Improved targeting of the alpha(v)beta (3) integrin by multimerisation of RGD peptides.

NARCIS (Netherlands)

Dijkgraaf, I.; Kruijtzer, J.A.; Liu, S.; Soede, A.C.; Oyen, W.J.G.; Corstens, F.H.M.; Liskamp, R.M.; Boerman, O.C.

2007-01-01

PURPOSE: The integrin alpha(v)beta(3) is expressed on sprouting endothelial cells and on various tumour cell types. Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3) binding

Regulation of human lung fibroblast C1q-receptors by transforming growth factor-beta and tumor necrosis factor-alpha.

Science.gov (United States)

Lurton, J; Soto, H; Narayanan, A S; Raghu, G

1999-03-01

Transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) are two polypeptide mediators which are believed to play a role in the evolution of idiopathic pulmonary fibrosis (IPF). We have evaluated the effect of these two substances on the expression of receptors for collagen (cC1q-R) and globular (gC1q-R) domains of C1q and on type I collagen in human lung fibroblasts. Two fibroblast subpopulations differing in C1q receptor expression were obtained by culturing human lung explants in medium containing fresh human serum and heated plasma-derived serum and separating them based on C1q binding [Narayanan, Lurton and Raghu: Am J Resp Cell Mol Biol. 1998; 17:84]. The cells, referred to as HH and NL cells, respectively, were exposed to TGF-beta and TNF-alpha in serum-free conditions. The levels of mRNA were assessed by in situ hybridization and Northern analysis, and protein levels compared after SDS-polyacrylamide gel electrophoresis and Western blotting. NL cells exposed to TGF-beta and TNF-alpha contained 1.4 and 1.6 times as much cC1q-R mRNA, respectively, whereas in HH cells cC1q-R mRNA increased 2.0- and 2.4-fold. The gC1q-R mRNA levels increased to a lesser extent in both cells. These increases were not reflected in protein levels of CC1q-R and gC1q-R, which were similar to or less than controls. Both TGF-beta and TNF-alpha also increased procollagen [I] mRNA levels in both cells. Overall, TNF-alpha caused a greater increase and the degree of response by HH fibroblasts to both TGF-beta and TNF-alpha was higher than NL cells. These results indicated that TGF-beta and TNF-alpha upregulate the mRNA levels for cC1q-R and collagen and that they do not affect gC1q-R mRNA levels significantly. They also indicated different subsets of human lung fibroblasts respond differently to inflammatory mediators.

Characterization of a series of anabaseine-derived compounds reveals that the 3-(4)-dimethylaminocinnamylidine derivative is a selective agonist at neuronal nicotinic alpha 7/125I-alpha-bungarotoxin receptor subtypes.

Science.gov (United States)

de Fiebre, C M; Meyer, E M; Henry, J C; Muraskin, S I; Kem, W R; Papke, R L

1995-01-01

Investigation of the naturally occurring, nicotinic agonist anabaseine and novel derivatives has shown that these compounds have cytoprotective and memory-enhancing effects. The hypothesis that these arise at least in part through actions on brain nicotinic receptors was evaluated by examining the ability of these compounds to displace the binding of nicotinic ligands and to affect the function of the alpha 4 beta 2 and alpha 7 receptor subtypes expressed in Xenopus oocytes. The derivative 3-(4)-dimethylaminocinnamylidine anabaseine (DMAC) was found to be a selective alpha 7 receptor agonist; it was more potent than nicotine, acetylcholine, anabaseine, and other derivatives at activating the alpha 7 receptor subtype, while displaying little agonist activity at alpha 4 beta 2 and other receptor subtypes. Compared with anabaseine and the other derivatives, DMAC was the most potent at displacing 125I-alpha-bungarotoxin binding (putative alpha 7) and the least potent at displacing [3H]cytisine binding (putative alpha 4 beta 2) to brain membranes. Independently of agonist activities, all of the novel compounds displayed secondary inhibitory activity at both receptor subtypes. At the alpha 4 beta 2 receptor subtype, inhibition by the 3-(2,4)-dimethoxybenzylidene derivative was enhanced by coapplication of acetylcholine, suggesting a noncompetitive form of inhibition. Anabaseine and nicotine prolonged the time course of activation of alpha 4 beta 2 receptors, compared with acetylcholine, suggesting sequential channel-blocking activity. As selective agonists, anabaseine derivatives such as DMAC may be useful for elucidating the function of alpha 7 nicotinic receptors, including their potential role(s) in the cytoprotective and memory-enhancing effects of nicotinic agents.

The insecticide fipronil and its metabolite fipronil sulphone inhibit the rat alpha1beta2gamma2L GABA(A) receptor.

Science.gov (United States)

Li, P; Akk, G

2008-11-01

Fipronil is the active ingredient in a number of widely used insecticides. Human exposure to fipronil leads to symptoms (headache, nausea and seizures) typically associated with the antagonism of GABA(A) receptors in the brain. In this study, we have examined the modulation of the common brain GABA(A) receptor subtype by fipronil and its major metabolite, fipronil sulphone. Whole-cell and single-channel recordings were made from HEK 293 cells transiently expressing rat alpha1beta2gamma2L GABA(A) receptors. The major effect of fipronil was to increase the rate of current decay in macroscopic recordings. In single-channel recordings, the presence of fipronil resulted in shorter cluster durations without affecting the intracluster open and closed time distributions or the single-channel conductance. The alpha1V256S mutation, previously shown alleviate channel inhibition by inhibitory steroids and several insecticides, had a relatively small effect on channel block by fipronil. The mode of action of fipronil sulphone was similar to that of its parent compound but the metabolite was less potent at inhibiting the alpha1beta2gamma2L receptor. We conclude that exposure to fipronil induces accumulation of receptors in a novel, long-lived blocked state. This process proceeds in parallel with and independently of, channel desensitization. The lower potency of fipronil sulphone indicates that the conversion serves as a detoxifying process in mammalian brain.

Interactions between an alpha-helix and a beta-sheet. Energetics of alpha/beta packing in proteins.

Science.gov (United States)

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

1985-12-05

Conformational energy computations have been carried out to determine the favorable ways of packing a right-handed alpha-helix on a right-twisted antiparallel or parallel beta-sheet. Co-ordinate transformations have been developed to relate the position and orientation of the alpha-helix to the beta-sheet. The packing was investigated for a CH3CO-(L-Ala)16-NHCH3 alpha-helix interacting with five-stranded beta-sheets composed of CH3CO-(L-Val)6-NHCH3 chains. All internal and external variables for both the alpha-helix and the beta-sheet were allowed to change during energy minimization. Four distinct classes of low-energy packing arrangements were found for the alpha-helix interacting with both the parallel and the anti-parallel beta-sheet. The classes differ in the orientation of the axis of the alpha-helix relative to the direction of the strands of the right-twisted beta-sheet. In the class with the most favorable arrangement, the alpha-helix is oriented along the strands of the beta-sheet, as a result of attractive non-bonded side-chain-side-chain interactions along the entire length of the alpha-helix. A class with nearly perpendicular orientation of the helix axis to the strands is also of low energy, because it allows similarly extensive attractive interactions. In the other two classes, the helix is oriented diagonally relative to the strands of the beta-sheet. In one of them, it interacts with the convex surface near the middle of the saddle-shaped twisted beta-sheet. In the other, it is oriented along the concave diagonal of the beta-sheet and, therefore, it interacts only with the corner regions of the sheet, so that this packing is energetically less favorable. The packing arrangements involving an antiparallel and a parallel beta-sheet are generally similar, although the antiparallel beta-sheet has been found to be more flexible. The major features of 163 observed alpha/beta packing arrangements in 37 proteins are accounted for in terms of the computed

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

Science.gov (United States)

Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

2006-10-01

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

The Z-isomer of 11 beta-methoxy-17 alpha-[123I]iodovinylestradiol is a promising radioligand for estrogen receptor imaging in human breast cancer

NARCIS (Netherlands)

Rijks, L. J.; Boer, G. J.; Endert, E.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.

1997-01-01

The potential of both stereoisomers of 11 beta-methoxy-17 alpha-[123I] iodovinylestradiol (E- and Z-[123I]MIVE) as suitable radioligands for imaging of estrogen receptor (ER)-positive human breast tumours was studied. The 17 alpha-[123I]iodovinylestradiol derivatives were prepared stereospecifically

Sterol synthesis. A novel reductive rearrangement of an alpha,beta-unsaturated steroidal epoxide; a new chemical synthesis of 5alpha-cholest-8(14)-en-3beta, 15alpha-diol.

Science.gov (United States)

Parish, E J; Schroepfer, G J

1977-04-01

Reduction of 3beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with either lithium triethylboro-hydride or lithium aluminum hydride (4 molar excess) gave 5-alpha-cholest-8(14)-en-3beta,15alpha-diol in high yield. Reduction of the epoxy ester with lithium triethylborodeuteride or lithium aluminum deuteride (4 molar excess) gave [7alpha-2-H]-5alpha-cholest-8(14)-en-3beta,15alpha-diol. Reduction of 2beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with a large excess (24 molar excess) of lithium aluminum hydride gave, in addition to the expected 5alpha-cholest-8(14)-en-3beta,15alpha-diol, a significant yield (33%) of 5alpha-cholest-8(14)-en-3beta-o1. Reduction of the epoxy ester with a large excess (24 molar excess) of lithium aluminum deuteride gave [7alpha-2H]-5alpha-cholest-8(14)-en-3beta,15alpha-diol and 5alpha-cholest-8(14)-en-3beta-o1 which contained two atoms of stably bound deuterium.

Discovery of an imidazopyridine-containing 1,4-benzodiazepine nonpeptide vitronectin receptor (alpha v beta 3) antagonist with efficacy in a restenosis model.

Science.gov (United States)

Keenan, R M; Lago, M A; Miller, W H; Ali, F E; Cousins, R D; Hall, L B; Hwang, S M; Jakas, D R; Kwon, C; Louden, C; Nguyen, T T; Ohlstein, E H; Rieman, D J; Ross, S T; Samanen, J M; Smith, B R; Stadel, J; Takata, D T; Vickery, L; Yuan, C C; Yue, T L

1998-11-17

In the 3-oxo-1,4-benzodiazepine-2-acetic acid series of vitronectin receptor (alpha v beta 3) antagonists, a compound containing an imidazopyridine arginine mimetic was discovered which had sufficient potency and i.v. pharmacokinetics for demonstration of efficacy in a rat restenosis model.

Decreased agonist sensitivity of human GABA(A) receptors by an amino acid variant, isoleucine to valine, in the alpha1 subunit.

Science.gov (United States)

Westh-Hansen, S E; Rasmussen, P B; Hastrup, S; Nabekura, J; Noguchi, K; Akaike, N; Witt, M R; Nielsen, M

1997-06-25

Recombinant human GABA(A) receptors were investigated in vitro by coexpression of cDNAs coding for alpha1, beta2, and gamma2 subunits in the baculovirus/Sf-9 insect cell system. We report that a single amino acid exchange (isoleucine 121 to valine 121) in the N-terminal, extracellular part of the alpha1 subunit induces a marked decrease in agonist GABA(A) receptor ligand sensitivity. The potency of muscimol and GABA to inhibit the binding of the GABA(A) receptor antagonist [3H]SR 95531 (2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide) was higher in receptor complexes of alpha1(ile 121) beta2gamma2 than in those of alpha1(val 121) beta2gamma2 (IC50 values were 32-fold and 26-fold lower for muscimol and GABA, respectively). The apparent affinity of the GABA(A) receptor antagonist bicuculline methiodide to inhibit the binding of [3H]SR 95531 did not differ between the two receptor complex variants. Electrophysiological measurements of GABA induced whole-cell Cl- currents showed a ten-fold decrease in the GABA(A) receptor sensitivity of alpha1 (val 121) beta2gamma2 as compared to alpha1(ile 121) beta2gamma2 receptor complexes. Thus, a relatively small change in the primary structure of the alpha1 subunit leads to a decrease selective for GABA(A) receptor sensitivity to agonist ligands, since no changes were observed in a GABA(A) receptor antagonist affinity and benzodiazepine receptor binding.

A gut-homing, oligoclonal CD4+ T cell population in severe-combined immunodeficient mice expressing a rearranged, transgenic class I-restricted alpha beta T cell receptor

DEFF Research Database (Denmark)

Reimann, J; Rudolphi, A; Spiess, S

1995-01-01

We studied the peripheral T cell compartment of H-2b severe combined immunodeficient (scid) mice that express a transgenic (tg) alpha beta T cell receptor (TcR) specific for the H-Y (male) epitope presented by the H-2 class I Db molecule. Large populations of CD3+ NK1.1-TCR beta T+ T cells were...

Evaluation of estrogen receptor alpha and beta and progesterone receptor expression and correlation with clinicopathologic factors and proliferative marker Ki-67 in breast cancers

DEFF Research Database (Denmark)

Rosa, Fabíola E; Caldeira, José R F; Felipes, Joice

2008-01-01

To elucidate the molecular profile of hormonal steroid receptor status, we analyzed ER-alpha, ER-beta, and PGR mRNA and protein expression in 80 breast carcinomas using reverse transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR, and immunohistochemical analysis. Qualitative ana...

Characterization of receptors for recombinant human tumor necrosis factor-alpha from human placental membranes

International Nuclear Information System (INIS)

Aiyer, R.A.; Aggarwal, B.B.

1990-01-01

High affinity receptors for recombinant human tumor necrosis factor-alpha (rhTNF-alpha) were identified on membranes prepared from full term human placenta. Highly purified rhTNF-alpha iodinated by the iodogen method was found to bind placental membranes in a displaceable manner with an approximate dissociation constant (KD) of 1.9 nM. The membrane bound TNF-alpha receptor could be solubilized by several detergents with optimum extraction being obtained with 1% Triton X-100. The binding of 125I-rhTNF-alpha to the solubilized receptor was found to be time and temperature dependent, yielding maximum binding within 1 h, 24 h and 48 h at 37 degrees C, 24 degrees C and 4 degrees C, respectively. However, the maximum binding obtainable at 4 degrees C was only 40% of that at 37 degrees C. The binding 125I-rhTNF-alpha to solubilized placental membrane extracts was displaceable by unlabeled rhTNF-alpha, but not by a related protein recombinant human tumor necrosis factor-beta (rhTNF-beta; previously called lymphotoxin). This is similar to the behavior of TNF-alpha receptors derived from detergent-solubilized cell extracts, although on intact cells, both rhTNF-alpha and rhTNF-beta bind with equal affinity to TNF receptors. The Scatchard analysis of the binding data of the solubilized receptor revealed high affinity binding sites with a KD of approximately 0.5 nM and a receptor concentration of about 1 pmole/mg protein. Gel filtration of the solubilized receptor-ligand complexes on Sephacryl S-300 revealed two different peaks of radioactivity at approximate molecular masses of 50,000 Da and 400,000 Da. The 400,000 dalton peak corresponded to the receptor-ligand complex. Overall, our results suggest that high affinity receptors for TNF-alpha are present on human placental membranes and provide evidence that these receptors may be different from that of rhTNF-beta

QSAR of estrogen receptor modulators: exploring selectivity requirements for ER(alpha) versus ER(beta) binding of tetrahydroisoquinoline derivatives using E-state and physicochemical parameters.

Science.gov (United States)

Mukherjee, Subhendu; Saha, Achintya; Roy, Kunal

2005-02-15

Considering importance of developing selective estrogen receptor modulators (SERMs), the present paper explores selectivity requirements of tetrahydroisoquinoline derivatives for binding with ER(alpha) versus ER(beta) receptors using E-state index and physicochemical parameters. The best model [n=21, Q(2)=0.512, R(a)(2)=0.613, R=0.819, F=11.6 (df 3,17)] for ER(alpha) binding data obtained from radioligand binding assay showed importance of C(1), C(15) and lipophilicity (logP) while the best model [n=21, Q(2)=0.768, R(a)(2)=0.796, R=0.904, F=40.1 (df 2,18)] for ER(beta) binding data showed importance of C(1) and molar refractivity (MR). While modeling ER(alpha)/ER(beta) selectivity [n=21, Q(2)=0.695, R(a)(2)=0.739, R=0.882, F=19.8 (df 3,17)], C(1), C(15) and molar refractivity were found to be significant contributors. The data obtained from cellular transcription assay were also modeled. In case of ER(alpha), the best equation involving E-state values of C(1) and C(14) and logP explained 62.1% of the variance while the best equation for ER(beta) involving E-state values of C(1) and C(15) and MR explained 64.6% of the variance of the response variable. In case of ER(alpha)/ER(beta) selectivity, the best equation involving E-state values of O(8), C(14) and N(27) showed 48.3% explained variance, which increased to 63.5% on deletion of single outlier. From the analysis it appears that the nitrogen atom of the aminoethoxyphenyl substituent and 6-hydroxy substituent of the tetrahydroisoquinoline nucleus play important roles for ER(alpha)/ER(beta) selectivity in addition to R(1) and R(2) substituents.

PGC-1{beta} regulates mouse carnitine-acylcarnitine translocase through estrogen-related receptor {alpha}

Energy Technology Data Exchange (ETDEWEB)

Gacias, Mar; Perez-Marti, Albert; Pujol-Vidal, Magdalena; Marrero, Pedro F. [Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona (IBUB) (Spain); Haro, Diego, E-mail: dharo@ub.edu [Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona (IBUB) (Spain); Relat, Joana [Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona (IBUB) (Spain)

2012-07-13

Highlights: Black-Right-Pointing-Pointer The Cact gene is induced in mouse skeletal muscle after 24 h of fasting. Black-Right-Pointing-Pointer The Cact gene contains a functional consensus sequence for ERR. Black-Right-Pointing-Pointer This sequence binds ERR{alpha} both in vivo and in vitro. Black-Right-Pointing-Pointer This ERRE is required for the activation of Cact expression by the PGC-1/ERR axis. Black-Right-Pointing-Pointer Our results add Cact as a genuine gene target of these transcriptional regulators. -- Abstract: Carnitine/acylcarnitine translocase (CACT) is a mitochondrial-membrane carrier proteins that mediates the transport of acylcarnitines into the mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. CACT deficiency causes a variety of pathological conditions, such as hypoketotic hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and it can be fatal in newborns and infants. Here we report that expression of the Cact gene is induced in mouse skeletal muscle after 24 h of fasting. To gain insight into the control of Cact gene expression, we examine the transcriptional regulation of the mouse Cact gene. We show that the 5 Prime -flanking region of this gene is transcriptionally active and contains a consensus sequence for the estrogen-related receptor (ERR), a member of the nuclear receptor family of transcription factors. This sequence binds ERR{alpha}in vivo and in vitro and is required for the activation of Cact expression by the peroxisome proliferator-activated receptor gamma coactivator (PGC)-1/ERR axis. We also demonstrate that XTC790, the inverse agonist of ERR{alpha}, specifically blocks Cact activation by PGC-1{beta} in C2C12 cells.

The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus.

Directory of Open Access Journals (Sweden)

Chad Steele

2005-12-01

Full Text Available Alveolar macrophages represent a first-line innate host defense mechanism for clearing inhaled Aspergillus fumigatus from the lungs, yet contradictory data exist as to which alveolar macrophage recognition receptor is critical for innate immunity to A. fumigatus. Acknowledging that the A. fumigatus cell wall contains a high beta-1,3-glucan content, we questioned whether the beta-glucan receptor dectin-1 played a role in this recognition process. Monoclonal antibody, soluble receptor, and competitive carbohydrate blockage indicated that the alveolar macrophage inflammatory response, specifically the production of tumor necrosis factor-alpha (TNF-alpha, interleukin-1alpha (IL-1alpha, IL-1beta, IL-6, CXCL2/macrophage inflammatory protein-2 (MIP-2, CCL3/macrophage inflammatory protein-1alpha (MIP-1alpha, granulocyte-colony stimulating factor (G-CSF, and granulocyte monocyte-CSF (GM-CSF, to live A. fumigatus was dependent on recognition via the beta-glucan receptor dectin-1. The inflammatory response was triggered at the highest level by A. fumigatus swollen conidia and early germlings and correlated to the levels of surface-exposed beta glucans, indicating that dectin-1 preferentially recognizes specific morphological forms of A. fumigatus. Intratracheal administration of A. fumigatus conidia to mice in the presence of a soluble dectin-Fc fusion protein reduced both lung proinflammatory cytokine/chemokine levels and cellular recruitment while modestly increasing the A. fumigatus fungal burden, illustrating the importance of beta-glucan-initiated dectin-1 signaling in defense against this pathogen. Collectively, these data show that dectin-1 is centrally required for the generation of alveolar macrophage proinflammatory responses to A. fumigatus and to our knowledge provides the first in vivo evidence for the role of dectin-1 in fungal innate defense.

The nicotinic alpha7 acetylcholine receptor agonist ssr180711 is unable to activate limbic neurons in mice overexpressing human amyloid-beta1-42

DEFF Research Database (Denmark)

Soderman, A.; Spang-Thomsen, Mogens; Hansen, H.

2008-01-01

Recent studies have demonstrated that amyloid-beta1-42 (Abeta1-42) binds to the nicotinergic alpha7 acetylcholine receptor (alpha7 nAChR) and that the application of Abeta1-42 to cells inhibits the function of the alpha7 nAChR. The in vivo consequences of the pharmacological activation of the alp...

Alpha and beta adrenergic effects on metabolism in contracting, perfused muscle

DEFF Research Database (Denmark)

Richter, Erik; Ruderman, N B; Galbo, H

1982-01-01

The role of alpha- and beta-adrenergic receptor stimulation for the effect of epinephrine on muscle glycogenolysis, glucose- and oxygen uptake and muscle performance was studied in the perfused rat hindquarter at rest and during electrical stimulation (60 contractions/min). Adrenergic stimulation...... was obtained by epinephrine in a physiological concentration (2.4 X 10(-8) M) and alpha- and beta-adrenergic blockade by 10(-5) M phentolamine and propranolol, respectively. Epinephrine enhanced net glycogenolysis during contractions most markedly in slow-twitch red fibers. In these fibers the effect...... was mediated by alpha- as well as by beta-adrenergic stimulation, the latter involving production of cAMP, phosphorylase activation and synthase inactivation. In contrast, in fast-twitch fibers only beta-adrenergic mechanisms were involved in the glycogenolytic effect of epinephrine. Moreover, inactivation...

Use of antibodies against the variable regions of the T-cell receptor alpha/beta heterodimer for the study of cutaneous T-cell lymphomas.

Science.gov (United States)

Ralfkiaer, E; Wollf-Sneedorff, A; Vejlsgaard, G L

1991-11-01

Recent studies have suggested that antibodies against the variable (V) regions of the T-cell antigen receptor (TCR) may be used as markers for clonality and malignancy in T-cell infiltrates. We have investigated this by examining biopsy samples from 45 patients with cutaneous T-cell lymphomas (CTCL) for reactivity with seven antibodies against different V-gene families on the TCR alpha/beta heterodimer, i.e. ICI (V beta 5a), W112 (V beta 5b), OT145 (V beta 6a), 16G8 (V beta 8a), S511 (V beta 12a), F1 (V alpha 2a) and LC4 (alpha beta Va). Serial biopsies were available in 13 patients and a total of 62 samples were studied. The neoplastic cells in five cases were positive for either V beta 5 (one case), V beta 6 (one case), V beta 8 (two cases) or V beta 12 (one case). In the remaining 40 cases, no staining was seen of the neoplastic cells. These findings indicate that while antibodies against the TCR V-regions may be used as clonotypic markers for certain T-cell neoplasms, there is as yet not a sufficient number of anti-TCR V-region antibodies available for the routine diagnosis of these conditions.

Effects of cigarette smoke exposure on nicotinic acetylcholine receptor subunits {alpha}7 and {beta}2 in the sudden infant death syndrome (SIDS) brainstem

Energy Technology Data Exchange (ETDEWEB)

Machaalani, Rita, E-mail: rita.machaalani@sydney.edu.au [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Say, Meichien [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); Waters, Karen A. [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia)

2011-12-15

It is postulated that nicotine, as the main neurotoxic constituent of cigarette smoke, influences SIDS risk through effects on nicotinic acetylcholine receptors (nAChRs) in brainstem nuclei that control respiration and arousal. This study compared {alpha}7 and {beta}2 nAChR subunit expression in eight nuclei of the caudal and rostral medulla and seven nuclei of the pons between SIDS (n = 46) and non-SIDS infants (n = 14). Evaluation for associations with known SIDS risk factors included comparison according to whether infants had a history of exposure to cigarette smoke in the home, and stratification for sleep position and gender. Compared to non-SIDS infants, SIDS infants had significantly decreased {alpha}7 in the caudal nucleus of the solitary tract (cNTS), gracile and cuneate nuclei, with decreased {beta}2 in the cNTS and increased {beta}2 in the facial. When considering only the SIDS cohort: 1-cigarette smoke exposure was associated with increased {alpha}7 in the vestibular nucleus and increased {beta}2 in the rostral dorsal motor nucleus of the vagus, rNTS and Cuneate, 2-there was a gender interaction for {alpha}7 in the gracile and cuneate, and {beta}2 in the cNTS and rostral arcuate nucleus, and 3-there was no effect of sleep position on {alpha}7, but prone sleep was associated with decreased {beta}2 in three nuclei of the pons. In conclusion, SIDS infants demonstrate differences in expression of {alpha}7 and {beta}2 nAChRs within brainstem nuclei that control respiration and arousal, which is independent on prior history of cigarette smoke exposure, especially for the NTS, with additional differences for smoke exposure ({beta}2), gender ({alpha}7 and {beta}2) and sleep position ({beta}2) evident. -- Highlights: Black-Right-Pointing-Pointer The 'normal' response to smoke exposure is decreased {alpha}7 and {beta}2 in certain nuclei. Black-Right-Pointing-Pointer SIDS infants have decreased {alpha}7 in cNTS, Grac and Cun. Black

A transmembrane polar interaction is involved in the functional regulation of integrin alpha L beta 2.

Science.gov (United States)

Vararattanavech, Ardcharaporn; Chng, Choon-Peng; Parthasarathy, Krupakar; Tang, Xiao-Yan; Torres, Jaume; Tan, Suet-Mien

2010-05-14

Integrins are heterodimeric transmembrane (TM) receptors formed by noncovalent associations of alpha and beta subunits. Each subunit contains a single alpha-helical TM domain. Inside-out activation of an integrin involves the separation of its cytoplasmic tails, leading to disruption of alphabeta TM packing. The leukocyte integrin alpha L beta 2 is required for leukocyte adhesion, migration, proliferation, cytotoxic function, and antigen presentation. In this study, we show by mutagenesis experiments that the packing of alpha L beta 2 TMs is consistent with that of the integrin alpha IIb beta 3 TMs. However, molecular dynamics simulations of alpha L beta 2 TMs in lipids predicted a polar interaction involving the side chains of alpha L Ser1071 and beta2 Thr686 in the outer-membrane association clasp (OMC). This is supported by carbonyl vibrational shifts observed in isotope-labeled alpha L beta 2 TM peptides that were incorporated into lipid bilayers. Molecular dynamics studies simulating the separation of alpha L beta 2 tails showed the presence of polar interaction during the initial perturbation of the inner-membrane association clasp. When the TMs underwent further separation, the polar interaction was disrupted. OMC polar interaction is important in regulating the functions of beta2 integrins because mutations that disrupt the OMC polar interaction generated constitutively activated alpha L beta 2, alpha M beta 2, and alpha X beta 2 in 293T transfectants. We also show that the expression of mutant beta2 Thr686Gly in beta2-deficient T cells rescued cell adhesion to intercellular adhesion molecule 1, but the cells showed overt elongated morphologies in response to chemokine stromal-cell-derived factor 1 alpha treatment as compared to wild-type beta2-expressing cells. These two TM polar residues are totally conserved in other members of the beta2 integrins in humans and across different species. Our results provide an example of the stabilizing effect of polar

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

Science.gov (United States)

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

2009-08-15

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

Localization of integrin alpha(v)beta3 and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in cutaneous and oral melanomas of dog.

Science.gov (United States)

Rawlings, N G; Simko, E; Bebchuk, T; Caldwell, S J; Singh, B

2003-07-01

Melanomas are common neoplasms of dogs and arise from pigment-producing cells called melanocytes or melanoblasts. Melanomas of skin are often easily cured by surgical excision, but those of oral mucosa are aggressive, metastasize to the regional lymph nodes and lungs, and respond poorly to conventional therapy. Tumor growth is sustained by proliferation of microvessels via a process called angiogenesis. Integrin alpha(v)beta3 is expressed in proliferating but not in quiescent microvessels suggesting a role in angiogenesis. Vascular endothelial growth factor (VEGF) manifests its mitogenic and angiogenic effects mainly via VEGF receptor-2 (VEGFR-2/Flk-1). We conducted this immunocytochemical study to investigate the expression of integrin alpha(v)beta3 and VEGFR-2 in archival and fresh samples from cases of canine melanomas. Results show that integrin alpha(v)beta3 was expressed in 72% and 88% of cutaneous and oral melanomas, respectively, and the expression was restricted to and immediately around the melanocytes and endothelial cells. VEGFR-2 staining of selected cases of melanoma revealed that its expression overlapped with the alpha(v)beta3 integrin. Dual immuno-gold electron microscopy confirmed co-localization of integrin alpha(v)beta3 and VEGFR-2 in melanocytes and endothelial cells. These data demonstrate expression and co-localization of integrin alpha(v)beta3 and VEGFR-2 in cutaneous and oral melanomas of dogs.

Association of coatomer proteins with the beta-receptor for platelet-derived growth factor

DEFF Research Database (Denmark)

Hansen, Klaus; Rönnstrand, L; Rorsman, C

1997-01-01

The nonreceptor tyrosine kinase Src binds to and is activated by the beta-receptor for platelet-derived growth factor (PDGF). The interaction leads to Src phosphorylation of Tyr934 in the kinase domain of the receptor. In the course of the functional characterization of this phosphorylation, we...... of intracellular vesicle transport. In order to explore the functional significance of the interaction between alpha- and beta'-COP and the PDGF receptor, a receptor mutant was made in which the conserved histidine residue 928 was mutated to an alanine residue. The mutant receptor, which was unable to bind alpha...

Alpha 2-adrenergic receptor turnover in adipose tissue and kidney: irreversible blockade of alpha 2-adrenergic receptors by benextramine

International Nuclear Information System (INIS)

Taouis, M.; Berlan, M.; Lafontan, M.

1987-01-01

The recovery of post- and extrasynaptic alpha 2-adrenergic receptor-binding sites was studied in vivo in male golden hamsters after treatment with an irreversible alpha-adrenoceptor antagonist benextramine, a tetramine disulfide that possesses a high affinity for alpha 2-binding sites. The kidney alpha 2-adrenergic receptor number was measured with [ 3 H]yohimbine, whereas [ 3 H]clonidine was used for fat cell and brain membrane alpha 2-binding site identification. Benextramine treatment of fat cell, kidney, and brain membranes reduced or completely suppressed, in an irreversible manner, [ 3 H] clonidine and [ 3 H]yohimbine binding without modifying adenosine (A1-receptor) and beta-adrenergic receptor sites. This irreversible binding was also found 1 and 2 hr after intraperitoneal administration of benextramine to the hamsters. Although it bound irreversibly to peripheral and central alpha 2-adrenergic receptors on isolated membranes, benextramine was unable to cross the blood-brain barrier of the hamster at the concentrations used (10-20 mg/kg). After the irreversible blockade, alpha 2-binding sites reappeared in kidney and adipose tissue following a monoexponential time course. Recovery of binding sites was more rapid in kidney than in adipose tissue; the half-lives of the receptor were 31 and 46 hr, respectively in the tissues. The rates of receptor production were 1.5 and 1.8 fmol/mg of protein/hr in kidney and adipose tissue. Reappearance of alpha 2-binding sites was associated with a rapid recovery of function (antilipolytic potencies of alpha 2-agonists) in fat cells inasmuch as occupancy of 15% of [ 3 H]clonidine-binding sites was sufficient to promote 40% inhibition of lipolysis. Benextramine is a useful tool to estimate turnover of alpha 2-adrenergic receptors under normal and pathological situations

Alpha and beta detection and spectrometry

International Nuclear Information System (INIS)

Saro, S.

1984-01-01

The theory of alpha and beta radioactive decay, the interaction of alpha and beta particles with matter, and their detection and spectrometry are dealt with in seven chapters: 1. Alpha transformation of atomic nuclei; 2. Basic properties of detectors and statistics of detection; 3. Alpha detectors and spectrometers; 4. Applications of alpha detection and spectrometry; 5. Beta transformation of atomic nuclei; 6. Beta particle detectors and spectrometers; 7. Detection of low energy beta particles. Chapter 8 is devoted to sampling and preparation of samples for radiometry. (E.F.)

Pharmacological characterisation of strychnine and brucine analogues at glycine and alpha7 nicotinic acetylcholine receptors

DEFF Research Database (Denmark)

Jensen, Anders A.; Gharagozloo, Parviz; Birdsall, Nigel J M

2006-01-01

of tertiary and quaternary analogues as well as bisquaternary dimers of strychnine and brucine at human alpha1 and alpha1beta glycine receptors and at a chimera consisting of the amino-terminal domain of the alpha7 nicotinic receptor (containing the orthosteric ligand binding site) and the ion channel domain...... of strychnine and brucine, none of the analogues displayed significant selectivity between the alpha1 and alpha1beta subtypes. The structure-activity relationships for the compounds at the alpha7/5-HT3 chimera were significantly different from those at the glycine receptors. Most strikingly, quaternization...... of strychnine and brucine with substituents possessing different steric and electronic properties completely eliminated the activity at the glycine receptors, whereas binding affinity to the alpha7/5-HT3 chimera was retained for the majority of the quaternary analogues. This study provides an insight...

Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. I. Recognition by two alpha beta T cell receptors

DEFF Research Database (Denmark)

Rognan, D; Stryhn, A; Fugger, L

2000-01-01

dynamics. Next, three-dimensional models of two different T cell receptors (TCRs) both specific for the Ha255-262/Kk complex were generated based on previously published TCR X-ray structures. Finally, guided by the recently published X-ray structures of ternary TCR/peptide/MHC-I complexes, the TCR models...... the models. They were found to account well for the experimentally obtained data, lending considerable support to the proposed models and suggesting a universal docking mode for alpha beta TCRs to MHC-peptide complexes. Such models may also be useful in guiding future rational experimentation....

15 beta-hydroxysteroids (Part IV). Steroids of the human perinatal period: the synthesis of 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one and its A/B-ring configurational isomers.

Science.gov (United States)

Reeder, A Y; Joannou, G E

1995-12-01

In recent years several 15 beta-hydroxysteroids have emerged pathognomonic of adrenal disorders in human neonates of which 3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) was the first to be identified in the urine of newborn infants affected with congenital adrenal hyperplasia. In this investigation we report the synthesis of the three remaining 3 xi,5 xi-isomers, namely 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (3), 3 beta,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (7) and 3 beta,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (8) for their definitive identification in pathological conditions in human neonates. 3 beta,15 beta-Diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (11), a product of chemical synthesis was converted to the isomeric 3 and 7, while conversion of 15 beta,17 alpha-dihydroxy-4-pregnen-3,20-dione (4), a product of microbiological transformation, resulted in the preparation of 8. In brief, selective acetate hydrolysis of 11 gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5-pregnen-20-one (12) which on catalytic hydrogenation gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5 alpha-pregnan-20-one (13) a common intermediate for the synthesis of the 3 beta(and alpha),5 alpha-isomers. Hydrolysis of the 15 beta-acetate gave 7, whereas oxidation with pyridinium chlorochromate gave 15 beta-acetoxy-17 alpha-hydroxy-5 alpha-pregnan-3,20-dione (14) which on reduction with L-Selectride and hydrolysis of the 15 beta-acetate gave 3. Finally, hydrogenation of 4 gave 15 beta, 17 alpha-dihydroxy-5 beta-pregnan-3,20-dione (10) which on reduction with L-Selectride gave 8.

The alpha3 laminin subunit, alpha6beta4 and alpha3beta1 integrin coordinately regulate wound healing in cultured epithelial cells and in the skin

DEFF Research Database (Denmark)

Goldfinger, L E; Hopkinson, S B; deHart, G W

1999-01-01

Previously, we demonstrated that proteolytic processing within the globular domain of the alpha3 subunit of laminin-5 (LN5) converts LN5 from a cell motility-inducing factor to a protein complex that can trigger the formation of hemidesmosomes, certain cell-matrix attachment sites found in epithe......-inhibiting antibodies, we provide evidence that LN5 and its two integrin receptors (alpha6beta4 and alpha3beta1) appear necessary for wound healing to occur in MCF-10A cell culture wounds. We propose a model for healing of wounded epithelial tissues based on these results....... in epithelial cells. We have prepared a monoclonal antibody (12C4) whose epitope is located toward the carboxy terminus of the globular domain of the alpha3 laminin subunit. This epitope is lost from the alpha3 subunit as a consequence of proteolytic processing. Antibody 12C4 stains throughout the matrix...... the wound site. A similar phenomenon is observed in human skin wounds, since we also detect expression of the unprocessed alpha3 laminin subunit at the leading tip of the sheet of epidermal cells that epithelializes skin wounds in vivo. In addition, using alpha3 laminin subunit and integrin function...

