by cleaving a 1 {yields} 4 bond and making a new 1 {yields} 6 bond. Here, we show the crystal structure of full-length MtbGlgB (MtbGlgBWT) at 2.33-{angstrom} resolution. MtbGlgBWT contains four domains: N1 {beta}-sandwich, N2 {beta}-sandwich, a central ({beta}/{alpha}){sub 8} domain that houses the catalytic site, and a C-terminal {beta}-sandwich. We have assayed the amylase activity with amylose and starch as substrates and the glycogen branching activity using amylose as a substrate for MtbGlgBWT and the N1 domain-deleted (the first 108 residues deleted) Mtb{Delta}108GlgB protein. The N1 {beta}-sandwich, which is formed by the first 105 amino acids and superimposes well with the N2 {beta}-sandwich, is shown to have an influence in substrate binding in the amylase assay. Also, we have checked and shown that several GH13 family inhibitors are ineffective against MtbGlgBWT and Mtb{Delta}108GlgB. We propose a two-step reaction mechanism, for the amylase activity (1 {yields} 4 bond breakage) and isomerization (1 {yields} 6 bond formation), which occurs in the same catalytic pocket. The structural and functional properties of MtbGlgB and Mtb{Delta}108GlgB are compared with those of the N-terminal 112-amino acid-deleted Escherichia coli GlgB (EC{Delta}112GlgB).

Antibiogram Studies and Extended Spectrum Beta-lactamase Activity Profile of Salmonella-like Species Isolated from Poultry Soil of the University of Uyo, Nigeria

Directory of Open Access Journals (Sweden)

Ikpeme, E. M.

2012-01-01

Full Text Available Aims: The contribution of beta-lactamase activity of various bacterial species to the increased antimicrobial resistance being experienced worldwide is very scanty in the literature. This study was undertaken to investigate the antibiotic resistance pattern (antibiogram of Salmonella-like bacterial species against some antibiotics, and the role beta-lactamase assumably produced by the Salmonella-like species, played in producing resistance.Methodology and Results: The antimicrobial sensitivity test and the beta-lactamase test of the Salmonella-like species were carried out using the methods of Kirby Bauer sensitivity test and the Double Disk Synergy test respectively, following isolation and identification of the organisms from poultry soil. Results revealed that Salmonella-like species were most highly resistant to Nalidixic acid (20, 66.66%, followed by Tetracycline (19, 63.33%, Cotrimoxazole, Amoxicillin and Augmentin (18, 60%, while the least was Ofloxacin (8, 26.66%. Multiple resistance of 4 or more antibiotics among the isolates from the soil outside the broilers enclosure was observed, while there was a significant difference (P <0.05 between poultry soil and control soil. This implied that the antibiotics with the highest resistance were most often applied to the birds, the droppings of which contaminated the soil. The resistant pattern of the isolates from the control soil is lower than that from the poultry soil. Extended Spectrum Beta-lactamase activity was expressed by all the isolates against Cefotazime, while the least resistance was against mostly Cefotazime.Conclusion, significance and impact of study: It is concluded that there is a widespread Beta-lactamase activity causing antibiotic resistance by many species of bacteria as well as poultry Salmonella, thus exacerbating the global problem of antibiotic resistance and a serious health related implication for antibiotic use in poultry.

Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells.

Science.gov (United States)

Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E

1998-12-01

Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

Purification of beta-acetylglucosaminase and beta-galactosidase from ram testis.

Science.gov (United States)

Caygill, J C; Roston, C P; Jevons, F R

1966-02-01

1. The presence of beta-galactosidase (EC 3.2.1.23) in an acetic acid extract of ram testis is reported. Some properties of the crude enzyme preparation were studied. 2. The purification of beta-acetylglucosaminase (EC 3.2.1.30) and of beta-galactosidase from the ram-testis extract by ammonium sulphate precipitation and chromatography on a CM-cellulose column is described. 3. The final purifications of the separated enzymes achieved were for the beta-acetylglucosaminase 35 times and for the beta-galactosidase 99 times. 4. The possibility of using DEAE-cellulose and Sephadex G-200 to purify the enzymes was investigated.

Inhibition of Alzheimer amyloid {beta} aggregation by polyvalent trehalose

Energy Technology Data Exchange (ETDEWEB)

Miura, Yoshiko; You, Chouga [School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292 (Japan); Ohnishi, Reiko [Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan)], E-mail: miuray@jaist.ac.jp

2008-04-15

A glycopolymer carrying trehalose was found to suppress the formation of amyloid fibrils from the amyloid {beta} peptide (1-42) (A{beta}), as evaluated by thioflavin T assay and atomic force microscopy. Glycopolymers carrying sugar alcohols also changed the aggregation properties of A{beta}, and the inhibitory effect depended on the type of sugar and alkyl side chain. Neutralization activity was confirmed by in vitro assay using HeLa cells. The glycopolymer carrying trehalose strongly inhibited amyloid formation and neutralized cytotoxicity.

Novel {beta}-Carboline Alkaloid from Peganum Harmala As Antibacterial Agent

Energy Technology Data Exchange (ETDEWEB)

Abdel Aziz, H G; Abdel Kader, S M; El-Sayed, M M; EL-Malt, E A; Shaker, E S [Chem. Dept., Fac. Agric., Minia Univ., Minia (Egypt)

2011-07-01

A novel {beta}-carboline alkaloid isolated from the aerial parts of Peganum harmala L. (Gen: Phyeophylaceae) have been characterized as l-thioformyl-8-{beta}-D-glucopyranoside-bis-2,3-dihydro-isopyridinopyrrol. It is one of {beta}-carboline alkaloids derivatives. The chemical structure was elucidated on the basis of elementary analysis and spectroscopic studies (UV, IR, {sup 1}H-NMR and MS). The isolated compound showed significant antibacterial activity against Streptococcus pyogenus.

Quality control on the accuracy of the total Beta activity index in different sample matrices water

International Nuclear Information System (INIS)

Pujol, L.; Pablo, M. A. de; Payeras, J.

2013-01-01

The standard ISO/IEC 17025:2005 of general requirements for the technical competence of testing and calibration laboratories, provides that a laboratory shall have quality control procedures for monitoring the validity of tests and calibrations ago. In this paper, the experience of Isotopic Applications Laboratory (CEDEX) in controlling the accuracy rate of total beta activity in samples of drinking water, inland waters and marine waters is presented. (Author)

Betting Against Beta

DEFF Research Database (Denmark)

Frazzini, Andrea; Heje Pedersen, Lasse

We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model’s five central predictions: (1) Since constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for U...... of the BAB factor is low; (4) Increased funding liquidity risk compresses betas toward one; (5) More constrained investors hold riskier assets........S. equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures; (2) A betting-against-beta (BAB) factor, which is long leveraged low beta assets and short high-beta assets, produces significant positive risk-adjusted returns; (3) When funding constraints tighten, the return...

Conversion of beta-methylbutyric acid to beta-hydroxy-beta-methylbutyric acid by Galactomyces reessii.

OpenAIRE

Lee, I Y; Nissen, S L; Rosazza, J P

1997-01-01

beta-Hydroxy-beta-methylbutyric acid (HMB) has been shown to increase strength and lean mass gains in humans undergoing resistance-exercise training. HMB is currently marketed as a calcium salt of HMB, and thus, environmentally sound and inexpensive methods of manufacture are being sought. This study investigates the microbial conversion of beta-methylbutyric acid (MBA) to HMB by cultures of Galactomyces reessii. Optimal concentrations of MBA were in the range of 5 to 20 g/liter for HMB produ...

A clinical perspective of IL-1beta as the gatekeeper of inflammation.

NARCIS (Netherlands)

Dinarello, C.A.

2011-01-01

An expanding spectrum of acute and chronic non-infectious inflammatory diseases is uniquely responsive to IL-1beta neutralization. IL-1beta-mediated diseases are often called "auto-inflammatory" and the dominant finding is the release of the active form of IL-1beta driven by endogenous molecules

Beta activity in the premotor cortex is increased during stabilized as compared to normal walking

Directory of Open Access Journals (Sweden)

Sjoerd M. Bruijn

2015-10-01

Full Text Available Walking on two legs is inherently unstable. Still, we humans perform remarkable well at it, mostly without falling. To gain more understanding of the role of the brain in controlling gait stability we measured brain activity using electro-encephalography (EEG during stabilized and normal walking.Subjects walked on a treadmill in two conditions, each lasting 10 minutes; normal, and while being laterally stabilized by elastic cords. Kinematics of trunk and feet, electro-myography (EMG of neck muscles, as well as 64-channel EEG were recorded. To assess gait stability the local divergence exponent, step width, and trunk range of motion were calculated from the kinematic data. We used independent component analysis to remove movement, EMG, and eyeblink artifacts from the EEG, after which dynamic imaging of coherent sources beamformers were determined to identify cortical sources that showed a significant difference between conditions. Stabilized walking led to a significant increase in gait stability, i.e. lower local divergence exponents. Beamforming analysis of the beta band activity revealed significant sources in bilateral pre-motor cortices. Projection of sensor data on these sources showed a significant difference only in the left premotor area, with higher beta power during stabilized walking, specifically around push-off, although only significant around contralateral push-off. It appears that even during steady gait the cortex is involved in the control of stability.

Code Betal to calculation Alpha/Beta activities in environmental samples; Programa de ordenador Betal para el calculo de la actividad Beta/Alfa de muestras ambientales

Energy Technology Data Exchange (ETDEWEB)

Romero, L.; Travesi, A.

1983-07-01

A codes, BETAL, was developed, written in FORTRAN IV, to automatize calculations and presentations of the result of the total alpha-beta activities measurements in environmental samples. This code performs the necessary calculations for transformation the activities measured in total counts, to pCi/1., bearing in mind the efficiency of the detector used and the other necessary parameters. Further more, it appraise the standard deviation of the result, and calculus the Lower limit of detection for each measurement. This code is written in iterative way by screen-operator dialogue, and asking the necessary data to perform the calculation of the activity in each case by a screen label. The code could be executed through any screen and keyboard terminal, (whose computer accepts Fortran IV) with a printer connected to the said computer. (Author) 5 refs.

CCAAT/enhancer binding protein {beta} deletion increases mitochondrial function and protects mice from LXR-induced hepatic steatosis

Energy Technology Data Exchange (ETDEWEB)

Rahman, Shaikh M., E-mail: rmizanoor@hotmail.com [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Choudhury, Mahua; Janssen, Rachel C.; Baquero, Karalee C. [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Miyazaki, Makoto [Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Friedman, Jacob E. [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States)

2013-01-04

Highlights: Black-Right-Pointing-Pointer LXR agonist activation increases liver TG accumulation by increasing lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta}{sup -/-} mouse prevents LXR activation-mediated induction of hepatic lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta} deletion increases mitochondrial transport chain function. Black-Right-Pointing-Pointer Beneficial effects of LXR activation on liver cholesterol metabolism did not change. Black-Right-Pointing-Pointer C/EBP{beta} inhibition might have important therapeutic potential. -- Abstract: Drugs designed specifically to activate liver X receptors (LXRs) have beneficial effects on lowering cholesterol metabolism and inflammation but unfortunately lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding protein beta (C/EBP{beta}) is an important regulator of liver gene expression but little is known about its involvement in LXR-based steatosis and cholesterol metabolism. The present study investigated the role of C/EBP{beta} expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBP{beta} deletion in mice prevented LXR agonist-mediated induction of lipogenic gene expression in liver in conjunction with significant reduction of liver TG accumulation. Surprisingly, C/EBP{beta}{sup -/-} mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBP{beta}{sup -/-} mice increased the expression of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol efflux and reducing blood levels of total and LDL-cholesterol. Together, these findings establish a central role for C/EBP{beta} in the LXR-mediated steatosis and mitochondrial function, without impairing the influence of LXR activation on lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBP{beta} might therefore be an important therapeutic strategy to prevent LXR

Forward-Looking Betas

DEFF Research Database (Denmark)

Christoffersen, Peter; Jacobs, Kris; Vainberg, Gregory

Few issues are more important for finance practice than the computation of market betas. Existing approaches compute market betas using historical data. While these approaches differ in terms of statistical sophistication and the modeling of the time-variation in the betas, they are all backward......-looking. This paper introduces a radically different approach to estimating market betas. Using the tools in Bakshi and Madan (2000) and Bakshi, Kapadia and Madan (2003) we employ the information embedded in the prices of individual stock options and index options to compute our forward-looking market beta...

Oxidative status and serum PON1 activity in beta-thalassemia minor.

Science.gov (United States)

Selek, Sahbettin; Aslan, Mehmet; Horoz, Mehmet; Gur, Mustafa; Erel, Ozcan

2007-03-01

Paraoxonase-1 (PON1) deficiency is related to increased susceptibility to low density lipoprotein oxidation and development of atherosclerosis. The aim of this study was to investigate paraoxonase and arylesterase activities along with oxidative status parameters, and to find out if there is any increased susceptibility to atherogenesis, which might be reflected with increased oxidative stress and decreased serum PON1 activity in beta-thalassemia minor (BTM) subjects. Thirty-two subjects with BTM and 28 healthy subjects as control were enrolled in the study. Serum paraoxonase and arylesterase activities, lipid hydroperoxide (LOOH) levels, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined. Serum TAC, paraoxonase and arylesterase activities were significantly lower in BTM subjects than controls (for all p<0.001), while TOS, LOOH levels and OSI were significantly higher (p<0.001, p<0.05 and p<0.001; respectively). In BTM subjects, OSI, TOS, LOOH levels and TAC were significantly correlated with serum paraoxonase (r=-0.245, p<0.05; r=-0.231, p<0.05; r=-0.264, p<0.05 and, r=0.342, p<0.05, respectively) and arylesterase activities (r=-0.332, p<0.05, r=-0.308, p<0.05; r=-0.320, p<0.05 and r=0.443, p<0.05). Additionally, hemoglobin level was also correlated with serum paraoxonase (r=0.501, p<0.001) and arylesterase activities (r=0.501, p<0.001), TAC (r=0.402, p<0.05), TOS (r=-0.274, p<0.05) and OSI (r=-0.352, p<0.05). Oxidative stress is increased, while serum PON1 activity is decreased in BTM subjects. Decrease in PON1 activity seems to be associated with both the degree of oxidative stress and anemia. BTM subjects may be more prone to development of atherogenesis due to low serum PON1 activity.

The effect of smoking cessation pharmacotherapies on pancreatic beta cell function

International Nuclear Information System (INIS)

Woynillowicz, Amanda K.; Raha, Sandeep; Nicholson, Catherine J.; Holloway, Alison C.

2012-01-01

The goal of our study was to evaluate whether drugs currently used for smoking cessation (i.e., nicotine replacement therapy, varenicline [a partial agonist at nicotinic acetylcholine receptors (nAChR)] and bupropion [which acts in part as a nAChR antagonist]) can affect beta cell function and determine the mechanism(s) of this effect. INS-1E cells, a rat beta cell line, were treated with nicotine, varenicline and bupropion to determine their effects on beta cell function, mitochondrial electron transport chain enzyme activity and cellular/oxidative stress. Treatment of INS-1E cells with equimolar concentrations (1 μM) of three test compounds resulted in an ablation of normal glucose-stimulated insulin secretion by the cells. This disruption of normal beta cell function was associated with mitochondrial dysfunction since all three compounds tested significantly decreased the activity of mitochondrial electron transport chain enzyme activity. These results raise the possibility that the currently available smoking cessation pharmacotherapies may also have adverse effects on beta cell function and thus glycemic control in vivo. Therefore whether or not the use of nicotine replacement therapy, varenicline and bupropion can cause endocrine changes which are consistent with impaired pancreatic function warrants further investigation. -- Highlights: ► Smoking cessation drugs have the potential to disrupt beta cell function in vitro. ► The effects of nicotine, varenicline and bupropion are similar. ► The impaired beta cell function is mediated by mitochondrial dysfunction. ► If similar effects are seen in vivo, these drugs may increase the risk of diabetes.

The effect of smoking cessation pharmacotherapies on pancreatic beta cell function

Energy Technology Data Exchange (ETDEWEB)

Woynillowicz, Amanda K. [Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada L8N 3Z5 (Canada); Raha, Sandeep [Department of Pediatrics, McMaster University, Hamilton, ON, Canada L8N 3Z5 (Canada); Nicholson, Catherine J. [Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada L8N 3Z5 (Canada); Holloway, Alison C., E-mail: hollow@mcmaster.ca [Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada L8N 3Z5 (Canada)

2012-11-15

The goal of our study was to evaluate whether drugs currently used for smoking cessation (i.e., nicotine replacement therapy, varenicline [a partial agonist at nicotinic acetylcholine receptors (nAChR)] and bupropion [which acts in part as a nAChR antagonist]) can affect beta cell function and determine the mechanism(s) of this effect. INS-1E cells, a rat beta cell line, were treated with nicotine, varenicline and bupropion to determine their effects on beta cell function, mitochondrial electron transport chain enzyme activity and cellular/oxidative stress. Treatment of INS-1E cells with equimolar concentrations (1 μM) of three test compounds resulted in an ablation of normal glucose-stimulated insulin secretion by the cells. This disruption of normal beta cell function was associated with mitochondrial dysfunction since all three compounds tested significantly decreased the activity of mitochondrial electron transport chain enzyme activity. These results raise the possibility that the currently available smoking cessation pharmacotherapies may also have adverse effects on beta cell function and thus glycemic control in vivo. Therefore whether or not the use of nicotine replacement therapy, varenicline and bupropion can cause endocrine changes which are consistent with impaired pancreatic function warrants further investigation. -- Highlights: ► Smoking cessation drugs have the potential to disrupt beta cell function in vitro. ► The effects of nicotine, varenicline and bupropion are similar. ► The impaired beta cell function is mediated by mitochondrial dysfunction. ► If similar effects are seen in vivo, these drugs may increase the risk of diabetes.

Enantioselective synthesis of alpha,beta-disubstituted-beta-amino acids.

Science.gov (United States)

Sibi, Mukund P; Prabagaran, Narayanasamy; Ghorpade, Sandeep G; Jasperse, Craig P

2003-10-01

Highly diastereoselective and enantioselective addition of N-benzylhydroxylamine to imides 17 and 20-30 produces alpha,beta-trans-disubstituted N-benzylisoxazolidinones 19 and 31-41. These reactions proceed in 60-96% ee with 93-99% de's using 5 mol % of Mg(NTf2)2 and ligand 18. The product isoxazolidinones can be hydrogenolyzed directly to provide alpha,beta-disubstituted-beta-amino acids.

The function of the human interferon-beta 1a glycan determined in vivo

DEFF Research Database (Denmark)

Dissing-Olesen, Lasse; Thaysen-Andersen, Morten; Meldgaard, Michael

2008-01-01

Recombinant human interferon-beta (rhIFN-beta) is the leading therapeutic intervention shown to change the cause of relapsing-remitting multiple sclerosis, and both a nonglycosylated and a significantly more active glycosylated variant of rhIFN-beta are used in treatment. This study investigates...... into the role of the rhIFN-beta1a glycan and its carbohydrate residues. The possibilities of improving the pharmacological properties of rhIFN-beta1a using glycoengineering are discussed...

Cetamolol: a new cardioselective beta-adrenoceptor blocking agent without membrane-stabilizing activity.

Science.gov (United States)

Beaulieu, G; Jaramillo, J; Cummings, J R

1984-03-01

Cetamolol, a new beta-adrenoceptor blocker with partial agonist activity and cardioselectivity, was studied in vivo to determine its membrane-stabilizing effects. Comparisons were carried out with atenolol, pindolol, practolol, propranolol, timolol, dexpropranolol, lidocaine, and procaine. The following results indicated that cetamolol lacked membrane-stabilizing activity: (i) failure to cause local anesthesia on the rabbit cornea and motor nerve of the rat tail; (ii) ineffectiveness in reversing ventricular arrhythmias induced by coronary artery litigation in dogs; (iii) failure to reduce cardiac automaticity in catecholamine-depleted dogs as determined by the rate of a subatrial rhythm during ventricular (vagal) escape; and (iv) lack of a significant increase in atrioventricular conduction time in vagotomized or atropinized dogs in contrast to the effect in normal dogs indicating a reflex effect of cetamolol. Other results include a restoration of sinus rhythm in dogs with ventricular tachycardia induced by ouabain, and a dose-related decline in the force of cardiac contraction in anesthetized dogs at doses from 3 to 15 mg/kg, which occurred after an initial increase in force owing to intrinsic sympathomimetic activity. Although the mechanisms for the latter two effects are not clear at this time, explanations other than membrane-stabilizing activity have been considered in view of the other findings. It is concluded that cetamolol lacks membrane-stabilizing activity even at inordinately high doses.

Validation the quantification of beta emitters activity in urine by scintillation spectrometry in the liquid phase

International Nuclear Information System (INIS)

Sierra, I.; Hernandez, C.; Benito, P.; Lopez, C.

2013-01-01

In this paper the methodology used in the validation of the technique for quantifying activity of some beta emitters in urine ( 3 H, 1 4C, 3 5S, 3 2P and 9 0Sr) by scintillation spectrometry Liquid Phase (Liquid Scintillation Counting, LSC) is described in bio elimination Laboratory Service CIEMAT Radiation Dosimetry accredited since last year for carrying out assays measure radiation dose based on ISO forth above. (Author)

Beta-D-xylosidase from Selenomonas ruminantium: thermodynamics of enzyme-catalyzed and noncatalyzed reactions

Science.gov (United States)

Beta-D-xylosidase/alpha-L-arabinofuranosidase from Selenomonas ruminantium (SXA) is the most active enzyme known for catalyzing hydrolysis of 1,4-beta-D-xylooligosaccharides to D-xylose. Temperature dependence for hydrolysis of 4-nitrophenyl-beta-D-xylopyranoside (4NPX), 4-nitrophenyl-alpha-L-arabi...

Entrappment of alkaline protease and {beta}-galactosidase in radiation stitched together poly-N-vinylcaprolactam.; Vklyuchenie shchelochnoj proteazy i {beta}-galaktozidazy v radiatsionno sshityj poli-N-vinilkaprolaktam.