Monitor for alpha beta contamination of hands; Moniteur de contamination alpha beta des mains

Energy Technology Data Exchange (ETDEWEB)

Guitton, J

1958-07-01

The following specifications of hands alpha beta contamination monitor are presented: the position of the hands, the detection and separation of alpha and beta, the information processing, the programming, the results presentation and general characteristics. (A.L.B.)

Variations in maternal care alter corticosterone and 17beta-estradiol levels, estrous cycle and folliculogenesis and stimulate the expression of estrogen receptors alpha and beta in the ovaries of UCh rats

Directory of Open Access Journals (Sweden)

Amorim João PA

2011-12-01

Full Text Available Abstract Background Variations in maternal care are associated with neonatal stress, hormonal disturbances and reproductive injuries during adulthood. However, the effects of these variations on sex hormones and steroid receptors during ovary development remain undetermined. This study aimed to investigate whether variations in maternal care are able to influence the hormonal profile, follicular dynamics and expression of AR, ER-alpha and ER-beta in the ovaries of UCh rat offspring. Methods Twenty-four adult UCh rats, aged 120 days, were randomly divided into two groups (UChA and UChB and mated. Maternal care was assessed from birth (day 0 to the 10th postnatal day (PND. In adulthood, twenty adult female rats (UChA and UChB offspring; n = 10/group, aged 120 days, were euthanized by decapitation during the morning estrus. Results UChA females (providing high maternal care more frequently displayed the behaviors of carrying pups, as well as licking/grooming and arched back nursing cares. Also, mothers providing high care had elevated corticosterone levels. Additionally, offspring receiving low maternal care showed the highest estrous cycle duration, increased corticosterone and 17beta-estradiol levels, overexpression of receptors ER-alpha and ER-beta, increased numbers of primordial, antral and mature follicles and accentuated granulosa cell proliferation. Conclusions Our study suggests that low maternal care alters corticosterone and 17beta-estradiol levels, disrupting the estrous cycle and folliculogenesis and differentially regulating the expression of ER-alpha and ER-beta in the ovaries of adult rats.

DNA Repair, Redox Regulation and Modulation of Estrogen Receptor Alpha Mediated Transcription

Science.gov (United States)

Curtis-Ducey, Carol Dianne

2009-01-01

Interaction of estrogen receptor [alpha] (ER[alpha]) with 17[beta]-estradiol (E[subscript 2]) facilitates binding of the receptor to estrogen response elements (EREs) in target genes, which in turn leads to recruitment of coregulatory proteins. To better understand how estrogen-responsive genes are regulated, our laboratory identified a number of…

Genetic variants of estrogen beta and leptin receptors may cause gynecomastia in adolescent.

Science.gov (United States)

Eren, Erdal; Edgunlu, Tuba; Korkmaz, Huseyin Anil; Cakir, Esra Deniz Papatya; Demir, Korcan; Cetin, Esin Sakalli; Celik, Sevim Karakas

2014-05-15

Gynecomastia is a benign breast enlargement in males that affects approximately one-third of adolescents. The exact mechanism is not fully understood; however, it has been proposed that estrogen receptors and aromatase enzyme activity may play important roles in the pathogenesis of gynecomastia. While many studies have reported that aromatase enzyme (CYP19) gene polymorphism is associated with gynecomastia, only one study has shown a relationship between estrogen receptor (ER) alpha and beta gene polymorphism and gynecomastia. Thus, the aim of this study was to evaluate the relationships between CYP19 (rs2414096), ER alpha (rs2234693), ER beta (rs4986938), leptin (rs7799039), and leptin receptor (rs1137101) gene polymorphisms and gynecomastia. This study included 107 male adolescents with gynecomastia and 97 controls. Total serum testosterone (T) and estradiol (E2) levels were measured, and DNA was extracted from whole blood using the PCR-RFLP technique. The polymorphic distributions of CYP19, ER alpha, ER beta, leptin and leptin receptor genes were compared. The median E2 level was 12.41 (5.00-65.40) pg/ml in the control group and 16.86 (2.58-78.47) pg/ml in the study group (pgynecomastia and leptin receptor rs1137101 (p=0.002) and ER beta receptor rs4986938 gene polymorphisms (p=0.002). According to our results, increased E2 level and ER beta gene rs4986938 polymorphism might explain why some adolescents have gynecomastia. Leptin receptor gene rs1137101 polymorphism might affect susceptibility to gynecomastia. Copyright © 2014 Elsevier B.V. All rights reserved.

Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

Energy Technology Data Exchange (ETDEWEB)

Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.; Shyamala, G.; Moses, Harold L.; Barcellos-Hoff, Mary Helen

2005-03-03

Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha} co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.

PET imaging of alpha(v)beta(3) integrin expression in tumours with Ga-68-labelled mono-, di- and tetrameric RGD peptides

NARCIS (Netherlands)

Dijkgraaf, Ingrid; Yim, Cheng-Bin; Franssen, Gerben M.; Schuit, Robert C.; Luurtsema, Gert; Liu, Shuang; Oyen, Wim J. G.; Boerman, Otto C.

Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of Ga-68-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their

Expression and putative function of fibronectin and its receptor (integrin alpha(5)beta(1)) in male and female gametes during bovine fertilization in vitro.

Science.gov (United States)

Thys, Mirjan; Nauwynck, Hans; Maes, Dominiek; Hoogewijs, Maarten; Vercauteren, Dries; Rijsselaere, Tom; Favoreel, Herman; Van Soom, Ann

2009-09-01

Fibronectin (Fn) is a 440 kDa glycoprotein assumed to participate in sperm-egg interaction in human. Recently, it has been demonstrated that Fn--when present during bovine IVF--strongly inhibits sperm penetration. The present study was conducted firstly to evaluate the expression of Fn and its integrin receptor (alpha(5)beta(1)) on male and female bovine gametes using indirect immunofluorescence and secondly, to determine the function of Fn during bovine IVF. Endogenous Fn was detected underneath the zona pellucida (ZP) and integrin alpha(5) on the oolemma of cumulus-denuded oocytes. Bovine spermatozoa displayed integrin alpha(5) at their equatorial segment after acrosome reaction. We established that the main inhibitory effect of exogenously supplemented Fn was located at the sperm-oolemma binding, with a (concurrent) effect on fusion, and this can probably be attributed to the binding of Fn to spermatozoa at the equatorial segment, as shown by means of Alexa Fluor 488-conjugated Fn. Combining these results, the inhibitory effect of exogenously supplemented Fn seemed to be exerted on the male gamete by binding to the exposed integrin alpha(5)beta(1) receptor after acrosome reaction. The presence of endogenous Fn underneath the ZP together with integrin alpha(5) expression on oolemma and acrosome-reacted (AR) sperm cell surface suggests a 'velcro' interaction between the endogenous Fn ligand and corresponding receptors on both (AR) sperm cell and oolemma, initiating sperm-egg binding.

Partitioning diversity into independent alpha and beta components.

Science.gov (United States)

Jost, Lou

2007-10-01

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

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.

Molecular cloning and phylogenetic analysis of integrins alpha v beta 1 and alpha v beta 6 of one-humped camel (Camelus dromedarius)

DEFF Research Database (Denmark)

Du, Junzheng; Larska, Magdalena Larska; Chang, Huiyun

2010-01-01

Bactrian camels can relatively easily be infected with FMDV, but dromedary camels remain resistant even to high doses of the virus. To understand the different susceptibility between the two camel species from the standpoint of viral receptors, this work reports the sequences of the dromedary camel...... into the Artiodactyla group, together with those of Bactrian camel, pig, sheep, and cattle that are susceptible to FMDV infection. Compared with the Bactrian camel integrins, 4, 10, and 8 amino acid changes were found in the dromedary camel alpha v, beta 1, and beta 6 subunits, respectively. This study...... will be of importance in understanding the differences of integrins as FMDV receptors among dromedary camel and other species. Crown...

The membrane-cytoplasm interface of integrin alpha subunits is critical for receptor latency.

OpenAIRE

Briesewitz, R; Kern, A; Smilenov, L B; David, F S; Marcantonio, E E

1996-01-01

Localization of integrin receptors to focal contact sites occurs upon ligand binding. This activity is latent, since unoccupied integrin receptors do not localize to focal contacts. Deletion analysis has revealed that the alpha cytoplasmic domains is required for the maintenance of integrin receptor latency. Our current hypothesis for the mechanism of integrin post-ligand binding events is that there is a change in relationship of alpha and beta cytoplasmic domains, which overcomes receptor l...

Variability and repertoire size of T-cell receptor V alpha gene segments.

Science.gov (United States)

Becker, D M; Pattern, P; Chien, Y; Yokota, T; Eshhar, Z; Giedlin, M; Gascoigne, N R; Goodnow, C; Wolf, R; Arai, K

The immune system of higher organisms is composed largely of two distinct cell types, B lymphocytes and T lymphocytes, each of which is independently capable of recognizing an enormous number of distinct entities through their antigen receptors; surface immunoglobulin in the case of the former, and the T-cell receptor (TCR) in the case of the latter. In both cell types, the genes encoding the antigen receptors consist of multiple gene segments which recombine during maturation to produce many possible peptides. One striking difference between B- and T-cell recognition that has not yet been resolved by the structural data is the fact that T cells generally require a major histocompatibility determinant together with an antigen whereas, in most cases, antibodies recognize antigen alone. Recently, we and others have found that a series of TCR V beta gene sequences show conservation of many of the same residues that are conserved between heavy- and light-chain immunoglobulin V regions, and these V beta sequences are predicted to have an immunoglobulin-like secondary structure. To extend these studies, we have isolated and sequenced eight additional alpha-chain complementary cDNA clones and compared them with published sequences. Analyses of these sequences, reported here, indicate that V alpha regions have many of the characteristics of V beta gene segments but differ in that they almost always occur as cross-hybridizing gene families. We conclude that there may be very different selective pressures operating on V alpha and V beta sequences and that the V alpha repertoire may be considerably larger than that of V beta.

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.

Extrasynaptic location of alpha-2 and noninnervated beta-2 adrenoceptors in the vascular system of the pithed normotensive rat

NARCIS (Netherlands)

Wilffert, B.; Timmermans, P.B.M.W.M.; Van Zwieten, P.A.

1982-01-01

The receptors involved in the pressor and tachycardic effects of catecholamines applied systemically or released from sympathetic nerve endings were compared. Intravenously administered (-)-epinephrine activated alpha-1, alpha-2, beta-1 and beta-2 adrenoceptors as demonstrated in pithed rats, using

Changes in estrogen receptor-alpha and -beta in the infundibular nucleus of the human hypothalamus are related to the occurrence of Alzheimer's disease neuropathology

NARCIS (Netherlands)

Hestiantoro, Andon; Swaab, Dick F.

2004-01-01

The expression of estrogen receptor (ER)alpha and -beta in the infundibular nucleus of the hypothalamus was studied immunocytochemically in 28 control subjects and 14 patients with Alzheimer's disease (AD). A shift was found from more nuclear staining of ERalpha in young female controls to more

Negative feedback regulation of human platelets via autocrine activation of the platelet-derived growth factor alpha-receptor.

Science.gov (United States)

Vassbotn, F S; Havnen, O K; Heldin, C H; Holmsen, H

1994-05-13

Human platelets contain platelet-derived growth factor (PDGF) in their alpha-granules which is released during platelet exocytosis. We show by immunoprecipitation and 125I-PDGF binding experiments that human platelets have functionally active PDGF alpha-receptors, but not beta-receptors. The PDGF alpha-receptor (PDGFR-alpha) was identified as a 170-kDa glycosylated protein-tyrosine kinase as found in other cell types. Stimulation of platelets with 0.1 unit/ml thrombin resulted in a significant increase (2-5-fold) of the tyrosine phosphorylation of the PDGFR-alpha, as determined by immunoprecipitation with phosphotyrosine antiserum as well as with PDGFR-alpha antiserum. The observed thrombin-induced autophosphorylation of the PDGFR-alpha was inhibited by the addition of a neutralizing monoclonal PDGF antibody. Thus, our results suggest that the platelet PDGFR-alpha is stimulated in an autocrine manner by PDGF secreted during platelet activation. Preincubation of platelets with PDGF inhibited thrombin-induced platelet aggregation and secretion of ATP + ADP and beta-hexosaminidase. Thrombin-induced platelet aggregation was also reversed when PDGF was added 30 s after thrombin stimulation. Inhibition of the autocrine PDGF pathway during platelet activation by the PDGF antibody led to a potentiation of thrombin-induced beta-hexosaminidase secretion. Thus, the PDGFR-alpha takes part in a negative feedback regulation during platelet activation. Our demonstration of PDGF alpha-receptors on human platelets and its inhibitory function during platelet activation identifies a new possible role of PDGF in the regulation of thrombosis.

Expression and functional importance of collagen-binding integrins, alpha 1 beta 1 and alpha 2 beta 1, on virus-activated T cells

DEFF Research Database (Denmark)

Andreasen, Susanne Ø; Thomsen, Allan R; Koteliansky, Victor E

2003-01-01

decreased responses were seen upon transfer of alpha(1)-deficient activated/memory T cells. Thus, expression of alpha(1)beta(1) and alpha(2)beta(1) integrins on activated T cells is directly functionally important for generation of inflammatory responses within tissues. Finally, the inhibitory effect......Adhesive interactions are crucial to cell migration into inflammatory sites. Using murine lymphocytic choriomeningitis virus as an Ag model system, we have investigated expression and function of collagen-binding integrins, alpha(1)beta(1) and alpha(2)beta(1), on activated and memory T cells. Using...... this system and MHC tetramers to define Ag-specific T cells, we demonstrate that contrary to being VLAs, expression of alpha(1)beta(1) and alpha(2)beta(1) can be rapidly induced on acutely activated T cells, that expression of alpha(1)beta(1) remains elevated on memory T cells, and that expression of alpha(1...

Alpha/beta separation in liquid scintillation gel samples

International Nuclear Information System (INIS)

Grau Carles, A.; Grau Malonda, A.

1994-01-01

The pulse shape analysis commonly used in liquid scintillation alpha/beta separations is satisfactory for moderate quench levels. However, for gel samples, the alpha particle counting efficiency is never greater than 10%, and an optimum separation of the alpha component cannot be achieved when beta to alpha counting rate ratios are greater than 100. In such cases, it is better to use a spectrum analysis method for alpha/beta separation. ((orig.))

Magnitude of a conformational change in the glycine receptor beta1-beta2 loop is correlated with agonist efficacy

DEFF Research Database (Denmark)

Pless, Stephan Alexander; Lynch, Joseph W

2009-01-01

associated with the closed-flip transition in the alpha1-glycine receptor. We employed voltage-clamp fluorometry to compare ligand-binding domain conformational changes induced by the following agonists, listed from highest to lowest affinity and efficacy: glycine > beta-alanine > taurine. Voltage...

Alpha5beta1 integrin-fibronectin interactions specify liquid to solid phase transition of 3D cellular aggregates.

Directory of Open Access Journals (Sweden)

Carlos E Caicedo-Carvajal

2010-07-01

Full Text Available Tissue organization during embryonic development and wound healing depends on the ability of cells on the one hand to exchange adhesive bonds during active rearrangement and on the other to become fixed in place as tissue homeostasis is reached. Cells achieve these contradictory tasks by regulating either cell-cell adhesive bonds, mediated by cadherins, or cell-extracellular matrix (ECM connections, regulated by integrins. Integrin alpha5beta1 and soluble fibronectin (sFN are key players in cell-ECM force generation and in ECM polymerization. Here, we explore the interplay between integrin alpha5beta1 and sFN and its influence on tissue mechanical properties and cell sorting behavior.We generated a series of cell lines varying in alpha5beta1 receptor density. We then systematically explored the effects of different sFN concentrations on aggregate biomechanical properties using tissue surface tensiometry. We found previously unreported complex behaviors including the observation that interactions between fibronectin and integrin alpha5beta1 generates biphasic tissue cohesion profiles. Specifically, we show that at constant sFn concentration, aggregate cohesion increases linearly as alpha5beta1 receptor density is increased from low to moderate levels, producing a transition from viscoelastic-liquid to pseudo viscoelastic-solid behavior. However, further increase in receptor density causes an abrupt drop in tissue cohesion and a transition back to viscoelastic-liquid properties. We propose that this may be due to depletion of sFn below a critical value in the aggregate microenvironment at high alpha5beta1 levels. We also show that differential expression of alpha5beta1 integrin can promote phase-separation between cells.The interplay between alpha5-integrin and sFn contributes significantly to tissue cohesion and, depending on their level of expression, can mediate a shift from liquid to elastic behavior. This interplay represents a tunable level

In vitro pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107.

Science.gov (United States)

Malysz, John; Anderson, David J; Grønlien, Jens H; Ji, Jianguo; Bunnelle, William H; Håkerud, Monika; Thorin-Hagene, Kirten; Ween, Hilde; Helfrich, Rosalind; Hu, Min; Gubbins, Earl; Gopalakrishnan, Sujatha; Puttfarcken, Pamela S; Briggs, Clark A; Li, Jinhe; Meyer, Michael D; Dyhring, Tino; Ahring, Philip K; Nielsen, Elsebet Ø; Peters, Dan; Timmermann, Daniel B; Gopalakrishnan, Murali

2010-09-01

Enhancement of alpha7 nicotinic acetylcholine receptor (nAChR) activity is considered a therapeutic approach for ameliorating cognitive deficits present in Alzheimer's disease and schizophrenia. In this study, we describe the in vitro profile of a novel selective alpha7 nAChR agonist, 5-(6-[(3R)-1-azabicyclo[2,2,2]oct-3-yloxy]pyridazin-3-yl)-1H-indole (ABT-107). ABT-107 displayed high affinity binding to alpha7 nAChRs [rat or human cortex, [(3)H](1S,4S)-2,2-dimethyl-5-(6-phenylpyridazin-3-yl)-5-aza-2-azoniabicyclo[2.2.1]heptane (A-585539), K(i) = 0.2-0.6 nM or [(3)H]methyllycaconitine (MLA), 7 nM] that was at least 100-fold selective versus non-alpha7 nAChRs and other receptors. Functionally, ABT-107 did not evoke detectible currents in Xenopus oocytes expressing human or nonhuman alpha3beta4, chimeric (alpha6/alpha3)beta4, or 5-HT(3A) receptors, and weak or negligible Ca(2+) responses in human neuroblastoma IMR-32 cells (alpha3* function) and human alpha4beta2 and alpha4beta4 nAChRs expressed in human embryonic kidney 293 cells. ABT-107 potently evoked human and rat alpha7 nAChR current responses in oocytes (EC(50), 50-90 nM total charge, approximately 80% normalized to acetylcholine) that were enhanced by the positive allosteric modulator (PAM) 4-[5-(4-chloro-phenyl)-2-methyl-3-propionyl-pyrrol-1-yl]-benzenesulfonamide (A-867744). In rat hippocampus, ABT-107 alone evoked alpha7-like currents, which were inhibited by the alpha7 antagonist MLA. In dentate gyrus granule cells, ABT-107 enhanced spontaneous inhibitory postsynaptic current activity when coapplied with A-867744. In the presence of an alpha7 PAM [A-867744 or N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-120596)], the addition of ABT-107 elicited MLA-sensitive alpha7 nAChR-mediated Ca(2+) signals in IMR-32 cells and rat cortical cultures and enhanced extracellular signal-regulated kinase phosphorylation in differentiated PC-12 cells. ABT-107 was also effective in protecting rat

Human CRF{sub 2} {alpha} and {beta} splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay

Energy Technology Data Exchange (ETDEWEB)

Ardati, A. [Rhone-Poulenc Rorer, Cardiovascular Biology, NW4, 500 Arcola Road, Collegeville, PA (United States); Goetschy, V.; Gottowick, J.; Henriot, S.; Deuschle, U.; Kilpatrick, G.J. [Central Nervous System, Pharma Division, F. Hoffmann-La Roche AG, CH-4070 Basel (Switzerland); Valdenaire, O. [Cardiovascular Research, Pharma Division, F. Hoffmann-La Roche AG, CH-4070 Basel (Switzerland)

1999-03-14

Corticotropin releasing factor (CRF) receptors belong to the super-family of G protein-coupled receptors. These receptors are classified into two subtypes (CRF{sub 1} and CRF{sub 2}). Both receptors are positively coupled to adenylyl cyclase but they have a distinct pharmacology and distribution in brain. Two isoforms belonging to the CRF{sub 2} subtype receptors, CRF{sub 2{alpha}} and CRF{sub 2{beta}}, have been identified in rat and man. The neuropeptides CRF and urocortin mediate their actions through this CRF G protein-coupled receptor family. In this report, we describe the pharmacological characterization of the recently identified hCRF{sub 2{beta}} receptor. We have used radioligand binding with [{sup 125}I]-tyr{sup 0}-sauvagine and a gene expression assay in which the firefly luciferase gene expression is under the control of cAMP responsive elements. Association kinetics of [{sup 125}I]-tyr{sup 0}-sauvagine binding to the hCRF{sub 2{beta}} receptor were monophasic while dissociation kinetics were biphasic, in agreement with the kinetics results obtained with the hCRF{sub 2{alpha}} receptor. Saturation binding analysis revealed two affinity states in HEK 293 cells with binding parameters in accord with those determined kinetically and with parameters obtained with the hCRF{sub 2{alpha}} receptor. A non-hydrolysable GTP analog, Gpp(NH)p, reduced the high affinity binding of [{sup 125}I]-tyr{sup 0}-sauvagine to both hCRF{sub 2} receptor isoforms in a similar manner. The rank order of potency of CRF agonist peptides in competition experiments was identical for both hCRF{sub 2}{alpha}-helical CRF{sub (9-41)}oCRF). Similarly, agonist potency was similar for the two isoforms when studied using the luciferase gene reporter system. The peptide antagonist {alpha}-helical CRF{sub (9-41)} exhibited a non-competitive antagonism of urocortin-stimulated luciferase expression with both hCRF{sub 2} receptor isoforms. Taken together, these results indicate that the

The loss of alpha2beta1 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis.

NARCIS (Netherlands)

Peters, M.E.W.J.; Wendholt, D.; Strietholt, S.; Frank, S.; Pundt, N.; Korb-Pap, A.; Joosten, L.A.B.; Berg, W.B. van den; Kollias, G.; Eckes, B.; Pap, T.

2012-01-01

OBJECTIVE: Integrin alpha2beta1 functions as a major receptor for type I collagen on different cell types, including fibroblasts and inflammatory cells. Although in vitro data suggest a role for alpha2beta1 integrin in regulating both cell attachment and expression of matrix-degrading enzymes such

Gd-EDDA/HYNIC-RGD as an MR molecular probe imaging integrin {alpha}{nu}{beta}3 receptor-expressed tumor-MR molecular imaging of angiogenesis

Energy Technology Data Exchange (ETDEWEB)

Huo Tianlong [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: huotianlong@bjmu.edu.cn; Du Xiangke [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: duxk@263.net; Zhang Sen [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: skagerrak_s@yahoo.com.cn; Liu Xia [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: iamliuxia@126.com; Li Xubing [Peking University People' s Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044 (China)], E-mail: lixb@bjmu.edu.cn

2010-02-15

Rationale and objective: The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin {alpha}{nu}{beta}3 receptor-expressed tumor. Materials and methods: Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd{sup 3+}, and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA/HYNIC-RGD. Human hepatocellular carcinoma (HHCC) cell line BEL-7402 was cultured and the cells harvested and suspended in serum-free Dulbecco's modified Eagle medium (DMEM) were subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin {alpha}{nu}{beta}3 receptor and cell viability experiments were conducted. The in vivo imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at time points of 0, 30, 60, 90 min and 24-h post-intravenous injection (p.i.). Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Results: Gd-EDDA/HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The nude mice model bearing HHCC was well established. There was approx. 30% signal enhancement on T1WI FSE images at 90 min post-intravenous injection of the Gd-EDDA/HYNIC-RGD compared with baseline, and the signal to time curve is straightforward over time in the span of 0-90 min p.i., while the control arms do not show this tendency. Conclusion: Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin {alpha}{nu}{beta}3 receptor-expressed tumor.

Photoaffinity cross-linking of a radioiodinated probe, 125I-A55453, into alpha 1-adrenergic receptors

International Nuclear Information System (INIS)

Dickinson, K.E.; Leeb-Lundberg, L.M.; Heald, S.L.; Wikberg, J.E.; DeBernardis, J.F.; Caron, M.G.; Lefkowitz, R.J.

1984-01-01

We have synthesized and characterized a high-affinity alpha 1-adrenergic receptor probe, 4-amino-6,7-dimethoxy-2[4'- [5''(3'''- 125 I-iodo-4'''-aminophenyl)pentanoyl]-1'-piperazinyl] quinazoline ( 125 I-A55453). This ligand binds reversibly to rat hepatic plasma membranes with high affinity (KD . 77 +/- 6 pM), and it labels the same number of specific prazosin-competable sites as the alpha 1-adrenergic receptor-selective radioligand [ 125 I] iodo-2-[beta-(4-hydroxyphenyl)-ethylaminomethyl]tetralone. Specific binding is stereoselective and competed for by alpha-adrenergic agents with an alpha 1-adrenergic receptor specificity. 125 I-A55453 can be covalently photoincorporated into peptides of rat hepatic and splenic membranes using the bifunctional photoactive cross-linker, N-succinimidyl-6- (4'-azido-2'-nitrophenylamino)hexanoate. Following photolysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of labeled hepatic membranes reveals a major specifically labeled peptide of Mr . 82,000 (+/- 1,000) with minor peptides at Mr . 50,000 (+/- 500), and 40,000 (+/- 300). Covalent incorporation of 125 I-A55453 into the Mr . 82,000 peptide is inhibited by adrenergic drugs with an alpha 1-adrenergic receptor specificity. Labeled splenic membranes demonstrate a broad band of photoincorporated radioactivity centered at Mr . 82,000, and covalent incorporation into this peptide is also attenuated with an alpha 1-adrenergic receptor specificity. This new high-affinity radioiodinated probe has features which should make it useful for the molecular characterization of alpha 1-adrenergic receptors in tissues

Impact of the Tamsulosin in Alpha Adrenergic Receptor of Airways at Patients with Increased Bronchial Reactibility.

Science.gov (United States)

Mustafa, Lirim; Ilazi, Ali; Dauti, Arta; Islami, Pellumb; Kastrati, Bashkim; Islami, Hilmi

2015-08-01

In this work, effect of tamsulosin as antagonist of alpha1A and alpha1B adrenergic receptor and effect of agonists of beta2 adrenergic receptor-salbutamol in patients with increased bronchial reactibility was studied. Parameters of the lung function are determined with Body plethysmography six (6) hours after administration of tamsulosin. Raw and ITGV were registered and specific resistance (SRaw) was calculated as well. Tamsulosin was administered in per os manner as a preparation in the shape of the capsules with a brand name of "Prolosin", produced by Niche Generics Limited, Hitchin, Herts. After six (6) hours of administration of tamsulosin, results gained indicate that blockage of alpha1A and alpha1B-adrenergic receptor (0.8 mg per os) has not changed significantly (p > 0.1) the bronchomotor tonus of tracheobronchial tree in comparison to the check-up that has inhaled salbutamol agonist of adrenergic beta2 receptor (2 inh. x 0.2 mg), (p tamsulosin. This suggests that even after six hours of administration of tamsulosin, and determining of lung function parameters, the activity of alpha1A and alpha1B-adrenergic receptor in the smooth bronchial musculature has not changed in patients with increased bronchial reactibility.

Characterization of high specific activity [16 alpha-123I]Iodo-17 beta-estradiol as an estrogen receptor-specific radioligand capable of imaging estrogen receptor-positive tumors

International Nuclear Information System (INIS)

Pavlik, E.J.; Nelson, K.; Gallion, H.H.; van Nagell, J.R. Jr.; Donaldson, E.S.; Shih, W.J.; Spicer, J.A.; Preston, D.F.; Baranczuk, R.J.; Kenady, D.E.

1990-01-01

16 alpha-[123I]Iodo-17 beta-estradiol (16 alpha-[123I]E2) has been characterized for use as a selective radioligand for estrogen receptor (ERc) that is capable of generating in situ images of ERc-positive tumors. High specific activity 16 alpha-[123I]E2 (7,500-10,000 Ci/mmol) was used in all determinations. Radiochemical purity was determined by thin layer chromatography, and the selectivity of radioligand for ERc was evaluated using size exclusion high performance liquid chromatography on ERc prepared from rodent uteri. Efficiencies of radioidination approaching 100% were achieved, and excellent receptor selectivity was obtained even when the efficiency of radioiodination was as low as 10%. Low radiochemical purity was always associated with poor selectivity for ERc. No new radioligand species was generated during the course of radiodecay; however, reduced binding over time, even when increased activity was used to compensate for radiodecay, indicated that the formation of a radioinert competitor does occur. 16 alpha-[123I]E2 demonstrated stable, high affinity binding to ERc and was concentrated by ERc-positive tissues. After injecting 16 alpha-[123I]E2 in vivo, images of ERc-containing tissues were obtained, including rabbit reproductive tract and dimethylbenzanthracene-induced tumors. The demonstrations of ERc selectivity and image formation both indicate that 16 alpha-[123I]E2 should have promise as a useful new radiopharmaceutical for imaging ERc-positive cancers

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)

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)

Determinants of RNA polymerase alpha subunit for interaction with beta, beta', and sigma subunits: hydroxyl-radical protein footprinting.

OpenAIRE

Heyduk, T; Heyduk, E; Severinov, K; Tang, H; Ebright, R H

1996-01-01

Escherichia coli RNA polymerase (RNAP) alpha subunit serves as the initiator for RNAP assembly, which proceeds according to the pathway 2 alpha-->alpha 2-->alpha 2 beta-->alpha 2 beta beta'-->alpha 2 beta beta' sigma. In this work, we have used hydroxyl-radical protein footprinting to define determinants of alpha for interaction with beta, beta', and sigma. Our results indicate that amino acids 30-75 of alpha are protected from hydroxyl-radical-mediated proteolysis upon interaction with beta ...

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....

Tc-labeling of Peptidomimetic Antagonist to Selectively Target alpha(v)beta(3) Receptor-Positive Tumor: Comparison of PDA and EDDA as co-Ligands.

Science.gov (United States)

Shin, In Soo; Maeng, Jin Soo; Jang, Beom-Su; You, Eric; Cheng, Kenneth; Li, King C P; Wood, Bradford; Carrasquillo, Jorge A; Danthi, S Narasimhan; Paik, Chang H

2010-01-01

OBJECTIVES: The aim of this research was to synthesize radiolabeled peptidomimetic integrin alpha(v)beta(3) antagonist with (99m)Tc for rapid targeting of integrin alpha(v)beta(3) receptors in tumor to produce a high tumor to background ratio. METHODS: The amino terminus of 4-[2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-beta-alanine hydrochloride (IAC) was conjugated with N-hydroxysuccinimide ester of HYNIC and labeled with (99m)Tc using tricine with either 1,5-pyridinedicarboxylic acid (PDA) or ethylenediamine-N,N'-diacetic acid (EDDA) as the co-ligand. The products, (99m)Tc EDDA(2)/HYNIC-IAC (P1) and (99m)Tc PDA (tricin)/HYNIC-IAC (P2) were subjected to in vitro serum stability, receptor-binding, biodistribution and imaging studies. RESULTS: P1 and P2 were synthesized with an overall yield of >80%. P1 was slightly more stable than P2 when incubated in serum at 37 degrees C for 18 hrs (84 vs 77% intact). The In vitro receptor-binding of P1 was higher than that of P2 (78.02 +/- 13.48 vs 51.05 +/- 14.05%) when incubated with alpha(v)beta(3) at a molar excess (0.8 muM). This receptor binding was completely blocked by a molar excess of an unlabeled peptidomimetic antagonist. Their differences shown in serum stability and the receptor-binding appeared to be related to their biological behaviors in tumor uptake and retention; the 1 h tumor uptakes of P1 and P2 were 3.17+/-0.52 and 2.13+/-0.17 % ID/g, respectively. P1 was retained in the tumor longer than P2. P1 was excreted primarily through the renal system whereas P2 complex was excreted equally via both renal and hepatobiliary systems. Thus, P1 was retained in the whole-body with 27.25 +/- 3.67% ID at 4 h whereas 54.04 +/- 3.57% ID of P2 remained in the whole-body at 4 h. This higher whole-body retention of P2 appeared to be resulted from a higher amount of radioactivity retained in liver and intestine. These findings were supported by

Topology characterization of a benzodiazepine-binding beta-rich domain of the GABAA receptor alpha1 subunit.

Science.gov (United States)

Xu, Zhiwen; Fang, Shisong; Shi, Haifeng; Li, Hoiming; Deng, Yiqun; Liao, Yinglei; Wu, Jiun-Ming; Zheng, Hui; Zhu, Huaimin; Chen, Hueih-Min; Tsang, Shui Ying; Xue, Hong

2005-10-01

Structural investigation of GABAA receptors has been limited by difficulties imposed by its trans-membrane-complex nature. In the present study, the topology of a membrane-proximal beta-rich (MPB) domain in the C139-L269 segment of the receptor alpha1 subunit was probed by mapping the benzodiazepine (BZ)-binding and epitopic sites, as well as fluorescence resonance energy transfer (FRET) analysis. Ala-scanning and semiconservative substitutions within this segment revealed the contribution of the phenyl rings of Y160 and Y210, the hydroxy group of S186 and the positive charge on R187 to BZ-binding. FRET with the bound BZ ligand indicated the proximity of Y160, S186, R187, and S206 to the BZ-binding site. On the other hand, epitope-mapping using the monoclonal antibodies (mAbs) against the MPB domain established a clustering of T172, R173, E174, Q196, and T197. Based on the lack of FRET between Trp substitutionally placed at R173 or V198 and bound BZ, this epitope-mapped cluster is located on a separate end of the folded protein from the BZ-binding site. Mutations of the five conserved Cys and Trp residues in the MPB domain gave rise to synergistic and rescuing effects on protein secondary structures and unfolding stability that point to a CCWCW-pentad, reminiscent to the CWC-triad "pin" of immunoglobulin (Ig)-like domains, important for the structural maintenance. These findings, together with secondary structure and fold predictions suggest an anti-parallel beta-strand topology with resemblance to Ig-like fold, having the BZ-binding and the epitopic residues being clustered at two different ends of the fold.

Expression of the alpha 6 beta 4 integrin by squamous cell carcinomas and basal cell carcinomas: possible relation to invasive potential?

DEFF Research Database (Denmark)

Rossen, K; Dahlstrøm, K K; Mercurio, A M

1994-01-01

We have studied the expression of alpha 6 beta 4 integrin, a carcinoma laminin receptor in ten squamous cell carcinomas (SCCs) and ten basal cell carcinomas (BCCs) of the skin in order to examine whether changes in alpha 6 beta 4 integrin expression may be related to invasive and metastatic...... potential. Monoclonal antibodies specific for each subunit were applied on cryosections, using a three step indirect peroxidase technique. In normal epidermis the basal cells expressed both the alpha 6 and the beta 4 subunits, and the expression was polarized against the basement membrane. In SCCs...

Isothermal and aniso-thermal creep in the {alpha} phase domain, {beta} phase domain and {alpha}+{beta} two phase domain in a Zr-1%NbO alloy; Fluage isotherme et anisotherme dans les domaines monophases ({alpha} et {beta}) et biphases ({alpha} et {beta}) d'un alliage Zr-1%NbO

Energy Technology Data Exchange (ETDEWEB)

Kaddour, D

2004-12-15

The coupling between phase transformation and mechanical behaviour of a Zr-1%NbO alloy was studied using an original experimental device already used in a previous study devoted to the Zy-4 alloy. The Zr-1%NbO alloy undergoes a phase transformation {alpha} (hc) {r_reversible} (cc) typically between 750 and 1000 C. The transformation temperatures were measured in situ by using the resistivity and dilatometry techniques. The isothermal creep behaviour of fuel cladding tubes was studied, first after heating, in the {alpha} phase domain between 650 and 760 C, in the {beta} phase domain between 960 and 1100 C, as well as in the ({alpha} + {beta}) two phase domain between 800 and 900 C. The results are summarized in Ashby deformation mechanism maps. It is confirmed that the {beta} phase is much more sensitive to creep flow than the {alpha} phase. The effect of microstructure on the isothermal creep flow behaviour was then investigated by first applying a thermal cycle involving either a full or a partial transformation from {alpha} to {beta}. It was investigated both in the {alpha} phase domain, and after direct cooling into the ({alpha} + {beta}) phase domain. The behaviour in aniso-thermal conditions was finally studied at heating and cooling rates of 10 and 200 C/min. In both cases, we showed that there is no significant transformation plasticity in the stress range under investigation ({<=} 5 MPa). A finite element model using Voronoi polyhedra and eventually meshing a film of intergranular {beta} phase was used to describe the behaviour of material in the ({alpha} + {beta}) domain in various microstructural states. The model predictions are in good agreement with the experimental results for the microstructure obtained after cooling, but the model underestimates creep deformation in the as-received state. This difference is probably related to the fact that interface sliding is not taken into account in the model. (author)

Quartz luminescence response to a mixed alpha-beta field: Investigations on Romanian loess

International Nuclear Information System (INIS)

Constantin, Daniela; Jain, Mayank; Murray, Andrew S.; Buylaert, Jan-Pieter; Timar-Gabor, Alida

2015-01-01

Previous SAR-OSL dating studies using quartz extracted from Romanian and Serbian loess samples report SAR-OSL dose–response curves on fine grained (4–11 μm) quartz that grow to much higher doses compared to those of coarse-grained (63–90, 90–125, 125–180 μm) quartz. Furthermore, quartz SAR-OSL laboratory dose response curves do not reflect the growth of the OSL signal in nature. A main difference in coarse- and fine-grained quartz dating lies in the alpha irradiation history, but the effect of mixed alpha-beta fields has so far received little attention. In the present study we investigate whether the alpha dose experienced by fine grains over geological cycles of irradiation and bleaching may have an effect on the saturation characteristics of the laboratory dose response. By applying time resolved optically stimulated luminescence we confirm that the OSL signals induced in quartz by alpha and beta radiation follow the same recombination path. We also show that a mixed alpha-beta dose response reproduces the beta dose response only up to about 800 Gy. Assuming an a-value of 0.04 we have shown that laboratory alpha and beta dose response curves overlap up to effective alpha doses of ∼50 Gy. Based on these results, we conclude that exposure of fine grains to alpha radiation during burial and transport cycles prior to deposition, as well exposure to the mixed radiation field experienced during burial are not responsible for the age discrepancies previously reported on fine and coarse grained quartz extracted from Romanian and Serbian loess. - Highlights: • Prior alpha irradiation history does not influence the laboratory beta growth curves. • Alpha and beta induced photon emissions in quartz follow the same recombination path. • Laboratory alpha and beta growth curves overlap up to total alpha doses of ∼1250 Gy. • Mixed alpha-beta growth curves reproduce the beta dose response curves up to ∼800 Gy. • Mixed radiation field is not

Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

Energy Technology Data Exchange (ETDEWEB)

Tachibana, Keisuke, E-mail: nya@phs.osaka-u.ac.jp [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takeuchi, Kentaro; Inada, Hirohiko [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yamasaki, Daisuke [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ishimoto, Kenji [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko [Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 (Japan); Doi, Takefumi [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

2009-11-20

Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial {beta}-oxidation. The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a ligand-activated transcription factor that plays an important role in the regulation of {beta}-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPAR{alpha} and found that PPAR{alpha} induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPAR{alpha} regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

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)

Noninvasive visualization and quantification of tumor {alpha}{sub V{beta}3} integrin expression using a novel positron emission tomography probe, {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4}

Energy Technology Data Exchange (ETDEWEB)

Jin, Zhao-Hui [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Furukawa, Takako, E-mail: tfuru@nirs.go.j [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Galibert, Mathieu; Boturyn, Didier [Departement de Chimie Moleculaire, UMR 5250, CNRS-Universite Joseph Fourier, 38041 Grenoble Cedex 9 (France); Coll, Jean-Luc [INSERM U823, Institut Albert Bonniot and Universite Joseph Fourier, 38706 La Tronche Cedex, Grenoble (France); Fukumura, Toshimitsu; Saga, Tsuneo [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Dumy, Pascal [Departement de Chimie Moleculaire, UMR 5250, CNRS-Universite Joseph Fourier, 38041 Grenoble Cedex 9 (France); Fujibayashi, Yasuhisa [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan)

2011-05-15

Introduction: The {alpha}{sub V{beta}3} integrin is a well-known transmembrane receptor involved in tumor invasion, angiogenesis and metastasis. Our aim was to evaluate a novel positron emission tomography (PET) probe, {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4}, for noninvasive visualization and quantification of {alpha}{sub V{beta}3} integrin expression. Methods: RAFT-c(-RGDfK-){sub 4}, a tetrameric cyclic Arg-Gly-Asp (RGD)-based peptide, was conjugated with a bifunctional chelator, 1,4,8,11-tetraazacyclotetradecane (cyclam), radiolabeled with the positron emitter {sup 64}Cu and evaluated in vitro by cell binding and competitive inhibition assays and in vivo by biodistribution and receptor blocking studies, and PET imaging. The following cell lines, human embryonic kidney HEK293({beta}{sub 1}) [{alpha}{sub V{beta}3}-negative] and HEK293({beta}{sub 3}) [{alpha}{sub V{beta}3}-overexpressing] and human glioblastoma U87MG [naturally expressing {alpha}{sub V{beta}3}], together with their subcutaneous xenografts in athymic nude mice, were used for the present study. The expression levels of {alpha}{sub V{beta}3} on these cell lines and tumor xenografts were analyzed by flow cytometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography, respectively. Results: {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4} demonstrated the in vitro and in vivo specificity for the {alpha}{sub V{beta}3} integrin and displayed rapid blood clearance, predominantly renal excretion and low uptake in nontumor tissues. Tumor uptake of {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4} (3 h postinjection) in HEK293({beta}{sub 3}) (high levels of {alpha}{sub V{beta}3}), U87MG (moderate levels of {alpha}{sub V{beta}3}) and HEK293({beta}{sub 1}) (undetectable levels of {alpha}{sub V{beta}3}) tumors was 9.35%{+-}1.19%, 3.46%{+-}0.45% and 1.18%{+-}0.30% injected dose per gram, respectively, with a strong and positive correlation with the tumor {alpha}{sub V{beta}3} expression levels

DB-1900 low-background measuring device of alpha and beta

International Nuclear Information System (INIS)

Liu Hongquan; Gan Jinbang; Chen Qi; Zhao Yunqing

1997-08-01

The device is a box-type detector used to measure the emissivity of Alpha and Beta from dry samples under 2π geometry in radionuclide metrology. It is composed of a high efficiency αβ detector with electrostatic screen of zero potential [patent ZL92111938.0 (in China)] and anticoincidence detector in lead chamber, and has been reasonably combined with double anticoincidence technique to form integral equipment. The characteristics of the device are as follows: It can stably measure the emissivity of Alpha and Beta from dry samples with less surface conductivity (the surface resistance of the samples: 13 Ω) in detector. It can measure Beta emissivity from samples in which Alpha coexist with Beta, and discrimination between Alpha and Beta emissivities can be made simultaneously by two paths. It is a good quantitative means for measuring Alpha and Beta radiation in radiometry, radiation protection and environmental protection. It could be used to measure weak radiativity of Alpha and Beta samples from scientific research, minerals, building materials, plastics, medicinal materials, seas and oceans biology, et al. (7 refs., 8 tabs., 17 figs.)

Prevalence of Co-Inheritance of Alpha-Thalassemia with Beta-Thalassemia and Beta-Hemoglobinopathy in Ahvaz City

Directory of Open Access Journals (Sweden)

Najmaddin Saki

2013-09-01

Full Text Available Background: Co-inheritance of hemoglobin gene defects is a rare important status that can lead to double heterozygote or homozygote with significant clinical manifestations. Such conditions can be observed in co-inheritance of alpha-thalassemia with beta-thalassemia or hemoglobinopathy. The aim of this study was to evaluate the prevalence of alpha-thalassemia with beta-thalassemia and hemoglobinopathy co-inheritance in a considerable number of Iranian.   Methods: This descriptive study was performed on patients with abnormal hematological findings in favor of alpha-thalassemia, beta-thalassemia or beta-hemoglobinopathies. Patients with low MCV and MCH levels and high HbA2 (>3.5 and those with low MCV and MCH and normal or low HbA2 were candidate for molecular analysis for beta and alpha thalassemia respectively. Abnormal Hb electrophoresis was diagnostic criteria for molecular analysis of beta-hemoglobinopathies.   Results: Study revealed that more than half of the patients with alpha-thalassemia affected simultaneously by beta-thalassemia and about thirty percent inherited beta-hemoglobinopathies. Among patients with beta-thalassemia, HbSCd6 (A-T was the most common mutation and in alpha-thalassemic patients α 3.7 was the commonest mutation.   Conclusion: Relatively high prevalence of co-inheritance of alfa-thalassemia with beta-thalassemia and hemoglobinopathies reflect the necessity of genetic consulting and molecular analysis in diagnosis of such conditions.

SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.

Science.gov (United States)

McGlade, C J; Ellis, C; Reedijk, M; Anderson, D; Mbamalu, G; Reith, A D; Panayotou, G; End, P; Bernstein, A; Kazlauskas, A

1992-01-01

The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors. Images PMID:1372092

RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages

DEFF Research Database (Denmark)

von Wichert, Gotz; Jiang, Guoying; Kostic, Ana

2003-01-01

Cell motility on ECM critically depends on the cellular response to force from the matrix. We find that force-dependent reinforcement of alphav/beta3-integrin-mediated cell-matrix connections requires the receptor-like tyrosine phosphatase alpha (RPTPalpha). RPTPalpha colocalizes with alphav...... of alphav/beta3-integrin-cytoskeleton connections during the initial phase of ECM contact. These observations indicate that Src family kinases have distinct functions during adhesion site assembly, and that RPTPalpha is an early component in force-dependent signal transduction pathways leading...

Expression and Regulation of the Bile Acid Transporter, OST alpha-OST beta in Rat and Human Intestine and Liver

NARCIS (Netherlands)

Khan, Ansar A.; Chow, Edwin C. Y.; Porte, Robert J.; Pang, K. Sandy; Groothuis, Geny M. M.

The regulation of the OST alpha and OST beta expression was studied in the rat jejunum, ileum, colon and liver and in human ileum and liver by ligands for the farnesoid X receptor (FXR), pregnane X receptor (PXR), vitamin D receptor (VDR) and glucocorticoid receptor (GR) using precision cut tissue

Protective effect of ciliary neurotrophic factor (CNTF) in a model of endotoxic shock: action mechanisms and role of CNTF receptor alpha.

Science.gov (United States)

Demitri, M T; Benigni, F; Meazza, C; Zinetti, M; Fratelli, M; Villa, P; Acheson, A; Panayotatos, N; Ghezzi, P

1998-01-01

Ciliary neurotrophic factor (CNTF) inhibits the production of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-treated mice and protects against LPS lethality when coadministered with its soluble receptor (sCNTFR alpha). Both of these activities are abolished in adrenalectomized (ADX) mice. LPS-induced pulmonary polymorphonuclear neutrophil (PMN) infiltration and nitric oxide (NO) production were also inhibited by CNTF + sCNTFR alpha but not by CNTF alone. sCNTFR alpha did not alter the clearance or tissue distribution of CNTF. Furthermore, CNTF variants coadministered with sCNTFR alpha protected against LPS toxicity in a manner related to their affinity for the beta components of CNTFR. Thus, inhibition of TNF production and protection against LPS lethality by CNTF/sCNTFR alpha require an intact hypothalamus-pituitary-adrenal axis (HPAA) and may be mediated by endogenous glucocorticoids. This protective effect is, at least in part, due to the inhibition of PMN infiltration and NO production, and appears to be mediated by cells displaying only beta-receptor subtypes.

Beta-endorphin and alpha-n-acetyl beta-endorphin; synthesis, conformation and binding parameter

Energy Technology Data Exchange (ETDEWEB)

Lovegren, E.S.

1986-01-01

Beta-endorphin (EP) is a 31-residue opioid peptide found in many tissues, including the pituitary, brain and reproductive tract. Alpha-amino-acetyl beta-endorphin (AcEP) was characterized spectroscopically by proton nuclear magnetic resonance (NMR) and circular dichroism in deuterated water and trifluoroethanol (TFE). Both EP and AcEP bind to neuroblastoma N2a cells. This binding was not mediated through opiate receptors, and both peptides seemed to bind at common sites. Ovarian immunoreactive-EP levels were determined for immature and mature rates. These levels were found to be responsive to exogenous gonadotropin treatment in immature animals. A large percentage of the immunoreactive-EP is present in follicular fluid, and most of the endorphin-like peptides were acetylated, as measured by radioimmunoassay. Chromatogaphic analysis suggested at least three EP-like species: EP, a carboxy-terminally cleaved and an amino-terminally acetylated EP.

Cow's milk increases the activities of human nuclear receptors peroxisome proliferator-activated receptors alpha and delta and retinoid X receptor alpha involved in the regulation of energy homeostasis, obesity, and inflammation.

Science.gov (United States)

Suhara, W; Koide, H; Okuzawa, T; Hayashi, D; Hashimoto, T; Kojo, H

2009-09-01

The nuclear peroxisome proliferator-activated receptors (PPAR) have been shown to play crucial roles in regulating energy homeostasis including lipid and carbohydrate metabolism, inflammatory responses, and cell proliferation, differentiation, and survival. Because PPAR agonists have the potential to prevent or ameliorate diseases such as hyperlipidemia, diabetes, atherosclerosis, and obesity, we have explored new natural agonists for PPAR. For this purpose, cow's milk was tested for agonistic activity toward human PPAR subtypes using a reporter gene assay. Milk increased human PPARalpha activity in a dose-dependent manner with a 3.2-fold increase at 0.5% (vol/vol). It also enhanced human PPARdelta activity in a dose-dependent manner with an 11.5-fold increase at 0.5%. However, it only slightly affected human PPARgamma activity. Ice cream, butter, and yogurt also increased the activities of PPARalpha and PPARdelta, whereas vegetable cream affected activity of PPARdelta but not PPARalpha. Skim milk enhanced the activity of PPAR to a lesser degree than regular milk. Milk and fresh cream increased the activity of human retinoid X receptor (RXR)alpha as well as PPARalpha and PPARdelta, whereas neither affected vitamin D3 receptor, estrogen receptors alpha and beta, or thyroid receptors alpha and beta. Both milk and fresh cream were shown by quantitative real-time PCR to increase the quantity of mRNA for uncoupling protein 2 (UCP2), an energy expenditure gene, in a dose-dependent manner. The increase in UCP2 mRNA was found to be reduced by treatment with PPARdelta-short interfering (si)RNA. This study unambiguously clarified at the cellular level that cow's milk increased the activities of human PPARalpha, PPARdelta, and RXRalpha. The possible role in enhancing the activities of PPARalpha, PPARdelta, and RXRalpha, and the health benefits of cow's milk were discussed.

Biotinylated human. beta. -endorphins as probes for the opioid receptor

Energy Technology Data Exchange (ETDEWEB)

Hochhaus, G.; Gibson, B.W.; Sadee, W.

1988-01-05

The reaction of human ..beta..-endorphin and biotinyl N-hydroxysuccinimide with or without spacer arm, afforded a series of products that were separated by high performance liquid chromatography (HPLC). Liquid secondary ion mass spectrometry of the biotinylated products and their tryptic digests produced abundant protonated molecular ions (MH/sup +/), which specified the number and location of biotinylation. Between 1 and 4 biotinyl residues were incorporated per human ..beta..-endorphin molecule, at Lys-9, -19, -24, -28, and -29, but not at the amino-terminal Try-1. Three HPLC fractions were isolated for receptor binding studies monobiotinylation of Lys-9, Lys-19, and a mixture of Lys-24, Lys-28, and Lys-29 derivatives. IC/sub 50/ values for binding to ..mu.. and delta opioid receptor sites were 3-8 times higher for monobiotinylated derivatives than for the parent human ..beta..-endorphin. Association with avidin decreased opioid receptor affinities for the C/sub 6/ spacer derivative biotinylated at position Lys-9, which is close to the (1-5) enkephalin receptor region. In contrast, avidin did not affect or even increased apparent affinities to ..mu.. and delta sites for derivatives biotinylated at the ..cap alpha..-helical part of the molecule (Lys-19, -24, -28, and -29). Biotinylated human ..beta..-endorphins also bound to low affinity nonopioid binding sites on NG-108-15 cells; however, affinities to these sites were considerably reduced when derivatives were bound to avidin. The ability of biotinylated human ..beta..-endorphin to cross-link the ..mu.. and delta opioid receptors to avidin allows application of the biotin-avidin system as a molecular probe of the opioid receptor.

Synthesis of plastic scintillation microspheres: Alpha/beta discrimination

International Nuclear Information System (INIS)

Santiago, L.M.; Bagán, H.; Tarancón, A.; Garcia, J.F.

2014-01-01

Plastic scintillation microspheres (PSm) have been developed as an alternative for liquid scintillation cocktails due to their ability to avoid the mixed waste, besides other strengths in which the possibility for alpha/beta discrimination is included. The aim of this work was to evaluate the capability of PSm containing two combinations of fluorescence solutes (PPO/POPOP and pT/Bis-MSB) and variable amounts of a second organic solvent (naphthalene) to enhance the alpha/beta discrimination. Two commercial detectors with different Pulse Shape Discrimination performances (Quantulus and Triathler) were used to evaluate the alpha/beta discrimination. An optimal discrimination of alpha/beta particles was reached, with very low misclassification values (2% for beta particles and 0.5% for alpha particles), when PSm containing PPO/POPOP and between 0.6 and 2.0 g of naphthalene were evaluated using Triathler and the appropriate programme for data processing. - Highlights: • Plastic scintillation microspheres for α/β discrimination have been synthesised. • The energy transfer process in PSm with different compositions has been investigated. • The α/β discrimination capabilities of two commercial detectors have been evaluated. • 2% and 0.5% of misclassifications for β and α radionuclides have been achieved respectively

Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

International Nuclear Information System (INIS)

Engl, Tobias; Makarević, Jasmina; Relja, Borna; Natsheh, Iyad; Müller, Iris; Beecken, Wolf-Dietrich; Jonas, Dietger; Blaheta, Roman A

2005-01-01

Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF) on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a), alpha2beta1 (CD49b), alpha3beta1 (CD49c), alpha4beta1 (CD49d), alpha5beta1 (CD49e), and alpha6beta1 (CD49f) receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype

Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors.

Science.gov (United States)

Kelley, Joshua B; Talley, Ashley M; Spencer, Adam; Gioeli, Daniel; Paschal, Bryce M

2010-08-11

Classical nuclear localization signal (NLS) dependent nuclear import is carried out by a heterodimer of importin alpha and importin beta. NLS cargo is recognized by importin alpha, which is bound by importin beta. Importin beta mediates translocation of the complex through the central channel of the nuclear pore, and upon reaching the nucleus, RanGTP binding to importin beta triggers disassembly of the complex. To date, six importin alpha family members, encoded by separate genes, have been described in humans. We sequenced and characterized a seventh member of the importin alpha family of transport factors, karyopherin alpha 7 (KPNA7), which is most closely related to KPNA2. The domain of KPNA7 that binds Importin beta (IBB) is divergent, and shows stronger binding to importin beta than the IBB domains from of other importin alpha family members. With regard to NLS recognition, KPNA7 binds to the retinoblastoma (RB) NLS to a similar degree as KPNA2, but it fails to bind the SV40-NLS and the human nucleoplasmin (NPM) NLS. KPNA7 shows a predominantly nuclear distribution under steady state conditions, which contrasts with KPNA2 which is primarily cytoplasmic. KPNA7 is a novel importin alpha family member in humans that belongs to the importin alpha2 subfamily. KPNA7 shows different subcellular localization and NLS binding characteristics compared to other members of the importin alpha family. These properties suggest that KPNA7 could be specialized for interactions with select NLS-containing proteins, potentially impacting developmental regulation.

Identification of a novel bile acid in swans, tree ducks, and geese: 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid.

Science.gov (United States)

Kakiyama, Genta; Iida, Takashi; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Nambara, Toshio; Hagey, Lee R; Schteingart, Claudio D; Hofmann, Alan F

2006-07-01

By HPLC, a taurine-conjugated bile acid with a retention time different from that of taurocholate was found to be present in the bile of the black-necked swan, Cygnus melanocoryphus. The bile acid was isolated and its structure, established by (1)H and (13)C NMR and mass spectrometry, was that of the taurine N-acyl amidate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid. The compound was shown to have chromatographic and spectroscopic properties that were identical to those of the taurine conjugate of authentic 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid, previously synthesized by us from ursodeoxycholic acid. By HPLC, the taurine conjugate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid was found to be present in 6 of 6 species in the subfamily Dendrocygninae (tree ducks) and in 10 of 13 species in the subfamily Anserinae (swans and geese) but not in other subfamilies in the Anatidae family. It was also not present in species from the other two families of the order Anseriformes. 3alpha,7alpha,15alpha-Trihydroxy-5beta-cholan-24-oic acid is a new primary bile acid that is present in the biliary bile acids of swans, tree ducks, and geese and may be termed 15alpha-hydroxy-chenodeoxycholic acid.

PGC-1alpha and PGC-1beta have both similar and distinct effects on myofiber switching toward an oxidative phenotype

DEFF Research Database (Denmark)

Mortensen, Ole Hartvig; Frandsen, Lis; Schjerling, Peter

2006-01-01

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta (PGC-1alpha and PGC-1beta) were overexpressed by adenovirus-mediated gene transfer in cultures of primary rat skeletal muscle cells derived from neonatal myoblasts. Effects on muscle fiber type transition and metabolism...... an increase in the mRNA expression of TRB3, a negative regulator of insulin signaling. These results show that both PGC-1alpha and PGC-1beta are involved in the regulation of skeletal muscle fiber transition and metabolism and that they have both overlapping and differing effects....... were studied from days 5 to 22 of culture. PGC-1alpha and PGC-1beta overexpression caused a three- to fourfold increase in mRNA level, a doubling of enzymatic activity of citrate synthase, a slight increase in short-chain acyl-CoA dehydrogenase mRNA, a doubling of the mRNA level, and a 30-50% increase...

High Affinity IgE-Fc Receptor alpha and gamma Subunit Interactions

International Nuclear Information System (INIS)

Rashid, A.; Housden, J. E. M.; Sabban, S.; Helm, B.

2014-01-01

Objective: To explore the relationships between the subunits (alpha, beta and gamma) of the high affinity IgE receptor (Fc and RI) and its ability to mediate transmembrane signaling. Study Design: Experimental study. Place and Duration of Study: Department of Molecular Biology and Biotechnology, University of Sheffield, UK, from 2008 to 2009. Methodology: The approach employed was to create a chimera (human alpha-gamma-gamma) using the extracellular (EC) domain of the human high affinity IgE receptor. The alpha subunit (huFc and RIalpha) of IgE receptor was spliced onto the rodent gamma TM and cytoplasmic domain (CD). This was transfected into the Rat Basophilic Leukemia cell line in order to assess the possibility of selectively activating cells transfected with this single pass construct for antigen induced mediator release. Results: The RBLs cell lines transfected with the huFc and RIalpha/gamma/gamma cDNA constructs were assessed for the cell surface expression of the huFc and RIalpha subunit and the response to the antigenic stimulus by looking for degranulation and intracellular Ca2+ mobilisation. The results obtained showed the absence of huFc and RIalpha subunit expression on the surface of transfected cells as seen by flowcytometric studies, beta-hexosaminidase assays and intracellular calcium mobilisation studies. Conclusion: In the present study the grounds for non-expression of huFc and RIalpha/gamma/gamma cDNA remains elusive but may be due to the fact that the human-rodent chimeric receptors are assembled differently than the endogenous rodent receptors as seen in study in which COS 7 cells were transfected with human/rat chimeric complexes. (author)

Inhibition of HIF-2.alpha. heterodimerization with HIF1.beta. (ARNT)

Science.gov (United States)

Bruick, Richard K.; Caldwell, Charles G.; Frantz, Doug E.; Gardner, Kevin H.; MacMillan, John B.; Scheuermann, Thomas H.; Tambar, Uttam K.

2017-09-12

Provided is a method of inhibiting heterodimerization of HIF-2.alpha. to HIF1.beta. (ARNT) comprising binding certain small molecules to the HIF-2.alpha. PAS-B domain cavity but not to HIF1.alpha. and inhibiting HIF-2.alpha. heterodimerization to HIF1.beta. (ARNT) but not inhibiting HIF1.alpha. heterodimerization to HIF1.beta. (ARNT). Those certain small molecules are also referenced synonymously as HIF2-HDI and HIF2.alpha. heterodimerization inhibitors and also simply as certain small molecules.

Über die Reaktion von [alpha]- und [beta]-Tetralon mit Kaliumsuperoxid

OpenAIRE

Lissel, Manfred

1984-01-01

The reaction of [alpha]- and [beta]-tetralone with potassium superoxide is described. In addition to 2-hydroxy-1,4-naphthoquinone [alpha]-naphthol is formed from [alpha]-tetralone and [beta]-naphthol and 2-carboxy-benzenepropionic acid from [beta]-tetralone.

Alpha/beta(gamma ray) discrimination and spillover quantification with a BaF2 scintillator

International Nuclear Information System (INIS)

DeVol, T.A.; Fjeld, R.A.

1994-01-01

A simple pulse shape discrimination technique was used to separate alpha and beta(gamma ray) interactions in a BaF 2 scintillator. The separation was not ideal, resulting in a 5.1% spillover of alpha interactions into the beta(gamma ray) channel and 11.9% spillover of beta(gamma ray) interactions into the alpha channel for a set pulse shape discriminator. The misclassification of events was reduced by post-processing the data using either a simple analytical technique or a more complex linear least squares technique. Both techniques typically reduced the difference between the expected and calculated interaction rates to <10% when the ratio of beta(gamma ray) to alpha count rate was less than 100 : 1. ((orig.))

A manual low background alpha beta counting system

Energy Technology Data Exchange (ETDEWEB)

Levison, S; German, U; Peled, O; Turgeman, S; Vangrovitz, U; Tirosh, D; Piestum, S; Assido, H [Israel Atomic Energy Commission, Beersheba (Israel). Nuclear Research Center-Negev

1996-12-01

An Alpha and Beta counting system consisting of a micro controller-based electronic unit and detectors assembly was developed. The radiation detection unit consists of two proportional detectors (a main detector and a cosmic-ray guard detector) which can be easily disassembled for decontamination or repair. The detectors are mounted in a manual operating sample changer shielded by 5 cm of lead. Simplicity of maintenance and functional operation were taken into consideration in the design. The electronic unit supplies the high voltage and enables the operational functions including controls anti alarms. Calculations of net cpm of Alpha and Beta counting are displayed and can be printed. RS-232 communication option enables connection to a computer and operation of more sophisticated programs for calculations and data storage in the future (authors).

A manual low background alpha beta counting system

International Nuclear Information System (INIS)

Levison, S.; German, U.; Peled, O.; Turgeman, S.; Vangrovitz, U.; Tirosh, D.; Piestum, S.; Assido, H.

1996-01-01

An Alpha and Beta counting system consisting of a micro controller-based electronic unit and detectors assembly was developed. The radiation detection unit consists of two proportional detectors (a main detector and a cosmic-ray guard detector) which can be easily disassembled for decontamination or repair. The detectors are mounted in a manual operating sample changer shielded by 5 cm of lead. Simplicity of maintenance and functional operation were taken into consideration in the design. The electronic unit supplies the high voltage and enables the operational functions including controls anti alarms. Calculations of net cpm of Alpha and Beta counting are displayed and can be printed. RS-232 communication option enables connection to a computer and operation of more sophisticated programs for calculations and data storage in the future (authors)

Molecular determinants of desensitization and assembly of the chimeric GABA(A) receptor subunits (alpha1/gamma2) and (gamma2/alpha1) in combinations with beta2 and gamma2

DEFF Research Database (Denmark)

Elster, L; Kristiansen, U; Pickering, D S

2001-01-01

Two gamma-aminobutyric acid(A) (GABA(A)) receptor chimeras were designed in order to elucidate the structural requirements for GABA(A) receptor desensitization and assembly. The (alpha1/gamma2) and (gamma2/alpha1) chimeric subunits representing the extracellular N-terminal domain of alpha1 or gamma......, as opposed to the staining of the (gamma2/alpha1)-containing receptors, which was only slightly higher than background. To explain this, the (alpha1/gamma2) and (gamma2/alpha1) chimeras may act like alpha1 and gamma2 subunits, respectively, indicating that the extracellular N-terminal segment is important...... for assembly. However, the (alpha1/gamma2) chimeric subunit had characteristics different from the alpha1 subunit, since the (alpha1/gamma2) chimera gave rise to no desensitization after GABA stimulation in whole-cell patch-clamp recordings, which was independent of whether the chimera was expressed...

Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-{alpha}

Energy Technology Data Exchange (ETDEWEB)

Lee, Ji Hae; Jun, Hee-jin; Hoang, Minh-Hien; Jia, Yaoyao [Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Han, Xiang Hua [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Lee, Dong-Ho [Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Lee, Hak-Ju [Division of Green Business Management, Department of Forest Resources Utilization, Korean Forest Research Institute, Seoul 130-712 (Korea, Republic of); Hwang, Bang Yeon, E-mail: byhwang@chungbuk.ac.kr [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Lee, Sung-Joon, E-mail: junelee@korea.ac.kr [Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

2012-06-15

Highlights: Black-Right-Pointing-Pointer Catalposide is a novel ligand for PPAR{alpha}. Black-Right-Pointing-Pointer Cell stimulated with catalposide improved fatty acid uptake, regulated target genes in fatty acid {beta}-oxidation and synthesis. Black-Right-Pointing-Pointer Catalposdie reduces hepatic triacylglycerides. Black-Right-Pointing-Pointer Theses demonstrate catalposide could ameliorate hyperlipidemia and hepatic steatosis. -- Abstract: Peroxisome proliferator-activated receptor-alpha (PPAR{alpha}) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPAR{alpha} agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPAR{alpha} agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts. Results of time-resolved fluorescence resonance energy transfer analyses suggested that the compound interacted directly with the ligand-binding domain of PPAR{alpha}. Cultured hepatocytes stimulated with catalposide exhibited significantly reduced cellular triglyceride concentrations, by 21%, while cellular uptake of fatty acids was increased, by 70% (P < 0.05). Quantitative PCR analysis revealed that the increase in cellular fatty acid uptake was due to upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells stimulated with catalposide. Additionally, expression of genes related to fatty acid oxidation and high-density lipoprotein metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed. In conclusion, catalposide is hypolipidemic by activation of PPAR{alpha} via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.

Biaxial creep deformation of Zircaloy-4 PWR fuel cladding in the alpha,(alpha + beta) and beta phase temperature ranges

International Nuclear Information System (INIS)

Donaldson, A.T.; Healey, T.; Horwood, R.A.L.

1985-01-01

The biaxial creep behaviour of Zircaloy-4 fuel cladding has been determined at temperatures between 973 - 1073 K in the alpha phase range, in the duplex (alpha + beta) region between 1098 - 1223 K and in the beta phase range between 1323 - 1473 K. This paper presents the creep data together with empirical equations which describe the creep deformation response within each phase region. (author)

The 2.0-A resolution structure of soybean beta-amylase complexed with alpha-cyclodextrin.

Science.gov (United States)

Mikami, B; Hehre, E J; Sato, M; Katsube, Y; Hirose, M; Morita, Y; Sacchettini, J C

1993-07-13

New crystallographic findings are presented which offer a deeper understanding of the structure and functioning of beta-amylase, the first known exo-type starch-hydrolyzing enzyme. A refined three-dimensional structure of soybean beta-amylase, complexed with the inhibitor alpha-cyclodextrin, has been determined at 2.0-A resolution with a conventional R-value of 17.5%. The model contains 491 amino acid residues, 319 water molecules, 1 sulfate ion, and 1 alpha-cyclodextrin molecule. The protein consists of a core with an (alpha/beta)8 supersecondary structure, plus a smaller globular region formed by long loops (L3, L4, and L5) extending from beta-strands beta 3, beta 4, and beta 5. Between the two regions is a cleft that opens into a pocket whose floor contains the postulated catalytic center near the carboxyl group of Glu 186. The annular alpha-cyclodextrin binds in (and partly projects from) the cleft with its glucosyl O-2/O-3 face abutting the (alpha/beta)8 side and with its alpha-D(1 --> 4) glucosidic linkage progression running clockwise as viewed from that side. The ligand does not bind deeply enough to interact with the carboxyl group of Glu 186. Rather, it occupies most of the cleft entrance, strongly suggesting that alpha-cyclodextrin inhibits catalysis by blocking substrate access to the more deeply located reaction center. Of the various alpha-cyclodextrin interactions with protein residues in loops L4, L5, L6, and L7, most notable is the shallow inclusion complex formed with Leu 383 (in L7, on the core side of the cleft) through contacts of its methyl groups with the C-3 atoms of four of the ligand's D-glucopyranosyl residues. All six residues of the bound alpha-cyclodextrin are of 4C1 conformation and are joined by alpha-1,4 linkages with similar torsional angles to form a nearly symmetrical torus as reported for crystalline inclusion complexes with alpha-cyclodextrin. We envision a significant role for the methyl groups of Leu 383 at the cleft entrance

Platelet-derived growth factor receptors in the human central nervous system : autoradiographic distribution and receptor densities in multiple sclerosis

NARCIS (Netherlands)

De Keyser, J; Wilczak, N

1997-01-01

Platelet derived growth factor (PDGF) receptors were studied in postmortem adult human brain and cervical spinal cord using autoradiography with human recombinant I-125-PDGF-BB. PDGF-BB binds to the three different dimers of PDGF receptors (alpha alpha, alpha beta and beta beta) PDGF receptors were

Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

Directory of Open Access Journals (Sweden)

Beecken Wolf-Dietrich

2005-01-01

Full Text Available Abstract Background Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Methods Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a, alpha2beta1 (CD49b, alpha3beta1 (CD49c, alpha4beta1 (CD49d, alpha5beta1 (CD49e, and alpha6beta1 (CD49f receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Results Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. Conclusion We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype.

Decreased cerebral {alpha}4{beta}2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer's disease assessed with positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Kendziorra, Kai; Meyer, Philipp Mael; Barthel, Henryk; Hesse, Swen; Becker, Georg Alexander; Luthardt, Julia; Schildan, Andreas; Patt, Marianne; Sorger, Dietlind; Seese, Anita; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Wolf, Henrike [University of Leipzig, Department of Psychiatry, Leipzig (Germany); University of Zurich, Department of Old Age Psychiatry and Psychiatry Research, Psychiatric University Hospital (PUK) Zurich, Zurich (Switzerland); Gertz, Herman-Josef [University of Leipzig, Department of Psychiatry, Leipzig (Germany)

2011-03-15

Postmortem studies indicate a loss of nicotinic acetylcholine receptor (nAChRs) in Alzheimer's disease (AD). In order to establish whether these changes in the cholinergic system occur at an early stage of AD, we carried out positron emission tomography (PET) with a specific radioligand for the {alpha}4{beta}2* nicotinic acetylcholine receptor ({alpha}4{beta}2* nAChR) in patients with mild to moderate AD and in patients with amnestic mild cognitive impairment (MCI), who have a high risk to progress to AD. Nine patients with moderate AD, eight patients with MCI and seven age-matched healthy controls underwent 2-[{sup 18}F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[{sup 18}F]FA-85380) PET. After coregistration with individual magnetic resonance imaging the binding potential (BP{sub ND}) of 2-[{sup 18}F]FA-85380 was calculated using either the corpus callosum or the cerebellum as reference regions. PET data were analysed by region of interest analysis and by voxel-based analysis. Both patients with AD and MCI showed a significant reduction in 2-[{sup 18}F]FA-85380 BP{sub ND} in typical AD-affected brain regions. Thereby, the corpus callosum was identified as the most suitable reference region. The 2-[{sup 18}F]FA-85380 BP{sub ND} correlated with the severity of cognitive impairment. Only MCI patients that converted to AD in the later course (n = 5) had a reduction in 2-[{sup 18}F]FA-85380 BP{sub ND}. 2-[{sup 18}F]FA-85380 PET appears to be a sensitive and feasible tool for the detection of a reduction in {alpha}4{beta}2* nAChRs which seems to be an early event in AD. In addition, 2-[{sup 18}F]FA-85380 PET might give prognostic information about a conversion from MCI to AD. (orig.)