Energy Technology Data Exchange (ETDEWEB)

Davidenko, T I; Kravchenko, I A [AN Ukrainskoj SSR, Odessa (Ukraine). Fiziko-Khimicheskij Inst.

1996-03-01

The gel formations by poly-N-vinylcaprolactam upon its {gamma}-irradiation by the 20-25 kGy dose as a results of partial polymer stitching together is shown, which is confirmed by the CD-and thermogravimetric data. By the alkaline protease and {beta}-galactosidase entrapment in poly-N- vinylcaprolactam stitched together by {gamma}-irradiation, the active preparations are obtained with 90-98 % and 30-35 % activity retained for alkaline protease and {beta}-galactosidase, respectively. The increased stability of alkaline protease at acidic pH values and higher temperature was noted, and for {beta}-galactosidase - the possibility of repeated use of the obtained preparation for lactose hydrolysis.

PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3.

Science.gov (United States)

Remy, Ingrid; Montmarquette, Annie; Michnick, Stephen W

2004-04-01

Transforming growth factor beta (TGF-beta) has a major role in cell proliferation, differentiation and apoptosis in many cell types. Integration of the TGF-beta pathway with other signalling cascades that control the same cellular processes may modulate TGF-beta responses. Here we report the discovery of a new functional link between TGF-beta and growth factor signalling pathways, mediated by a physical interaction between the serine-threonine kinase PKB (protein kinase B)/Akt and the transcriptional activator Smad3. Formation of the complex is induced by insulin, but inhibited by TGF-beta stimulation, placing PKB-Smad3 at a point of convergence between these two pathways. PKB inhibits Smad3 by preventing its phosphorylation, binding to Smad4 and nuclear translocation. In contrast, Smad3 does not inhibit PKB. Inhibition of Smad3 by PKB occurs through a kinase-activity-independent mechanism, resulting in a decrease in Smad3-mediated transcription and protection of cells against TGF-beta-induced apoptosis. Consistently, knockdown of the endogenous PKB gene with small-interfering RNA (siRNA) has the opposite effect. Our results suggest a very simple mechanism for the integration of signals arising from growth-factor- and TGF-beta-mediated pathways.

In-trap decay spectroscopy for {beta}{beta} decays

Energy Technology Data Exchange (ETDEWEB)

Brunner, Thomas

2011-01-18

The presented work describes the implementation of a new technique to measure electron-capture (EC) branching ratios (BRs) of intermediate nuclei in {beta}{beta} decays. This technique has been developed at TRIUMF in Vancouver, Canada. It facilitates one of TRIUMF's Ion Traps for Atomic and Nuclear science (TITAN), the Electron Beam Ion Trap (EBIT) that is used as a spectroscopy Penning trap. Radioactive ions, produced at the radioactive isotope facility ISAC, are injected and stored in the spectroscopy Penning trap while their decays are observed. A key feature of this technique is the use of a strong magnetic field, required for trapping. It radially confines electrons from {beta} decays along the trap axis while X-rays, following an EC, are emitted isotropically. This provides spatial separation of X-ray and {beta} detection with almost no {beta}-induced background at the X-ray detector, allowing weak EC branches to be measured. Furthermore, the combination of several traps allows one to isobarically clean the sample prior to the in-trap decay spectroscopy measurement. This technique has been developed to measure ECBRs of transition nuclei in {beta}{beta} decays. Detailed knowledge of these electron capture branches is crucial for a better understanding of the underlying nuclear physics in {beta}{beta} decays. These branches are typically of the order of 10{sup -5} and therefore difficult to measure. Conventional measurements suffer from isobaric contamination and a dominating {beta} background at theX-ray detector. Additionally, X-rays are attenuated by the material where the radioactive sample is implanted. To overcome these limitations, the technique of in-trap decay spectroscopy has been developed. In this work, the EBIT was connected to the TITAN beam line and has been commissioned. Using the developed beam diagnostics, ions were injected into the Penning trap and systematic studies on injection and storage optimization were performed. Furthermore, Ge

Increased oral AUC of baicalin in streptozotocin-induced diabetic rats due to the increased activity of intestinal beta-glucuronidase.

Science.gov (United States)

Liu, Li; Deng, Yuan-Xiong; Liang, Yan; Pang, Xiao-Yan; Liu, Xiao-Dong; Liu, Yao-Wu; Yang, Jian-Song; Xie, Lin; Wang, Guang-Ji

2010-01-01

The purpose of the study was to investigate the pharmacokinetics of baicalin, a major bioactive component of Scutellariae radix, in diabetic conditions. The 4-week diabetic rats were induced by intraperitoneal administration of streptozotocin. Plasma concentrations of baicalin were measured following oral (200 mg/kg) or intravenous (12 mg/kg) administration. Everted intestinal transport, intestinal mucosal metabolism of baicalin and intestinal beta-glucuronidase activity were also investigated. It was found that the diabetic condition significantly increased the exposure of baicalin following oral doses (AUC 100.77 +/- 4.16 microg x h/mL in diabetic rats vs. 48.48 +/- 7.94 microg x h/mL in normal rats). In contrast, the diabetic condition significantly decreased the exposure of baicalin following intravenous doses (AUC 11.20 +/- 2.28 microg x h/mL in diabetic rats vs. 18.02 +/- 3.45 microg x h/mL in normal rats). We also found lower apparent permeability coefficients of baicalin in the ileum of diabetic rats (8.43 x 10 (-6) +/- 2.40 x 10 (-6) cm/s in diabetic rats vs. 5.21 x 10 (-5) +/- 1.55 x 10 (-5) cm/s in normal rats). Further studies showed that the diabetic condition enhanced the hydrolysis of baicalin to baicalein in intestinal mucosal, accompanied by an increase of beta-glucuronidase activity. All these results suggested that the higher oral exposure of baicalin in diabetic rats did not result from the decreased hepatic metabolism or increased intestinal absorption of baicalin. The enhancement of intestinal beta-glucuronidase activity may partly account for the higher exposure of baicalin in diabetic rats after oral administration. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Performance of a Low Activity Beta-Sensitive SR{sup 90} Water Monitor for Fukushima

Energy Technology Data Exchange (ETDEWEB)

Zickefoose, J.; Bronson, F.; Ilie, G.; Jaderstrom, H.; Venkataraman, R. [Canberra Industries Inc. (United States)

2015-07-01

There are large volumes of contaminated water from the stabilization efforts at the damaged Fukushima Nuclear Power Plants. This water is being processed to remove radioactivity for eventual release to the environment. An on-line continuously operating system to confirm that the clean-up system is working properly, and to provide prompt feedback of the results is required by the system operator. While gamma emitting nuclides allow for the straight forward approach of gamma spectroscopy to identify and quantify radioactivity in water, pure beta emitting nuclides such as Sr{sup 90} pose a challenging problem. The relatively short range of beta radiation in water requires optimization of the measurement geometry in terms of the source-detector distance and source-detector interface while retaining a background sensitivity low enough to meet the Minimum Detectable Concentration (MDC) of 10 Bq/kg in 180 minutes. This issue is complicated by the continuum nature of the beta spectrum which does not allow for simple nuclide identification. The use of the Monte-Carlo code MCNP to estimate system performance before prototyping vastly increases the success of the end product. Various parameters such as detector size and thickness, water chamber size, water chamber construction materials were evaluated to help choose the optimum geometry. The final design was a system consisting of two large-area (16 x 35 cm) and thin (0.15 mm) plastic scintillators placed very close to a sealed a water chamber. The size of the chamber was optimized to obtain the maximum efficiency for the nuclide being measured (Sr/Y{sup 90}) but to minimize the efficiency for possible interferences (Ru/Rh{sup 106}, Cs{sup 137}). A thin carbon fiber window was selected with adequate material and thickness to contain the water under pressure, but also thin enough (0.5 mm) to allow enough beta radiation to pass through to the active detector volume. The entire measurement geometry is then housed in a thick lead

Cortisol metabolism in healthy young adults: sexual dimorphism in activities of A-ring reductases, but not 11beta-hydroxysteroid dehydrogenases.

Science.gov (United States)

Finken, M J; Andrews, R C; Andrew, R; Walker, B R

1999-09-01

Cortisol is metabolized irreversibly by A-ring reductases (5alpha- and 5beta-reductases) and reversibly (to cortisone) by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). In rats, estradiol down-regulates 11betaHSD1 expression. In humans, ratios of urinary cortisol/cortisone metabolites differ in men and women. In this study, urinary cortisol metabolites and hepatic 11betaHSD1 activity were measured in healthy young men and women at different phases of the menstrual cycle. Ten men and 10 women with regular menstrual cycles collected a 24-h urine sample, took 250 microg oral dexamethasone at 2300 h, took 25 mg oral cortisone at 0900 h (after fasting), and had blood sampled for plasma cortisol estimation over the subsequent 150 min. Women repeated the tests in random order in menstrual, follicular, and luteal phases. Women excreted disproportionately less A-ring-reduced metabolites of cortisol [median 5alpha-tetrahydrocortisol, 1811 (interquartile range, 1391-2300) microg/day in menstrual phase vs. 2723 (interquartile range, 2454-3154) in men (P = 0.01); 5beta-tetrahydrocortisol, 1600 (interquartile range, 1419-1968) vs. 2197 (interquartile range, 1748-2995; P = 0.03)] but similar amounts of cortisol, cortisone, and tetrahydrocortisone. Analogous differences were observed in urinary excretion of androgen metabolites. Conversion of cortisone to cortisol on hepatic first pass metabolism was not different (peak plasma cortisol, 733 +/- 60 nmol/L in women vs. 684 +/- 53 nmol/L in men; mean +/- SEM; P = 0.55). There were no differences in cortisol or androgen metabolism between phases of the menstrual cycle. We conclude that sexual dimorphism in cortisol metabolite excretion is attributable to less A-ring reduction of cortisol in women, rather than less reactivation of cortisone to cortisol by 11betaHSD1. This difference is not influenced acutely by gonadal steroids. 11BetaHSD1 has been suggested to modulate insulin sensitivity and body fat distribution, but caution

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

Science.gov (United States)

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/

Design, synthesis and bioactivity evaluation of tribactam beta lactamase inhibitors.

Science.gov (United States)

Copar, Anton; Prevec, Tadeja; Anzic, Borut; Mesar, Tomaz; Selic, Lovro; Vilar, Mateja; Solmajer, Tom

2002-03-25

Known carbapenem compounds with inhibitory effect towards beta-lactamase enzymes are formed from bicyclical beta lactam structural scaffolds. On the basis of results from theoretical computational methods and molecular modelling we have designed and developed a synthetic route towards novel, biologically active tricyclic derivatives of carbapenems.