PAR-2, IL-4R, TGF-beta and TNF-alpha in bronchoalveolar lavage distinguishes extrinsic allergic alveolitis from sarcoidosis

Czech Academy of Sciences Publication Activity Database

Matěj, R.; Smětáková, M.; Vašáková, M.; Nováková, J.; Šterclová, M.; Kukal, J.; Olejár, Tomáš

2014-01-01

Roč. 8, č. 2 (2014), s. 533-538 ISSN 1792-0981 Institutional support: RVO:67985823 Keywords : sarcoidosis * extrinsic allergic alveolitis * interleukin 4 receptor * transforming growth factor beta * tumor necrosis factor alpha * proteinase activated receptor 2 Subject RIV: EC - Immunology Impact factor: 1.269, year: 2014

ALPHA-BETA SEPARATION PORTFOLIO STRATEGIES FOR ISLAMIC FINANCE

Directory of Open Access Journals (Sweden)

Valentyn Khokhlov

2016-11-01

Full Text Available The purpose of this paper is to develop a mathematical alpha-beta separation model that can be used to create a core-satellite portfolio management strategy that complies with the principles of Islamic finance. Methodology. Core-satellite portfolio construction methodology is used to implement the alpha-beta separation approach, where the core part of the portfolio is managed using the tracking error minimization strategy, and the satellite part of the portfolio is managed using the mean-variance optimization strategy. Results of the portfolio dynamics clearly show that a significant amount of value was created by alpha-beta separation. The typical alpha ranges from 4% to 5.7%. The most aggressive portfolio strategies that allow short positions in the satellite portfolio work best with frequent rebalancing and benefit from the active bets. Smoothing technique that was introduced to decrease the portfolio turnover and stabilize its composition works better when active bets are less efficient, particularly with less frequent rebalancing. The best risk-return combinations are achieved with modest (3% to 10% allocation of the total portfolio to the satellite, and the remaining part (90% to 97% being managed in order to minimize the tracking error. Practical implications. The alpha-beta separation framework suggested in this paper can be used to enhance the portfolio management techniques for the hedge funds that operate under tight restrictions, particularly under the Islamic finance principles. The mathematical models developed in this paper allow practical implementation of the alphabeta separation concept. Originality/value. While the idea of alpha-beta separation existed in hedge fund management before, there was no comprehensive mathematical model under it, so its implementation was based on the ad hoc approach. This paper introduces such a mathematical model and demonstrates how portfolio managers can create value for their clients using it.

Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures

DEFF Research Database (Denmark)

Bernardino, Liliana; Xapelli, Sara; Silva, Ana P

2005-01-01

The inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects...... of mouse recombinant TNF-alpha (10 ng/ml) enhanced excitotoxicity when the cultures were simultaneously exposed to AMPA and to this cytokine. Decreasing the concentration of TNF-alpha to 1 ng/ml resulted in neuroprotection against AMPA-induced neuronal death independently on the application protocol....... By using TNF-alpha receptor (TNFR) knock-out mice, we demonstrated that the potentiation of AMPA-induced toxicity by TNF-alpha involves TNF receptor-1, whereas the neuroprotective effect is mediated by TNF receptor-2. AMPA exposure was associated with activation and proliferation of microglia as assessed...

The fibronectin-binding integrins alpha5beta1 and alphavbeta3 differentially modulate RhoA-GTP loading, organization of cell matrix adhesions, and fibronectin fibrillogenesis

DEFF Research Database (Denmark)

Danen, Erik H J; Sonneveld, Petra; Brakebusch, Cord

2002-01-01

We have studied the formation of different types of cell matrix adhesions in cells that bind to fibronectin via either alpha5beta1 or alphavbeta3. In both cases, cell adhesion to fibronectin leads to a rapid decrease in RhoA activity. However, alpha5beta1 but not alphavbeta3 supports high levels ...... receptors expressed on a cell dictates the ability of fibronectin to stimulate RhoA-mediated organization of cell matrix adhesions.......We have studied the formation of different types of cell matrix adhesions in cells that bind to fibronectin via either alpha5beta1 or alphavbeta3. In both cases, cell adhesion to fibronectin leads to a rapid decrease in RhoA activity. However, alpha5beta1 but not alphavbeta3 supports high levels...... of RhoA activity at later stages of cell spreading, which are associated with a translocation of focal contacts to peripheral cell protrusions, recruitment of tensin into fibrillar adhesions, and fibronectin fibrillogenesis. Expression of an activated mutant of RhoA stimulates alphavbeta3-mediated...

Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis.

Science.gov (United States)

Elliot, S J; Berho, M; Korach, K; Doublier, S; Lupia, E; Striker, G E; Karl, M

2007-08-01

Young female mice on a C57Bl/6J (B6) background are considered glomerulosclerosis (GS)-resistant but aging B6 mice develop mild GS. Estrogen deficiency accelerates while estrogen replacement retards GS in young sclerosis-prone oligosyndactyly mutant mice on an ROP background. To explore the effects of sex hormones on glomerular structure and function in the context of gender and genetic background, we studied mice in which the estrogen-receptor (ER) genes alpha- or -beta were deleted (alpha- or betaER knockout (KO)) and crossed into the B6 background. We also studied ovariectomized (Ovx) B6 mice given testosterone. Male and female betaERKO and male alphaERKO mice had no glomerular dysfunction at 9 months of age; however, alphaERKO female mice displayed albuminuria and GS. Ovx prevented glomerular dysfunction in alphaERKO female mice by eliminating endogenous testosterone production while exogenous testosterone induced GS in Ovx B6 mice. Androgen receptor (AR) expression and function was found in microdissected glomeruli and cultured mesangial cells. Testosterone compared to placebo increased both AR expression and TGF-beta1 mRNA levels in glomeruli isolated from female B6 mice. Estrogen deficiency had no deleterious effects on the glomeruli in B6 mice. Our study shows that genetic traits strongly influence the GS-promoting effects of estrogen deficiency while testosterone induces GS in a gender-specific manner.

alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex.

Science.gov (United States)

Livingstone, Phil D; Srinivasan, Jayaraman; Kew, James N C; Dawson, Lee A; Gotti, Cecilia; Moretti, Milena; Shoaib, Mohammed; Wonnacott, Susan

2009-02-01

Nicotine enhances attentional and working memory aspects of executive function in the prefrontal cortex (PFC) where dopamine plays a major role. Here, we have determined the nicotinic acetylcholine receptor (nAChR) subtypes that can modulate dopamine release in rat PFC using subtype-selective drugs. Nicotine and 5-Iodo-A-85380 (beta2* selective) elicited [(3)H]dopamine release from both PFC and striatal prisms in vitro and dopamine overflow from medial PFC in vivo. Blockade by dihydro-beta-erythroidine supports the participation of beta2* nAChRs. However, insensitivity of nicotine-evoked [(3)H]dopamine release to alpha-conotoxin-MII in PFC prisms suggests no involvement of alpha6beta2* nAChRs, in contrast to the striatum, and this distinction is supported by immunoprecipitation of nAChR subunits from these tissues. The alpha7 nAChR-selective agonists choline and Compound A also promoted dopamine release from PFC in vitro and in vivo, and their effects were enhanced by the alpha7 nAChR-selective allosteric potentiator PNU-120596 and blocked by specific antagonists. DNQX and MK801 inhibited [(3)H]dopamine release evoked by choline and PNU-120596, suggesting crosstalk between alpha7 nAChRs, glutamate and dopamine in the PFC. In vivo, systemic (but not local) administration of PNU-120596, in the absence of agonist, facilitated dopamine overflow in the medial PFC, consistent with the activation of extracortical alpha7 nAChRs by endogenous acetylcholine or choline. These data establish that both beta2* and alpha7 nAChRs can modulate dopamine release in the PFC in vitro and in vivo. Through their distinct actions on dopamine release, these nAChR subtypes could contribute to executive function, making them specific therapeutic targets for conditions such as schizophrenia and attention deficit hyperactivity disorder.

Coronin-1A links cytoskeleton dynamics to TCR alpha beta-induced cell signaling.

Directory of Open Access Journals (Sweden)

Bénédicte Mugnier

Full Text Available Actin polymerization plays a critical role in activated T lymphocytes both in regulating T cell receptor (TCR-induced immunological synapse (IS formation and signaling. Using gene targeting, we demonstrate that the hematopoietic specific, actin- and Arp2/3 complex-binding protein coronin-1A contributes to both processes. Coronin-1A-deficient mice specifically showed alterations in terminal development and the survival of alpha beta T cells, together with defects in cell activation and cytokine production following TCR triggering. The mutant T cells further displayed excessive accumulation yet reduced dynamics of F-actin and the WASP-Arp2/3 machinery at the IS, correlating with extended cell-cell contact. Cell signaling was also affected with the basal activation of the stress kinases sAPK/JNK1/2; and deficits in TCR-induced Ca2+ influx and phosphorylation and degradation of the inhibitor of NF-kappaB (I kappa B. Coronin-1A therefore links cytoskeleton plasticity with the functioning of discrete TCR signaling components. This function may be required to adjust TCR responses to selecting ligands accounting in part for the homeostasis defect that impacts alpha beta T cells in coronin-1A deficient mice, with the exclusion of other lympho/hematopoietic lineages.

Gut-homing CD4+ T cell receptor alpha beta+ T cells in the pathogenesis of murine inflammatory bowel disease

DEFF Research Database (Denmark)

Rudolphi, A; Boll, G; Poulsen, S S

1994-01-01

reconstituted a CD3+ T cell receptor alpha beta+ CD4+ T cell subset. CD4+ cells of this subset expressed the surface phenotype of mucosa-seeking, memory T cells. In the immunodeficient scid host, this gut-derived CD4+ T cell subset was found in spleen, peritoneal cavity, mesenteric lymph nodes (LN), epithelial...... compartments with CD4+ T cells from normal GALT plays an essential role in the pathogenesis of IBD in an immunodeficient host.......We studied which T cell subsets from the gut-associated lymphoid tissue (GALT) can migrate out of the gut mucosa and repopulate GALT compartments of an immunodeficient (semi)syngeneic host. Many distinct lymphocyte subsets were found in GALT of immunocompetent H-2d (BALB/c, BALB/cdm2, C.B-17...

[beta]-hexosaminidase isozymes from cells cotransfected with [alpha] and [beta] cDNA constructs: Analysis of the [alpha]-subunit missense mutation associated with the adult form of Tay-Sachs disease

Energy Technology Data Exchange (ETDEWEB)

Brown, C.A.; Mahuran, D.J. (Univ. of Toronto (Canada))

1993-08-01

In vitro mutagenesis and transient expression in COS cells has been used to associate a missense mutation with a clinical or biochemical phenotype. Mutations affecting the [alpha]-subunit of [beta]-hexosaminidase A ([alpha][beta]) (E.C.3.2.1.52) result in Tay-Sachs disease. Because hexosaminidase A is heterodimeric, analysis of [alpha]-chain mutations is not straightforward. The authors examine three approaches utilizing previously identified mutations affecting [alpha]-chain folding. These involve transfection of (1) the [alpha] cDNA alone; (2) a [beta] cDNA construct encoding a [beta]-subunit substituted at a position homologous to that of the [alpha]-subunit, and (3) both [alpha] and [beta] cDNAs. The latter two procedures amplified residual activity levels over that of patient samples, an effect not previously found with mutations affecting an [open quotes]active[close quotes] [alpha]Arg residue. This effect may help to discriminate between protein-folding and active-site mutations. The authors conclude that, with proper controls, the latter method of cotransfection can be used to evaluate the effects and perhaps to predict the clinical course of some [alpha]-chain mutations. Using this technique, they demonstrate that the adult-onset Tay-Sachs mutation, [alpha]Gly[yields]Ser[sup 269], does not directly affect [alpha][beta] dimerization but exerts an indirect effect on the dimer through destabilizing the folded [alpha]-subunit at physiological temperatures. Two other [alpha] mutations linked to more severe phenotypes appear to inhibit the initial folding of the subunit. 36 refs., 2 figs., 5 tabs.

Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety.

Science.gov (United States)

Schank, Jesse R; Liles, L Cameron; Weinshenker, David

2008-06-01

Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.

[Prevalence survey and molecular characterization of alpha and beta thalassemia in Liuzhou city of Guangxi].

Science.gov (United States)

Cai, Ren; Li, Liyan; Liang, Xin; Liu, Zhongying; Su, Liu; Li, Wenjun; Zhu, Qiangui; Mo, Qiuhua; Pan, Lizhen; Ouyang, Hong; Huang, Lihua; Xu, Xiangmin

2002-08-01

To investigate the gene frequencies and mutation patterns of alpha thalassemia (alpha-thal) and beta thalassemia (beta-thal) in Liuzhou city of Guangxi Zhuang Autonomous Region. Cluster sampling was used. A total of 1 028 of umbilical blood samples were collected for a prevalence study of alpha-thal and a total of 1 312 healthy young people when receiving pre-marriage consultation were recruited for a beta-thal prevalence survey. Individuals live in city or town area of Liuzhou. A complete blood count as well as hemoglobin electrophoresis analysis were done in all of samples for phenotyping of alpha and beta-thals. Those with Hb Bart's for alpha-thal indicator and those with both microcytosis (MCV /=4.0%) for beta-thal were further studied by DNA analysis. PCR-based methodologies were used to characterize the mutation contributions of alpha and beta-thals. All the subjects were tested for the state of carrying beta-thala alleles for evaluating the situation of the compound heterozygotes of alpha-thal with beta-thal. Of 1 028 random samples of umbilical blood screened, 112 of subjects were defined to be the gene carriers of alpha-thal. The alpha-thal carrier rate was as high as 11.19% including 3 compound heterozygotes. Five well-known types of alpha-thal alleles were detected with gene contributions of 37.4% (--(SEA) deletion), 31.3% (-alpha(3.7) deletion), 17.4% (-alpha(4.2) deletion), 12.1% (alpha(CS)alpha mutation), and 0.9% (alpha(QS)alpha mutation), successively. Of the 1 312 adult specimens studied, 89 with beta-thal including 14 of the compound higher Hb F subjects were detected. All of the 89 phenotypic beta-thal carriers had the mutations in the beta-globin gene, making the overall prevalence 6.78%. The commonly seen three mutations, beta CD41 - 42 (-CTTT) frameshift, beta CD17 (T-A) nonsense mutation and beta-28 (A-G) promoter variation were accounted for 90% of the beta-thal alleles in Liuzhou. Of these beta-thal subjects, 16 (accounting for 18%) were

Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1{alpha}, suppress amyloid {beta}-induced neurotoxicity

Energy Technology Data Exchange (ETDEWEB)

Raman, Dayanidhi; Milatovic, Snjezana-Zaja [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Milatovic, Dejan [Department of Pediatrics/Pediatric Toxicology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Splittgerber, Ryan [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Fan, Guo-Huang [Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37221 (United States); Richmond, Ann, E-mail: ann.richmond@vanderbilt.edu [VA Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States)

2011-11-15

Alzheimer's disease (AD) is characterized by a progressive cognitive decline and accumulation of neurotoxic oligomeric peptides amyloid-{beta} (A{beta}). Although the molecular events are not entirely known, it has become evident that inflammation, environmental and other risk factors may play a causal, disruptive and/or protective role in the development of AD. The present study investigated the ability of the chemokines, macrophage inflammatory protein-2 (MIP-2) and stromal cell-derived factor-1{alpha} (SDF-1{alpha}), the respective ligands for chemokine receptors CXCR2 and CXCR4, to suppress A{beta}-induced neurotoxicity in vitro and in vivo. Pretreatment with MIP-2 or SDF-1{alpha} significantly protected neurons from A{beta}-induced dendritic regression and apoptosis in vitro through activation of Akt, ERK1/2 and maintenance of metalloproteinase ADAM17 especially with SDF-1{alpha}. Intra-cerebroventricular (ICV) injection of A{beta} led to reduction in dendritic length and spine density of pyramidal neurons in the CA1 area of the hippocampus and increased oxidative damage 24 h following the exposure. The A{beta}-induced morphometric changes of neurons and increase in biomarkers of oxidative damage, F{sub 2}-isoprostanes, were significantly inhibited by pretreatment with the chemokines MIP-2 or SDF-1{alpha}. Additionally, MIP-2 or SDF-1{alpha} was able to suppress the aberrant mislocalization of p21-activated kinase (PAK), one of the proteins involved in the maintenance of dendritic spines. Furthermore, MIP-2 also protected neurons against A{beta} neurotoxicity in CXCR2-/- mice, potentially through observed up regulation of CXCR1 mRNA. Understanding the neuroprotective potential of chemokines is crucial in defining the role for their employment during the early stages of neurodegeneration. -- Research highlights: Black-Right-Pointing-Pointer Neuroprotective ability of the chemokines MIP2 and CXCL12 against A{beta} toxicity. Black-Right-Pointing-Pointer MIP

Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart.

OpenAIRE

Ping, P; Gelzer-Bell, R; Roth, D A; Kiel, D; Insel, P A; Hammond, H K

1995-01-01

To determine whether beta-adrenergic receptor agonist activation influences guanosine 5'-triphosphate-binding protein (G-protein) expression and beta-adrenergic receptor kinase activity in the heart, we examined the effects of chronic beta 1-adrenergic receptor antagonist treatment (bisoprolol, 0.2 mg/kg per d i.v., 35 d) on components of the myocardial beta-adrenergic receptor-G-protein-adenylyl cyclase pathway in porcine myocardium. Three novel alterations in cardiac adrenergic signaling as...

ALPHA-BETA SEPARATION PORTFOLIO STRATEGIES FOR ISLAMIC FINANCE

OpenAIRE

Valentyn Khokhlov

2016-01-01

The purpose of this paper is to develop a mathematical alpha-beta separation model that can be used to create a core-satellite portfolio management strategy that complies with the principles of Islamic finance. Methodology. Core-satellite portfolio construction methodology is used to implement the alpha-beta separation approach, where the core part of the portfolio is managed using the tracking error minimization strategy, and the satellite part of the portfolio is managed using the mean-vari...

Characterization of glucagon-like peptide-1 receptor beta-arrestin 2 interaction: a high-affinity receptor phenotype

DEFF Research Database (Denmark)

Jorgensen, Rasmus; Martini, Lene; Schwartz, Thue W

2005-01-01

To dissect the interaction between beta-arrestin ((beta)arr) and family B G protein-coupled receptors, we constructed fusion proteins between the glucagon-like peptide 1 receptor and (beta)arr2. The fusion constructs had an increase in apparent affinity selectively for glucagon, suggesting...... that (beta)arr2 interaction locks the receptor in a high-affinity conformation, which can be explored by some, but not all, ligands. The fusion constructs adopted a signaling phenotype governed by the tethered (beta)arr2 with an attenuated G protein-mediated cAMP signal and a higher maximal internalization...... of that which has previously been characterized for family A G protein-coupled receptors, suggesting similarities in the effect of (beta)arr interaction between family A and B receptors also at the molecular level....

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

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}.

Catalytic asymmetric epoxidation of alpha,beta-unsaturated amides: efficient synthesis of beta-aryl alpha-hydroxy amides using a one-pot tandem catalytic asymmetric epoxidation-Pd-catalyzed epoxide opening process.

Science.gov (United States)

Nemoto, Tetsuhiro; Kakei, Hiroyuki; Gnanadesikan, Vijay; Tosaki, Shin-Ya; Ohshima, Takashi; Shibasaki, Masakatsu

2002-12-11

The catalytic asymmetric epoxidation of alpha,beta-unsaturated amides using Sm-BINOL-Ph3As=O complex was succeeded. Using 5-10 mol % of the asymmetric catalyst, a variety of amides were epoxidized efficiently, yielding the corresponding alpha,beta-epoxy amides in up to 99% yield and in more than 99% ee. Moreover, the novel one-pot tandem process, one-pot tandem catalytic asymmetric epoxidation-Pd-catalyzed epoxide opening process, was developed. This method was successfully utilized for the efficient synthesis of beta-aryl alpha-hydroxy amides, including beta-aryllactyl-leucine methyl esters. Interestingly, it was found that beneficial modifications on the Pd catalyst were achieved by the constituents of the first epoxidation, producing a more suitable catalyst for the Pd-catalyzed epoxide opening reaction in terms of chemoselectivity.

Phospholipase C-{delta}{sub 1} regulates interleukin-1{beta} and tumor necrosis factor-{alpha} mRNA expression

Energy Technology Data Exchange (ETDEWEB)

Chung, Eric; Jakinovich, Paul; Bae, Aekyung [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States); Rebecchi, Mario, E-mail: Mario.rebecchi@SBUmed.org [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States)

2012-10-01

Phospholipase C-{delta}{sub 1} (PLC{delta}{sub 1}) is a widely expressed highly active PLC isoform, modulated by Ca{sup 2+} that appears to operate downstream from receptor signaling and has been linked to regulation of cytokine production. Here we investigated whether PLC{delta}{sub 1} modulated expression of the pro-inflammatory cytokines interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) in rat C6 glioma cells. Expression of PLC{delta}{sub 1} was specifically suppressed by small interfering RNA (siRNA) and the effects on cytokine mRNA expression, stimulated by the Toll-like receptor (TLR) agonist, lipopolysaccharide (LPS), were examined. Real-time polymerase chain reaction (RT-PCR) results showed that PLC{delta}{sub 1} knockdown enhanced expression IL-1{beta} and tumor necrosis factor-{alpha} (TNF-{alpha}) mRNA by at least 100 fold after 4 h of LPS stimulation compared to control siRNA treatment. PLC{delta}{sub 1} knock down caused persistently high Nf{kappa}b levels at 4 h of LPS stimulation compared to control siRNA-treated cells. PLC{delta}{sub 1} knockdown was also associated with elevated nuclear levels of c-Jun after 30 min of LPS stimulation, but did not affect LPS-stimulated p38 or p42/44 MAPK phosphorylation, normally associated with TLR activation of cytokine gene expression; rather, enhanced protein kinase C (PKC) phosphorylation of cellular proteins was observed in the absence of LPS stimulation. An inhibitor of PKC, bisindolylmaleimide II (BIM), reversed phosphorylation, prevented elevation of nuclear c-Jun levels, and inhibited LPS-induced increases of IL-1{beta} and TNF-{alpha} mRNA's induced by PLC{delta}{sub 1} knockdown. Our results show that loss of PLC{delta}{sub 1} enhances PKC/c-Jun signaling and up-modulates pro-inflammatory cytokine gene transcription in concert with the TLR-stimulated p38MAPK/Nf{kappa}b pathway. Our findings are consistent with the idea that PLC{delta}{sub 1} is a

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

Science.gov (United States)

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

1996-07-01

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

Quartz luminescence response to a mixed alpha-beta field: Investigations on Romanian loess

DEFF Research Database (Denmark)

Constantin, Daniela; Jain, Mayank; Murray, Andrew S.

2015-01-01

-OSL laboratory dose response curves do not reflect the growth of the OSL signal in nature. A main difference in coarse- and fine-grained quartz dating lies in the alpha irradiation history, but the effect of mixed alpha-beta fields has so far received little attention. In the present study we investigate whether...... the alpha dose experienced by fine grains over geological cycles of irradiation and bleaching may have an effect on the saturation characteristics of the laboratory dose response. By applying time resolved optically stimulated luminescence we confirm that the OSL signals induced in quartz by alpha and beta...

Studies with 17 beta(16 alpha-[125I]iodo)-estradiol, an estrogen receptor-binding radiopharmaceutical, in rats bearing mammary tumors

International Nuclear Information System (INIS)

Gatley, S.J.; Shaughnessy, W.J.; Inhorn, L.; Leiberman, L.M.

1981-01-01

We have studied the distribution of 17 beta(16 alpha-[125I]iodo)-estradiol (I-E2) in tumor-bearing and normal rats. High early adrenal-to-blood ratios (up to 22 at 5 min) were seen in all groups, but this fell to six at 1 hr. Uterus-to-blood ratios of 15 were found, and these were fairly constant up to 2 hr after administration. Uptake of label in the uterus, but not in the adrenals, was sensitive to excess diethylstilbestrol, which competes with I-E2 for estrogen receptors. Mean tumor-to-blood ratios of 1.4, 5.5, and 8.7 were seen at 1 hr in rats with transplanted, spontaneous, and N-nitrosomethylurea-induced tumors, respectively. Diethylstilbestrol was shown to reduce uptake of label by spontaneous tumors. Most of the radioactivity was excreted in the bile by 1 hr. Better estrogen-receptor-binding radiopharmaceuticals can probably be designed

Phoswich Detector for Simultaneous Counting of Alpha- and Beta-ray in a Pipe during Decommissioning

International Nuclear Information System (INIS)

Seo, B.K.; Kim, G.H.; Woo, Z.H.; Jung, Y.H.; Oh, W.Z.; Lee, K.W.; Han, M.J.

2006-01-01

A great quantity of waste has been generated during the decommissioning of nuclear facilities. These wastes are contaminated with various types of alpha, beta, and gamma nuclides. The contamination level of the decommissioning wastes must be surveyed for free release, but it is very difficult to monitor the radioactive contamination level of the pipe inside using conventional counting methods because of the small diameter. In this study a Phoswich detector for simultaneous counting of alpha- and beta-rays in a pipe was developed. The Phoswich detector is convenient for monitoring of alpha and beta contamination using only a single detector, which was composed of thin cylindrical ZnS(Ag) and plastic scintillator. The scintillator for counting an alpha particle has been applied a cylindrical polymer composite sheet, having a double layer structure of an inorganic scintillator ZnS(Ag) layer adhered onto a polymer sub-layer. The sub-layer in an alpha particle counting sheet is made of polysulfone, working as a mechanical and optical support. The ZnS(Ag) layer is formed by coating a ternary mixture of ZnS(Ag), cyano resin as a binder and solvent onto the top of a sub-layer via the screen printing method. The other layer for counting a beta particle used a commercially available plastic scintillator. The plastic scintillator was simulated by using the Monte Carlo simulation method for detection of beta radiation emitted from internal surfaces of small diameter pipe. Simulation results predicted the optimum thickness and geometry of plastic scintillator at which energy absorption for beta radiation was maximized. Characteristics of the detector fabricated were also estimated. As a result, it was confirmed that detector capability was suitable for counting the beta ray. The overall counting results reveal that the developed Phoswich detector is efficient for simultaneous counting of alpha and beta ray in a pipe. (authors)

Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. II. Cross-reaction between a monoclonal antibody and two alpha beta T cell receptors

DEFF Research Database (Denmark)

Rognan, D; Engberg, J; Stryhn, A

2000-01-01

-peptide pair into the Fab combining site. Interestingly, the most energetically favored binding mode shows numerous analogies to the recently determined recognition of class I MHC-peptide complexes by alpha beta T cell receptors (TCRs). The pSAN13.4.1 also binds diagonally across the MHC binding groove......The recombinant antibody, pSAN13.4.1, has a unique T cell like specificity; it binds an Influenza Hemagglutinin octapeptide (Ha255-262) in an MHC (H-2Kk)-restricted manner, and a detailed comparison of the fine specificity of pSAN13.4.1 with the fine specificity of two Ha255-262-specific, H-2Kk......-restricted T cell hybridomas has supported this contention. A three-dimensional model of pSAN13.4.1 has been derived by homology modeling techniques. Subsequently, the structure of the pSAN13.4.1 antibody in complex with the antigenic Ha-Kk ligand was derived after a flexible and automated docking of the MHC...

Alpha and beta-adrenoceptors in hypertension. I. Cardiac and renal alpha 1-, beta 1-, and beta 2-adrenoceptors in rat models of acquired hypertension

NARCIS (Netherlands)

Michel, M. C.; Kanczik, R.; Khamssi, M.; Knorr, A.; Siegl, H.; Beckeringh, J. J.; Brodde, O. E.

1989-01-01

To determine whether adrenoceptor changes in genetic hypertension occur primary or secondary to blood pressure elevation, we measured cardiac and renal alpha 1- (by [125I]Be 2254 binding) and beta 1- and beta 2-adrenoceptors (by (-)-[125I]iodocyanopindolol binding) densities in various rat models of

The calculation of the detection efficiency in the calibration of gross alpha-beta systems

International Nuclear Information System (INIS)

Marian Romeo Calin; Ileana Radulescu; Alexandru Erminiu Druker

2013-01-01

This paper presents a method for efficiency calibration of a measuring alpha-beta system PROTEAN ORTEC, MPC-2000-DP, using standard radioactive sources. The system is used to measure gross alpha-beta activity concentrations in environmental samples. The calculated efficiencies of detection were subsequently introduced in the system for two working geometries: measuring geometry-gross alpha-beta ε α g = 31,37 ± 0.25 (%)-the alpha efficiency and ε β g 44.94 ± 0.69 (%)-the beta efficiency, where the spillover factor is X talk g = 25.59 ± 0.50 (%) and measuring geometry up alpha-beta ε α u 36.23 ± 0.29 (%)-the alpha efficiency and ε β u = 48.53 ± 0.74 (%)-the beta efficiency, where the spillover factor is X talk u 31.08 ± 0.60 (%). (author)

A highly conserved phenylalanine in the alpha, beta-T cell receptor (TCR) constant region determines the integrity of TCR/CD3 complexes

DEFF Research Database (Denmark)

Caspar-Bauguil, S; Arnaud, J; Huchenq, A

1994-01-01

In the present study, we have investigated the importance of a phenylalanine (phe195) in the Tcr-C alpha region on Tcr-alpha,beta/CD3 membrane expression. An exchange of phe195 with a tyrosine residue does not affect Tcr/CD3 membrane expression; however, exchange with aspartic acid, histidine or ...

Spectral and Temporal Properties of the Alpha and Beta Subunits and (alpha Beta) Monomer Isolated from Nostoc SP. Using Picosecond Laser Spectroscopy.

Science.gov (United States)

Dagen, Aaron J.

1985-12-01

The fluorescence decay profiles, relative quantum yield and transmission of the (alpha), (beta) and ((alpha)(beta)) complexes from phycoerythrin isolated from the photosynthetic antenna system of Nostoc sp. and measured by single picosecond laser spectroscopic techniques is studied. The fluorescence decay profiles of all three complexes are found to be intensity independent for the intensity range investigated ((TURN)4 x 10('13) to (TURN)4 x 10('15) photons-cm('-2) per pulse). The apparent decrease in the relative quantum yield of all three complexes as intensity increases is offset by a corresponding increase in the relative transmission. This evidence, along with the intensity independent fluorescence kinetics, suggests that exciton annihilation is absent in these complexes. The decay profiles are fit to models assuming energy transfer amongst fluorescing chromophores. The intraprotein transfer rate is found to be 100 ps in the (alpha) subunit, 666 ps in the (beta) subunit. Constraining these rates to be identical in the monomer results in explaining the monomer kinetics by an increase in the nonradiative rate of the f(,(beta)) chromophore, an apparent result of aggregation effects.

Energy response of detectors to alpha/beta particles and compatibility of the equivalent factors

International Nuclear Information System (INIS)

Lin Bingxing; Li Guangxian; Lin Lixiong

2011-01-01

By measuring detect efficiency and equivalent factors of alpha/beta radiation with different energies on three types of detectors, this paper compares compatibility of their equivalent factors and discusses applicability of detectors to measuring total alpha/beta radiation. The result shows the relationship between efficiency of alpha/beta radiation and their energies on 3 types of detectors, such as scintillation and proportional and semiconductor counters, are overall identical. Alpha count efficiency display exponential relation with alpha-particle energy. While beta count efficiency display logarithm relation with beta-particle energy, but the curves appears deflection at low energy. Comparison test of energy response also shows that alpha and beta equivalent factors of scintillation and proportional counters have a good compatibility, and alpha equivalent factors of the semiconductor counters are in good agreement with those of the above two types of counters, but beta equivalent factors have obvious difference, or equivalent factors of low energy beta-particle are lower than those of other detectors. So, the semiconductor counter can not be used for measuring total radioactivity or for the measurements for the purpose of food safety. (authors)

Estrogen receptor-independent catechol estrogen binding activity: protein binding studies in wild-type, Estrogen receptor-alpha KO, and aromatase KO mice tissues.

Science.gov (United States)

Philips, Brian J; Ansell, Pete J; Newton, Leslie G; Harada, Nobuhiro; Honda, Shin-Ichiro; Ganjam, Venkataseshu K; Rottinghaus, George E; Welshons, Wade V; Lubahn, Dennis B

2004-06-01

Primary evidence for novel estrogen signaling pathways is based upon well-documented estrogenic responses not inhibited by estrogen receptor antagonists. In addition to 17beta-E2, the catechol estrogen 4-hydroxyestradiol (4OHE2) has been shown to elicit biological responses independent of classical estrogen receptors in estrogen receptor-alpha knockout (ERalphaKO) mice. Consequently, our research was designed to biochemically characterize the protein(s) that could be mediating the biological effects of catechol estrogens using enzymatically synthesized, radiolabeled 4-hydroxyestrone (4OHE1) and 4OHE2. Scatchard analyses identified a single class of high-affinity (K(d) approximately 1.6 nM), saturable cytosolic binding sites in several ERalphaKO estrogen-responsive tissues. Specific catechol estrogen binding was competitively inhibited by unlabeled catechol estrogens, but not by 17beta-E2 or the estrogen receptor antagonist ICI 182,780. Tissue distribution studies indicated significant binding differences both within and among various tissues in wild-type, ERalphaKO, and aromatase knockout female mice. Ligand metabolism experiments revealed extensive metabolism of labeled catechol estrogen, suggesting that catechol estrogen metabolites were responsible for the specific binding. Collectively, our data provide compelling evidence for the interaction of catechol estrogen metabolites with a novel binding protein that exhibits high affinity, specificity, and selective tissue distribution. The extensive biochemical characterization of this binding protein indicates that this protein may be a receptor, and thus may mediate ERalpha/beta-independent effects of catechol estrogens and their metabolites.

Gross alpha and beta activities in Tunisian mineral water

International Nuclear Information System (INIS)

Hamrouni Benbelgacem, Samar

2011-01-01

The quality of natural mineral water is a universal health problem seeing its vital importance. This problem is related to the presence of the radionuclides since this water is coming from underground, during their circulation it dissolves and conveys the radionuclides which are present in the earth's crust. This problem which leads to the contamination of the mineral water urged the World Health Organization to set standards and to recommend the respect of the median values of the activities alpha and beta within the framework of the man protection against this internal exhibition. Concerning the radiological quality of Tunisian mineral water studied in this project, we showed, by using the gross alpha and beta activities counting, that this water is specific to human consumption since their gross alpha and beta activities do not forward any risk on health.

Nature and regulation of the insulin receptor: structure and function

International Nuclear Information System (INIS)

Czech, M.P.

1985-01-01

Native, cell-surface insulin receptor consists of two glycoprotein subunit types with apparent masses of about 125,000 daltons (alpha subunit) and 90,000 daltons (beta subunit). The alpha and beta insulin-receptor subunits seem to have distinct functions such that alpha appears to bind hormone whereas beta appears to possess intrinsic tyrosine kinase activity. In detergent extracts, insulin activates receptor autophosphorylation of tyrosine residues on its beta subunit, whereas in the presence of reductant, the alpha subunit is also phosphorylated. In intact cells, insulin activates serine/threonine phosphorylation of insulin receptor beta subunit as well as tyrosine phosphorylation. The biological role of the receptor-associated tyrosine kinase is not known. The insulin receptor kinase is regulated by beta-adrenergic agonists and other agents that elevate cAMP in adipocytes, presumably via the cAMP-dependent protein kinase. Such agents decrease receptor affinity for insulin and partially uncouple receptor tyrosine kinase activity from activation by insulin. These effects appear to contribute to the biological antagonism between insulin and beta-agonists. These data suggest the hypothesis that a complex network of tyrosine and serine/threonine phosphorylations on the insulin receptor modulate its binding and kinase activities in an antagonistic manner

Unsaturated free fatty acids increase benzodiazepine receptor agonist binding depending on the subunit composition of the GABAA receptor complex.

Science.gov (United States)

Witt, M R; Westh-Hansen, S E; Rasmussen, P B; Hastrup, S; Nielsen, M

1996-11-01

It has been shown previously that unsaturated free fatty acids (FFAs) strongly enhance the binding of agonist benzodiazepine receptor ligands and GABAA receptor ligands in the CNS in vitro. To investigate the selectivity of this effect, recombinant human GABAA/benzodiazepine receptor complexes formed by different subunit compositions (alpha x beta y gamma 2, x = 1, 2, 3, and 5; y = 1, 2, and 3) were expressed using the baculovirus-transfected Sf9 insect cell system. At 10(-4) M, unsaturated FFAs, particularly arachidonic (20:4) and docosahexaenoic (22:6) acids, strongly stimulated (> 200% of control values) the binding of [3H]flunitrazepam ([3H]FNM) to the alpha 3 beta 2 gamma 2 receptor combination in whole cell preparations. No effect or small increases in levels of unsaturated FFAs on [3H]FNM binding to alpha 1 beta x gamma 2 and alpha 2 beta x gamma 2 receptor combinations were observed, and weak effects (130% of control values) were detected using the alpha 5 beta 2 gamma 2 receptor combination. The saturated FFAs, stearic and palmitic acids, were without effect on [3H]FNM binding to any combination of receptor complexes. The hydroxylated unsaturated FFAs, ricinoleic and ricinelaidic acids, were shown to decrease the binding of [3H]FNM only if an alpha 1 beta 2 gamma 2 receptor combination was used. Given the heterogeneity of the GABAA/ benzodiazepine receptor subunit distribution in the CNS, the effects of FFAs on the benzodiazepine receptor can be assumed to vary at both cellular and regional levels.

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...

Beta adrenergic receptors in human cavernous tissue

Energy Technology Data Exchange (ETDEWEB)

Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

1985-04-01

Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

Anxiety and beta-adrenergic receptor function in a normal population.

Science.gov (United States)

Kang, Eun-Ho; Yu, Bum-Hee

2005-06-01

Many studies have shown a close relationship between anxiety and beta-adrenergic receptor function in patients with anxiety disorders. This study examined the relationship between beta-adrenergic receptor function and anxiety levels in a normal population. Subjects for this study included 36 men and 44 women between the ages of 20 and 40 years whose Body Mass Index (BMI) was between 18 and 26. All of them were healthy subjects who had no previous history of medical or psychiatric illnesses. The authors measured the Spielberger State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Chronotropic 25 Dose (CD25) of isoproterenol, previously developed to assess in vivo beta-adrenergic receptor sensitivity. We also examined correlations between log normalized CD25 and mood states. The mean of CD25 was 2.64+/-1.37 mug and the mean of CD25 in men was significantly higher (i.e., lower beta-adrenergic receptor sensitivity) than that of women (3.26+/-1.35 vs. 2.14+/-1.17 microg; t = 3.99, p anxiety (r = -0.344, p = 0.002), trait anxiety (r = -0.331, p = 0.003), and BDI (r = -0.283, p = 0.011). CD25 was positively correlated with BMI (r = 0.423, p anxiety, and BMI. The sensitivity of beta-adrenergic receptors increased as anxiety levels became higher in a normal population. Thus, the relationship between anxiety and beta-adrenergic receptor function in healthy subjects may be different from that of patients with anxiety disorders.

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.

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...

Development of methodology for detection of long lived alpha emitters in air based on simultaneous alpha and beta activity measurement

International Nuclear Information System (INIS)

Kaushik, Vivek; Rath, D.P.; Vinayagami, Bhakti; Ashokkumar, P.; Umashankar, C.; Gopalakrishnan, R.K.; Kulkarni, M.S.

2018-01-01

Interference of the radon and thoron progeny co-deposited on the filtration media is the long-standing problem related to prompt analyses in continuous air sampling or monitoring of any potential suspect radionuclides. The solutions to this problem have been quite diverse, and included, for example, simple gross-alpha counting, the use of beta-to-alpha ratios, and the use of alpha spectrum analyses. The techniques based on beta to alpha disintegration ratios make use of the naturally occurring alpha to beta disintegration ratios and departures therefrom. This ratio is found empirically to be relatively constant. With the help of the solution of differential equation, which govern the deposition of radionuclide on filter paper, one can easily estimate theoretically the behavior of the radon progeny alpha to beta disintegration (or count) rate ratio

IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain.

Science.gov (United States)

Wang, H Y; Paul, W E; Keegan, A D

1996-02-01

IL-4 binds to a cell surface receptor complex that consists of the IL-4 binding protein (IL-4R alpha) and the gamma chain of the IL-2 receptor complex (gamma c). The receptors for IL-4 and IL-2 have several features in common; both use the gamma c as a receptor component, and both activate the Janus kinases JAK-1 and JAK-3. In spite of these similarities, IL-4 evokes specific responses, including the tyrosine phosphorylation of 4PS/IRS-2 and the induction of CD23. To determine whether sequences within the cytoplasmic domain of the IL-4R alpha specify these IL-4-specific responses, we transplanted the insulin IL-4 receptor motif (I4R motif) of the huIL-4R alpha to the cytoplasmic domain of a truncated IL-2R beta. In addition, we transplanted a region that contains peptide sequences shown to block Stat6 binding to DNA. We analyzed the ability of cells expressing these IL-2R-IL-4R chimeric constructs to respond to IL-2. We found that IL-4 function could be transplanted to the IL-2 receptor by these regions and that proliferative and differentiative functions can be induced by different receptor sequences.

Synthesis and characterization of arylamine derivatives of rauwolscine as molecular probes for alpha 2-adrenergic receptors

International Nuclear Information System (INIS)

Lanier, S.M.; Graham, R.M.; Hess, H.J.; Grodski, A.; Repaske, M.G.; Nunnari, J.M.; Limbird, L.E.; Homcy, C.J.

1987-01-01

The selective alpha 2-adrenergic receptor antagonist rauwolscine was structurally modified to yield a series of arylamine carboxamide derivatives, which were investigated as potential molecular probes for the localization and structural characterization of alpha 2-adrenergic receptors. The arylamine carboxamides differ in the number of carbon atoms separating the reactive phenyl moiety from the fused ring structure of the parent compound, rauwolscine carboxylate. Competitive inhibition studies with [ 3 H]rauwolscine in rat kidney membranes indicate that the affinity for the carboxamide derivatives is inversely related to the length of the carbon spacer arm with rauwolscine 4-aminophenyl carboxamide exhibiting the highest affinity (Kd = 2.3 +/- 0.2 nM). Radioiodination of rau-AMPC yields a ligand, 125 I-rau-AMPC, which binds to rat kidney alpha 2-adrenergic receptors with high affinity, as determined by both kinetic analysis (Kd = k2/k1 = 0.016 min-1/2.1 X 10(7) M-1 min-1 = 0.76 nM) and equilibrium binding studies (Kd = 0.78 +/- 0.16 nM). 125 I-rau-AMPC was quantitatively converted to the photolabile arylazide derivative 17 alpha-hydroxy-20 alpha-yohimban-16 beta-(N-4-azido-3-[ 125 I]iodophenyl) carboxamide ( 125 I-rau-AZPC). In a partially purified receptor preparation from porcine brain, this compound photolabels a major (Mr = 62,000) peptide. The labeling of this peptide is inhibited by adrenergic agonists and antagonists with a rank order of potency consistent with an alpha 2-adrenergic receptor binding site. Both 125 I-rau-AMPC and the photolabile arylazide derivative, 125 I-rau-AZPC, should prove useful as molecular probes for the structural and biochemical characterization of alpha 2-adrenergic receptors

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

PC based alpha, beta and gamma counting system

International Nuclear Information System (INIS)

Bhattacharya, S.; Gopalakrishnan, K.R.; Bairi, B.R.

1992-01-01

In the field of radiation protection and safety a large number of samples have to be assayed for estimation of their radioactivity at various stages in nuclear fuel. A PC based alpha, beta and gamma counting system has been designed for the above application. The system is fully automatic and requires minimum of operator intervention. The main units in the system are detector and pulse processing electronics, sample changer and assembly and IBM PC interface and supporting software. The main function of interface is to control the sample changer which is basically loading and unloading of sample, data acquisition and further processing by software. The pulses from detector are analysed in a pulse shape discriminator. A pulse identified as an alpha, beta or gamma event is converted to digital pulse. These digital pulses are accumulated in the three channels on PC interface each corresponding to alpha, beta and gamma. The sample movements are controlled by interface depending upon sample position. The software has been developed so as to maintain user friendliness and convenience of the operator. Various selection modes for parameters and operation of system provide lot of flexibility in operation of the system. (author). 1 fig

Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists

International Nuclear Information System (INIS)

Galitzky, J.; Mauriege, P.; Berlan, M.; Lafontan, M.

1989-01-01

This study was undertaken to investigate more fully the pharmacological characteristics of the human fat cell alpha-2 adrenoceptor. Biological assays were performed on intact isolated fat cells while radioligand binding studies were carried out with [ 3 H]yohimbine in membranes. These pharmacological studies brought: (1) a critical definition of the limits of the experimental conditions required for the exploration of alpha-2 adrenergic responsiveness on human fat cells and membranes; (2) an improvement in the pharmacological definition of the human fat cell postsynaptic alpha-2 adrenoceptor. Among alpha-2 agonists, UK-14,304 was the most potent and the relative order of potency was: UK-14,304 greater than p-aminoclonidine greater than clonidine = B-HT 920 greater than rilmenidine. For alpha-2 antagonists, the potency order was: yohimbine greater than idazoxan greater than SK ampersand F-86,466 much greater than benextramine; (3) a description of the impact of benextramine (irreversible alpha-1/alpha-2 antagonist) on human fat cell alpha-2 adrenergic receptors and on human fat cell function; the drug inactivates the alpha-2 adrenergic receptors with a minor impact on beta adrenergic receptors and without noticeable alterations of fat cell function as assessed by preservation of beta adrenergic and Al-adenosine receptor-mediated lipolytic responses; and (4) a definition of the relationship existing between alpha-2 adrenergic receptor occupancy, inhibition of adenylate cyclase activity and antilipolysis with full and partial agonists. The existence of a receptor reserve must be taken into account when evaluating alpha-2 adrenergic receptor distribution and regulation of human fat cells

Overexpression of thyroid hormone beta1 nuclear receptor is associated with an increased proliferation of human hepatoma cells

Energy Technology Data Exchange (ETDEWEB)

Lin, K; Lin, Y; McPhie, P [Chang-Gung College of Medicine and Technology, Graduate Institute of Clinical Medicine, Taoyuan (Taiwan, Province of China); Cheng, S [National Cancer Inst., Bethesda, MD (United States)

1994-12-31

It is evaluated the expression of thyroid hormone nuclear receptors (TRs) and their possible roles in the carcinogenesis of human hepatocarcinoma. The expression of TR{beta}1 and TR{alpha} genes was evaluated at both the mRNA and protein levels. The expression of TR{beta}1 and TR{alpha}1 mRNAs is similar to those found in normal liver. However, the expression of TR isoform proteins depends on the cell-type. The expression of TRaplha1 protein is low in all cell lines examined. However, TR{Beta}1 protein is overexpressed in Mahlavu, SK-Hep-1, and HA22T, moderately expressed in J5, J7, and J328 and is very low HepG2, Hep3B, and PLC/PRF/5 cells. The proliferation of cells in which TR{beta}1 is overexpressed is stimulated by the thyroid hormone, 3,3`,5- triiodo-L-thyronine. These results suggest that TR{beta}1, not TR{alpha}1, is probably involved in the prolifaration of hepatoma cells.

17-beta estradiol inhibits oxidative stress-induced accumulation of AIF into nucleolus and PARP1-dependent cell death via estrogen receptor alpha.

Science.gov (United States)

Batnasan, Enkhzaya; Wang, Ruoxi; Wen, Jitao; Ke, Yueshuang; Li, Xiaoxue; Bohio, Ameer Ali; Zeng, Xianlu; Huo, Hongliang; Han, Liping; Boldogh, Istvan; Ba, Xueqing

2015-01-05

Oxidative stress-induced DNA damage results in over-activation of poly(ADP-ribose) polymerase 1 (PARP1), leading to parthanatos, a newly discovered cell elimination pathway. Inhibition of PARP1-dependent cell death has shown to improve the outcome of diseases, including stroke, heart ischemia, and neurodegenerative diseases. In the present study we aimed to detect whether estrogen plays a protective role in inhibiting parthanatos. We utilized human mammary adenocarcinoma cells (MCF7) that abundantly express the estrogen receptor alpha and beta (ERα and ERβ). Parthanatos was induced by challenging the cells with hydrogen peroxide (H2O2). Microscopic imaging and molecular biological techniques, such as Western blot analysis and RNA interference, were performed. The results showed 17β estradiol (E2) protected MCF7 cells from PARP1-dependent cell death by decreasing protein PARylation, and AIF translocation into nuclei/nucleoli. Down-regulation of ERα expression by siRNA before E2 addition resulted in the failure of the E2-mediated inhibition of H2O2-induced protein PARylation and AIF nucleolar translocation. Together these data suggest that estrogen via its alpha-type receptor inhibits oxidative stress-induced, PARP1-dependent cell death. The present study provided us insight into how to apply hormone therapy in intervention of parthanatos-implicated ischemic and degenerative diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Z-isomer of 11{beta}-methoxy-17{alpha}-[{sup 123}I]iodovinylestradiol is a promising radioligand for estrogen receptor imaging in human breast cancer

Energy Technology Data Exchange (ETDEWEB)

Rijks, Leonie J. M.; Boer, Gerard J.; Endert, Erik; Bruin, Kora de; Janssen, Anton G. M.; Royen, Eric A. van

1997-01-01

The potential of both stereoisomers of 11{beta}-methoxy-17{alpha}-[{sup 123}I]iodovinylestradiol (E- and Z-[{sup 123}I]MIVE) as suitable radioligands for imaging of estrogen receptor(ER)-positive human breast tumours was studied. The 17{alpha}-[{sup 123}I]iodovinylestradiol derivatives were prepared stereospecifically by oxidative radioiododestannylation of the corresponding 17{alpha}-tri-n-butylstannylvinylestradiol precursors. Both isomers of MIVE showed high in vitro affinity for dimethylbenzanthracene-induced rat and fresh human mammary tumour ER, that of Z-MIVE however being manyfold higher than that of E-MIVE. In vivo distribution studies with E- and Z-[{sup 123}I]MIVE in normal and tumour-bearing female rats showed ER-mediated uptake and retention in uterus, ovaries, pituitary, hypothalamus and mammary tumours, again the highest for Z-[{sup 123}I]MIVE. The uterus- and tumour-to-nontarget tissue (fat, muscle) uptake ratios were also highest for Z-[{sup 123}I]MIVE. Additionally, planar whole body imaging of two breast cancer patients 1-2 h after injection of Z-[{sup 123}I]MIVE showed increased focal uptake at known tumour sites. Therefore, we conclude that Z-[{sup 123}I]MIVE is a promising radioligand for the diagnostic imaging of ER in human breast cancer.

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.

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.

Quantitation of alpha 1-adrenergic receptors in porcine uterine and mesenteric arteries

International Nuclear Information System (INIS)

Farley, D.B.; Ford, S.P.; Reynolds, L.P.; Bhatnagar, R.K.; Van Orden, D.E.

1984-01-01

The activation of vascular alpha-adrenergic receptors may be involved in the control of uterine blood flow. A radioligand binding assay with the use of the alpha 1-adrenergic antagonist 3 H-WB-4101 was established to characterize the alpha-adrenergic receptors in uterine and mesenteric arterial membranes obtained from nonpregnant pigs. Specific binding of 3 H-WB-4101 was rapid, saturable, and exhibited the alpha-adrenergic agonist potency order of (-)-epinephrine inhibition constant [Ki] . 0.6 mumol/L greater than (-)-norepinephrine (Ki . 1.5 mumol/L) much greater than (-)-isoproterenol (Ki . 120 mumol/L). The alpha-adrenergic antagonist phentolamine (Ki . 6.0 nmol/L) was 200 times more potent than the beta-adrenergic antagonist (+/-)-propranolol (Ki . 1,200 nmol/L); the alpha 1-selective antagonist prazosin (Ki . 1.2 nmol/L) was 130 times more potent than the alpha 2-selective antagonist yohimbine (Ki . 160 nmol/L). Scatchard analysis, as well as iterative curve-fitting analysis, demonstrated that 3 H-WB-4101 binding by arterial membranes was to a single class of binding sites. Uterine arteries exhibited greater maximal binding capacity (BMax) than that of mesenteric arteries (47.5 +/- 3.2 versus 30.9 +/- 3.6 fmol per milligram of protein, p less than 0.01), but the uterine artery dissociation constant (Kd) was higher, thus indicating a lower affinity, when compared with mesenteric artery (0.43 +/- 0.04 versus 0.33 +/- 0.04 nmol/L, p less than 0.05)

Design and device construction for plane tables preparation for counter alpha/beta total

International Nuclear Information System (INIS)

Galicia C, F. J.; Monroy G, F.

2014-10-01

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)

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.

Prevalence of Co-Inheritance of Alpha-Thalassemia with Beta-Thalassemia and Beta-Hemoglobinopathy in Ahvaz City

OpenAIRE

Najmaddin Saki; Akbar Dorgalaleh; Zahra Kashani Khatib; Shaban Alizadeh; Fakher Rahim; Hamid Galehdari; Bijan Kaikhaei; Mohammad Pedram; Ali Dehghani Fard

2013-01-01

Background: Co-inheritance of hemoglobin gene defects is a rare important status that can lead to double heterozygote or homozygote with significant clinical manifestations. Such conditions can be observed in co-inheritance of alpha-thalassemia with beta-thalassemia or hemoglobinopathy. The aim of this study was to evaluate the prevalence of alpha-thalassemia with beta-thalassemia and hemoglobinopathy co-inheritance in a considerable number of Iranian.   Methods: This descriptive study was pe...

Evidence for Alpha Receptors in the Human Ureter

Science.gov (United States)

Madeb, Ralph; Knopf, Joy; Golijanin, Dragan; Bourne, Patricia; Erturk, Erdal

2007-04-01

An immunohistochemical and western blot expression analysis of human ureters was performed in order to characterize the alpha-1-adrenergic receptor distribution along the length of the human ureteral wall. Mapping the distribution will assist in understanding the potential role alpha -1-adrenergic receptors and their subtype density might have in the pathophysiology of ureteral colic and stone passage. Patients diagnosed with renal cancer or bladder cancer undergoing nephrectomy, nephroureterectomy, or cystectomy had ureteral specimens taken from the proximal, mid, distal and tunneled ureter. Tissues were processed for fresh frozen examination and fixed in formalin. None of the ureteral specimens were involved with cancer. Serial histologic sections and immunohistochemical studies were performed using antibodies specific for alpha-1-adrenergic receptor subtypes (alpha 1a, alpha 1b, alpha 1d). The sections were examined under a light microscope and scored as positive or negative. In order to validate and quantify the alpha receptor subtypes along the human ureter. Western blotting techniques were applied. Human ureter stained positively for alpha -1-adrenergic receptors. Immunostaining appeared red, with intense reaction in the smooth muscle of the ureter and endothelium of the neighboring blood vessels. There was differential expression between all the receptors with the highest staining for alpha-1D subtype. The highest protein expression for all three subtypes was in the renal pelvis and decreased with advancement along the ureter to the distal ureter. At the distal ureter, there was marked increase in expression as one progressed towards the ureteral orifice. The same pattern of protein expression was exhibited for all three alpha -1-adrenergic receptor subtypes. We provide preliminary evidence for the ability to detect and quantify the alpha-1-receptor subtypes along the human ureter which to the best of our knowledge has never been done with

TNF{alpha} and IL-1{beta} are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS

Energy Technology Data Exchange (ETDEWEB)

Zheng, Wenwen; Zheng, Xuexing [College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province (China); Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Liu, Shue [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Ouyang, Hongsheng [College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province (China); Levitt, Roy C.; Candiotti, Keith A. [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Hao, Shuanglin, E-mail: shao@med.miami.edu [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States)

2012-04-20

Highlights: Black-Right-Pointing-Pointer LPS induces proinflammatory cytokine release in HAPI cells. Black-Right-Pointing-Pointer JNK pathway is dependent on TLR4 signaling to release cytokines. Black-Right-Pointing-Pointer NF-{kappa}B pathway is dependent on Nod1 signaling to release cytokines. -- Abstract: A growing body of evidence recently suggests that glial cell activation plays an important role in several neurodegenerative diseases and neuropathic pain. Microglia in the central nervous system express toll-like receptor 4 (TLR4) that is traditionally accepted as the primary receptor of lipopolysaccharide (LPS). LPS activates TLR4 signaling pathways to induce the production of proinflammatory molecules. In the present studies, we verified the LPS signaling pathways using cultured highly aggressively proliferating immortalized (HAPI) microglial cells. We found that HAPI cells treated with LPS upregulated the expression of TLR4, phospho-JNK (pJNK) and phospho-NF-{kappa}B (pNF-{kappa}B), TNF{alpha} and IL-1{beta}. Silencing TLR4 with siRNA reduced the expression of pJNK, TNF{alpha} and IL-1{beta}, but not pNF-{kappa}B in the cells. Inhibition of JNK with SP600125 (a JNK inhibitor) decreased the expression of TNF{alpha} and IL-1{beta}. Unexpectedly, we found that inhibition of Nod1 with ML130 significantly reduced the expression of pNF-{kappa}B. Inhibition of NF-{kappa}B also reduced the expression of TNF{alpha} and IL-1{beta}. Nod1 ligand, DAP induced the upregulation of pNF-{kappa}B which was blocked by Nod1 inhibitor. These data indicate that LPS-induced pJNK is TLR4-dependent, and that pNF-{kappa}B is Nod1-dependent in HAPI cells treated with LPS. Either TLR4-JNK or Nod1-NF-{kappa}B pathways is involved in the expression of TNF{alpha} and IL-1{beta}.

Membranes of activated CD4+ T cells expressing T cell receptor (TcR) alpha beta or TcR gamma delta induce IgE synthesis by human B cells in the presence of interleukin-4

NARCIS (Netherlands)

Gascan, H.; Aversa, G. G.; Gauchat, J. F.; van Vlasselaer, P.; Roncarolo, M. G.; Yssel, H.; Kehry, M.; Spits, H.; de Vries, J. E.

1992-01-01

In the present study it is demonstrated that human B cells can be induced to switch to IgE production following a contact-mediated signal provided by activated T cell receptor (TcR) gamma delta+, CD4+ and TcR alpha beta+, CD4+ T cell clones and interleukin (IL)-4. The signal provided by these T cell

Alpha- and beta-adrenoceptors in hypertension. II. Platelet alpha 2- and lymphocyte beta 2-adrenoceptors in children of parents with essential hypertension. A model for the pathogenesis of the genetically determined hypertension

NARCIS (Netherlands)

Michel, M. C.; Galal, O.; Stoermer, J.; Bock, K. D.; Brodde, O. E.

1989-01-01

To study whether changes in alpha- and beta-adrenoceptors in human essential hypertension (EHT) might be genetically determined, we assessed platelet alpha 2- and lymphocyte beta 2-adrenoceptor density in 48 normotensive children of normotensive parents (NT) and in 41 normotensive children with one

In vitro bioactivity of 17alpha-estradiol.

Science.gov (United States)

Sievernich, André; Wildt, Ludwig; Lichtenberg-Fraté, Hella

2004-12-01

A miniaturised short-term in vitro assay based on the activation of the human estrogen receptor alpha and genetically modified yeast (Saccharomyces cerevisiae) cells was performed to explore the capacity of this system to monitor the bioactivity of estrogenic compounds, particularly 17alpha- and 17beta-estradiol. Together with the human estrogen receptor (hER)-alpha plasmid, the reporter plasmid containing a yeast-optimised version of the green fluorescent protein (yEGFP) linked to three repeats of the cis-acting estrogen hormone-responsive element (ERE) were expressed in a strain being deleted in the pleiotropic drug resistance transporters Pdr5, Snq2 and Yor1, known to facilitate efflux of organic compounds including steroids and chemotherapeutics. Agonists that bind to hER in vitro trigger estrogen receptor-mediated transcriptional activation of the GFP reporter gene monitored by fluorescence emission at 535 nm. The sensitivity of the assay was tested with various 17alpha- and 17beta-estradiol concentrations, yielding a detection limit of 5 pg/ml (0.018 nM) for the agonist 17beta-E2 in solvent and in human charcoal-stripped serum using a S. cerevisiae pdr5, snq2 and yor1 mutant strain. For 17alpha-estradiol only, at approximately 1500 pg/ml a similar fluorescence response compared to 100 pg/ml 17beta-E2 was observed implicating a much weaker potency of this stereoisomer. The specificity of the system was tested by expression of a truncated hER lacking the ligand-binding domain E and by administration of the androgen, 4-androsten 3,17 dione. Both controls did not yield an increase in fluorescence emission. This fluorescence emission assay enables detection of estrogenic biological activity induced by direct agonists, such as 17beta-E2 at concentrations similar to those found in human sera or by estrogen-like chemicals.

Bidirectional modulation of hippocampal gamma (20-80 Hz) frequency activity in vitro via alpha(α)- and beta(β)-adrenergic receptors (AR).

Science.gov (United States)

Haggerty, D C; Glykos, V; Adams, N E; Lebeau, F E N

2013-12-03

Noradrenaline (NA) in the hippocampus plays an important role in memory function and has been shown to modulate different forms of synaptic plasticity. Oscillations in the gamma frequency (20-80 Hz) band in the hippocampus have also been proposed to play an important role in memory functions and, evidence from both in vitro and in vivo studies, has suggested this activity can be modulated by NA. However, the role of different NA receptor subtypes in the modulation of gamma frequency activity has not been fully elucidated. We have found that NA (30 μM) exerts a bidirectional control on the magnitude of kainate-evoked (50-200 nM) gamma frequency oscillations in the cornu Ammonis (CA3) region of the rat hippocampus in vitro via activation of different receptor subtypes. Activation of alpha-adrenergic receptors (α-AR) reduced the power of the gamma frequency oscillation. In contrast, activation of beta-adrenergic receptors (β-AR) caused an increase in the power of the gamma frequency oscillations. Using specific agonists and antagonists of AR receptor subtypes we demonstrated that these effects are mediated specifically via α1A-AR and β1-AR subtypes. NA activated both receptor subtypes, but the α1A-AR-mediated effect predominated, resulting in a reversible suppression of gamma frequency activity. These results suggest that NA is able to differentially modulate on-going gamma frequency oscillatory activity that could result in either increased or decreased information flow through the hippocampus. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

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)

Characterization of the binding of radioiodinated hybrid recombinant IFN-alpha A/D to murine and human lymphoid cell lines

International Nuclear Information System (INIS)

Faltynek, C.R.; Princler, G.L.; Schwabe, M.; Shata, M.T.; Lewis, G.K.; Kamin-Lewis, R.M.

1990-01-01

The hybrid recombinant human interferon (IFN) rIFN-alpha A/D was radioiodinated. Specific binding of [125I]rIFN-alpha A/D was observed with both human and murine cell lines. The binding of [125I]rIFN-alpha A/D to human Daudi cells had similar characteristics to the previously described binding of [125I]rIFN-alpha A or -alpha 2. The following lines of evidence demonstrated that [125I]rIFN-alpha A/D bound with high affinity to the same receptor on murine cells as murine IFN-alpha and -beta: (i) the binding of [125I]rIFN-alpha A/D to murine LBRM cells was inhibited to a similar extent by natural murine IFN-alpha, natural murine IFN-beta, and rIFN-A/D; (ii) the Kd (approximately 2 X 10(-10) M) obtained from both competition experiments and saturation binding experiments with [125I]rIFN-alpha A/D was comparable to the previously reported Kd for the binding of natural murine IFN-alpha and -beta to other murine cell lines; (iii) the size of the cross-linked [125I]rIFN-alpha A/D receptor complex formed on murine LBRM cells was similar to the previously reported cross-linked complex formed after binding radioiodinated natural murine IFN-beta to other murine cell lines. Due to the current lack of readily available recombinant murine IFN-alpha or -beta for radiolabeling and the previously demonstrated biological activity of rIFN-alpha A/D on murine cells, [125I]rIFN-alpha A/D should prove to be a useful reagent for further studies of murine IFN receptors

Application of a novel design paradigm to generate general nonpeptide combinatorial templates mimicking beta-turns: synthesis of ligands for melanocortin receptors.

Science.gov (United States)

Webb, Thomas R; Jiang, Luyong; Sviridov, Sergey; Venegas, Ruben E; Vlaskina, Anna V; McGrath, Douglas; Tucker, John; Wang, Jian; Deschenes, Alain; Li, Rongshi

2007-01-01

We report the further application of a novel approach to template and ligand design by the synthesis of agonists of the melanocortin receptor. This design method uses the conserved structural data from the three-dimensional conformations of beta-turn peptides to design rigid nonpeptide templates that mimic the orientation of the main chain C-alpha atoms in a peptide beta-turn. We report details on a new synthesis of derivatives of template 1 that are useful for the synthesis of exploratory libraries. The utility of this technique is further exemplified by several iterative rounds of high-throughput synthesis and screening, which result in new partially optimized nonpeptide agonists for several melanocortin receptors.

Humidity measurement using alpha-ray and beta-ray

International Nuclear Information System (INIS)

Matsumoto, Shigeaki; Kobayashi, Hisanobu

1981-01-01

Two new hygrometers using radioisotopes were proposed, and the results of tests are described. The one is a dew-point hygrometer utilizing the backscattering phenomena of beta-ray by dew, and the other is a hygrometer by measuring the variation of ionization current by alpha ray due to humidity. The backscattering of beta-ray depends on the atomic number of scatters and the energy of beta-ray. Therefore, the backscattering from dew on a gold plate is different from that from the gold itself. The temperature dependence of the backscattering intensity was measured with a GM counter. Decrease of the intensity was seen at the dew point. A control circuit was designed to measure the dew point automatically. The error of the measurement was within 1 degree C. An alpha-ray ionization hygrometer was constructed. The dependence of ionization current on humidity was measured with an operational amplifier. The resolution of humidity measurement was within 5 percent. (Kato, T.)

Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation.

Science.gov (United States)

Lam, Sum; Patel, Priti N

2007-01-01

Tobacco smoking remains a significant health problem in the United States. It has been associated with staggering morbidity and mortality, specifically due to malignancies and cardiovascular disease. Smoking cessation can be difficult and frequently requires pharmacologic interventions in addition to nonpharmacologic measures. Previously available agents are nicotine replacement products and bupropion, which increased quit rates by about 2-fold compared with placebo. Varenicline is the first drug in a new class known as the selective alpha4beta2 nicotinic receptor partial agonists. In several randomized, double-blind, 52-week clinical trials involving healthy chronic smokers, varenicline demonstrated superiority to placebo and bupropion in terms of efficacy measures. Additionally, it improved tobacco withdrawal symptoms and reinforcing effects of smoking in relapsed patients. Patients should start therapy in combination with tobacco cessation counseling 1 week before quit date and continue the regimen for 12 weeks. The dose of varenicline should be titrated to minimize nausea. The recommended dosage is 0.5 mg once daily (QD) on days 1-3; titrate to 0.5 mg twice daily (BID) on days 4-7; and 1 mg BID starting on day 8. An additional 12-week maintenance therapy may be considered for those who achieve abstinence. The most common side effects are nausea (30%), insomnia (18%), headache (15%), abnormal dreams (13%), constipation (8%), and abdominal pain (7%). Overall, varenicline is a breakthrough in the management of tobacco addiction and has demonstrated good efficacy in motivated quitters. It also provides an option for smokers who cannot tolerate other pharmacologic interventions.

Three-residue turns in alpha/beta-peptides and their application in the design of tertiary structures.

Science.gov (United States)

Sharma, Gangavaram V M; Nagendar, Pendem; Ramakrishna, Kallaganti V S; Chandramouli, Nagula; Choudhary, Madavi; Kunwar, Ajit C

2008-06-02

A new three-residue turn was serendipitously discovered in alpha/beta hybrid peptides derived from alternating C-linked carbo-beta-amino acids (beta-Caa) and L-Ala residues. The three-residue beta-alpha-beta turn at the C termini, nucleated by a helix at the N termini, resulted in helix-turn (HT) supersecondary structures in these peptides. The turn in the HT motif is stabilized by two H bonds-CO(i-2)-NH(i), with a seven-membered pseudoring (gamma turn) in the backward direction, and NH(i-2)-CO(i), with a 13-membered pseudoring in the forward direction (i being the last residue)--at the C termini. The study was extended to generalize the new three-residue turn (beta-alpha-beta) by using different alpha- and beta-amino acids. Furthermore, the HT motifs were efficiently converted, by an extension with helical oligomers at the C termini, into peptides with novel helix-turn-helix (HTH) tertiary structures. However, this resulted in the destabilization of the beta-alpha-beta turn with the concomitant nucleation of another three-residue turn, alpha-beta-beta, which is stabilized by 11- and 15-membered bifurcated H bonds. Extensive NMR spectroscopic studies were carried out to delineate the secondary and tertiary structures in these peptides, which are further supported by molecular dynamics (MD) investigations.

Cardiac beta-receptors in experimental Chagas' disease Receptores beta cardíacos na doença de Chagas experimental

Directory of Open Access Journals (Sweden)

Julio E. Enders

1995-02-01

Full Text Available Experimental Chagas' disease (45 to 90 days post-infection showed serious cardiac alterations in the contractility and in the pharmacological response to beta adrenergic receptors in normal and T. cruzi infected mice (post-acute phase. Chagasic infection did not change the beta receptors density (78.591 ± 3.125 fmol/mg protein and 73.647 ± 2.194 fmol/mg protein for controls but their affinity was significantly diminished (Kd = 7.299 ± 0.426 nM and Kd = 3.759 ± 0.212 nM for the control p Estudaram-se os receptores beta cardíacos de camundongos infectados pelo Trypanosoma cruzi na fase pós-aguda da doença de Chagas para estabelecer em que medida os mesmos contribuem a gerar respostas anômalas às catecolaminas observadas nestes miocardios. Utilizara-se 3-H/DHA para a marcação dos receptores beta cardíacos dos camundongos normais e dos infectados na fase pós-aguda (45 a 90 dias pós-infecção. O número dos sítios de fixação foi similar nos dois grupos, 78.591 ± 3.125 fmol/mg. Proteína nos chagásicos e 73.647 ± 2.194 fmol/mg. Proteína no grupo controle. Em vez disso, a afinidade verificou-se significativamente diminuida no grupo chagásico (Kd = 7.299 ± 0.426 nM respeito do controle (Kd = 3.759 ± 0.212 nM p < 0.001. Os resultados obtidos demonstram que as modificações observadas na estimulação adrenérgica do miocárdio chagásico se correlacionam com a menor afinidade dos receptores beta cardíacos e que estas alterações exerceriam uma parte determinante para as consequências funcionais que são detectadas na fase crônica.

Expression of Estrogen Receptor Alpha in Malignant Melanoma

Directory of Open Access Journals (Sweden)

Parvin Rajabi

2017-01-01

Full Text Available Background: Features of malignant melanoma (MM vary in the different geographic regions of the world. This may be attributable to environmental, ethnic, and genetic factors. The aim of this study was to determine the expression of estrogen receptor alpha (ER-α in MM in Isfahan, Iran. Materials and Methods: This study was planned as a descriptive, analytical, cross-sectional investigation. During this study, paraffin-embedded tissue blocks of patients with a histopathologic diagnosis of MM was studied for ER-α using immunohistochemistry (IHC. Results: In this study, 38 patients (female/male; 20/18 with a definite diagnosis of malignant cutaneous melanoma and mean age of 52.4 ± 11.2 years were investigated. Using envision IHC staining, there were not any cases with ER-α expression. Conclusion: In confirmation to the most previous studies, expression of ER-α was negative in MM. It is recommended to investigate the expression of estrogen receptor beta and other markers in MM.

Alpha/beta pulse shape discrimination in plastic scintillation using commercial scintillation detectors

International Nuclear Information System (INIS)

Bagan, H.; Tarancon, A.; Rauret, G.; Garcia, J.F.

2010-01-01

Activity determination in different types of samples is a current need in many different fields. Simultaneously analysing alpha and beta emitters is now a routine option when using liquid scintillation (LS) and pulse shape discrimination. However, LS has an important drawback, the generation of mixed waste. Recently, several studies have shown the capability of plastic scintillation (PS) as an alternative to LS, but no research has been carried out to determine its capability for alpha/beta discrimination. The objective of this study was to evaluate the capability of PS to discriminate alpha/beta emitters on the basis of pulse shape analysis (PSA). The results obtained show that PS pulses had lower energy than LS pulses. As a consequence, a lower detection efficiency, a shift to lower energies and a better discrimination of beta and a worst discrimination of alpha disintegrations was observed for PS. Colour quenching also produced a decrease in the energy of the particles, as well as the effects described above. It is clear that in PS, the discrimination capability was correlated with the energy of the particles detected. Taking into account the discrimination capabilities of PS, a protocol for the measurement and the calculation of alpha and beta activities in mixtures using PS and commercial scintillation detectors has been proposed. The new protocol was applied to the quantification of spiked river water samples containing a pair of radionuclides ( 3 H- 241 Am or 90 Sr/ 90 Y- 241 Am) in different activity proportions. The relative errors in all determinations were lower than 7%. These results demonstrate the capability of PS to discriminate alpha/beta emitters on the basis of pulse shape and to quantify mixtures without generating mixed waste.

Improvement and automatization of a proportional alpha-beta counting system - FAG

International Nuclear Information System (INIS)

German, U.; Levinson, S.; Pelled, O.; Shemesh, Y.; Assido, H.

1997-01-01

An alpha and beta counting system - FAG*, for planchette samples is operated at the Health Physics department's laboratory of the NRCN. The original operation mode of the system was based on manual tasks handled by the FHT1 100 electronics. An option for a basic computer keyboard operation was available too. A computer with an appropriate I/O card was connected to the system and a new operating program was developed which enables full automatic control of the various components. The program includes activity calculations and statistical checks as well as data management. A bar-code laser system for sample number reading was integrated into the Alpha-Beta automatic counting system. The sample identification by means of an attached bar-code label enables unmistakable and reliable attribution of results to the counted sample. authors)

Phenotypical and functional characterization of double-negative (CD4-CD8-) alpha beta T-cell receptor positive cells from an immunodeficient patient

DEFF Research Database (Denmark)

Illum, N; Ralfkiaer, E; Pallesen, G

1991-01-01

We have characterized CD4-CD8- double-negative (DN) alpha beta TCR+ T cells from a patient with immunodeficiency, lymphocytosis, lymphadenopathy, and hepatosplenomegaly. The majority of peripheral blood lymphocytes were DN alpha beta TCR+ T cells as evaluated by FACS and biochemical analysis...... (MoAbs) indicated a polyclonal T-cell expansion. Thymic biopsy showed normal histology, whereas lymph node biopsy samples showed altered histological and immunohistological patterns with markedly expanded paracortical areas containing the DN T cells of the same phenotype as found in peripheral blood T...

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...

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)

Muscarinic and alpha 1-adrenergic receptor binding characteristics of saw palmetto extract in rat lower urinary tract.