TGF-{beta} receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation

Energy Technology Data Exchange (ETDEWEB)

Droguett, Rebeca; Cabello-Verrugio, Claudio; Santander, Cristian [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile); Brandan, Enrique, E-mail: ebrandan@bio.puc.cl [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile)

2010-09-10

Skeletal muscle differentiation is strongly inhibited by transforming growth factor type {beta} (TGF-{beta}), although muscle formation as well as regeneration normally occurs in an environment rich in this growth factor. In this study, we evaluated the role of intracellular regulatory Smads proteins as well as TGF-{beta}-receptors (TGF-{beta}-Rs) during skeletal muscle differentiation. We found a decrease of TGF-{beta} signaling during differentiation. This phenomenon is explained by a decline in the levels of the regulatory proteins Smad-2, -3, and -4, a decrease in the phosphorylation of Smad-2 and lost of nuclear translocation of Smad-3 and -4 in response to TGF-{beta}. No change in the levels and inhibitory function of Smad-7 was observed. In contrast, we found that TGF-{beta}-R type I (TGF-{beta}-RI) and type II (TGF-{beta}-RII) increased on the cell surface during skeletal muscle differentiation. To analyze the direct role of the serine/threonine kinase activities of TGF-{beta}-Rs, we used the specific inhibitor SB 431542 and the dominant-negative form of TGF-{beta}-RII lacking the cytoplasmic domain. The TGF-{beta}-Rs were important for successful muscle formation, determined by the induction of myogenin, creatine kinase activity, and myosin. Silencing of Smad-2/3 expression by specific siRNA treatments accelerated myogenin, myosin expression, and myotube formation; although when SB 431542 was present inhibition in myosin induction and myotube formation was observed, suggesting that these last steps of skeletal muscle differentiation require active TGF-{beta}-Rs. These results suggest that both down-regulation of Smad regulatory proteins and cell signaling through the TGF-{beta} receptors independent of Smad proteins are essential for skeletal muscle differentiation.

Roughing up Beta

DEFF Research Database (Denmark)

Bollerslev, Tim; Li, Sophia Zhengzi; Todorov, Viktor

-section. An investment strategy that goes long stocks with high jump betas and short stocks with low jump betas produces significant average excess returns. These higher risk premiums for the discontinuous and overnight market betas remain significant after controlling for a long list of other firm characteristics......Motivated by the implications from a stylized equilibrium pricing framework, we investigate empirically how individual equity prices respond to continuous, or \\smooth," and jumpy, or \\rough," market price moves, and how these different market price risks, or betas, are priced in the cross......-section of expected returns. Based on a novel highfrequency dataset of almost one-thousand individual stocks over two decades, we find that the two rough betas associated with intraday discontinuous and overnight returns entail significant risk premiums, while the intraday continuous beta is not priced in the cross...

GSK-3beta is required for memory reconsolidation in adult brain.

Directory of Open Access Journals (Sweden)

Tetsuya Kimura

Full Text Available Activation of GSK-3beta is presumed to be involved in various neurodegenerative diseases, including Alzheimer's disease (AD, which is characterized by memory disturbances during early stages of the disease. The normal function of GSK-3beta in adult brain is not well understood. Here, we analyzed the ability of heterozygote GSK-3beta knockout (GSK+/- mice to form memories. In the Morris water maze (MWM, learning and memory performance of GSK+/- mice was no different from that of wild-type (WT mice for the first 3 days of training. With continued learning on subsequent days, however, retrograde amnesia was induced in GSK+/- mice, suggesting that GSK+/- mice might be impaired in their ability to form long-term memories. In contextual fear conditioning (CFC, context memory was normally consolidated in GSK+/- mice, but once the original memory was reactivated, they showed reduced freezing, suggesting that GSK+/- mice had impaired memory reconsolidation. Biochemical analysis showed that GSK-3beta was activated after memory reactivation in WT mice. Intraperitoneal injection of a GSK-3 inhibitor before memory reactivation impaired memory reconsolidation in WT mice. These results suggest that memory reconsolidation requires activation of GSK-3beta in the adult brain.

Delta(9)-tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells.

Science.gov (United States)

von Bueren, A O; Schlumpf, M; Lichtensteiger, W

2008-01-01

Delta(9)-tetrahydrocannabinol (THC) exerts palliative effects in cancer patients, but produces adverse effects on the endocrine and reproductive systems. Experimental evidence concerning such effects is controversial. Whether THC exhibits estrogenic or androgenic activity in vitro was investigated. Estrogenic effects of THC were analyzed in vitro by measuring the proliferation of estrogen-sensitive MCF7 cells. Androgenic activity was investigated by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1. In contrast to 17beta-estradiol, included as positive control with an EC50 value (concentration required for 50% of maximal 17beta-estradiol-induced proliferation) of 1.00 x 10(-12) M, THC failed to induce cell proliferation in the MCF7 cell line at concentrations between 10(-13) and 10(-4) M. THC inhibited 17beta-estradiol-induced proliferation in wild-type MCF7 and MCF7-AR1 cells, with an IC50 value of 2.6 x 10(-5) M and 9 x 10(-6) M, respectively. THC failed to act as an estrogen, but antagonized 17beta-estradiol-induced proliferation. This effect was independent of the AR expression level.

Variação no conteúdo de beta-glucanas em cultivares brasileiros de aveia Beta-glucan content variation in brasilian oat cultivars

Directory of Open Access Journals (Sweden)

Roberta M. de SÁ

2000-04-01

Full Text Available Com o crescente interesse em alimentos funcionais e nutracêuticos, a aveia (Avena sativa L. tem se destacado, devido ao seu teor de fibras alimentares e principalmente às beta-glucanas. As (1,3(1,4-beta-D-glucanas, fibras alimentares na maioria solúveis, atuam na redução do colesterol em indivíduos com hipercolesterolemia. Existem estudos para determinar as causas de variação do teor desta fibra em aveia, porém, pouco se sabe sobre a aveia cultivada no Brasil. O objetivo deste trabalho foi verificar se existem diferenças no conteúdo de beta-glucanas entre cultivares brasileiros e se há variação na porcentagem desta fibra devido ao ano de cultivo. Os cultivares IAC7, UFRGS14, UPF16 e UPF17 (3 amostras de cada, e ainda três amostras do cultivar IAC7 para cada ano de cultivo (97 e 98, foram analisados segundo os métodos da AACC (American Association of Cereal Chemists. Os teores médios (peso seco de beta-glucanas foram 6,50% (IAC7, 4,30% (UFRGS14, 3,51% (UPF16 e 3,78% (UPF17, com erro padrão de ±0,084 e coeficiente de variação de 7,89 %. Observou-se efeito significativo dos cultivares (p=0,03 e grande variabilidade entre as amostras (p=0,0001. O cultivar IAC7 apresentou média de beta-glucanas de 5,11% em 97 e 6,50 % em 98 (erro padrão ±0,14; CV=10,53% e observou-se efeito significativo do ano de cultivo.With the increasing interest in functional foods and nutraceuticals, oats (Avena sativa L. have received special attention because of their dietary fiber contents, and specially of their beta-glucans. The mostly soluble dietary fibers (1,3(1,4-beta-D-glucans, reduce serum cholesterol in individuals with hypercholesterolemia. There are studies about the causes of variation in the contents of this fiber in oats, however, very little is known about Brazilian cultivars. The objective of this work was to verify if there were differences in the beta-glucan contents among brazilian cultivars and if there was variation in the

A Method Validation for Determination of Gross Alpha and Gross Beta in Water Sample Using Low Background Gross Alpha/ Beta Counting System

International Nuclear Information System (INIS)

Zal Uyun Wan Mahmood; Norfaizal Mohamed; Nita Salina Abu Bakar

2016-01-01

Method validation (MV) for the measurement of gross alpha and gross beta activity in water (drinking, mineral and environmental) samples using Low Background Gross Alpha/ Beta Counting System was performed to characterize precision, accuracy and reliable results. The main objective of this assignment is to ensure that both the instrument and method always good performed and resulting accuracy and reliable results. Generally, almost the results of estimated RSD, z-score and U_s_c_o_r_e were reliable which are recorded as ≤30 %, less than 2 and less than 1.5, respectively. Minimum Detected Activity (MDA) was estimated based on the counting time of 100 minutes and present background counting value of gross alpha (0.01 - 0.35 cpm) and gross beta (0.50 - 2.18 cpm). Estimated Detection Limit (DL) was 0.1 Bq/ L for gross alpha and 0.2 Bq/ L for gross beta and expended uncertainty was relatively small of 9.77 % for gross alpha and 10.57 % for gross beta. Align with that, background counting for gross alpha and gross beta was ranged of 0.01 - 0.35 cpm and 0.50 - 2.18 cpm, respectively. While, sample volume was set at minimum of 500 mL and maximum of 2000 mL. These proven the accuracy and precision result that are generated from developed method/ technique is satisfactory and method is recommended to be used. Therefore, it can be concluded that the MV found no doubtful on the ability of the developed method. The test result showed the method is suitable for all types of water samples which are contained several radionuclides and elements as well as any impurities that interfere the measurement analysis of gross alpha and gross beta. (author)

Akt interacts directly with Smad3 to regulate the sensitivity to TGF-beta induced apoptosis.

Science.gov (United States)

Conery, Andrew R; Cao, Yanna; Thompson, E Aubrey; Townsend, Courtney M; Ko, Tien C; Luo, Kunxin

2004-04-01

Transforming growth factor beta (TGF-beta) induces both apoptosis and cell-cycle arrest in some cell lines, but only growth arrest in others. It is not clear how this differential response to TGF-beta is specified. Smad proteins are critical mediators of TGF-beta signalling. After stimulation by TGF-beta, Smad2 and Smad3 become phosphorylated by the activated TGF-beta receptor kinases, oligomerize with Smad4, translocate to the nucleus and regulate the expression of TGF-beta target genes. Here we report that the sensitivity to TGF-beta induced apoptosis is regulated by crosstalk between the Akt/PKB serine/threonine kinase and Smad3 through a mechanism that is independent of Akt kinase activity. Akt interacts directly with unphosphorylated Smad3 to sequester it outside the nucleus, preventing its phosphorylation and nuclear translocation. This results in inhibition of Smad3-mediated transcription and apoptosis. Furthermore, the ratio of Smad3 to Akt correlates with the sensitivity of cells to TGF-beta induced apoptosis. Alteration of this ratio changes the apoptotic, but not the growth-inhibitory, responses of cells to TGF-beta. These findings identify an important determinant of sensitivity to TGF-beta-induced apoptosis that involves crosstalk between the TGF-beta and phosphatidylinositol-3-OH kinase (PI(3)K) pathways.

Rev-erb beta regulates the Srebp-1c promoter and mRNA expression in skeletal muscle cells

Energy Technology Data Exchange (ETDEWEB)

Ramakrishnan, Sathiya N.; Lau, Patrick; Crowther, Lisa M. [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia); Cleasby, Mark E. [Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent' s Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 (Australia); Millard, Susan; Leong, Gary M. [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia); Cooney, Gregory J. [Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent' s Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 (Australia); Muscat, George E.O., E-mail: g.muscat@imb.uq.edu.au [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia)

2009-10-30

The nuclear hormone receptor, Rev-erb beta operates as a transcriptional silencer. We previously demonstrated that exogenous expression of Rev-erb{beta}{Delta}E in skeletal muscle cells increased Srebp-1c mRNA expression. We validated these in vitro observations by injection of an expression vector driving Rev-erb{beta}{Delta}E expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. Paradoxically, Rev-erb{beta} siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erb{beta} expression was necessary for Srebp-1c expression. ChIP analysis demonstrated that Rev-erb{beta} was recruited to the Srebp-1c promoter. Moreover, Rev-erb{beta} trans-activated the Srebp-1c promoter, in contrast, Rev-erb{beta} efficiently repressed the Rev-erb{alpha} promoter, a previously characterized target gene. Finally, treatment with the Rev-erb agonist (hemin) (i) increased the trans-activation of the Srebp-1c promoter by Rev-erb{beta}; and (ii) increased Rev-erb{beta} and Srebp-1c mRNA expression. These data suggest that Rev-erb{beta} has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis.

Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha

DEFF Research Database (Denmark)

Bergmeier, W; Bouvard, D; Eble, J A

2001-01-01

Although alpha(2)beta(1) integrin (glycoprotein Ia/IIa) has been established as a platelet collagen receptor, its role in collagen-induced platelet activation has been controversial. Recently, it has been demonstrated that rhodocytin (also termed aggretin), a snake venom toxin purified from the v...

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

Science.gov (United States)

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.

TGF-{beta}1 increases invasiveness of SW1990 cells through Rac1/ROS/NF-{kappa}B/IL-6/MMP-2

Energy Technology Data Exchange (ETDEWEB)

Binker, Marcelo G. [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); CBRHC Research Center, Buenos Aires (Argentina); Binker-Cosen, Andres A. [CBRHC Research Center, Buenos Aires (Argentina); Gaisano, Herbert Y. [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); Cosen, Rodica H. de [CBRHC Research Center, Buenos Aires (Argentina); Cosen-Binker, Laura I., E-mail: laura.cosen.binker@utoronto.ca [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); CBRHC Research Center, Buenos Aires (Argentina)

2011-02-04

Research highlights: {yields} Rac1 mediates TGF-{beta}1-induced SW1990 invasion through MMP-2 secretion and activation. {yields} NADPH-generated ROS act downstream of Rac1 in TGF-{beta}1-challenged SW1990 cells. {yields} TGF-{beta}1-stimulated ROS activate NF-{kappa}B in SW1990 cells. {yields} NF{kappa}B-induced IL-6 release is required for secretion and activation of MMP-2 in SW1990 cells. -- Abstract: Human pancreatic cancer invasion and metastasis have been found to correlate with increased levels of active matrix metalloproteinase 2 (MMP-2). The multifunctional cytokine transforming growth factor beta 1 (TGF-{beta}1) has been shown to increase both secretion of MMP-2 and invasion by several pancreatic cancer cell types. In the present study, we investigated the signaling pathway involved in TGF-{beta}1-promoted MMP-2 secretion and invasion by human pancreatic cancer cells SW1990. Using specific inhibitors, we found that stimulation of these tumor cells with TGF-{beta}1 induced secretion and activation of the collagenase MMP-2, which was required for TGF-{beta}1-stimulated invasion. Our results also indicate that signaling events involved in TGF-{beta}1-enhanced SW1990 invasiveness comprehend activation of Rac1 followed by generation of reactive oxygen species through nicotinamide adenine dinucleotide phosphate-oxidase, activation of nuclear factor-kappa beta, release of interleukin-6, and secretion and activation of MMP-2.

Beta-endorphin and the immune system--possible role in autoimmune diseases

DEFF Research Database (Denmark)

Mørch, H; Pedersen, B K

1995-01-01

The immune system and the neuroendocrine system are closely interconnected having such means of bidirectional communication and regulation. In this review, a hypothesis is put forward regarding the possible role of beta-endorphins in the pathogenesis of autoimmune diseases: It is suggested...... that the increased cytokine production in immunoinflammatory disorders induces production of beta-endorphins from the pituitary and the lymphocytes; the enhanced level of beta-endorphin causes inhibition of human T helper cell function, which potentially down-regulate the antibody production. Also the beta......-endorphin-induced enhancement of the natural killer cell activity may suppress the B cell function. In addition, beta-endorphin also exerts a direct inhibitory effect on the antibody production. Thus, in autoimmune disorders the enhanced cytokine level may via stimulation of the production of beta-endorphins exert a negative...

Need for beta-blockade in hypertension reduced with long-term minoxidil.

Science.gov (United States)

Brunner, H R; Jaeger, P; Ferguson, R K; Jequier, E; Turini, G; Gavras, H

1978-01-01

Sequential changes in plasma renin activity and urinary aldosterone and noradrenaline were assessed in eight patients with severe hypertension after minoxidil had been added to their treatment. Doses of 2.5--27.5 (mean 12.5) mg/day reduced the mean blood pressure from 166/113 +/-6/2 mm Hg to 124/88+/-4/2 mm Hg in one week. Plasma renin activity and urinary aldosterone and noradrenaline increased twofold to threefold initially but returned to baseline values within two to three weeks and remained unchanged during a mean follow-up of 5.1 months. Beta-blocking drugs were then withdrawn slowly in six patients without adverse effects, though blood pressure and heart rate increased in three patients, who required minimal doses of beta-blockers. Plasma renin activity and urinary aldosterone and noradrenaline did not change significantly after beta-blockade had been stopped. We conclude that the need for beta-blockade is greatly reduced with long-term minoxidil treatment and that it may be unnecessary in some patients. PMID:28811

beta-catenin tyrosine 654 phosphorylation increases Wnt signalling and intestinal tumorigenesis

NARCIS (Netherlands)

van Veelen, Wendy; Le, Ngoc H.; Helvensteijn, Werner; Blonden, Lau; Theeuwes, Myrte; Bakker, Elvira R. M.; Franken, Patrick F.; van Gurp, Leon; Meijlink, Frits; van der Valk, Martin A.; Kuipers, Ernst J.; Fodde, Riccardo; Smits, Ron

Objective Deregulation of the Wnt signalling pathway by mutations in the Apc or beta-catenin genes underlies colorectal carcinogenesis. As a result, beta-catenin stabilises, translocates to the nucleus, and activates gene transcription. Intestinal tumours show a heterogeneous pattern of nuclear

beta-catenin tyrosine 654 phosphorylation increases Wnt signalling and intestinal tumorigenesis

NARCIS (Netherlands)

van Veelen, W.; Le, N.H.; Helvensteijn, W.; Blonden, L.; Theeuwes, M.; Bakker, E.R.; Franken, P.F.; van Gurp, L.; Meijlink, F.; van der Valk, M.A.; Kuipers, E.J.; Fodde, R.; Smits, R.E.H.M.

2011-01-01

Objective Deregulation of the Wnt signalling pathway by mutations in the Apc or beta-catenin genes underlies colorectal carcinogenesis. As a result, beta-catenin stabilises, translocates to the nucleus, and activates gene transcription. Intestinal tumours show a heterogeneous pattern of nuclear

Properties of native and immobilised preparations of. beta. -D-glucosidase from Aspergillus niger

Energy Technology Data Exchange (ETDEWEB)

Woodward, J.; Wohlpart, D.L.

1982-01-01

The enzyme ..beta..-D-glucosidase from Aspergillus niger has been immobilised through its carbohydrate moiety on concanavalin A-Sepharose and on cyanogen bromide-activated Sepharose after aminoalkylation of the carbohydrate side chains of the enzyme. For comparison, the enzyme was also immobilised on microcrystalline cellulose through its protein moiety. High retention of activity and a decrease in K/sub m/ and V/sub max/ were observed when ..beta..-D-glucosidase was immobilised by these methods. An increase in the thermal stability of the immobilised ..beta..-D-glucosidase preparations over the soluble enzyme was achieved if it was treated with glutaraldehyde before its adsorption on concanavalin A-Sepharose or if the enzyme immobilised on cyanogen bromide-activated Sepharose was subsequently treated with glutaralydehyde. Treatment of ..beta..-D-glucosidase immobilised on microcrystalline cellulose with glutaraldehyde hardy increased its thermal stability over the soluble enzyme.

Properties of native and immobilised preparations of beta-d-glucosidase from Aspergillus niger

Energy Technology Data Exchange (ETDEWEB)

Woodward, J.; Wohlpart, D.L.

1982-04-01

The enzyme beta-glucosidase from Aspergillus niger has been immobilised through its carbohydrate moiety on concanavalin A-Sepharose and on cyanogen bromide-activated Sepharose after aminoalkylation of the carbohydrate side chains of the enzyme. For comparison, the enzyme was also immobilised on microcrystalline cellulose through its protein moiety. High retention of activity and a decrease in Km and Vmax were observed when beta-D-glucosidase was immobilised by these methods. An increase in the thermal stability of the immobilized beta-D-glucosidase preparations over the soluble enzyme was achieved if it was treated with glutaraldehyde before its adsorption on concanavalin A-Sepharose or if the enzyme immobilised on cyanogen bromide-activated Sepharose was subsequently treated with glutaraldehyde. Treatment of beta-D-glucosidase immobilised on microcrystalline cellulose with glutaraldehyde hardly increased its thermal stability over the soluble enzyme. (Refs. 24).

Top-down beta rhythms support selective attention via interlaminar interaction: a model.

Directory of Open Access Journals (Sweden)

Jung H Lee

Full Text Available Cortical rhythms have been thought to play crucial roles in our cognitive abilities. Rhythmic activity in the beta frequency band, around 20 Hz, has been reported in recent studies that focused on neural correlates of attention, indicating that top-down beta rhythms, generated in higher cognitive areas and delivered to earlier sensory areas, can support attentional gain modulation. To elucidate functional roles of beta rhythms and underlying mechanisms, we built a computational model of sensory cortical areas. Our simulation results show that top-down beta rhythms can activate ascending synaptic projections from L5 to L4 and L2/3, responsible for biased competition in superficial layers. In the simulation, slow-inhibitory interneurons are shown to resonate to the 20 Hz input and modulate the activity in superficial layers in an attention-related manner. The predicted critical roles of these cells in attentional gain provide a potential mechanism by which cholinergic drive can support selective attention.

Design and device construction for plane tables preparation for counter alpha/beta total; Diseno y construccion de dispositivo para preparacion de planchetas para contador alfa/beta total

Energy Technology Data Exchange (ETDEWEB)

Galicia C, F. J.; Monroy G, F., E-mail: fgalicia82@yahoo.com [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

2014-10-15

This work presents the design and assembly of a device for plane tables preparation for quantification alpha/beta total of radioactive waste samples. The determination of the activity index alpha/beta total is used to detect a wide variety of matrices quickly and the concentration of alpha and/or beta emitters of the contained radionuclides in different samples. In particular, the determination of the activity index alpha and beta total of radioactive wastes involves the digestion of samples in aggressive means that will be evaporated to dryness for its quantification. With the purpose of controlling the emission of corrosive gases during the preparation of the plane tables for the quantification of the index alpha and beta total, was designed and built the device in the Radioactive Waste Laboratory that allows to prepare plane tables for proportional counters in a sure and efficient way. The device is constituted by heating equipment, evaporation cylinder and a gases cleaning system. The self-absorption curve got ready starting from the device. (Author)

Correlation of beta-catenin localization with cyclooxygenase-2 expression and CpG island methylator phenotype (CIMP) in colorectal cancer.