Science.gov (United States)

Suzuki, Mayumi; Oki, Tomomi; Sugiyama, Tomomi; Umegaki, Keizo; Uchida, Shinya; Yamada, Shizuo

2007-06-01

To elucidate the in vitro and ex vivo effects of saw palmetto extract (SPE) on autonomic receptors in the rat lower urinary tract. The in vitro binding affinities for alpha 1-adrenergic, muscarinic, and purinergic receptors in the rat prostate and bladder were measured by radioligand binding assays. Rats received vehicle or SPE (0.6 to 60 mg/kg/day) orally for 4 weeks, and alpha 1-adrenergic and muscarinic receptor binding in tissues of these rats were measured. Saw palmetto extract inhibited specific binding of [3H]prazosin and [N-methyl-3H]scopolamine methyl chloride (NMS) but not alpha, beta-methylene adenosine triphosphate [2,8-(3)H]tetrasodium salt in the rat prostate and bladder. The binding activity of SPE for muscarinic receptors was four times greater than that for alpha 1-adrenergic receptors. Scatchard analysis revealed that SPE significantly reduced the maximal number of binding sites (Bmax) for each radioligand in the prostate and bladder under in vitro condition. Repeated oral administration of SPE to rats brought about significant alteration in Bmax for prostatic [3H]prazosin binding and for bladder [3H]NMS binding. Such alteration by SPE was selective to the receptors in the lower urinary tract. Saw palmetto extract exerts significant binding activity on autonomic receptors in the lower urinary tract under in vitro and in vivo conditions.

Advanced computer-controlled automatic alpha-beta air sample counter

International Nuclear Information System (INIS)

Howell, W.P.; Bruinekool, D.J.; Stapleton, E.E.

1983-01-01

An improved computer controlled automatic alpha-beta air sample counter was developed, based upon an earlier automatic air sample counter design. The system consists of an automatic sample changer, an electronic counting system utilizing a large silicon diode detector, a small desk-type microcomputer, a high speed matrix printer, and the necessary data interfaces. The system is operated by commands from the keyboard and programs stored on magnetic tape cassettes. The programs provide for background counting, Chi 2 test, radon subtraction, and sample counting for sample periods of one day to one week. Output data are printed by the matrix printer on standard multifold paper. The data output includes gross beta, gross alpha, and plutonium results. Data are automatically corrected for background, counter efficiency, and in the gross alpha and plutonium channels, for the presence of radon

Absolute measurement of the $\\beta\\alpha$ decay of $^{16}$N

CERN Multimedia

We propose to study the $\\beta$-decay of $^{16}$N at ISOLDE with the aim of determining the branching ratio for $\\beta\\alpha$ decay on an absolute scale. There are indications that the previously measured branching ratio is in error by an amount significantly larger than the quoted uncertainty. This limits the precision with which the S-factor of the astrophysically important $^{12}$C($\\alpha, \\gamma)^{16}$O reaction can be determined.

(-)[125I]-iodopindolol, a new highly selective radioiodinated beta-adrenergic receptor antagonist: measurement of beta-receptors on intact rat astrocytoma cells

International Nuclear Information System (INIS)

Barovsky, K.; Brooker, G.

1980-01-01

(-)-Pindolol, one of the most potent beta-adrenergic receptor antagonists, was radioiodinated using chloramine-T oxidation of carrier-free Na 125I and separated from unreacted pindolol to yield 2200 Ci/mmole (-)-[125I]-iodopindolol ((-)-[125I]-IPin). Mass and ultraviolet spectra confirmed that the iodination occurred on the indole ring, presumably at the 3 position. The binding of radiolabeled (-)-[125I]-IPin to beta-adrenergic receptors has been studied using intact C6 rat astrocytoma cells (2B subclone) grown in monolayer cultures. Binding of (-)[125IPin was saturable with time and concentration. Using 13 pM (-)-[125I]IPin, binding equilibrium was reached in 90 min at 21-22 degrees C. The reverse rate constant was 0.026 min-1 at 21 0 C. Specific binding (expressed as 1 microM(-)-propranolol displaceable counts) of (-)-[125I]-IPin was 95% of total binding. Scatchard analysis of (-)-[125I]-I]Pin binding revealed approximately 4300 receptors/cell and a dissociation constant of 30 pM. This was in excellent agreement with the kinetically determined dissociation constant of 35 pM. Displacement by propranolol and isoproterenol showed that (-)-[125I]-IPin binding sites were pharmacologically and stereospecifically selective. These results indicate that (-)-[125I]-IPin, a pure (-)-stereoisomer, high specific activity radioligand, selectively binds to beta-adrenergic receptors in whole cells with a high percentage of specific binding and should therefore be useful in the study and measurement of cellular beta-adrenergic receptors

Calibration and validation of measures a total alpha beta counter in the tunisian mineral water

International Nuclear Information System (INIS)

Nasri, Sihem; Skhiri, Noura

2009-01-01

The risks due to contamination of mineral waters are essentially risk internal radiation following ingestion of radionuclides which brought us in this study to determine the global alpha and beta of the Tunisian mineral water. We used an alpha beta global counter. The results obtained by this technique have shown that alpha activity of these 10 waters are all lower than 50 mBq / l and are varied between 3.75 and 8.4 mBq / l and beta activity was found only 9 waters are also lower than 50 mBq / l (between 7.17 and 18.25) when only one is between 100 and 500 mBq / l (101.17).

Synthesis of (19E)-3 beta,7 alpha-dihydroxy-17-oxoandrost-5-en-19-al 19-(O-carboxymethyl)oxime, a new hapten for 7 alpha-hydroxydehydroepiandrosterone (3 beta,7 alpha-dihydroxyandrost-5-en-17-one).

Science.gov (United States)

Pouzar, V; Slavíková, T; Cerńy, I

1998-09-01

The title compound was prepared in 11 steps from 17,17-ethylenedioxy-19-hydroxyandrost-5-en-3 beta-yl acetate. After tert-butyldimethylsilyl protection of the 19-hydroxyl group, a 7-oxo group was introduced by oxidation with 3,5-dimethylpyrazole-chromium trioxide complex, and then selectively reduced with L-Selectride to give a 7 alpha-hydroxy derivative. This partially protected triol was acetylated and desilylated to 3,7-diacetate. Subsequent oxidation with pyridine-chromium trioxide complex gave 19-aldehyde, which was transformed into the corresponding protected 19-(O-carboxymethyl)oxime. Successive ketal cleavage, deacetylation, and methyl ester splitting gave the final (19E)-3 beta,7 alpha-dihydroxy-17-oxoandrost-5-en-19-al 19-(O-carboxymethyl)oxime, designed as a hapten for 7 alpha-hydroxydehydroepiandrosterone immunoassays.

Source preparations for alpha and beta measurements

Energy Technology Data Exchange (ETDEWEB)

Holm, E. [Risoe National Lab., Roskilde (Denmark)

2001-01-01

Regarding alpha particle emitters subject for environmental studies, electrodeposition or co-precipitation as fluorides are the most common methods. For electro deposition stainless steel is generally used as cathode material but also other metals such as Ni, Ag, and Cu showed promising results. The use of other anode material than platinum, such as graphite should be investigated. For other purposes such as optimal resolution other more sophisticated methods are used but often resulting in poorer recovery. For beta particle emitters the type of detection system will decide the source preparation. Similar methods as for alpha particle emitters, electrodeposition or precipitation techniques can be used. Due to the continuous energy distribution of the beta pulse height distribution a high resolution is not required. Thicker sources from the precipitates or a stable isotopic carrier can be accepted but correction for absorption in the source must be done. (au)

Flow cytometric analysis of expression of interleukin-2 receptor beta chain (p70-75) on various leukemic cells

International Nuclear Information System (INIS)

Hoshino, S.; Oshimi, K.; Tsudo, M.; Miyasaka, M.; Teramura, M.; Masuda, M.; Motoji, T.; Mizoguchi, H.

1990-01-01

We analyzed the expression of the interleukin-2 receptor (IL-2R) beta chain (p70-75) on various leukemic cells from 44 patients by flow cytometric analysis using the IL-2R beta chain-specific monoclonal antibody, designated Mik-beta 1. Flow cytometric analysis demonstrated the expression of the IL-2R beta chain on granular lymphocytes (GLs) from all eight patients with granular lymphocyte proliferative disorders (GLPDs), on adult T-cell leukemia (ATL) cells from all three patients with ATL, and on T-cell acute lymphoblastic leukemia (T-ALL) cells from one of three patients with T-ALL. Although GLs from all the GLPD patients expressed the IL-2R beta chain alone and not the IL-2R alpha chain (Tac-antigen: p55), ATL and T-ALL cells expressing the beta chain coexpressed the alpha chain. In two of seven patients with common ALL (cALL) and in both patients with B-cell chronic lymphocytic leukemia, the leukemic cells expressed the alpha chain alone. Neither the alpha chain nor the beta chain was expressed on leukemic cells from the remaining 28 patients, including all 18 patients with acute nonlymphocytic leukemia, five of seven patients with cALL, all three patients with multiple myeloma, and two of three patients with T-ALL. These results indicate that three different forms of IL-2R chain expression exist on leukemic cells: the alpha chain alone; the beta chain alone; and both the alpha and beta chains. To examine whether the results obtained by flow cytometric analysis actually reflect functional aspects of the expressed IL-2Rs, we studied the specific binding of 125I-labeled IL-2 (125I-IL-2) to leukemic cells in 18 of the 44 patients. In addition, we performed 125I-IL-2 crosslinking studies in seven patients. The results of IL-2R expression of both 125I-IL-2 binding assay and crosslinking studies were in agreement with those obtained by flow cytometric analysis

Central alpha2 adrenergic receptors in the rat cerebral cortex: repopulation kinetics and receptor reserve

International Nuclear Information System (INIS)

Adler, C.H.

1986-01-01

The alpha 2 adrenergic receptor subtype is thought to play a role in the mechanism of action of antidepressant and antihypertensive drugs. This thesis has attempted to shed light on the regulation of central alpha 2 adrenergic receptors in the rat cerebral cortex. Repopulation kinetics analysis allows for the determination of the rate of receptor production, rate constant of degradation, and half-life of the receptor. This analysis was carried out using both radioligand binding and functional receptor assays at various times following the irreversible inactivation of central alpha 2 adrenergic receptors by in vivo administration of N-ethoxycarbonyl-2-ethyoxy-1,2-dihydroquinoline (EEDQ). Both alpha 2 agonist and antagonist ligand binding sites recovered with a t/sub 1/2/ equal to approximately 4 days. The function of alpha 2 adrenergic autoreceptors, which inhibit stimulation-evoked release of 3 H-norepinephrine ( 3 H-NE) and alpha 2 adrenergic heteroreceptors which inhibit stimulation-evoked release of 3 H-serotonin ( 3 H-5-HT) were assayed. The t/sub 1/2/ for recovery of maximal autoreceptor and heteroreceptor function was 2.4 days and 4.6 days, respectively. The demonstration of a receptor reserve is critical to the interpretation of past and future studies of the alpha 2 adrenergic receptor since it demonstrates that: (1) alterations in the number of alpha 2 adrenergic receptor binding sites cannot be extrapolated to the actual function of the alpha 2 adrenergic receptor; and (2) alterations in the number of alpha 2 receptors is not necessarily accompanied by a change in the maximum function being studied, but may only result in shifting of the dose-response curve

Measurement of biologically active interleukin-1 by a soluble receptor binding assay

International Nuclear Information System (INIS)

Riske, F.; Chizzonite, R.; Nunes, P.; Stern, A.S.

1990-01-01

A soluble receptor binding assay has been developed for measuring human interleukin-1 alpha (IL-1 alpha), human IL-1 beta, and mouse IL-1 alpha. The assay is based on a competition between unlabeled IL-1 and 125I-labeled mouse recombinant IL-1 alpha for binding to soluble IL-1 receptor prepared from mouse EL-4 cells. The assay measures only biologically active IL-1 folded in its native conformation. The ratio of human IL-1 alpha to human IL-1 beta can be measured in the same sample by a pretreatment step which removes human IL-1 beta from samples prior to assay. This technique has been used to monitor the purification of recombinant IL-1, and may be utilized to specifically and accurately measure bioactive IL-1 in human serum and cell culture supernatants

The grand partition function Z ({alpha},{beta}) of a quantum system is studied, using diagrammatic representations of the perturbation expansion; La grande fonction de partition Z ({alpha},{beta}) d'un systeme quantique est etudies en utilisant des representations diagrammatiques du developpement en serie des perturbations

Energy Technology Data Exchange (ETDEWEB)

Dominicis, C de [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1961-07-01

The grand partition function Z ({alpha},{beta}) of a quantum system is studied, using diagrammatic representations of the perturbation expansion. For a fermions system, it is possible to show, by proper resummation, without approximations but under some 'regularity hypothesis', that Log Z ({alpha},{beta}) takes a form where, besides trivial dependences, {alpha} and {beta} only appear through a statistical factor F{sub k}{sup -} = [1 + e{sup -{alpha}}{sup +{beta}}{sup {epsilon}{sub k}{sup 0}}{sup -{beta}}{sup W{sub k}}]{sup -1}. W{sub k} is a (real) self-consistent potential, generalized to all orders and can be defined by a stationary condition on Log Z ({alpha},{beta}) under variations of F{sub k}{sup -}. The thermodynamical quantities take a form analogous to the expressions Landau introduced for the Fermi liquids. The zero temperature limit (for isotropic systems) gives back Goldstone expressions for the ground state of a system. (author) [French] La grande fonction de partition Z ({alpha},{beta}) d'un systeme quantique est etudiee en utilisant des representations diagrammatiques du developpement en serie des perturbations. Pour un systeme de fermions on peut, par des resommations adequates, sans approximations mais sous reserve d'une 'hypothese de regularite', mettre Log Z ({alpha},{beta}) sous une forme ou, en dehors de dependances triviales, {alpha} et {beta} n'interviennent que par l'intermediaire d'un facteur statistique F{sub k}{sup -} = [1 + e{sup -{alpha}}{sup +{beta}}{sup {epsilon}{sub k}{sup 0}}{sup -{beta}}{sup W{sub k}}]{sup -1}. W{sub k} est ici un potentiel self-consistant (reel) generalise a tous les ordres et peut etre defini par une condition de stationnarite de Log Z ({alpha},{beta}) pour des variations de F{sub k}{sup -}. Les grandeurs thermodynamiques prennent une forme analogue aux expressions que LANDAU a introduites pour les liquides de FERMI. A la limite de la temperature nulle (et pour un systeme isotrope) on retrouve terme a terme les

Crystalline anhydrous {alpha},{alpha}-trehalose (polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose: A calorimetric study

Energy Technology Data Exchange (ETDEWEB)

Pinto, Susana S. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: susanapinto@ist.utl.pt; Diogo, Herminio P. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: hdiogo@ist.utl.pt; Moura-Ramos, Joaquim J. [Centro de Quimica-Fisica Molecular, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: mouraramos@ist.utl.pt

2006-09-15

The mean values of the standard massic energy of combustion of crystalline anhydrous {alpha},{alpha}-trehalose (C{sub 12}H{sub 22}O{sub 11}, polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose (C{sub 12}H{sub 26}O{sub 13}) measured by static-bomb combustion calorimetry in oxygen, at the temperature T=298.15K, are {delta}{sub c}u{sup o}=-(16434.05+/-4.50)J.g{sup -1} and {delta}{sub c}u{sup o}=-(14816.05+/-3.52)J.g{sup -1}, respectively. The standard (p{sup o}=0.1MPa) molar enthalpy of formation of these compounds were derived from the corresponding standard molar enthalpies of combustion, respectively, {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 22}O{sub 11},cr)=-(2240.9+/-3.9)kJ.mol{sup -1}, and {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 26}O{sub 13},cr)=-(2832.6+/-3.6)kJ.mol{sup -1}. The values of the standard enthalpies of formation obtained in this work, together with data on enthalpies of solution at infinite dilution ({delta}{sub sol}H{sup {approx}}) for crystalline dihydrate and amorphous anhydrous trehalose, allow a better insight on the thermodynamic description of the trehalose system which can provide, together with the future research on the subject, a contribution for understanding the metabolism in several organisms, as well as the phase transition between the different polymorphs.

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...

Reduced Fragment Diversity for Alpha and Alpha-Beta Protein Structure Prediction using Rosetta.

Science.gov (United States)

Abbass, Jad; Nebel, Jean-Christophe

2017-01-01

Protein structure prediction is considered a main challenge in computational biology. The biannual international competition, Critical Assessment of protein Structure Prediction (CASP), has shown in its eleventh experiment that free modelling target predictions are still beyond reliable accuracy, therefore, much effort should be made to improve ab initio methods. Arguably, Rosetta is considered as the most competitive method when it comes to targets with no homologues. Relying on fragments of length 9 and 3 from known structures, Rosetta creates putative structures by assembling candidate fragments. Generally, the structure with the lowest energy score, also known as first model, is chosen to be the "predicted one". A thorough study has been conducted on the role and diversity of 3-mers involved in Rosetta's model "refinement" phase. Usage of the standard number of 3-mers - i.e. 200 - has been shown to degrade alpha and alpha-beta protein conformations initially achieved by assembling 9-mers. Therefore, a new prediction pipeline is proposed for Rosetta where the "refinement" phase is customised according to a target's structural class prediction. Over 8% improvement in terms of first model structure accuracy is reported for alpha and alpha-beta classes when decreasing the number of 3- mers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Action of nereistoxin on recombinant neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes.

Science.gov (United States)

Raymond Delpech, Valérie; Ihara, Makoto; Coddou, Claudio; Matsuda, Kazuhiko; Sattelle, David B

2003-11-01

Nereistoxin (NTX), a natural neurotoxin from the salivary glands of the marine annelid worm Lumbriconereis heteropoda, is highly toxic to insects. Its synthetic analogue, Cartap, was the first commercial insecticide based on a natural product. We have used voltage-clamp electrophysiology to compare the actions of NTX on recombinant nicotinic acetylcholine receptors (nicotinic AChRs) expressed in Xenopus laevis oocytes following nuclear injection of cDNAs. The recombinant nicotinic AChRs investigated were chicken alpha7, chicken alpha4beta2 and the Drosophila melanogaster/chicken hybrid receptors SAD/beta2 and ALS/beta2. No agonist action of NTX (0.1-100 microM) was observed on chicken alpha7, chicken alpha4beta2 and the Drosophila/chicken hybrid nicotinic AChRs. Currents elicited by ACh were reduced in amplitude by NTX in a dose-dependent manner. The toxin was slightly more potent on recombinant Drosophila/vertebrate hybrid receptors than on vertebrate homomeric (alpha7) or heteromeric (alpha4beta2) nicotinic AChRs. Block by NTX of the chicken alpha7, chicken alpha4beta2 and the SAD/beta2 and ALS/beta2 Drosophila/chicken hybrid receptors is in all cases non-competitive. Thus, the site of action on nicotinic AChRs of NTX, to which the insecticide Cartap is metabolised in insects, differs from that of the major nicotinic AChR-active insecticide, imidacloprid.

Inhibition of neointima formation by local delivery of estrogen receptor alpha and beta specific agonists

NARCIS (Netherlands)

Krom, Y.D.; Pires, N.M.M.; Jukema, J.W.; Vries, M.R. de; Frants, R.R.; Havekes, L.M.; Dijk, K.W. van; Quax, P.H.A.

2007-01-01

Objective: Neointima formation is the underlying mechanism of (in-stent) restenosis. 17β-Estradiol (E2) is known to inhibit injury-induced neointima formation and post-angioplasty restenosis. Estrogen receptor alpha (ERα) has been demonstrated to mediate E2 anti-restenotic properties. However, the

Corticotropin-releasing factor in the basolateral amygdala enhances memory consolidation via an interaction with the beta-adrenoceptor-cAMP pathway: dependence on glucocorticoid receptor activation.

Science.gov (United States)

Roozendaal, Benno; Schelling, Gustav; McGaugh, James L

2008-06-25

Extensive evidence indicates that stress hormone effects on the consolidation of emotionally influenced memory involve noradrenergic activation of the basolateral complex of the amygdala (BLA). The present experiments examined whether corticotropin-releasing factor (CRF) modulates memory consolidation via an interaction with the beta-adrenoceptor-cAMP system in the BLA. In a first experiment, male Sprague Dawley rats received bilateral infusions of the CRF-binding protein ligand inhibitor CRF(6-33) into the BLA either alone or together with the CRF receptor antagonist alpha-helical CRF(9-41) immediately after inhibitory avoidance training. CRF(6-33) induced dose-dependent enhancement of 48 h retention latencies, which was blocked by coadministration of alpha-helical CRF(9-41), suggesting that CRF(6-33) enhances memory consolidation by displacing CRF from its binding protein, thereby increasing "free" endogenous CRF concentrations. In a second experiment, intra-BLA infusions of atenolol (beta-adrenoceptor antagonist) and Rp-cAMPS (cAMP inhibitor), but not prazosin (alpha(1)-adrenoceptor antagonist), blocked CRF(6-33)-induced retention enhancement. In a third experiment, the CRF receptor antagonist alpha-helical CRF(9-41) administered into the BLA immediately after training attenuated the dose-response effects of concurrent intra-BLA infusions of clenbuterol (beta-adrenoceptor agonist). In contrast, alpha-helical CRF(9-41) did not alter retention enhancement induced by posttraining intra-BLA infusions of either cirazoline (alpha(1)-adrenoceptor agonist) or 8-br-cAMP (cAMP analog). These findings suggest that CRF facilitates the memory-modulatory effects of noradrenergic stimulation in the BLA via an interaction with the beta-adrenoceptor-cAMP cascade, at a locus between the membrane-bound beta-adrenoceptor and the intracellular cAMP formation site. Moreover, consistent with evidence that glucocorticoids enhance memory consolidation via a similar interaction with the

Tumor targeting with radiolabeled alpha(v)beta(3) integrin binding peptides in a nude mouse model.

NARCIS (Netherlands)

Janssen, M.L.H.; Oyen, W.J.G.; Dijkgraaf, I.; Massuger, L.F.A.G.; Frielink, C.; Edwards, D.S.; Rajopadhye, M.; Boonstra, H.; Corstens, F.H.M.; Boerman, O.C.

2002-01-01

The alpha(v)beta(3) integrin is expressed on proliferating endothelial cells such as those present in growing tumors, as well as on tumor cells of various origin. Tumor-induced angiogenesis can be blocked in vivo by antagonizing the alpha(v)beta(3) integrin with small peptides containing the

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)

[11C]CHIBA-1001 as a novel PET ligand for alpha7 nicotinic receptors in the brain: a PET study in conscious monkeys.

Directory of Open Access Journals (Sweden)

Kenji Hashimoto

Full Text Available BACKGROUND: The alpha7 nicotinic acetylcholine receptors (nAChRs play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable positron emission tomography (PET radioligands for imaging alpha7 nAChRs in the intact human brain. Here we report the novel PET radioligand [11C]CHIBA-1001 for in vivo imaging of alpha7 nAChRs in the non-human primate brain. METHODOLOGY/PRINCIPAL FINDINGS: A receptor binding assay showed that CHIBA-1001 was a highly selective ligand at alpha7 nAChRs. Using conscious monkeys, we found that the distribution of radioactivity in the monkey brain after intravenous administration of [11C]CHIBA-1001 was consistent with the regional distribution of alpha7 nAChRs in the monkey brain. The distribution of radioactivity in the brain regions after intravenous administration of [11C]CHIBA-1001 was blocked by pretreatment with the selective alpha7 nAChR agonist SSR180711 (5.0 mg/kg. However, the distribution of [11C]CHIBA-1001 was not altered by pretreatment with the selective alpha4beta2 nAChR agonist A85380 (1.0 mg/kg. Interestingly, the binding of [11C]CHIBA-1001 in the frontal cortex of the monkey brain was significantly decreased by subchronic administration of the N-methyl-D-aspartate (NMDA receptor antagonist phencyclidine (0.3 mg/kg, twice a day for 13 days; which is a non-human primate model of schizophrenia. CONCLUSIONS/SIGNIFICANCE: The present findings suggest that [11C]CHIBA-1001 could be a novel useful PET ligand for in vivo study of the receptor occupancy and pathophysiology of alpha7 nAChRs in the intact brain of patients with neuropsychiatric diseases such as schizophrenia and Alzheimer's disease.

Prognostic Value of Estrogen Receptor alpha and Progesterone Receptor Conversion in Distant Breast Cancer Metastases

NARCIS (Netherlands)

Hoefnagel, Laurien D. C.; Moelans, Cathy B.; Meijer, S. L.; van Slooten, Henk-Jan; Wesseling, Pieter; Wesseling, Jelle; Westenend, Pieter J.; Bart, Joost; Seldenrijk, Cornelis A.; Nagtegaal, Iris D.; Oudejans, Joost; van der Valk, Paul; van Gils, Carla H.; van der Wall, Elsken; van Diest, Paul J.

2012-01-01

BACKGROUND: Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor alpha (ER alpha) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ER alpha and

Excess alpha chains are lost from beta-thalassemic reticulocytes by proteolysis

International Nuclear Information System (INIS)

Testa, U.; Hinard, N.; Beuzard, Y.; Tsapis, A.; Galacteros, F.; Thomopoulos, P.; Rosa, J.

1981-01-01

During incubation of reticulocytes from patients with beta-thalassemia, after labeling of the hemoglobin with radioactive amino acids, the excess alpha chains are gradually lost from the cells. The aim of this study was to investigate the mechanism of this phenomenon. A system was developed in which reticulocytes from beta-thalassemia patients are labeled with [3H]leucine, washed several times in nonradioactive medium, and then incubated in the same medium containing puromycin added in order to stop further protein synthesis. The results have clearly shown that excess alpha chains are gradually degraded by proteolysis. N-ethylmaleimide or epsilon-aminocaproic acid inhibited the proteolysis of free alpha chains. The addition of either ATP or hemin did not change the rate of alpha chain degradation. The time required to degrade 50% of the pool of free alpha chains was directly dependent on the initial value of this pool. This finding suggests the absence of a significant individual variation in the ability to proteolyse free alpha chains

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....

Interactions of foot-and-mouth disease virus with soluble bovine alphaVbeta3 and alphaVbeta6 integrins.

Science.gov (United States)

Duque, Hernando; LaRocco, Michael; Golde, William T; Baxt, Barry

2004-09-01

At least four members of the integrin family of receptors, alphaVbeta1, alphaVbeta3, alphaVbeta6, and alphaVbeta8, have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro. Our investigators have recently shown that the efficiency of receptor usage appears to be related to the viral serotype and may be influenced by structural differences on the viral surface (H. Duque and B. Baxt, J. Virol. 77:2500-2511, 2003). To further examine these differences, we generated soluble alphaVbeta3 and alphaVbeta6 integrins. cDNA plasmids encoding the individual complete integrin alphaV, beta3, and beta6 subunits were used to amplify sequences encoding the subunits' signal peptide and ectodomain, resulting in subunits lacking transmembrane and cytoplasmic domains. COS-1 cells were transfected with plasmids encoding the soluble alphaV subunit and either the soluble beta3 or beta6 subunit and labeled with [35S]methionine-cysteine. Complete subunit heterodimeric integrins were secreted into the medium, as determined by radioimmunoprecipitation with specific monoclonal and polyclonal antibodies. For the examination of the integrins' biological activities, stable cell lines producing the soluble integrins were generated in HEK 293A cells. In the presence of divalent cations, soluble alphaVbeta6 bound to representatives of type A or O viruses, immobilized on plastic dishes, and significantly inhibited viral replication, as determined by plaque reduction assays. In contrast, soluble alphaVbeta3 was unable to bind to immobilized virus of either serotype; however, virus bound to the immobilized integrin, suggesting that FMDV binding to alphaVbeta3 is a low-affinity interaction. In addition, soluble alphaVbeta3 did not neutralize virus infectivity. Incubation of soluble alphaVbeta6 with labeled type A12 or O1 resulted in a significant inhibition of virus adsorption to BHK cells, while soluble alphaVbeta3 caused a low (20 to 30%), but consistent, inhibition of virus

Actions of alpha2 adrenoceptor ligands at alpha2A and 5-HT1A receptors: the antagonist, atipamezole, and the agonist, dexmedetomidine, are highly selective for alpha2A adrenoceptors.

Science.gov (United States)

Newman-Tancredi, A; Nicolas, J P; Audinot, V; Gavaudan, S; Verrièle, L; Touzard, M; Chaput, C; Richard, N; Millan, M J

1998-08-01

This study examined the activity of chemically diverse alpha2 adrenoceptor ligands at recombinant human (h) and native rat (r) alpha2A adrenoceptors compared with 5-HT1A receptors. First, in competition binding experiments at h alpha2A and h5-HT1A receptors expressed in CHO cells, several compounds, including the antagonists 1-(2-pyrimidinyl)piperazine (1-PP), (+/-)-idazoxan, benalfocin (SKF 86466), yohimbine and RX 821,002, displayed preference for h alpha2A versus h5-HT1A receptors of only 1.4-, 3.6-, 4-, 10- and 11-fold, respectively (based on differences in pKi values). Clonidine, brimonidine (UK 14304), the benzopyrrolidine fluparoxan and the guanidines guanfacine and guanabenz exhibited intermediate selectivity (22- to 31-fold) for h alpha2A receptors. Only the antagonist atipamezole and the agonist dexmedetomidine (DMT) displayed high preference for alpha2 adrenoceptors (1290- and 91-fold, respectively). Second, the compounds were tested for their ability to induce h5-HT1A receptor-mediated G-protein activation, as indicated by the stimulation of [35S]GTPgammaS binding. All except atipamezole and RX 821,002 exhibited agonist activity, with potencies which correlated with their affinity for h5-HT1A receptors. Relative efficacies (Emax values) were 25-35% for guanabenz, guanfacine, WB 4101 and benalfocin, 50-65% for 1-PP, (+/-)-idazoxan and clonidine, and over 70% for fluparoxan, oxymetazoline and yohimbine (relative to 5-HT = 100%). Yohimbine-induced [35S]GTPgammaS binding was inhibited by the selective 5-HT1A receptor antagonist WAY 100,635. In contrast, RX 821,002 was the only ligand which exhibited antagonist activity at h5-HT1A receptors, inhibiting 5-HT-stimulated [35S]GTPgammaS binding. Atipamezole, which exhibited negligeable affinity for 5-HT1A receptors, was inactive. Third, the affinities for r alpha2A differed considerably from the affinities for h alpha2A receptors whereas the affinities for r5-HT1A differed much less from the affinities for h5-HT

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.

Upregulation of Nicotinic Acetylcholine Receptor alph4+beta2 through a Ligand-Independent PI3Kbeta Mechanism That Is Enhanced by TNFalpha and the Jak2/p38Mapk Pathways.

Science.gov (United States)

Rogers, Scott W; Gahring, Lorise C

2015-01-01

High affinity nicotine-binding sites in the mammalian brain are neuronal nicotinic acetylcholine receptors (nAChR) assembled from at least alpha4 and beta2 subunits into pentameric ion channels. When exposed to ligands such as nicotine, these receptors respond by undergoing upregulation, a correlate of nicotine addiction. Upregulation can be measured using HEK293 (293) cells that stably express alpha4 and beta2 subunits using quantification of [3H]epibatidine ([3H]Eb) binding to measure mature receptors. Treatment of these cells with choline also produces upregulation through a hemicholinium3 (HC3)-sensitive (choline kinase) and an HC3-insensitive pathway which are both independent of the mechanism used by nicotine for upregulation. In both cases, upregulation is significantly enhanced by the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) which signals through its receptor Tnfr1 to activate p38Mapk. Here we report that the inhibition of class1 phosphoinositide 3-kinases isoform PI3Kbeta using the selective antagonist PI828 is alone sufficient to produce upregulation and enhance both nicotine and choline HC3-sensitive mediated upregulation. Further, these processes are impacted upon by an AG-490 sensitive Jak2-associated pathway. Both PI3Kbeta (negative) and Jak2 (positive) modulation of upregulation converge through p38Mapk and both overlap with TNFalpha enhancement of this process. Upregulation through the PI3Kbeta pathway did not require Akt. Collectively these findings support upregulation of endogenous alpha4beta2 as a balance among cellular signaling networks that are highly responsive to multiple environmental, inflammatory and metabolic agents. The findings also suggest how illness and metabolic stress could alter the expression of this important nicotinic receptor and novel avenues to intercede in modifying its expression.

Application of Bayesian neural network modeling to characterize the interrelationship between microstructure and mechanical property in alpha+beta-titanium alloys

Science.gov (United States)

Koduri, Santhosh K.

Titanium alloys, especially alpha+beta titanium alloys are used extensively in the aerospace industry because of their attractive balance of properties. The mechanical properties of these materials are very much sensitive to their microstructure. Microstructure in these alloys can be controlled essentially through alloy composition and various thermomechanical processing routes. Microstructures in these alloys are characterized in terms of size, distribution and volume fraction of both alpha (HCP crystal structure) and beta (BCC crystal structure) phases. The above-mentioned features can coexist and span different length scales. The interrelationships between the microstructure and mechanical properties are characterized qualitatively in the literature. Physics based models are difficult to implement due to the presence of a wide variety of microstructural features with different length scales and mutual interaction of these features. The modeling of such properties is much more complex when composition is added as an additional degree of freedom. In this work neural network models with a Bayesian framework have been employed to characterize the microstructure and mechanical property interrelationships in alpha+beta Ti alloys based on Ti-xAl-yV (4.76 alpha+beta Ti alloys based on Ti-xAl-yV (4.76alloys are subjected to various heat treatments and thermomechanical processing conditions such as beta annealing and alpha+beta processing to obtain a range of microstructure and mechanical properties. The important microstructural features in alpha+beta processed alpha+beta titanium alloys are equiaxed alpha grain size, volume fraction of equiaxed alpha grains, width of the alpha lamellae in transformed beta matrix and important features in beta heat treated alpha+beta titanium alloys are size of alpha colony, width of the alpha lamellae, prior beta grain size, volume fraction of colony and grain boundary alpha thickness. A database is populated with the above

Analysis of radionuclide mixtures by {alpha}-{gamma} and {beta}-{gamma} coincidences using a simple device; Analyse de melanges de radionucleides par un dispositif simple de coincidences {alpha}-{gamma} et {beta}-{gamma}

Energy Technology Data Exchange (ETDEWEB)

Pottier, R; Berger, R [Commissariat a l' Energie Atomique, Centre d' Etudes Nucleaires de Fontenay-aux-Roses, 92 (France)

1966-06-01

A procedure is described for the qualitative and quantitative spectrographic analysis of radioactive sources containing two alpha-gamma emitters having the same alpha energy or two beta-gamma emitters having the same gamma energy. The main apparatus is a multichannel pulse-height analyzer including a coincidence circuit. The principle of the method, the synoptic scheme, the electronic device, the type of sources, and the precautions to be taken or the corrections to take into account are reported. The results obtained in solving the three following problems are discussed as examples of applications of the method: analysis of {sup 241}Am in alpha-gamma sources containing {sup 238}Pu; analysis of {sup 237}Np in beta-gamma sources containing {sup 239}Pu; and analysis of {sup 106}Ru-{sup 106}Rh in beta-gamma sources containing {sup 95}Zr-{sup 95}Nb. (authors) [French] Dans ce. rapport, on presente une methode d'analyse spectrographique qualitative et quantitative de sources radioactives contenant deux emetteurs alpha-gamma de meme energie alpha et deux emetteurs beta-gamma de meme energie gamma. L'organe principal est un analyseur d'amplitude a 400 canaux comprenant un circuit de coincidence. On decrit le principe de la methode, le schema synoptique, l'appareillage, le type des sources, les precautions a prendre ou les corrections a faire. On discute les resultats obtenus dans la solution des trois problemes suivants traites a titre d'application de la methode: 1. analyse d'americium 241 en presence de plutonium 238; 2. analyse de neptunium 237 en presence de plutonium 239; 3. analyse de ruthenium 106-rhodium 106 en presence de zirconium 95-niobium 95. (auteurs)

Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets

DEFF Research Database (Denmark)

Adriaenssens, Alice E; Svendsen, Berit; Lam, Brian Y H

2016-01-01

cytometry and analysed by RNA sequencing. The role of the ghrelin receptor was validated by imaging delta cell calcium concentrations using islets with delta cell restricted expression of the calcium reporter GCaMP3, and in perfused mouse pancreases. RESULTS: A database was constructed of all genes...... expressed in alpha, beta and delta cells. The gene encoding the ghrelin receptor, Ghsr, was highlighted as being highly expressed and enriched in delta cells. Activation of the ghrelin receptor raised cytosolic calcium levels in primary pancreatic delta cells and enhanced somatostatin secretion in perfused...... pancreases, correlating with a decrease in insulin and glucagon release. The inhibition of insulin secretion by ghrelin was prevented by somatostatin receptor antagonism. CONCLUSIONS/INTERPRETATION: Our transcriptomic database of genes expressed in the principal islet cell populations will facilitate...