Science.gov (United States)

Kawasaki, Takako; Nosho, Katsuhiko; Ohnishi, Mutsuko; Suemoto, Yuko; Kirkner, Gregory J; Dehari, Reiko; Meyerhardt, Jeffrey A; Fuchs, Charles S; Ogino, Shuji

2007-07-01

The WNT/beta-catenin (CTNNB1) pathway is commonly activated in the carcinogenic process. Cross-talks between the WNT and cyclooxygenase-2 (COX-2 or PTGS2)/prostaglandin pathways have been suggested. The relationship between beta-catenin activation and microsatellite instability (MSI) in colorectal cancer has been controversial. The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer, which is associated with MSI-high. However, no study has examined the relationship between beta-catenin activation and CIMP status. Using 832 population-based colorectal cancer specimens, we assessed beta-catenin localization by immunohistochemistry. We quantified DNA methylation in eight CIMP-specific promoters [CACNA1G, CDKN2A(p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1] by real-time polymerase chain reaction (MethyLight). MSI-high, CIMP-high, and BRAF mutation were associated inversely with cytoplasmic and nuclear beta-catenin expressions (i.e., beta-catenin activation) and associated positively with membrane expression. The inverse relation between beta-catenin activation and CIMP was independent of MSI. COX-2 overexpression correlated with cytoplasmic beta-catenin expression (even after tumors were stratified by CIMP status), but did not correlate significantly with nuclear or membrane expression. In conclusion, beta-catenin activation is inversely associated with CIMP-high independent of MSI status. Cytoplasmic beta-catenin is associated with COX-2 overexpression, supporting the role of cytoplasmic beta-catenin in stabilizing PTGS2 (COX-2) mRNA.

Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway

Directory of Open Access Journals (Sweden)

Valentina Rapisarda

2017-03-01

Full Text Available Cellular senescence is an important in vivo mechanism that prevents the propagation of damaged cells. However, the precise mechanisms regulating senescence are not well characterized. Here, we find that ITGB3 (integrin beta 3 or β3 is regulated by the Polycomb protein CBX7. β3 expression accelerates the onset of senescence in human primary fibroblasts by activating the transforming growth factor β (TGF-β pathway in a cell-autonomous and non-cell-autonomous manner. β3 levels are dynamically increased during oncogene-induced senescence (OIS through CBX7 Polycomb regulation, and downregulation of β3 levels overrides OIS and therapy-induced senescence (TIS, independently of its ligand-binding activity. Moreover, cilengitide, an αvβ3 antagonist, has the ability to block the senescence-associated secretory phenotype (SASP without affecting proliferation. Finally, we show an increase in β3 levels in a subset of tissues during aging. Altogether, our data show that integrin β3 subunit is a marker and regulator of senescence.

On Fuzzy {beta}-I-open sets and Fuzzy {beta}-I-continuous functions

Energy Technology Data Exchange (ETDEWEB)

Keskin, Aynur [Department of Mathematics, Faculty of Science and Arts, Selcuk University, Campus, 42075 Konya (Turkey)], E-mail: akeskin@selcuk.edu.tr

2009-11-15

In this paper, first of all we obtain some properties and characterizations of fuzzy {beta}-I-open sets. After that, we also define the notion of {beta}-I-closed sets and obtain some properties. Lastly, we introduce the notions of fuzzy {beta}-I-continuity with the help of fuzzy {beta}-I-open sets to obtain decomposition of fuzzy continuity.

Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

DEFF Research Database (Denmark)

Martens, Geert A; Jiang, Lei; Hellemans, Karine H

2011-01-01

The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture...... microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators....

N-Benzylhydroxylamine addition to beta-aryl enoates. Enantioselective synthesis of beta-aryl-beta-amino acid precursors

Science.gov (United States)

Sibi; Liu

2000-10-19

Chiral Lewis acid catalyzed N-benzylhydroxylamine addition to pyrrolidinone-derived enoates afforded beta-aryl-beta-amino acid derivatives in high enantiomeric purity with moderate to very good chemical efficiency.

The Structural Basis of Substrate Recognition in an exo-beta-d-Glucosaminidase Involved in Chitosan Hydrolysis

Energy Technology Data Exchange (ETDEWEB)

Lammerts van Bueren, A.; Ghinet, M; Gregg, K; Fleury, A; Brzezinski, R; Boraston, A

2009-01-01

Family 2 of the glycoside hydrolase classification is one of the largest families. Structurally characterized members of this family include enzymes with beta-galactosidase activity (Escherichia coli LacZ), beta-glucuronidase activity (Homo sapiens GusB), and beta-mannosidase activity (Bacteroides thetaiotaomicron BtMan2A). Here, we describe the structure of a family 2 glycoside hydrolase, CsxA, from Amycolatopsis orientalis that has exo-beta-D-glucosaminidase (exo-chitosanase) activity. Analysis of a product complex (1.85 A resolution) reveals a unique negatively charged pocket that specifically accommodates the nitrogen of nonreducing end glucosamine residues, allowing this enzyme to discriminate between glucose and glucosamine. This also provides structural evidence for the role of E541 as the catalytic nucleophile and D469 as the catalytic acid/base. The structures of an E541A mutant in complex with a natural beta-1,4-D-glucosamine tetrasaccharide substrate and both E541A and D469A mutants in complex with a pNP-beta-D-glucosaminide synthetic substrate provide insight into interactions in the +1 subsite of this enzyme. Overall, a comparison with the active sites of other GH2 enzymes highlights the unique architecture of the CsxA active site, which imparts specificity for its cationic substrate.

Growth arrest- and DNA-damage-inducible 45beta gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1beta-induced apoptosis in insulin-producing INS-1E cells

DEFF Research Database (Denmark)

Larsen, Claus Morten; Døssing, M G; Papa, S

2006-01-01

IL-1beta is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1beta activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen...

Mechanism of the hydrolysis of 4-methylumbelliferyl-beta-D-glucoside by germinating and outgrowing spores of Bacillus species.

Science.gov (United States)

Setlow, B; Cabrera-Martinez, R-M; Setlow, P

2004-01-01

To determine the mechanism of the hydrolysis of 4-methylumbelliferyl-beta-D-glucopyranoside (beta-MUG) by germinating and outgrowing spores of Bacillus species. Spores of B. atrophaeus (formerly B. subtilis var. niger, Fritze and Pukall 2001) are used as biological indicators of the efficacy of ethylene oxide sterilization by measurement of beta-MUG hydrolysis during spore germination and outgrowth. It was previously shown that beta-MUG is hydrolysed to 4-methylumbelliferone (MU) during the germination and outgrowth of B. atrophaeus spores (Chandrapati and Woodson 2003), and this was also the case with spores of B. subtilis 168. Germination of spores of either B. atrophaeus or B. subtilis with chloramphenicol reduced beta-MUG hydrolysis by almost 99%, indicating that proteins needed for rapid beta-MUG hydrolysis are synthesized during spore outgrowth. However, the residual beta-MUG hydrolysis during spore germination with chloramphenicol indicated that dormant spores contain low levels of proteins needed for beta-MUG uptake and hydrolysis. With B. subtilis 168 spores that lacked several general proteins of the phosphotransferase system (PTS) for sugar uptake, beta-MUG hydrolysis during spore germination and outgrowth was decreased >99.9%. This indicated that beta-MUG is taken up by the PTS, resulting in the intracellular accumulation of the phosphorylated form of beta-MUG, beta-MUG-6-phosphate (beta-MUG-P). This was further demonstrated by the lack of detectable glucosidase activity on beta-MUG in dormant, germinated and outgrowing spore extracts, while phosphoglucosidase active on beta-MUG-P was readily detected. Dormant B. subtilis 168 spores had low levels of at least four phosphoglucosidases active on beta-MUG-P: BglA, BglH, BglC (originally called YckE) and BglD (originally called YdhP). These enzymes were also detected in spores germinating and outgrowing with beta-MUG, but levels of BglH were the highest, as this enzyme's synthesis was induced ca 100-fold

Automatic device for measuring {beta}-emitting sources: P.A.P.A. {beta}-meters; Dispositif automatique pour la mesure de sources emettrices de rayonnement {beta}: P.A.P.A. {beta} metres

Energy Technology Data Exchange (ETDEWEB)

Colomer, J; Valentin, M [Commissariat a l' Energie Atomique, Bruyeres-le-Chatel (France). Centre d' Etudes

1969-07-01

The apparatus described is designed for measuring {beta}-emitting elements by the absorption method; it is suitable for carrying out a large number of routine analyses. A mechanical device pushes an aluminium absorption set automatically between the source and the detector; the movement is programmed for cutting on and off by a transistorized electronic unit, with printing out and punching of the results on tape; then this can be mathematically processed by a computer (tracing of absorption spectra, extrapolation and calculation of the activity). The detector is either a {beta}-probe or a proportional counter with a specially designed loop. For routine measurements, the accuracy obtained, with all corrections made, is from 5 to 8 per cent; the reproducibility is about 2 per cent. (authors) [French] L'appareillage decrit est destine aux mesures des elements emetteurs {beta} par la methode d'absorption et il permet d'effectuer, en routine, un nombre important de mesures. Un ensemble mecanique effectue le passage automatique, sous vide primaire, d'un jeu d'absorption en aluminium entre la source et le detecteur, ce passage est programme en pre-temps ou pre-coup par un ensemble electronique a transistors, avec impression et perforation sur bandes des resultats des mesures pour traitement mathematique par un ordinateur (trace du spectre d'absorption, extrapolation et calcul d'activite). Le detecteur est soit une sonde {beta}, soit un compteur proportionnel a boucle specialement realise. Sur des mesures de routine, la precision obtenue, toutes corrections effectuees, est de 5 a 8 pour cent et la reproductibilite de l'ordre de 2 pour cent. (auteur)

Beta Emission and Bremsstrahlung

Energy Technology Data Exchange (ETDEWEB)

Karpius, Peter Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

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.

sup 86 Rb(K) influx and ( sup 3 H)ouabain binding by human platelets: Evidence for beta-adrenergic stimulation of Na-K ATPase activity

Energy Technology Data Exchange (ETDEWEB)

Turaihi, K.; Khokher, M.A.; Barradas, M.A.; Mikhailidis, D.P.; Dandona, P. (Royal Free Hospital and School of Medicine, London (England))

1989-08-01

Although active transport of potassium into human platelets has been demonstrated previously, there is hitherto no evidence that human platelets have an ouabain-inhibitable Na-K ATPase in their membrane. The present study demonstrates active rubidium (used as an index of potassium influx), {sup 86}Rb(K), influx into platelets, inhibitable by ouabain, and also demonstrates the presence of specific ({sup 3}H)ouabain binding by the human platelet. This {sup 86}Rb(K) influx was stimulated by adrenaline, isoprenaline, and salbutamol, but noradrenaline caused a mild inhibition. Active {sup 86}Rb(K) influx by platelets was inhibited markedly by timolol, mildly by atenolol, but not by phentolamine. Therefore, active {sup 86}Rb(K) influx in human platelets is enhanced by stimulation of beta adrenoceptors of the beta 2 subtype. The platelet may therefore replace the leukocyte in future studies of Na-K ATPase activity. This would be a considerable advantage in view of the ease and rapidity of preparation of platelets.