Irradiation effect on {alpha}- and {beta}-caseins of milk and Queso Blanco cheese determined by capillary electrophoresis

Energy Technology Data Exchange (ETDEWEB)

Ham, J.S.; Jeong, S.G.; Lee, S.G.; Han, G.S.; Chae, H.S.; Yoo, Y.M.; Kim, D.H. [Animal Food Processing Division, National Institute of Animal Science, Suwon 441-706 (Korea, Republic of); Lee, W.K. [College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Jo, C. [Department of Animal Science and Biotechnology, Chungnam National University, Daejeon 305-764 (Korea, Republic of)], E-mail: cheorun@cnu.ac.kr

2009-02-15

Milk and Queso Blanco cheese were exposed to irradiation with doses of 1, 2, 3, 5, and 10 kGy to investigate the irradiation effect on {alpha}- and {beta}-casein using a capillary electrophoresis. {alpha}{sub S1}-Casein to total protein ratio in raw milk was decreased from 19.63% to 8.64% by 10 kGy of gamma irradiation. The ratio of {alpha}{sub S1}- to {alpha}{sub S0}-casein was also decreased from 1.38 to 0.53, which showed {alpha}{sub S1}-casein is more susceptible to gamma irradiation than {alpha}{sub S0}-casein. Similarly, {alpha}{sub S1}-casein to total protein ratio in Queso Blanco cheese was decreased from 17.48% to 7.82% and the ratio of {alpha}{sub S1}- to {alpha}{sub S0}-casein was decreased from 1.16 to 0.43 by 10 kGy of gamma irradiation. Dose-dependent reduction of {beta}{sub A1}-casein was also found. {beta}{sub A1}-Casein to total protein ratios in raw milk and Queso Blanco cheese were decreased from 22.00% to 14.16% and from 21.96% to 13.89% after 10 kGy, respectively. The ratios of {beta}{sub A1}- to {beta}{sub A2}-casein were from 1.10 to 0.64 and 0.93 to 0.57 in milk and Queso Blanco cheese, respectively. However, {alpha}{sub S0}-, {beta}{sub B}-, and {beta}{sub A3}-casein increased by irradiation at 10 kGy. The results suggest that {alpha}{sub S1}-casein and {beta}{sub A1}-casein were more susceptible to gamma irradiation, and may be related to the reduction of milk allergenicity caused by gamma irradiation.

Application of semiempirical expressions to the alpha and beta radiometry of environmental depositions samples

International Nuclear Information System (INIS)

Perez Tamayo, L.

1996-01-01

Were applied two semiempirical equations exponential beta absorption and Bragg-Kleeman approximation complementary to experimental corrections for beta backscattering and auto absorption of beta and alpha radiations in measurements of environmental depositions samples In the first case was verified the validity of mentioned corrections with an application boundary to mass greater than 300 Pb-210 (0.015 mg/cm 2 ) In the second case, the Bragg-Kleeman approximation combined with the experimental beta corrections, bring a judgment to determine the fundamental alpha and beta emisors samples which results the Pb-210 group

Helium burning: a further measurement of the beta-delayed alpha-particle emission of 16 Na

International Nuclear Information System (INIS)

Gai, Moshe

1997-01-01

The 12 C (α,γ) 16 O is a key (but still unknown) reaction in helium burning. Several attempts to constrain the p-wave S-factor at Helium burning temperatures (200 M K) using the beta-delayed alpha-particle emission of 16 N have been made. However, some discrepancy exists between the spectra measured at Settle and that of TRIUMF. We have improved our previous study of the beta-delayed alpha-particle emission of 16 N by improving our statistical sample (by more than a factor of 5), improving the energy resolution of the experiment (by 20%), and in understanding our line shape, deduced from measured quantities. Our newly measured spectrum of the beta-delayed alpha-particle emission of 16 N is consistent with the Seattle ('95) data, as well as an earlier experiment performed at Mains ('71) and is not consistent with the TRIUMF ('94) data. (author)

First Accurate Normalization of the $\\beta$-delayed $\\alpha$ Decay of $^{16}$N and Implications for the $^{12}$C$(\\alpha,\\gamma)^{16}$O Astrophysical Reaction Rate arXiv

CERN Document Server

Kirsebom, O.S.; Lica, R.; Munch, M.; Riisager, K.; Fynbo, H.O.U.; Borge, M.J.G.; Madurga, M.; Marroquin, I.; Andreyev, A.N.; Berry, T.A.; Christensen, E.R.; Fernández, P. Díaz; Doherty, D.T.; Van Duppen, P.; Fraile, L.M.; Gallardo, M.C.; Greenlees, P.T.; Harkness-Brennan, L.J.; Hubbard, N.; Huyse, M.; Jensen, J.H.; Johansson, H.; Jonson, B.; Judson, D.S.; Konki, J.; Lazarus, I.; Lund, M.V.; Marginean, N.; Marginean, R.; Perea, A.; Mihai, C.; Negret, A.; Page, R.D.; Pucknell, V.; Rahkila, P.; Sorlin, O.; Sotty, C.; Swartz, J.A.; Sørensen, H.B.; Törnqvist, H.; Vedia, V.; Warr, N.; De Witte, H.

The $^{12}$C$(\\alpha,\\gamma)^{16}$O reaction plays a central role in astrophysics, but its cross section at energies relevant for astrophysical applications is only poorly constrained by laboratory data. The reduced $\\alpha$ width, $\\gamma_{11}$, of the bound $1^-$ level in $^{16}$O is particularly important to determine the cross section. The magnitude of $\\gamma_{11}$ is determined via sub-Coulomb $\\alpha$-transfer reactions or the $\\beta$-delayed $\\alpha$ decay of $^{16}$N, but the latter approach is presently hampered by the lack of sufficiently precise data on the $\\beta$-decay branching ratios. Here we report improved branching ratios for the bound $1^-$ level and for $\\beta$-delayed $\\alpha$ emission. In the case of the $\\beta$-delayed $\\alpha$ branch, we find a $5\\sigma$ deviation from the literature value. With our new branching ratios, the constraints imposed on $\\gamma_{11}$ by the $\\beta\\alpha$-decay and $\\alpha$-transfer data are of similar precision and, for the first time, in good agreement. Th...

ADAM12 and alpha9beta1 integrin are instrumental in human myogenic cell differentiation

DEFF Research Database (Denmark)

Lafuste, Peggy; Sonnet, Corinne; Chazaud, Bénédicte

2005-01-01

of alpha9 parallels that of ADAM12 and culminates at time of fusion. alpha9 and ADAM12 coimmunoprecipitate and participate to mpc adhesion. Inhibition of ADAM12/alpha9beta1 integrin interplay, by either ADAM12 antisense oligonucleotides or blocking antibody to alpha9beta1, inhibited overall mpc fusion...

Binding of benzo(a)pyrene and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo(a)pyrene to histones

International Nuclear Information System (INIS)

Sculley, T.B.; Zytkovicz, T.H.

1983-01-01

AKR-2B mouse embryo cells were incubated for 24 hr with [3H]benzo(a)pyrene, and the histones were isolated and analyzed using one- and two-dimensional gel electrophoresis and autoradiography. The results revealed that (a) histones H1, H2A, and H3 incorporated significant amounts of label whereas little or no label was associated with histones H2B and H4 and (b) electrophoresis of the histones in the Triton: acid: urea gel system caused labeled histones to have a slower migration than did the corresponding unlabeled histones. Additional studies such as incubation of (+/-)-7 beta,8 alpha-[3H]dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene with nuclei resulted in radioactive labeling of histones H1, H2A, H2B, and H3 and of high-mobility-group proteins HMG1 and HMG2. The low levels of label associated with histone H4 in the whole-cell and nuclear studies were further investigated by incubating isolated histones with (+/-)-7 beta,8 alpha-[3H]dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Under these conditions, negligible amounts of radioactivity were associated with H4, while significant labeling of H1, H2A, H2B, and H3 and other nuclear proteins was observed. The results suggest that factors other than the presence of suitable nucleophilic acceptor sites on the histones may be necessary for carcinogen binding

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.

CGRP receptors mediating CGRP-, adrenomedullin- and amylin-induced relaxation in porcine coronary arteries. Characterization with 'Compound 1' (WO98/11128), a non-peptide antagonist

DEFF Research Database (Denmark)

Hasbak, P; Sams, A; Schifter, S

2001-01-01

. The partial porcine mRNA sequences shared 82 - 92% nucleotide identity with human sequences. 3. The human peptides alphaCGRP, betaCGRP, AM and amylin induced relaxation with pEC(50) values of 8.1, 8.1, 6.7 and 6.1 M respectively. 4. The antagonistic properties of a novel non-peptide CGRP antagonist 'Compound...... 1' (WO98/11128), betaCGRP(8 - 37) and the proposed AM receptor antagonist AM(22 - 52) were compared to the well-known CGRP(1) receptor antagonist alphaCGRP(8 - 37). 5. The alphaCGRP(8 - 37) and betaCGRP(8 - 37) induced concentration-dependent (10(-7) - 10(-5) M) rightward shift of both the alpha......(-6) M) had no significant antagonistic effect. 7. In conclusion, the building blocks forming CGRP and AM receptors were present in the porcine LAD, whereas those of the amylin receptor were not. alphaCGRP, betaCGRP, AM and amylin mediated vasorelaxation via the CGRP receptors. No functional response...

Enhanced Noradrenergic Activity Potentiates Fear Memory Consolidation and Reconsolidation by Differentially Recruiting alpha1- and beta-Adrenergic Receptors

Science.gov (United States)

Gazarini, Lucas; Stern, Cristina A. Jark; Carobrez, Antonio P.; Bertoglio, Leandro J.

2013-01-01

Consolidation and reconsolidation are phases of memory stabilization that diverge slightly. Noradrenaline is known to influence both processes, but the relative contribution of alpha1- and beta-adrenoceptors is unclear. The present study sought to investigate this matter by comparing their recruitment to consolidate and/or reconsolidate a…

An advanced computer-controlled automatic alpha-beta air sample counter

International Nuclear Information System (INIS)

Howell, W.P.; Bruinekool, D.J.; Stapleton, E.E.

1984-01-01

An improved computer-controlled automatic alpha-beta air sample counter was developed, based upon an earlier automatic air sample counter design. The system consists of an automatic sample changer, an electronic counting system utilizing a large silicon diode detector, a small desk-type microcomputer, a high-speed matrix printer and the necessary data interfaces. The system is operated by commands from the keyboard and programs stored on magnetic tape cassettes. The programs provide for background counting, Chi 2 test, radon subtraction and sample counting for sample periods of one day to one week. Output data are printed by the matrix printer on standard multifold paper. The data output includes gross beta, gross alpha and plutonium results. Data are automatically corrected for background, counter efficiency, and in the gross alpha and plutonium channels, for the presence of radon

Method validation to determine total alpha beta emitters in water samples using LSC

International Nuclear Information System (INIS)

Al-Masri, M. S.; Nashawati, A.; Al-akel, B.; Saaid, S.

2006-06-01

In this work a method was validated to determine gross alpha and beta emitters in water samples using liquid scintillation counter. 200 ml of water from each sample were evaporated to 20 ml and 8 ml of them were mixed with 12 ml of the suitable cocktail to be measured by liquid scintillation counter Wallac Winspectral 1414. The lower detection limit by this method (LDL) was 0.33 DPM for total alpha emitters and 1.3 DPM for total beta emitters. and the reproducibility limit was (± 2.32 DPM) and (±1.41 DPM) for total alpha and beta emitters respectively, and the repeatability limit was (±2.19 DPM) and (±1.11 DPM) for total alpha and beta emitters respectively. The method is easy and fast because of the simple preparation steps and the large number of samples that can be measured at the same time. In addition, many real samples and standard samples were analyzed by the method and showed accurate results so it was concluded that the method can be used with various water samples. (author)

Ratio of Circulating Estrogen Receptors Beta and Alpha (ERβ/ERα) Indicates Endoscopic Activity in Patients with Crohn's Disease.

Science.gov (United States)

Linares, Pablo M; Algaba, Alicia; Urzainqui, Ana; Guijarro-Rojas, Mercedes; González-Tajuelo, Rafael; Garrido, Jesús; Chaparro, María; Gisbert, Javier P; Bermejo, Fernando; Guerra, Iván; Castellano, Víctor; Fernández-Contreras, María-Encarnación

2017-10-01

Data supporting a role of female hormones and/or their receptors in inflammatory bowel disease (IBD) are increasing, but most of them are derived from animal models. Estrogen receptors alpha (ERα) and beta (ERβ) participate in immune and inflammatory response, among a variety of biological processes. Their effects are antagonistic, and the net action of estrogens may depend on their relative proportions. To determine the possible association between the balance of circulating ERβ and ERα (ERβ/ERα) and IBD risk and activity. Serum samples from 145 patients with IBD (79 Crohn's disease [CD] and 66 ulcerative colitis [UC]) and 39 controls were retrospectively studied. Circulating ERα and ERβ were measured by ELISA. Disease activities were assessed by clinical and endoscopic indices specific for CD and UC. Low values of ERβ/ERα ratio were directly associated with clinical (p = 0.019) and endoscopic (p = 0.002) disease activity. Further analyses by type of IBD confirmed a strong association between low ERβ/ERα ratio and CD clinical (p = 0.011) and endoscopic activity (p = 0.002). The receiver operating curve (ROC) analysis showed that an ERβ/ERα ratio under 0.85 was a good marker of CD endoscopic activity (area under the curve [AUC]: 0.84; p = 0.002; sensitivity: 70%; specificity: 91%). ERβ/ERα ratio was not useful to predict UC activity. An ERβ/ERα ratio under 0.85 indicated CD endoscopic activity. The determination of serum ERβ/ERα might be a useful noninvasive screening tool for CD endoscopic activity.

The grand partition function Z ({alpha},{beta}) of a quantum system is studied, using diagrammatic representations of the perturbation expansion; La grande fonction de partition Z ({alpha},{beta}) d'un systeme quantique est etudies en utilisant des representations diagrammatiques du developpement en serie des perturbations

Energy Technology Data Exchange (ETDEWEB)

Dominicis, C. de [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1961-07-01

The grand partition function Z ({alpha},{beta}) of a quantum system is studied, using diagrammatic representations of the perturbation expansion. For a fermions system, it is possible to show, by proper resummation, without approximations but under some 'regularity hypothesis', that Log Z ({alpha},{beta}) takes a form where, besides trivial dependences, {alpha} and {beta} only appear through a statistical factor F{sub k}{sup -} = [1 + e{sup -{alpha}}{sup +{beta}}{sup {epsilon}{sub k}{sup 0}}{sup -{beta}}{sup W{sub k}}]{sup -1}. W{sub k} is a (real) self-consistent potential, generalized to all orders and can be defined by a stationary condition on Log Z ({alpha},{beta}) under variations of F{sub k}{sup -}. The thermodynamical quantities take a form analogous to the expressions Landau introduced for the Fermi liquids. The zero temperature limit (for isotropic systems) gives back Goldstone expressions for the ground state of a system. (author) [French] La grande fonction de partition Z ({alpha},{beta}) d'un systeme quantique est etudiee en utilisant des representations diagrammatiques du developpement en serie des perturbations. Pour un systeme de fermions on peut, par des resommations adequates, sans approximations mais sous reserve d'une 'hypothese de regularite', mettre Log Z ({alpha},{beta}) sous une forme ou, en dehors de dependances triviales, {alpha} et {beta} n'interviennent que par l'intermediaire d'un facteur statistique F{sub k}{sup -} = [1 + e{sup -{alpha}}{sup +{beta}}{sup {epsilon}{sub k}{sup 0}}{sup -{beta}}{sup W{sub k}}]{sup -1}. W{sub k} est ici un potentiel self-consistant (reel) generalise a tous les ordres et peut etre defini par une condition de stationnarite de Log Z ({alpha},{beta}) pour des variations de F{sub k}{sup -}. Les grandeurs thermodynamiques prennent une forme analogue aux expressions que LANDAU a introduites pour les liquides de FERMI. A la limite de la temperature nulle (et pour un

Estrogen increases smooth muscle expression of alpha2C-adrenoceptors and cold-induced constriction of cutaneous arteries.

Science.gov (United States)

Eid, A H; Maiti, K; Mitra, S; Chotani, M A; Flavahan, S; Bailey, S R; Thompson-Torgerson, C S; Flavahan, N A

2007-09-01

Raynaud's phenomenon, which is characterized by intense cold-induced constriction of cutaneous arteries, is more common in women compared with men. Cold-induced constriction is mediated in part by enhanced activity of alpha(2C)-adrenoceptors (alpha(2C)-ARs) located on vascular smooth muscle cells (VSMs). Experiments were therefore performed to determine whether 17beta-estradiol regulates alpha(2C)-AR expression and function in cutaneous VSMs. 17beta-Estradiol (0.01-10 nmol/l) increased expression of the alpha(2C)-AR protein and the activity of the alpha(2C)-AR gene promoter in human cultured dermal VSMs, which was assessed following transient transfection of the cells with a promoter-reporter construct. The effect of 17beta-estradiol was associated with increased accumulation of cAMP and activation of the cAMP-responsive Rap2 GTP-binding protein. Transient transfection of VSMs with a dominant-negative mutant of Rap2 inhibited the 17beta-estradiol-induced activation of the alpha(2C)-AR gene promoter, whereas a constitutively active mutant of Rap2 increased alpha(2C)-AR promoter activity. The effects of 17beta-estradiol were inhibited by the estrogen receptor (ER) antagonist, ICI-182780 (1 micromol/l), and were mimicked by a cell-impermeable form of the hormone (estrogen:BSA) or by the selective ER-alpha receptor agonist 4,4',4'''-(4-propyl-[(1)H]-pyrazole-1,3,5-triyl)tris-phenol (PPT; 10 nmol/l) or the selective ER-beta receptor agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; 10 nmol/l). Therefore, 17beta-estradiol increased expression of alpha(2C)-ARs by interacting with cell surface receptors to cause a cAMP/Rap2-dependent increase in alpha(2C)-AR transcription. In mouse tail arteries, 17beta-estradiol (10 nmol/l) increased alpha(2C)-AR expression and selectively increased the cold-induced amplification of alpha(2)-AR constriction, which is mediated by alpha(2C)-ARs. An estrogen-dependent increase in expression of cold-sensitive alpha(2C)-ARs may contribute

The Paramagnetism of Dissolved Mn in {alpha} and {beta} Brasses

Energy Technology Data Exchange (ETDEWEB)

Myers, H P; Westin, R

1962-12-15

Paramagnetic susceptibility measurements have been made on {alpha} and {beta} brasses containing {approx} 1 w/o Mn. The susceptibility varied with temperature according to the Curie Weiss law and the Curie constant and thereby the Bohr magneton number per Mn atom were determined. Interpreted in terms of valency, Mn monovalent in copper has a valency in {alpha} brass which decreases progressively with zinc content attaining the value 0.58 at the limiting of composition. Mn in {beta} brass exhibits a valency 0.8. These results are not in keeping with previous values for the valency of manganese as determined from phase boundary relationships and electron to atom ratios.

Enantioselective cycloadditions with alpha,beta-disubstituted acrylimides.

Science.gov (United States)

Sibi, Mukund P; Ma, Zhihua; Itoh, Kennosuke; Prabagaran, Narayanasamy; Jasperse, Craig P

2005-06-09

[reaction: see text] The use of N-H imide templates provides a solution to the problem of rotamer control in Lewis acid catalyzed reactions of alpha,beta-disubstituted acryloyl imides. Reactions proceed through the s-cis rotamer and with improved reactivity because A(1,3) strain is avoided. Enantioselective nitrone, nitrile oxide, and Diels-Alder cycloadditions demonstrate the principle.

Autonomic receptors in urinary tract: Sex and age differences

International Nuclear Information System (INIS)

Latifpour, J.; Kondo, S.; O'Hollaren, B.; Morita, T.; Weiss, R.M.

1990-01-01

As age and sex affect the function of the lower urinary tract, we studied the characteristics of adrenergic and cholinergic receptors in various parts of lower urinary tract smooth muscle of young (6 months) and old (4 1/2-5 years) male and female rabbits. Saturation experiments performed with [3H]prazosin, [3H]yohimbine, [3H]dihydroalprenolol and [3H]quinuclidinyl benzylate in rabbit bladder base, bladder dome and urethra indicate the presence of regional, sex- and age-related differences in the density of alpha-1, alpha-2, and beta adrenergic and muscarinic cholinergic receptors. Alpha-2 adrenergic receptor density is considerably higher in the female than in the male urethra of both age groups, whereas the higher density of beta adrenergic receptors in the female than in the male bladder base is observed only in the younger animals. The density of muscarinic receptors is higher in bladder dome than in bladder base or urethra in young rabbits of both sexes. In the old animals, the density of muscarinic receptors in bladder base increases to the level observed in bladder dome. Inhibition experiments with selective adrenergic agonists and antagonists indicate that the pharmacological profiles of alpha-2 adrenergic receptors in the urethra and beta adrenergic receptors in the bladder dome and bladder base are similar in both sexes and at both ages. Beta-2 adrenergic receptors are shown to be predominant in bladder base and bladder dome of rabbits. Parallel studies in rabbit urethra, adult rat cortex and neonatal rat lung show that the urethral alpha-2 adrenergic receptors are of the alpha-2A subtype

A study of membrane protein defects and alpha hemoglobin chains of red blood cells in human beta thalassemia

International Nuclear Information System (INIS)

Rouyer-Fessard, P.; Garel, M.C.; Domenget, C.; Guetarni, D.; Bachir, D.; Colonna, P.; Beuzard, Y.

1989-01-01

The soluble pool of alpha hemoglobin chains present in blood or bone marrow cells was measured with a new affinity method using a specific probe, beta A hemoglobin chain labeled with [ 3 H]N-ethylmaleimide. This pool of soluble alpha chains was 0.067 ± 0.017% of hemoglobin in blood of normal adult, 0.11 ± 0.03% in heterozygous beta thalassemia and ranged from 0.26 to 1.30% in homozygous beta thalassemia intermedia. This elevated pool of soluble alpha chains observed in human beta thalassemia intermedia decreased 33-fold from a value of 10% of total hemoglobin in bone marrow cells to 0.3% in the most dense red blood cells. The amount of insoluble alpha chains was measured by using the polyacrylamide gel electrophoresis in urea and Triton X-100. In beta thalassemia intermedia the amount of insoluble alpha chains was correlated with the decreased spectrin content of red cell membrane and was associated with a decrease in ankyrin and with other abnormalities of the electrophoretic pattern of membrane proteins. The loss and topology of the reactive thiol groups of membrane proteins was determined by using [ 3 H]N-ethylmaleimide added to membrane ghosts prior to urea and Triton X-100 electrophoresis. Spectrin and ankyrin were the major proteins with the most important decrease of thiol groups

Measurement of Gross Alpha and Gross Beta Radioactivity of River Yobe, North Eastern Nigeria

International Nuclear Information System (INIS)

Abba, H. T.; Sadiq, U.; Adeyemo, D. J.

2013-01-01

Measurement of the gross alpha and gross beta radioactivity of River Yobe has been carried out. Fifteen samples of the river water were collected from the farming, fishing, domestic/livestock and control areas along the river and were analyzed using desktop alpha/beta (MPC 2000- DP) counting system. The count results show the average alpha activities in farming, fishing, domestic/livestock and control areas are 0.207±0.082, 0.257±0.13, 0.437±0.315 and 0.237±0.10 Bq L -1 , respectively. The average beta activities in the four areas are 0.813±0.122, 0.308±0.0145, 0.563±0.230 and 0.225±0.0096 Bq L -1 , respectively. The overall results show that the alpha and beta activities in the four areas are far below the practical screening level of radioactivity in drinking water of 0.5 Bq L -1 for alpha and 1 Bq L -1 for beta recommended by CEC-FAO and WHO and therefore may not pose any serious detrimental health side-effects to the public users of the river.

Chronic underactivity of medial frontal cortical beta2-containing nicotinic receptors increases clozapine-induced working memory impairment in female rats.

Science.gov (United States)

Levin, Edward D; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N Channelle

2009-03-17

Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of beta2-containing nicotinic receptors with dihydro-beta-erythrodine (DHbetaE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal alpha7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical alpha7 and beta2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHbetaE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHbetaE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHbetaE infusion potentiated clozapine-induced memory impairment, whereas previously

Modeling of mechanical properties in alpha/beta-titanium alloys

Science.gov (United States)

Kar, Sujoy Kumar

2005-11-01

The accelerated insertion of titanium alloys in component application requires the development of predictive capabilities for various aspects of their behavior, for example, phase stability, microstructural evolution and property-microstructure relationships over a wide range of length and time scales. In this presentation some navel aspects of property-microstructure relationships and microstructural evolution in alpha/beta Ti alloys will be discussed. Neural Network (NN) Models based on a Bayesian framework have been developed to predict the mechanical properties of alpha/beta Ti alloys. The development of such rules-based model requires the population of extensive databases, which in the present case are microstructurally-based. The steps involved in database development include producing controlled variations of the microstructure using novel approaches to heat-treatments, the use of standardized stereology protocols to characterize and quantify microstructural features rapidly, and mechanical testing of the heat-treated specimens. These databases have been used to train and test NN Models for prediction of mechanical properties. In addition, these models have been used to identify the influence of individual microstructural features on the mechanical properties, consequently guiding the efforts towards development of more robust mechanistically based models. In order to understand the property-microstructure relationships, a detailed understanding of microstructure evolution is imperative. The crystallography of the microstructure developing as a result of the solid-state beta → beta+alpha transformation has been studied in detail by employing Scanning Electron Microscopy (SEM), Orientation Imaging Microscopy (in a high resolution SEM), site-specific TEM sample preparation using focused ion beam, and TEM based techniques. The influence of variant selection on the evolution of microstructure will be specifically addressed.

Human myometrial adrenergic receptors during pregnancy: identification of the alpha-adrenergic receptor by [3H] dihydroergocryptine binding

International Nuclear Information System (INIS)

Jacobs, M.M.; Hayashida, D.; Roberts, J.M.

1985-01-01

The radioactive alpha-adrenergic antagonist [ 3 H] dihydroergocryptine binds to particulate preparations of term pregnant human myometrium in a manner compatible with binding to the alpha-adrenergic receptor (alpha-receptor). [ 3 H] Dihydroergocryptine binds with high affinity (KD = 2 nmol/L and low capacity (receptor concentration = 100 fmol/mg of protein). Adrenergic agonists compete for [ 3 H] dihydroergocryptine binding sites stereo-selectively ([-]-norepinephrine is 100 times as potent as [+]-norepinephrine) and in a manner compatible with alpha-adrenergic potencies (epinephrine approximately equal to norepinephrine much greater than isoproterenol). Studies in which prazosin, an alpha 1-antagonist, and yohimbine, and alpha 2-antagonist, competed for [ 3 H] dihydroergocryptine binding sites in human myometrium indicated that approximately 70% are alpha 2-receptors and that 30% are alpha 1-receptors. [ 3 H] dihydroergocryptine binding to human myometrial membrane particulate provides an important tool with which to study the molecular mechanisms of uterine alpha-adrenergic response

Carbamoylcholine analogs as nicotinic acetylcholine receptor agonists--structural modifications of 3-(dimethylamino)butyl dimethylcarbamate (DMABC)

DEFF Research Database (Denmark)

Hansen, Camilla Petrycer; Jensen, Anders Asbjørn; Balle, Thomas

2009-01-01

Compounds based on the 3-(dimethylamino)butyl dimethylcarbamate (DMABC) scaffold were synthesized and pharmacologically characterized at the alpha(4)beta(2), alpha(3)beta(4,) alpha(4)beta(4) and alpha(7) neuronal nicotinic acetylcholine receptors (nAChRs). The carbamate functionality and a small...

Hydrogen bonds between the alpha and beta subunits of the F1-ATPase allow communication between the catalytic site and the interface of the beta catch loop and the gamma subunit.

Science.gov (United States)

Boltz, Kathryn W; Frasch, Wayne D

2006-09-19

F(1)-ATPase mutations in Escherichia coli that changed the strength of hydrogen bonds between the alpha and beta subunits in a location that links the catalytic site to the interface between the beta catch loop and the gamma subunit were examined. Loss of the ability to form the hydrogen bonds involving alphaS337, betaD301, and alphaD335 lowered the k(cat) of ATPase and decreased its susceptibility to Mg(2+)-ADP-AlF(n) inhibition, while mutations that maintain or strengthen these bonds increased the susceptibility to Mg(2+)-ADP-AlF(n) inhibition and lowered the k(cat) of ATPase. These data suggest that hydrogen bonds connecting alphaS337 to betaD301 and betaR323 and connecting alphaD335 to alphaS337 are important to transition state stabilization and catalytic function that may result from the proper alignment of catalytic site residues betaR182 and alphaR376 through the VISIT sequence (alpha344-348). Mutations betaD301E, betaR323K, and alphaR282Q changed the rate-limiting step of the reaction as determined by an isokinetic plot. Hydrophobic mutations of betaR323 decreased the susceptibility to Mg(2+)-ADP-AlF(n)() inhibition and lowered the number of interactions required in the rate-limiting step yet did not affect the k(cat) of ATPase, suggesting that betaR323 is important to transition state formation. The decreased rate of ATP synthase-dependent growth and decreased level of lactate-dependent quenching observed with alphaD335, betaD301, and alphaE283 mutations suggest that these residues may be important to the formation of an alternative set of hydrogen bonds at the interface of the alpha and beta subunits that permits the release of intersubunit bonds upon the binding of ATP, allowing gamma rotation in the escapement mechanism.

Microcalorimetric and spectrographic studies on host-guest interactions of {alpha}-, {beta}-, {gamma}- and M{beta}-cyclodextrin with resveratrol

Energy Technology Data Exchange (ETDEWEB)

Li, Hui; Xu, Xiangyu; Liu, Min [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China); Sun, Dezhi, E-mail: sundezhisdz@163.com [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China); Li, Linwei, E-mail: lilinwei@lcu.edu.cn [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China)

2010-10-20

Thermal effects of inclusion processes of {alpha}-, {beta}-, {gamma}- and M{beta}-cyclodextrin with resveratrol (RES) in aqueous solutions were determined by isothermal titration calorimetry (ITC) with nanowatt sensitivity at the temperature of 298.15 K. Standard enthalpy changes, stoichiometry and equilibrium constants of the inclusion complexes were derived from the direct calorimetric data utilizing nonlinear simulation. The thermodynamic parameters were discussed in the light of weak interactions between the host and the guest molecules combining with UV spectral message. The results indicate that all of the complexes formed in the aqueous solutions are in 1:1 stoichiometry. The binding processes of {alpha}-, {beta}- and M{beta}-cyclodextrin with the guest are mainly driven by enthalpy, while that of {gamma}-cyclodextrin with the drug is driven by both enthalpy and entropy.

Alpha-beta-gamma spectrometer as an aid in directing decontamination of soils

International Nuclear Information System (INIS)

Berger, C.D.

1981-01-01

This technique permits rapid assessment of alpha-beta-gamma-emitter contamination in soils at sufficiently low concentrations to direct field operations. Of particular importance is its applicability during initial decommissioning and decontamination surveys when characterization of alpha and beta contamination in the presence of a high gamma background is necessary. This system has not yet been made portable for in-situ use, but it is expected that results willbe favorable when operated as a field instrument, resulting in simplified standard decontamination operation

Human myometrial adrenergic receptors: identification of the beta-adrenergic receptor by [3H]dihydroalprenolol binding

International Nuclear Information System (INIS)

Hayashida, D.N.; Leung, R.; Goldfien, A.; Roberts, J.M.

1982-01-01

The radioactive beta-adrenergic antagonist [ 3 H] dihydroalprenolol (DHA) binds to particulate preparations of human myometrium in a manner compatible with binding to the beta-adrenergic receptor. The binding of DHA is rapid (attaining equilibrium in 12 minutes), readily reversible (half time = 16 minutes), high affinity (K/sub D/ = 0.50 nM), low capacity (Bmax = 70 fmoles/mg of protein), and stereoselective ([-]-propranolol is 100 times as potent as [+] -propranolol in inhibiting DHA binding). Adrenergic agonists competed for DHA binding sites in a manner compatible with beta-adrenergic interactions and mirrored β 2 pharmacologic potencies: isoproterenol > epinephrine >> norepinephrine. Studies in which zinterol, a β 2 -adrenergic agonist, competed for DHA binding sites in human myometrial particulate indicated that at least 87% of the beta-adrenergic receptors present are β 2 -adrenergic receptors. Binding of DHA to human myometrial beta-adrenergic receptors provides a tool which may be used in the examination of gonadal hormonal modification of adrenergic response in human uterus as well as in the analysis of beta-adrenergic agents as potentially useful tocolytic agents

GABA-A receptor beta3 and alpha5 subunit gene cluster on chromosome 15q11-q13 and bipolar disorder: a genetic association study.

Science.gov (United States)

Papadimitriou, G N; Dikeos, D G; Karadima, G; Avramopoulos, D; Daskalopoulou, E G; Stefanis, C N

2001-05-08

There is accumulated evidence that the genes coding for the receptor of gamma aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the CNS, may be involved in the pathogenesis of affective disorders. In a previous study, we have found a genetic association between the GABA-A receptor alpha5 subunit gene locus (GABRA5) on chromosome 15q11-of 13 and bipolar affective disorder. The aim of the present study was to examine the same subjects to see if there exists a genetic association between bipolar affective disorder and the GABA receptor beta3 subunit gene (GABRB3), which is located within 100 kb from GABRA5. The sample consisted of 48 bipolar patients compared to 44 controls (blood donors). All subjects were Greek, unrelated, and personally interviewed. Diagnosis was based on DSM-IV and ICD-10 criteria. The marker used was a dinucleotide (CA) repeat polymorphism with 12 alleles 179 to 201 bp long; genotyping was successful in all patients and 43 controls. The distribution of GABRB3 genotypes among the controls did not deviate significantly from the Hardy-Weinberg equilibrium. No differences in allelic frequencies between bipolar patients and controls were found for GABRB3, while this locus and GABRA5 did not seem to be in significant linkage disequilibrium. In conclusion, the GABRB3 CA-repeat polymorphism we investigated does not present the observed association between bipolar affective illness and GABRA5. This could be due to higher mutation rate in the GABRB3 CA-repeat polymorphism, but it might also signify that GABRA5 is the gene actually associated with the disease. Copyright 2001 Wiley-Liss, Inc.

Influence of beta instabilities on the early stages of nucleation and growth of alpha in beta titanium alloys

Science.gov (United States)

Nag, Soumya

Microstructural evolution in beta Titanium alloys is an important factor that governs the properties exhibited by them. Intricate understanding of complex phase transformations in these alloys is vital to tailor their microstructures and in turn their properties to our advantage. One such important subject of study is the nucleation and growth of alpha precipitates triggered by the compositional instabilities in the beta matrix, instilled in them during non equilibrium heat treatments. The present work is an effort to investigate such a phenomenon. Here studies have been conducted primarily on two different beta-Titanium alloys of commercial relevance- Ti5553 (Ti-5Al-5Mo-5V-3Cr-0.5Fe), an alloy used in the aerospace industry for landing gear applications and, TNZT (Ti-35Nb-7Zr-5Ta), a potential load bearing orthopedic implant alloy. Apart from the effect of thermal treatment on these alloys, the focus of this work is to study the interplay between different alpha and beta stabilizers present in them. For this, advanced nano-scale characterization tools such as High Resolution STEM, High Resolution TEM, EFTEM and 3D Atom Probe have been used to determine the structure, distribution and composition of the non equilibrium instabilities such as beta' and o, and also to investigate the subsequent nucleation of stable alpha. Thus in this work, very early stages of phase separation via spinodal decomposition and second phase nucleation in titanium alloys are successfully probed at an atomic resolution. For the first time, atomically resolved HRSTEM 'Z'-contrast image is recorded showing modulated structures within the as-quenched beta matrix. Also in the same condition HRTEM results showed the presence of nanoscale alpha regions. These studies are revalidated by conventional selected area diffraction and 3D atom probe reconstruction results. Also TEM dark field and selected are diffraction studies are conducted to understand the effect of quenching and subsequent aging of

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor suppressor in hepatocellular carcinoma.