Strategic Design of an Effective beta-Lactamase Inhibitor

Energy Technology Data Exchange (ETDEWEB)

Pattanaik, P.; Bethel, C; Hujer, A; Hujer, K; Distler, A; Taracila, M; Anderson, V; Fritsche, T; Jones, R; et. al.

2009-01-01

In an effort to devise strategies for overcoming bacterial beta-lactamases, we studied LN-1-255, a 6-alkylidene-2'-substituted penicillin sulfone inhibitor. By possessing a catecholic functionality that resembles a natural bacterial siderophore, LN-1-255 is unique among beta-lactamase inhibitors. LN-1-255 combined with piperacillin was more potent against Escherichia coli DH10B strains bearing bla(SHV) extended-spectrum and inhibitor-resistant beta-lactamases than an equivalent amount of tazobactam and piperacillin. In addition, LN-1-255 significantly enhanced the activity of ceftazidime and cefpirome against extended-spectrum cephalosporin and Sme-1 containing carbapenem-resistant clinical strains. LN-1-255 inhibited SHV-1 and SHV-2 beta-lactamases with nm affinity (K(I) = 110 +/- 10 and 100 +/- 10 nm, respectively). When LN-1-255 inactivated SHV beta-lactamases, a single intermediate was detected by mass spectrometry. The crystal structure of LN-1-255 in complex with SHV-1 was determined at 1.55A resolution. Interestingly, this novel inhibitor forms a bicyclic aromatic intermediate with its carbonyl oxygen pointing out of the oxyanion hole and forming hydrogen bonds with Lys-234 and Ser-130 in the active site. Electron density for the 'tail' of LN-1-255 is less ordered and modeled in two conformations. Both conformations have the LN-1-255 carboxyl group interacting with Arg-244, yet the remaining tails of the two conformations diverge. The observed presence of the bicyclic aromatic intermediate with its carbonyl oxygen positioned outside of the oxyanion hole provides a rationale for the stability of this inhibitory intermediate. The 2'-substituted penicillin sulfone, LN-1-255, is proving to be an important lead compound for novel beta-lactamase inhibitor design.

Primate beta oscillations and rhythmic behaviors.

Science.gov (United States)

Merchant, Hugo; Bartolo, Ramón

2018-03-01

The study of non-human primates in complex behaviors such as rhythm perception and entrainment is critical to understand the neurophysiological basis of human cognition. Next to reviewing the role of beta oscillations in human beat perception, here we discuss the role of primate putaminal oscillatory activity in the control of rhythmic movements that are guided by a sensory metronome or internally gated. The analysis of the local field potentials of the behaving macaques showed that gamma-oscillations reflect local computations associated with stimulus processing of the metronome, whereas beta-activity involves the entrainment of large putaminal circuits, probably in conjunction with other elements of cortico-basal ganglia-thalamo-cortical circuit, during internally driven rhythmic tapping. Thus, this review emphasizes the need of parametric neurophysiological observations in non-human primates that display a well-controlled behavior during high-level cognitive processes.

TGF beta-1 dependent fast stimulation of ATM and p53 phosphorylation following exposure to ionizing radiation does not involve TGF beta-receptor I signalling

NARCIS (Netherlands)

Wiegman, Erwin M.; Blaese, Marcet A.; Loeffler, Heidi; Coppes, Rob P.; Rodemann, H. Peter

Background and purpose: It has been proposed that radiation induced stimulation of ATM and downstream components involves activation of TGF beta-1 and that this may be due to TGF beta-1-receptor I-Smad signalling. Therefore, the aim of this study was to clarify the distinct role of TGF

Preadipocyte 11beta-hydroxysteroid dehydrogenase type 1 is a keto-reductase and contributes to diet-induced visceral obesity in vivo.

Science.gov (United States)

De Sousa Peixoto, R A; Turban, S; Battle, J H; Chapman, K E; Seckl, J R; Morton, N M

2008-04-01

Glucocorticoid excess promotes visceral obesity and cardiovascular disease. Similar features are found in the highly prevalent metabolic syndrome in the absence of high levels of systemic cortisol. Although elevated activity of the glucocorticoid-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) within adipocytes might explain this paradox, the potential role of 11beta-HSD1 in preadipocytes is less clear; human omental adipose stromal vascular (ASV) cells exhibit 11beta-dehydrogenase activity (inactivation of glucocorticoids) probably due to the absence of cofactor provision by hexose-6-phosphate dehydrogenase. To clarify the depot-specific impact of 11beta-HSD1, we assessed whether preadipocytes in ASV from mesenteric (as a representative of visceral adipose tissue) and sc tissue displayed 11beta-HSD1 activity in mice. 11beta-HSD1 was highly expressed in freshly isolated ASV cells, predominantly in preadipocytes. 11beta-HSD1 mRNA and protein levels were comparable between ASV and adipocyte fractions in both depots. 11beta-HSD1 was an 11beta-reductase, thus reactivating glucocorticoids in ASV cells, consistent with hexose-6-phosphate dehydrogenase mRNA expression. Unexpectedly, glucocorticoid reactivation was higher in intact mesenteric ASV cells despite a lower expression of 11beta-HSD1 mRNA and protein (homogenate activity) levels than sc ASV cells. This suggests a novel depot-specific control over 11beta-HSD1 enzyme activity. In vivo, high-fat diet-induced obesity was accompanied by increased visceral fat preadipocyte differentiation in wild-type but not 11beta-HSD1(-/-) mice. The results suggest that 11beta-HSD1 reductase activity is augmented in mouse mesenteric preadipocytes where it promotes preadipocyte differentiation and contributes to visceral fat accumulation in obesity.

Dysfunctional C8 beta chain in patients with C8 deficiency.

Science.gov (United States)

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.

Cortisone Dissociates the Shaker Family K Channels from their Beta Subunit

Energy Technology Data Exchange (ETDEWEB)

Pan, Y.; Weng, J; Kabaleeswaran, V; Li, H; Cao, Y; Bholse, R; Zhou, M

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 structure 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.

Nuclear Matrix Elements for the $\\beta\\beta$ Decay of the $^{76}$Ge

CERN Document Server

Brown, B A; Horoi, M

2015-01-01

The nuclear matrix elements for two-neutrino double-beta (2 n$\\beta\\beta$ ) and zero-neutrino double-beta (0 n$\\beta\\beta$) decay of 76 Ge are evaluated in terms of the configuration interaction (CI), quasiparticle random phase approximation (QRPA) and interacting boson model (IBM) methods. We show that the decomposition of the matrix elements in terms of interemediate states in 74 Ge is dominated by ground state of this nucleus. We consider corrections to the CI results that arise from configurations admixtures involving orbitals out-side of the CI configuration space by using results from QRPA, many-body-perturbation theory, and the connections to related observables. The CI two-neutrino matrix element is reduced due to the inclusion of spin-orbit partners, and to many-body correlations connected with Gamow-Teller beta decay. The CI zero-neutrino matrix element for the heavy neutrino is enhanced due to particle-particle correlations that are connected with the odd-even oscillations in the nuclear masse...

Beta-Excited Sources of Electromagnetic Radiation; Sources de rayonnements electromagnetiques excites par des particules beta; Vozbuzhdennye beta-chastitsami istochniki ehlektromagnitnogo izlucheniya; Fuentes de radiacion electromagnetica excitadas por particulas beta

Energy Technology Data Exchange (ETDEWEB)

Cameron, J F; Rhodes, J R [Physics Group, Isotope Research Division, (AERE), Wantage Research Laboratory, Wantage, Berks (United Kingdom)

1962-01-15

Beta-excited sources of electromagnetic radiation covering the energy region 1-200 keV and suitable for industrial use are described. H{sup 3}, Pm{sup 147}, Kr{sup 85}, Tl{sup 204} and (Sr+Y){sup 90} were chosen as sources of beta particles by the criteria of long half-life, low price, ready availability and high specific activity. The {beta}-excited sources have been designed on the basis of a compromise between practical source construction and the best theoretical efficiency in a given energy region. In their paper, the authors calculate the number of photons produced per beta particle and consider how the results must be corrected for self-absorption of the X-rays. In the calculations account is taken of both bremsstrahlung and characteristic {alpha}-radiation; optimum characteristic X-ray yield is achieved for targets with an atomic number between 40 and 60. ''Sandwich'' targets of 1-2 beta half-value thicknesses are found to give maximum photon-yields in the desired energy region. Al, Ag and Au are suitable from the manufacturing point of view as source coverings. They were also found to give satisfactory bremsstrahlung and X-ray yields and distribution for various energy regions in the range 1-200 keV when correctly combined with the above-mentioned D-emitters. Some energy spectra are given and absorption curves in Al and Fe are shown for the best source-target combinations. The difference between sources constructed of {beta}-emitters sandwiched between target foils and intimate source-target mixtures was found to be small. Tables are given as a guide to the best source to be used for a particular absorber thickness range. (author) [French] Les auteurs decrivent des sources de rayonnements electromagnetiques excites par des particules beta, couvrant une gamme d'energies allant de 1 a 200 keV et convenant aux usages industriels. Comme sources de particules beta on a choisi le tritium, le {sup 147}Pm, le {sup 85}Kr, le {sup 204}Tl et le {sup 90}(Sr+Y), en

Amyloid beta inhibits olfactory bulb activity and the ability to smell.

Directory of Open Access Journals (Sweden)

Reynaldo Alvarado-Martínez

Full Text Available Early olfactory dysfunction has been consistently reported in both Alzheimer's disease (AD and in transgenic mice that reproduce some features of this disease. In AD transgenic mice, alteration in olfaction has been associated with increased levels of soluble amyloid beta protein (Aβ as well as with alterations in the oscillatory network activity recorded in the olfactory bulb (OB and in the piriform cortex. However, since AD is a multifactorial disease and transgenic mice suffer a variety of adaptive changes, it is still unknown if soluble Aβ, by itself, is responsible for OB dysfunction both at electrophysiological and behavioral levels. Thus, here we tested whether or not Aβ directly affects OB network activity in vitro in slices obtained from mice and rats and if it affects olfactory ability in these rodents. Our results show that Aβ decreases, in a concentration- and time-dependent manner, the network activity of OB slices at clinically relevant concentrations (low nM and in a reversible manner. Moreover, we found that intrabulbar injection of Aβ decreases the olfactory ability of rodents two weeks after application, an effect that is not related to alterations in motor performance or motivation to seek food and that correlates with the presence of Aβ deposits. Our results indicate that Aβ disrupts, at clinically relevant concentrations, the network activity of the OB in vitro and can trigger a disruption in olfaction. These findings open the possibility of exploring the cellular mechanisms involved in early pathological AD as an approach to reduce or halt its progress.

Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter.

Science.gov (United States)

Jääskeläinen, Kirsi M; Kaukinen, Pasi; Minskaya, Ekaterina S; Plyusnina, Angelina; Vapalahti, Olli; Elliott, Richard M; Weber, Friedemann; Vaheri, Antti; Plyusnin, Alexander

2007-10-01

The S RNA genome segment of hantaviruses carried by Arvicolinae and Sigmodontinae rodents encodes the nucleocapsid (N) protein and has an overlapping (+1) open reading frame (ORF) for a putative nonstructural protein (NSs). The aim of this study was to determine whether the ORF is functional. A protein corresponding to the predicted size of Tula virus (TULV) NSs was detected using coupled in vitro transcription and translation from a cloned S segment cDNA, and a protein corresponding to the predicted size of Puumala virus (PUUV) NSs was detected in infected cells by Western blotting with an anti-peptide serum. The activities of the interferon beta (IFN-beta) promoter, and nuclear factor kappa B (NF-kappaB)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-beta mRNA levels in IFN-competent MRC5 cells either infected with TULV or transiently expressing NSs were decreased. These data demonstrate that Tula and Puumala hantaviruses have a functional NSs ORF. The findings may explain why the NSs ORF has been preserved in the genome of most hantaviruses during their long evolution and why hantavirus-infected cells secrete relatively low levels of IFNs. (c) 2007 Wiley-Liss, Inc.

Measurement of gross alpha and beta in air filter samples by using liquid scintillation counter

International Nuclear Information System (INIS)

Sudheendran, V.; Baburajan, A.; Gaikwad, R.H.; Ravi, P.M.; Tripathi, R.M.

2015-01-01

The determination of gross alpha and gross beta in particulate air filter samples was carried out by alpha, beta discrimination method using Liquid Scintillation Analyzer by setting the PSA value at 55 for 5 ml 0.1 HCl plus 15 ml of Ultima Gold AB cocktail by using 241 Am and 90 Sr/ 90 Y sources. The standardized method was compared with the gross alpha and gross beta activity determined by conventional method of direct counting with end window G.M. counter and ZnS (Ag). The minimum detectable activity of LSA method was found to be 9.3 mBq and 17.7 mBq for gross alpha and gross beta respectively for 6000 sec compared to the conventional method of 9.8 mBq and 189 mBq respectively at the same counting time. The result of analysis by both method indicate that the alpha, beta discrimination set up of LSA method is highly effective in the determination of low level alpha, beta activity in air filter samples. (author)

Regulation of pancreatic beta-cell mass and proliferation by SOCS-3

DEFF Research Database (Denmark)

Lindberg, K; Rønn, S G; Tornehave, D

2005-01-01

Growth hormone and prolactin are important growth factors for pancreatic beta-cells. The effects exerted by these hormones on proliferation and on insulin synthesis and secretion in beta-cells are largely mediated through the Janus kinase (JAK)/signal transducer and activator of transcription (ST...

Interactions Between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma on Neuroinflammation, Demyelination, and Remyelination in Multiple Sclerosis.

Science.gov (United States)

Vallée, Alexandre; Vallée, Jean-Noël; Guillevin, Rémy; Lecarpentier, Yves

2018-05-01

Multiple sclerosis (MS) is marked by neuroinflammation and demyelination with loss of oligodendrocytes in the central nervous system. The immune response is regulated by WNT/beta-catenin pathway in MS. Activated NF-kappaB, a major effector of neuroinflammation, and upregulated canonical WNT/beta-catenin pathway positively regulate each other. Demyelinating events present an upregulation of WNT/beta-catenin pathway, whereas proper myelinating phases show a downregulation of WNT/beta-catenin pathway essential for the promotion of oligodendrocytes precursors cells proliferation and differentiation. The activation of WNT/beta-catenin pathway results in differentiation failure and impairment in remyelination. However, PI3K/Akt pathway and TCF7L2, two downstream targets of WNT/beta-catenin pathway, are upregulated and promote proper remyelination. The interactions of these signaling pathways remain unclear. PPAR gamma activation can inhibit NF-kappaB, and can also downregulate the WNT/beta-catenin pathway. PPAR gamma and canonical WNT/beta-catenin pathway act in an opposite manner. PPAR gamma agonists appear as a promising treatment for the inhibition of demyelination and the promotion of proper remyelination through the control of both NF-kappaB activity and canonical WNT/beta-catenin pathway.

Dysregulation of Dicer1 in Beta Cells Impairs Islet Architecture and Glucose Metabolism

Directory of Open Access Journals (Sweden)

Amitai D. Mandelbaum

2012-01-01

Full Text Available microRNAs (miRNAs play important roles in pancreas development and in regulation of insulin expression in the adult. Here we show that loss of miRNAs activity in beta-cells during embryonic development results in lower beta-cell mass and in impaired glucose tolerance. Dicer1-null cells initially constitute a significant portion of the total beta-cell population. However, during postnatal development, Dicer1-null cells are depleted. Furthermore, wild-type beta cells are repopulating the islets in complex compensatory dynamics. Because loss of Dicer1 is also associated with changes in the distribution of membranous E-cadherin, we hypothesized that E-cadherin activity may play a role in beta cell survival or islet architecture. However, genetic loss of E-cadherin function does not impair islet architecture, suggesting that miRNAs likely function through other or redundant effectors in the endocrine pancreas.

Characterization of a Commercial Silicon Beta Cell

International Nuclear Information System (INIS)

Foxe, Michael P.; Hayes, James C.; Mayer, Michael F.; McIntyre, Justin I.; Sivels, Ciara B.; Suarez, Rey

2016-01-01

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 the 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.

Low-beta investment strategies

OpenAIRE

Korn, Olaf; Kuntz, Laura-Chloé

2015-01-01

This paper investigates investment strategies that exploit the low-beta anomaly. Although the notion of buying low-beta stocks and selling high-beta stocks is natural, a choice is necessary with respect to the relative weighting of high-beta stocks and low-beta stocks in the investment portfolio. Our empirical results for US large-cap stocks show that this choice is very important for the risk-return characteristics of the resulting portfolios and their sensitivities to common risk factors. W...

Monooxygenase, a novel beta-cypermethrin degrading enzyme from Streptomyces sp.

Directory of Open Access Journals (Sweden)

Shaohua Chen

Full Text Available The widely used insecticide beta-cypermethrin has become a public concern because of its environmental contamination and toxic effects on mammals. In this study, a novel beta-cypermethrin degrading enzyme designated as CMO was purified to apparent homogeneity from a Streptomyces sp. isolate capable of utilizing beta-cypermethrin as a growth substrate. The native enzyme showed a monomeric structure with a molecular mass of 41 kDa and pI of 5.4. The enzyme exhibited the maximal activity at pH 7.5 and 30°C. It was fairly stable in the pH range from 6.5-8.5 and at temperatures below 10°C. The enzyme activity was significantly stimulated by Fe(2+, but strongly inhibited by Ag(+, Al(3+, and Cu(2+. The enzyme catalyzed the degradation of beta-cypermethrin to form five products via hydroxylation and diaryl cleavage. A novel beta-cypermethrin detoxification pathway was proposed based on analysis of these products. The purified enzyme was identified as a monooxygenase by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry analysis (MALDI-TOF-MS and N-terminal protein sequencing. Given that all the characterized pyrethroid-degrading enzymes are the members of hydrolase family, CMO represents the first pyrethroid-degrading monooxygenase identified from environmental microorganisms. Taken together, our findings depict a novel pyrethroid degradation mechanism and indicate that the purified enzyme may be a promising candidate for detoxification of beta-cypermethrin and environmental protection.

Alpha-in-air monitor for continuous monitoring based on alpha to beta ratio

International Nuclear Information System (INIS)

Somayaji, K.S.; Venkataramani, R.; Swaminathan, N.; Pushparaja

1997-01-01

Measurement of long-lived alpha activity collected on a filter paper in continuous air monitoring of ambient working environment is difficult due to interference from much larger concentrations of short-lived alpha emitting daughter products of 222 Rn and 220 Rn. However, the ratio between the natural alpha and beta activity is approximately constant and this constancy of the ratio is used to discriminate against short-lived natural radioactivity in continuous air monitoring. Detection system was specially designed for the purpose of simultaneous counting of alpha and beta activity deposited on the filter paper during continuous monitoring. The activity ratios were calculated and plotted against the monitoring duration up to about six hours. Monitoring was carried out in three facilities with different ventilation conditions. Presence of any long-lived alpha contamination on the filter paper results in increase in the alpha to beta ratio. Long-lived 239 Pu contamination of about 16 DAC.h could be detected after about 45 minutes of commencement of the sampling. The experimental results using prototype units have shown that the approach of using alpha to beta activity ratio method to detect long-lived alpha activity in the presence of short-lived natural activity is satisfactory. (author)

SIRT1 inhibits proliferation of pancreatic cancer cells expressing pancreatic adenocarcinoma up-regulated factor (PAUF), a novel oncogene, by suppression of {beta}-catenin

Energy Technology Data Exchange (ETDEWEB)

Cho, Il-Rae [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Koh, Sang Seok [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Malilas, Waraporn; Srisuttee, Ratakorn; Moon, Jeong [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Choi, Young-Whan [Department of Horticultural Bioscience, Pusan National University, Miryang 627-706 (Korea, Republic of); Horio, Yoshiyuki [Department of Pharmacology, Sapporo Medical University, Sapporo 060-8556 (Japan); Oh, Sangtaek [Department of Advanced Fermentation Fusion Science and Technology, Kookmin University, Seoul 136-702 (Korea, Republic of); Chung, Young-Hwa, E-mail: younghc@pusan.ac.kr [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of)

2012-06-29

Highlights: Black-Right-Pointing-Pointer SIRT1 inhibits protein levels of {beta}-catenin and its transcriptional activity. Black-Right-Pointing-Pointer Nuclear localization of SIRT1 is not required for the decrease of {beta}-catenin expression. Black-Right-Pointing-Pointer SIRT1-mediated degradation of {beta}-catenin is not required for GSK-3{beta} and Siah-1 but for proteosome. Black-Right-Pointing-Pointer SIRT1 activation inhibits proliferation of pancreatic cancer cells expressing PAUF. -- Abstract: Because we found in a recent study that pancreatic adenocarcinoma up-regulated factor (PAUF), a novel oncogene, induces a rapid proliferation of pancreatic cells by up-regulation of {beta}-catenin, we postulated that {beta}-catenin might be a target molecule for pancreatic cancer treatment. We thus speculated whether SIRT1, known to target {beta}-catenin in a colon cancer model, suppresses {beta}-catenin in those pancreatic cancer cells that express PAUF (Panc-PAUF). We further evaluated whether such suppression would lead to inhibition of the proliferation of these cells. The ectopic expression of either SIRT1 or resveratrol (an activator of SIRT1) suppressed levels of {beta}-catenin protein and its transcriptional activity in Panc-PAUF cells. Conversely, suppression of SIRT1 expression by siRNA enhanced {beta}-catenin expression and transcriptional activity. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for reduction of {beta}-catenin. Treatment with MG132, a proteasomal inhibitor, restored {beta}-catenin protein levels, suggesting that SIRT1-mediated degradation of {beta}-catenin requires proteasomal activity. It was reported that inhibition of GSK-3{beta} or Siah-1 stabilizes {beta}-catenin in colon cancer cells, but suppression of GSK-3{beta} or Siah-1 using siRNA in the presence of resveratrol instead diminished {beta}-catenin protein levels in Panc-PAUF cells. This suggests that GSK-3{beta} and Siah-1 are not involved in SIRT1