Science.gov (United States)

Liu, Rui; Zhang, Haiyang; Zhang, Yan; Li, Shuang; Wang, Xinyi; Wang, Xia; Wang, Cheng; Liu, Bin; Zen, Ke; Zhang, Chen-Yu; Zhang, Chunni; Ba, Yi

2017-04-01

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha plays a crucial role in regulating the biosynthesis of mitochondria, which is closely linked to the energy metabolism in various tumors. This study investigated the regulatory role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha in the pathogenesis of hepatocellular carcinoma. In this study, the changes of peroxisome proliferator-activated receptor gamma coactivator-1 alpha messenger RNA levels between normal human liver and hepatocellular carcinoma tissue were examined by quantitative reverse transcription polymerase chain reaction. Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by RNA interference in the human liver cell line L02, while overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha complementary DNA in the human hepatocarcinoma cell line HepG2. Cellular morphological changes were observed via optical and electron microscopy. Cellular apoptosis was determined by Hoechst 33258 staining. In addition, the expression levels of 21,400 genes in tissues and cells were detected by microarray. It was shown that peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression was significantly downregulated in hepatocellular carcinoma compared with normal liver tissues. After knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression in L02 cells, cells reverted to immature and dedifferentiated morphology exhibiting cancerous tendency. Apoptosis occurred in the HepG2 cells after transfection by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Microarray analysis showed consistent results. The results suggest that peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor

HB KURDISTAN [ALPHA-47(CE5)ASP-]TYR], A NEW ALPHA-CHAIN VARIANT IN COMBINATION WITH BETA-THALASSEMIA

NARCIS (Netherlands)

GIORDANO, PC; HARTEVELD, CL; STRENG, H; Oosterwijk, Jan; HEISTER, JGAM; AMONS, R; BERNINI, LF

1994-01-01

We have characterized the structural abnormality of a new alpha chain mutant found in a Kurdish; family. The clinical and hematological investigation of eight individuals have shown that the a variant is associated with a beta degrees-thalassemia mutation (nonsense codon 39). The tryptic peptide map

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

Beta-adrenergic receptors are critical for weight loss but not for other metabolic adaptations to the consumption of a ketogenic diet in male mice

Directory of Open Access Journals (Sweden)

Nicholas Douris

2017-08-01

Conclusions: The response of β-less mice distinguishes at least two distinct categories of physiologic effects in mice consuming KD. In the liver, KD regulates peroxisome proliferator-activated receptor alpha (PPARα-dependent pathways through an action of FGF21 independent of the SNS and beta-adrenergic receptors. In sharp contrast, induction of interscapular brown adipose tissue (BAT and increased energy expenditure absolutely require SNS signals involving action on one or more β-adrenergic receptors. In this way, the key metabolic actions of FGF21 in response to KD have diverse effector mechanisms.

Agonist-induced affinity alterations of a central nervous system. cap alpha. -bungarotoxin receptor

Energy Technology Data Exchange (ETDEWEB)

Lukas, R.J.; Bennett, E.L.

1979-01-01

The ability of cholinergic agonists to block the specific interaction of ..cap alpha..-bungarotoxin (..cap alpha..-Bgt) with membrane-bound sites derived from rat brain is enhanced when membranes are preincubated with agonist. Thus, pretreatment of ..cap alpha..-Bgt receptors with agonist (but not antagonist) causes transformation of sites to a high-affinity form toward agonist. This change in receptor state occurs with a half-time on the order of minutes, and is fully reversible on dilution of agonist. The results are consistent with the identity of ..cap alpha..-Bgt binding sites as true central nicotinic acetylcholine receptors. Furthermore, this agonist-induced alteration in receptor state may represent an in vitro correlate of physiological desensitization. As determined from the effects of agonist on toxin binding isotherms, and on the rate of toxin binding to specific sites, agonist inhibition of toxin binding to the high-affinity state is non-competitive. This result suggests that there may exist discrete toxin-binding and agonist-binding sites on central toxin receptors.

Temporary increase in serum beta 2-microglobulin during treatment with interferon-alpha for AIDS-associated Kaposi's sarcoma

NARCIS (Netherlands)

de Wit, R.; Bakker, P. J.; Reiss, P.; Hoek, F. J.; Lange, J. M.; Goudsmit, J.; Veenhof, K. H.

1990-01-01

Beta 2-microglobulin (beta 2-M) levels were determined in the serum of 24 patients treated with high-dose human recombinant interferon-alpha (IFN alpha) for AIDS-associated Kaposi's sarcoma. There was a significant increase in serum beta 2-M levels, irrespective of the response to treatment.

Technetium-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptides for human melanoma imaging

Energy Technology Data Exchange (ETDEWEB)

Yang Jianquan; Guo Haixun [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin, E-mail: ymiao@salud.unm.ed [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Dermatology, University of New Mexico, Albuquerque, NM 87131 (United States)

2010-11-15

could block 66% of the tumor uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH. Conclusions: Targeting both MC1 and {alpha}{sub v{beta}3} integrin receptors enhanced the melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH in M21 human melanoma xenografts. Flank M21 human melanoma tumors were clearly visualized by single photon emission computed tomography/computed tomographic imaging using {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH as an imaging probe, highlighting its potential use as a dual-receptor-targeting imaging probe for human melanoma detection.

Study of the kinetics of beta-alpha transformation in uranium; Doprinos proucavanju kinetike beta-alfa transformacije u uranijumu

Energy Technology Data Exchange (ETDEWEB)

Drobnjak, Dj; Mihajlovic, A [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Yugoslavia)

1965-11-15

The objective of this task was to study the influence of cooling rate, heating temperature and the time of spent in beta state on the kinetics of the beta {yields} alpha transformation. The experimental results are presented in this report.

Concanavalin a increases beta-adrenergic and glucocorticoid receptors in porcine splenocytes

International Nuclear Information System (INIS)

Kelley, K.N.; Westly, H.J.

1986-01-01

We identified specific glucocorticoid and beta-adrenergic receptors on porcine splenocytes. There are 2000 to 4000 glucocorticoid receptors per cell with a K /SUB D/ of 2 to 4 nM and 1000 beta-adrenergic receptors with a K /SUB D/ of 0.3 to 0.6 nM. When splenocytes were incubated with concanavalin A (Con A), there was an approximate 2-fold increase in both gluococorticoid and beta-adrenergic receptors with no change in binding affinity. Incubation of splenocytes with cortisol as low as 40 nM (13 ng/ml) inhibited proliferation in response to Con A. This inhibitory effect of cortisol was not due to cytotoxic effects of glucocorticoids. At maximal physiologic concentrations (400 nM; 135 ng/ml), cortisol caused reductions in Con A activation of thymocytes and peripheral blood mononuclear cells. When eight wk old pigs were restrained, there was an increase in plasma cortisol, atrophy of thymus and reduction in skin test responses to phytohemagglutinin. On the basis of the data, we suggest that physiologic concentrations of stress asociated hormones affect functional activities of porcine lymphoid cells. Since activated splenocytes display increased numbers of receptors for these hormones, perhaps glucocorticoids or catecholamines normally function in vivo to suppress clonal expansion of antigen activated and autoreactive T lymphocytes

hnRNP L regulates differences in expression of mouse integrin alpha2beta1.

Science.gov (United States)

Cheli, Yann; Kunicki, Thomas J

2006-06-01

There is a 2-fold variation in platelet integrin alpha2beta1 levels among inbred mouse strains. Decreased alpha2beta1 in 4 strains carrying Itga2 haplotype 2 results from decreased affinity of heterogeneous ribonucleoprotein L (hnRNP L) for a 6 CA repeat sequence (CA6) within intron 1. Seven strains bearing haplotype 1 and a 21 CA repeat sequence at this position (CA21) express twice the level of platelet alpha2beta1 and exhibit an equivalent gain of platelet function in vitro. By UV crosslinking and immunoprecipitation, hnRNP L binds more avidly to CA21, relative to CA6. By cell-free, in vitro mRNA splicing, decreased binding of hnRNP L results in decreased splicing efficiency and an increased proportion of alternatively spliced product. The splicing enhancer activity of CA21 in vivo is abolished by prior treatment with hnRNP L-specific siRNA. Thus, decreased surface alpha2beta1 results from decreased Itga2 pre-mRNA splicing regulated by hnRNP L and depends on CA repeat length at a specific site in intron 1.

Spectral Ly{alpha}, Ly{beta}, and H{alpha} line shapes for the H atom in the presence of a magnetic field in a plasma; Profils des raies spectrales Ly{alpha}, Ly{beta}, et H{alpha} de l'atome H en presence d'un champ magnetique dans un plasma

Energy Technology Data Exchange (ETDEWEB)

Nguyen, H; Herman, L [Laboratoire de Recherches Physiques, Faculte des sciences, 9 Quai Saint Bernard, 75 - Paris (France); Drawin, H W [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1967-02-15

This report contains numerical data of the line shapes of Ly{alpha}, Ly{beta}, and H{alpha} for the following parameters: 1. 10{sup 2} {<=} H [gauss] {<=} 1.2. 10{sup 5} 1. 10{sup 15}{<=} N [cm{sup -3}] {<=} 1. 10{sup 18} cm{sup -3} 1. 10{sup 4} {<=} T [deg. K] {<=} 4. 10{sup 4} where H = magnetic field strength, K = density of plasma ions, T = electron temperature. (authors) [French] Dans ce rapport, on donne les valeurs numeriques des contours des raies spectrales Ly{alpha}, Ly{beta}, et H{alpha} pour les valeurs suivantes des parametres H, N et T 1. 10{sup 2} {<=} H [gauss] {<=} 1.2. 10{sup 5} 1. 10{sup 15}{<=} N [cm{sup -3}] {<=} 1. 10{sup 18} cm{sup -3} 1. 10{sup 4} {<=} T [deg. K] {<=} 4. 10{sup 4} ou H intensite du champ magnetique, N = densite des ions, T = temperature electronique. (auteurs)

Preliminary Molecular Dynamic Simulations of the Estrogen Receptor Alpha Ligand Binding Domain from Antagonist to Apo

Directory of Open Access Journals (Sweden)

Adrian E. Roitberg

2008-06-01

Full Text Available Estrogen receptors (ER are known as nuclear receptors. They exist in the cytoplasm of human cells and serves as a DNA binding transcription factor that regulates gene expression. However the estrogen receptor also has additional functions independent of DNA binding. The human estrogen receptor comes in two forms, alpha and beta. This work focuses on the alpha form of the estrogen receptor. The ERα is found in breast cancer cells, ovarian stroma cells, endometrium, and the hypothalamus. It has been suggested that exposure to DDE, a metabolite of DDT, and other pesticides causes conformational changes in the estrogen receptor. Before examining these factors, this work examines the protein unfolding from the antagonist form found in the 3ERT PDB crystal structure. The 3ERT PDB crystal structure has the estrogen receptor bound to the cancer drug 4-hydroxytamoxifen. The 4-hydroxytamoxifen ligand was extracted before the simulation, resulting in new conformational freedom due to absence of van der Waals contacts between the ligand and the receptor. The conformational changes that result expose the binding clef of the co peptide beside Helix 12 of the receptor forming an apo conformation. Two key conformations in the loops at either end of the H12 are produced resulting in the antagonist to apo conformation transformation. The results were produced over a 42ns Molecular Dynamics simulation using the AMBER FF99SB force field.

The dispersion of alpha and beta radioactivity to the environmental from spent fuel testing in RMI

International Nuclear Information System (INIS)

Yuwono, I.; Pudjadi, E.

1996-01-01

The destructive testing of 2 spent fuels in RMI and radioactivity air release monitoring to the environmental have been done. The monitoring equipment used alpha-beta particulate monitor, Berthold LB 150 D type. The calculations using the Gaussian plume model and distributions factor showed there were no radiological effect of alpha and beta radioactivity dispersion and contribution to the environmental. The maximum average construction of alpha and beta radioactivity are 0.002% and 0.05%. (author)

Homology-modeled ligand-binding domains of medaka estrogen receptors and androgen receptors: A model system for the study of reproduction

International Nuclear Information System (INIS)

Cui Jianzhou; Shen Xueyan; Yan Zuowei; Zhao Haobin; Nagahama, Yoshitaka

2009-01-01

Estrogen and androgen and their receptors play critical roles in physiological processes such as sexual differentiation and development. Using the available structural models for the human estrogen receptors alpha and beta and androgen receptor as templates, we designed in silico agonist and antagonist models of medaka estrogen receptor (meER) alpha, beta-1, and beta-2, and androgen receptor (meAR) alpha and beta. Using these models, we studied (1) the structural relationship between the ligand-binding domains (LBDs) of ERs and ARs of human and medaka, and (2) whether medaka ER and AR can be potential models for studying the ligand-binding activities of various agonists and antagonists of these receptors by docking analysis. A high level of conservation was observed between the sequences of the ligand-binding domains of meERα and huERα, meERβ1 and huERβ, meERβ2, and huERβ with 62.8%, 66.4%, and 65.1% identity, respectively. The sequence conservation between meARα and huAR, meARβ, and huAR was found with 70.1% and 61.0% of identity, respectively. Thirty-three selected endocrine disrupting chemicals (EDCs), including both agonists and antagonists, were docked into the LBD of ER and AR, and the corresponding docking score for medaka models and human templates were calculated. In order to confirm the conservation of the overall geometry and the binding pocket, the backbone root mean square deviation (RMSD) for Cα atoms was derived from the structure superposition of all 10 medaka homology models to the six human templates. Our results suggested conformational conservation between the ERs and ARs of medaka and human, Thus, medaka could be highly useful as a model system for studies involving estrogen and androgen interaction with their receptors.

Microstructure evolution and microstructure/mechanical properties relationships in alpha+beta titanium alloys

Science.gov (United States)

Lee, Eunha

In this study, the microstructural evolution of Timetal 550 was investigated. Timetal 550 showed two types of phase transformations (martensitic and nucleation and growth) depending on the cooling rate from the beta region. The alpha phase initially precipitated at the prior beta grain boundaries, and it had a Burgers OR with one of the adjacent grains. It was found that colonies could grow, even in the fast-cooled Timetal 550 sample, from the grain boundary alpha into the prior beta grain with which it exhibited the Burgers OR. Three orientation relationships were also found between alpha laths in the basketweave microstructure. Microhardness testing demonstrated that fast-cooled Timetal 550 samples with basketweave microstructure were harder than slowly-cooled samples with colony microstructure. Orientation-dependent deformation was found in the colony microstructure. Specifically, when the surface normal is perpendicular to the [0001] of alpha, the material deforms easily in the direction perpendicular to the [0001] of alpha. Fuzzy logic and Bayesian neural network models were developed to predict the room temperature tensile properties of Timetal 550. This involved the development of a database relating microstructural features to mechanical properties. A Gleeble 3800 thermal-mechanical simulator was used to develop various microstructures. Microstructural features of tensile-tested samples were quantified using stereological procedures. The quantified microstructural features and the tensile properties were used as inputs and outputs, respectively, for modeling the relationships between them. The individual influence of five microstructural features on tensile properties was determined using the established models. The microstructural features having the greatest impact on UTS and YS were the thickness of alpha laths and the width of grain boundary alpha layer, and the microstructural features having the greatest impact on elongation were the thickness of

Functional modulation of cerebral gamma-aminobutyric acidA receptor/benzodiazepine receptor/chloride ion channel complex with ethyl beta-carboline-3-carboxylate: Presence of independent binding site for ethyl beta-carboline-3-carboxylate

Energy Technology Data Exchange (ETDEWEB)

Taguchi, J.; Kuriyama, K. (Kyoto Prefectural Univ. of Medicine (Japan))

1990-05-01

Effect of ethyl beta-carboline-3-carboxylate (beta-CCE) on the function of gamma-aminobutyric acid (GABA)A receptor/benzodiazepine receptor/chloride ion channel complex was studied. Beta-CCE noncompetitively and competitively inhibited (3H)flunitrazepam binding to benzodiazepine receptor, but not (3H)muscimol binding to GABAA receptor as well as t-(3H)butylbicycloorthobenzoate (( 3H) TBOB) binding to chloride ion channel, in particulate fraction of the mouse brain. Ro15-1788 also inhibited competitively (3H) flunitrazepam binding. On the other hand, the binding of beta-(3H)CCE was inhibited noncompetitively and competitively by clonazepam and competitively by Ro15-1788. In agreement with these results, benzodiazepines-stimulated (3H)muscimol binding was antagonized by beta-CCE and Ro15-1788. Gel column chromatography for the solubilized fraction from cerebral particulate fraction by 0.2% sodium deoxycholate (DOC-Na) in the presence of 1 M KCl indicated that beta-(3H)CCE binding site was eluted in the same fraction (molecular weight, 250,000) as the binding sites for (3H)flunitrazepam, (3H)muscimol and (3H)TBOB. GABA-stimulated 36Cl- influx into membrane vesicles prepared from the bovine cerebral cortex was stimulated and attenuated by flunitrazepam and beta-CCE, respectively. These effects of flunitrazepam and beta-CCE on the GABA-stimulated 36Cl- influx were antagonized by Ro15-1788. The present results suggest that the binding site for beta-CCE, which resides on GABAA receptor/benzodiazepine receptor/chloride ion channel complex, may be different from that for benzodiazepine. Possible roles of beta-CCE binding site in the allosteric inhibitions on benzodiazepine binding site as well as on the functional coupling between chloride ion channel and GABAA receptor are also suggested.

Beta-adrenergic receptors of lymphocytes in children with allergic respiratory diseases

International Nuclear Information System (INIS)

Bittera, I.; Gyurkovits, K.; Falkay, G.; Eck, E.; Koltai, M.

1988-01-01

The beta-adrenergic receptor binding sites on peripheral lymphocytes in children with bronchial asthma (n = 16) and seasonal allergic rhinitis (n = 8) were examined in comparison with normal controls (n = 18) by means of 124 I-cyanopindolol. The number of beta-adrenergic receptors was significantly lower in the asthmatic group (858 +/- 460/lymphocyte) than in the controls (1564 +/- 983/lymphocyte). The value (1891 +/- 1502/lymphocyte in children with allergic rhinitis was slightly higher than that in healthy controls. Of the 24 patients suffering from allergic diseases of the lower or upper airways, the bronchial histamine provocation test was performed in 21; 16 gave positive results, while 5 were negative. No difference in beta-adrenergic receptor count was found between the histamine-positive and negative patients. Neither was there any correlation between the number of beta-adrenergic receptors and the high (16/24) and low (8/24) serum IgE concentrations found in allergic patients. The significant decrease in beta-adrenergic receptor count in asthmatic children lends support to Szentivanyi's concept. Further qualitative and quantitative analysis of lymphocyte beta-adrenergic receptors may provide an individual approach to the treatment of bronchial asthma with beta-sympathomimetic drugs

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)

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)

beta. -endorphin-like and. alpha. -MSH-like immunoreactivities in human milk

Energy Technology Data Exchange (ETDEWEB)

Ferrando, T.; Rainero, I.; De Gennaro, T.; Oggero, R.; Mostert, M.; Dattola, P.; Pinessi, L. (Univ. of Turin (Italy))

1990-01-01

We measured with radioimmunoassay the {beta}-endorphin-like and {alpha}-MSH-like immunoreactivities in milk and plasma of 8 lactating women. Mean {beta}-endorphin concentrations ({plus minus} SD) were 16.6 {plus minus} 6.7 fmol/ml in milk and 9.9 {plus minus} 4.1 fmol/ml in plasma. {alpha}-MSH concentrations were 39.4 {plus minus} 15.5 pg/ml in milk and 18.2 {plus minus} 8.4 pg/ml in plasma. The concentrations of both peptides in milk were significantly higher than in plasma. No significant correlation between milk and plasma concentrations of these peptides was found.

Enantioselective radical addition/trapping reactions with alpha,beta-disubstituted unsaturated imides. Synthesis of anti-propionate aldols.

Science.gov (United States)

Sibi, Mukund P; Petrovic, Goran; Zimmerman, Jake

2005-03-02

This manuscript describes a highly diastereo- and enantioselective intermolecular radical addition/hydrogen atom transfer to alpha,beta-disubstituted enoates. Additionally, we show that anti-propionate aldol-like products can be easily prepared from alpha-methyl-beta-acyloxyenoates in good yields and high diastereo- and enantioselectivities.

Antagonizing the alpha(4)beta(1) Integrin, but Not alpha(4)beta(7), Inhibits Leukocytic Infiltration of the Central Nervous System in Rhesus Monkey Experimental Autoimmune Encephalomyelitis

NARCIS (Netherlands)

Haanstra, Krista G.; Hofman, Sam O.; Estevao, Dave M. Lopes; Blezer, Erwin L. A.; Bauer, Jan; Yang, Li-Li; Wyant, Tim; Csizmadia, Vilmos; 't Hart, Bert A.; Fedyk, Eric R.

2013-01-01

The immune system is characterized by the preferential migration of lymphocytes through specific tissues (i.e., tissue tropism). Tissue tropism is mediated, in part, by the alpha(4) integrins expressed by T lymphocytes. The alpha(4)beta(1) integrin mediates migration of memory T lymphocytes into the

Relative response of TL and component-resolved OSL to alpha and beta radiations in annealed sedimentary quartz

International Nuclear Information System (INIS)

Polymeris, George S.; Afouxenidis, Dimitrios; Raptis, Spyridoula; Liritzis, Ioannis; Tsirliganis, Nestor C.; Kitis, George

2011-01-01

Knowledge of the relative luminescence response to alpha and beta radiation is very important in TL and OSL dating. In the present study the relative alpha to beta response is studied in a sedimentary quartz sample, previously fired at 900 deg. C for 1 h, in the dose region between 1 and 128 Gy, for both thermoluminescence (TL) and linearly modulated optically stimulated luminescence (LM - OSL). The LM - OSL measurements were performed at room temperature and at 125 deg. C. All OSL signals were deconvolved into their individual components. Comparison of OSL curves after alpha and beta irradiation strongly supports that quartz OSL components follow first order kinetics in both cases. In the case of TL, the relative alpha to beta response is found to be very different for each TL glow-peak, but it does not depend strongly on irradiation dose. In the case of LM - OSL measurements, it is found that the relative behaviour of the alpha to beta response is different for three distinct regions, namely the fast OSL component, the region of medium OSL component originating from the TL glow-peak at 110 deg. C when stimulation takes place at room temperature and finally the region of slow OSL component. Following stimulation at ambient temperature, the relative alpha to beta response of all components was not observed to depend significantly on dose, with the value of ratio being 0.03 and a tendency to decrease with increasing dose. However, in the case of measurements performed at 125 deg. C, the relative response of the fast components is much enhanced, and for the remaining components it increases with increasing dose. Special care must be taken to examine the relative alpha to beta response of the fast component at 125 deg. C which contrasts the relative response of the TL peak at ca. 325 deg. C. The implications for the dating of annealed quartz are also briefly discussed. - Highlights: → Relative alpha to beta response for TL and LM-OSL is studied in annealed

Effect of age on upregulation of the cardiac adrenergic beta receptors

International Nuclear Information System (INIS)

Tumer, N.; Houck, W.T.; Roberts, J.

1990-01-01

Radioligand binding studies were performed to determine whether upregulation of postjunctional beta receptors occurs in sympathectomized hearts of aged animals. Fischer 344 rats 6, 12, and 24 months of age (n = 10) were used in these experiments. To produce sympathectomy, rats were injected with 6-hydroxydopamine hydrobromide (6-OHDA; 2 x 50 mg/kg iv) on days 1 and 8; the animals were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. 125I-Iodopindolol (IPIN), a beta adrenergic receptor antagonist, was employed to determine the affinity and total number of beta adrenergic receptors in the ventricles of the rat heart. The maximal number of binding sites (Bmax) was significantly elevated by 37%, 48%, and 50% in hearts from sympathectomized 6-, 12-, and 24-month-old rats, respectively. These results indicate that beta receptor mechanisms in older hearts can respond to procedures that cause upregulation of the beta adrenergic receptors

Perimovement decrease of alpha/beta oscillations in the human nucleus accumbens.

Science.gov (United States)

Stenner, Max-Philipp; Dürschmid, Stefan; Rutledge, Robb B; Zaehle, Tino; Schmitt, Friedhelm C; Kaufmann, Jörn; Voges, Jürgen; Heinze, Hans-Jochen; Dolan, Raymond J; Schoenfeld, Mircea Ariel

2016-10-01

The human nucleus accumbens is thought to play an important role in guiding future action selection via an evaluation of current action outcomes. Here we provide electrophysiological evidence for a more direct, i.e., online, role during action preparation. We recorded local field potentials from the nucleus accumbens in patients with epilepsy undergoing surgery for deep brain stimulation. We found a consistent decrease in the power of alpha/beta oscillations (10-30 Hz) before and around the time of movements. This perimovement alpha/beta desynchronization was observed in seven of eight patients and was present both before instructed movements in a serial reaction time task as well as before self-paced, deliberate choices in a decision making task. A similar beta decrease over sensorimotor cortex and in the subthalamic nucleus has been directly related to movement preparation and execution. Our results support the idea of a direct role of the human nucleus accumbens in action preparation and execution. Copyright © 2016 the American Physiological Society.

Increased frequency of CD4{sup -}8{sup -}T cells bearing T-cell receptor {alpha}{beta} chains in peripheral blood of atomic bomb survivors exposed to high doses

Energy Technology Data Exchange (ETDEWEB)

Yoichiro Kusunoki; Seishi Kyoizumi; Yuko Hirai; Shoichiro Fujita; Mitoshi Akiyama [Radiation Effects Research Foundation, Hiroshima (Japan)

1994-07-01

A rare T-cell subpopulation, CD4{sup -z}8{sup -}{alpha}{beta} cells, may be differentiated through a pathway (or pathways) different from the pathway(s) of conventional CD4+ or CD8+ cells. In the present study, the frequencies of CD4{sup -}8{sup -} T cells in peripheral-blood {alpha}{beta} T cells in 409 atomic bomb survivors were determined to investigate late effects of radiation on the composition of human T-cell subpopulations. The frequency of CD4{sup -}8{sup -}{alpha}{beta} T-cell decreased significantly with the subject`s age and was higher in females than males. A significant increase in the frequency was found in the survivors exposed to more than 1.5Gy, suggesting that the previous radiation exposure altered differentiation and development of T cells. 25 refs., 4 figs., 3 tabs.

Evidence of an association between genetic variation of the coactivator PGC-1beta and obesity

DEFF Research Database (Denmark)

Andersen, G; Wegner, L; Yanagisawa, K

2005-01-01

Peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) is a recently identified homologue of the tissue specific coactivator PGC-1alpha, a coactivator of transcription factors such as the peroxisome proliferators activated receptors and nuclear respiratory factors. PGC-1...

Expression of G(alpha)(s) proteins and TSH receptor signalling in hyperfunctioning thyroid nodules with TSH receptor mutations.

Science.gov (United States)

Holzapfel, Hans-Peter; Bergner, Beate; Wonerow, Peter; Paschke, Ralf

2002-07-01

Constitutively activating mutations of the thyrotrophin receptor (TSHR) are the main molecular cause of hyperfunctioning thyroid nodules (HTNs). The G protein coupling is an important and critical step in the TSHR signalling which mainly includes G(alpha)(s), G(alpha)(i) and G(alpha)(q)/11 proteins. We investigated the in vitro consequences of overexpressing G(alpha) proteins on signalling of the wild-type (WT) or mutated TSHR. Moreover, we investigated whether changes in G(alpha) protein expression are pathophysiologically relevant in HTNs or cold thyroid nodules (CTNs). Wild-type TSH receptor and mutated TSH receptors were coexpressed with G(alpha)(s), G(alpha)(i) or G(alpha)(q)/11, and cAMP and inositol phosphate (IP) production was measured after stimulation with TSH. The expression of G(alpha)(s), G(alpha)(i) and G(alpha)(q)/11 proteins was examined by Western blotting in 28 HTNs and 14 CTNs. Coexpression of G(alpha)(s) with the WT TSH receptor in COS 7 cells significantly increased the basal and TSH-stimulated cAMP accumulation while coexpression of the G(alpha)(q) or G(alpha)11 protein significantly increased the production of cAMP and inositol triphosphate (IP(3)). The coexpression of the TSH receptor mutants (I486F, DEL613-621), known to couple constitutively to G(alpha)(s) and G(alpha)(q) with G(alpha)(s) and G(alpha)(q)/11, significantly increased the basal and stimulated cAMP and IP(3) accumulation. Coexpression of the TSH receptor mutant V556F with G(alpha)(s) only increased the basal and stimulated cAMP production while its coexpression with G(alpha)(q)/11 increased the basal and stimulated IP(3) signalling. The expression of G(alpha)(s) protein subunits determined by Western blotting was significantly decreased in 14 HTNs with a constitutively activating TSH receptor mutation in comparison with the corresponding surrounding tissue, while in 14 HTNs without TSH receptor or G(alpha)(s) protein mutation and in 14 CTNs the expression of G(alpha

Role of quenching on alpha/beta separation in liquid scintillation counting for several high capacity cocktails

International Nuclear Information System (INIS)

Pujol, L.; Sanchez-Cabeza, J.-A.

1997-01-01

The optimization of alpha/beta separation in liquid scintillation using pulse shape analysis is convenient for the simultaneous determination of alpha and beta emitters in natural water and other samples. In this work, alpha/beta separation was studied for different scintillant/vial combinations and it was observed that both the optimum pulse shape discrimination level and the total interference value (that is, the summed relative interference between alpha and beta spectra) were dependent on the sample quenching and independent of the scintillant/vial combination. These results provide a simple method for modifying the counting configuration, such as a change in the cocktail, vial or sample characteristics, without the need to perform exhaustive parameter optimizations. Also, it was observed that, for our counting conditions, the combination of Ultima Gold AB scintillation cocktail with Zinsser low diffusion vials presented the lowest total interference, namely 0.94 ± 0.28%, which is insignificant for the counting of environmental samples. (Author)

GABA regulates the rat hypothalamic-pituitary-adrenocortical axis via different GABA-A receptor alpha-subtypes

DEFF Research Database (Denmark)

Mikkelsen, Jens D; Bundzikova, Jana; Larsen, Marianne Hald

2008-01-01

dependent on the composition of the GABA-A receptor subunits through which they act. We show here that positive modulators of alpha(1)-subtype containing GABA-A receptors with zolpidem (10 mg/kg) increase HPA activity in terms of increase in plasma corticosterone and induction of Fos in the PVN, whereas...... after positive modulation of GABA-A receptors composed of alpha(1)-subunit(s) affects a selective afferent system than the PVN, which is distinct from another afferent system(s) activated by non alpha(1)-containing GABA-A receptors....

Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation

Directory of Open Access Journals (Sweden)

Papa Maria

2011-01-01

Full Text Available Abstract Background Estrogen receptors alpha (ERα and beta (ERβ are transcription factors (TFs that mediate estrogen signaling and define the hormone-responsive phenotype of breast cancer (BC. The two receptors can be found co-expressed and play specific, often opposite, roles, with ERβ being able to modulate the effects of ERα on gene transcription and cell proliferation. ERβ is frequently lost in BC, where its presence generally correlates with a better prognosis of the disease. The identification of the genomic targets of ERβ in hormone-responsive BC cells is thus a critical step to elucidate the roles of this receptor in estrogen signaling and tumor cell biology. Results Expression of full-length ERβ in hormone-responsive, ERα-positive MCF-7 cells resulted in a marked reduction in cell proliferation in response to estrogen and marked effects on the cell transcriptome. By ChIP-Seq we identified 9702 ERβ and 6024 ERα binding sites in estrogen-stimulated cells, comprising sites occupied by either ERβ, ERα or both ER subtypes. A search for TF binding matrices revealed that the majority of the binding sites identified comprise one or more Estrogen Response Element and the remaining show binding matrixes for other TFs known to mediate ER interaction with chromatin by tethering, including AP2, E2F and SP1. Of 921 genes differentially regulated by estrogen in ERβ+ vs ERβ- cells, 424 showed one or more ERβ site within 10 kb. These putative primary ERβ target genes control cell proliferation, death, differentiation, motility and adhesion, signal transduction and transcription, key cellular processes that might explain the biological and clinical phenotype of tumors expressing this ER subtype. ERβ binding in close proximity of several miRNA genes and in the mitochondrial genome, suggests the possible involvement of this receptor in small non-coding RNA biogenesis and mitochondrial genome functions. Conclusions Results indicate that the

Estrogen receptor beta in prostate cancer: friend or foe?

Science.gov (United States)

Nelson, Adam W; Tilley, Wayne D; Neal, David E; Carroll, Jason S

2014-08-01

Prostate cancer is the commonest, non-cutaneous cancer in men. At present, there is no cure for the advanced, castration-resistant form of the disease. Estrogen has been shown to be important in prostate carcinogenesis, with evidence resulting from epidemiological, cancer cell line, human tissue and animal studies. The prostate expresses both estrogen receptor alpha (ERA) and estrogen receptor beta (ERB). Most evidence suggests that ERA mediates the harmful effects of estrogen in the prostate, whereas ERB is tumour suppressive, but trials of ERB-selective agents have not translated into improved clinical outcomes. The role of ERB in the prostate remains unclear and there is increasing evidence that isoforms of ERB may be oncogenic. Detailed study of ERB and ERB isoforms in the prostate is required to establish their cell-specific roles, in order to determine if therapies can be directed towards ERB-dependent pathways. In this review, we summarise evidence on the role of ERB in prostate cancer and highlight areas for future research. © 2014 Society for Endocrinology.

Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

International Nuclear Information System (INIS)

Zhang, Yu; Cheng, Jung-Chien; Huang, He-Feng; Leung, Peter C.K.

2013-01-01

Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells

Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yu [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada); Cheng, Jung-Chien [Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada); Huang, He-Feng, E-mail: huanghefg@hotmail.com [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Leung, Peter C.K., E-mail: peter.leung@ubc.ca [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada)

2013-11-01

Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells.

Phylogenetic characterization of the ubiquitous electron transfer flavoprotein families ETF-alpha and ETF-beta.

Science.gov (United States)

Tsai, M H; Saier, M H

1995-06-01

Electron transfer flavoproteins (ETF) are alpha beta-heterodimers found in eukaryotic mitochondria and bacteria. We have identified currently sequenced protein members of the ETF-alpha and ETF-beta families. Members of these two families include (a) the ETF subunits of mammals and bacteria, (b) homologous pairs of proteins (FixB/FixA) that are essential for nitrogen fixation in some bacteria, and (c) a pair of carnitine-inducible proteins encoded by two open reading frames in Escherichia coli (YaaQ and YaaR). These three groups of proteins comprise three clusters on both the ETF-alpha and ETF-beta phylogenetic trees, separated from each other by comparable phylogenetic distances. This fact suggests that these two protein families evolved with similar overall rates of evolutionary divergence. Relative regions of sequence conservation are evaluated, and signature sequences for both families are derived.

Cross-linking of hCG to luteal receptors

Energy Technology Data Exchange (ETDEWEB)

Ji, T.H.; Ji, I.

1985-01-01

Photoaffinity labeling of the lutropin/choriogonadotropin (LH/hCG) receptor system on porcine granulosa cells has demonstrated that both the ..cap alpha.. and ..beta.. subunits of hCG directly photoaffinity label the hormone receptor. Three new bands appear on SDS-PAGE as a consequence of photoaffinity labeling by each subunit: the molecular weights of the three bands (106K, 88K, and 83K) produced by the subunit are larger by approximately 10K than those of the three bands (96K, 76K, and 73K) labeled by the ..cap alpha.. subunit. Although it could be a coincidence that the molecular weight of the ..beta.. subunit is approximately 10K larger than that of the ..cap alpha.. subunit, the similarity in these differences suggests the possibility that both the ..cap alpha.. and ..beta.. subunits have labeled the same polypeptides.

Evidence for a prolonged role of alpha 4 integrin throughout active experimental allergic encephalomyelitis.

Science.gov (United States)

Keszthelyi, E; Karlik, S; Hyduk, S; Rice, G P; Gordon, G; Yednock, T; Horner, H

1996-10-01

The leukocyte integrin receptor, alpha 4 beta 1, and its endothelial cell ligand, vascular cell adhesion molecule 1, appear to be of critical importance in the leukocyte trafficking that accompanies CNS damage in experimental allergic encephalomyelitis (EAE). In this study, the persistence of the role for alpha 4 beta 1/VCAM-1 in EAE was established by observing antibody-mediated disease reversal up to 1 month following disease onset. Limited treatment with a monoclonal antibody against alpha 4 integrin, GG5/3, resulted in a significant decrease in both clinical and histopathologic signs. This was not observed in isotype control experiments. In the latter phase of progressive disease, widespread demyelination occurred in the animals that did not respond to 6 days of anti-alpha 4 treatment. These results demonstrate an essential role for alpha 4 beta 1 interactions throughout active EAE and illustrate the difference between reversible clinical deficits caused by edema and irreversible deficits associated with demyelination.

Functional characterisation of human glycine receptors in a fluorescence-based high throughput screening assay

DEFF Research Database (Denmark)

Jensen, Anders A.

2005-01-01

The human glycine receptor subtypes alpha1beta and alpha2 have been expressed stably in HEK293 cells, and the functional characteristics of the receptors have been characterised in the FLIPR Membrane Potential Assay. The pharmacological properties obtained for nine standard ligands at the two rec...

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

Energy Technology Data Exchange (ETDEWEB)

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.

Improving the stability of alpha-conotoxin AuIB through N-to-C cyclization

DEFF Research Database (Denmark)

Armishaw, Christopher J; Jensen, Anders A; Balle, Lena D

2011-01-01

Modification of alpha-conotoxin frameworks through cyclization via an oligopeptide linker has previously been shown as an effective strategy for improving in vivo stability. We have extended this strategy by investigating cyclic analogs of alpha-conotoxin AuIB, a selective alpha3beta4 nicotinic a......-AuIB. As such, the cAuIB-2 globular isomer could constitute a useful probe for studying the role of the alpha3beta4 nicotinic acetylcholine receptor in a range of in vivo experimental paradigms....

Copper(II) 12-metallacrown-4 complexes of alpha-, beta- and gamma-aminohydroxamic acids: a comparative thermodynamic study in aqueous solution.

Science.gov (United States)

Tegoni, Matteo; Remelli, Maurizio; Bacco, Dimitri; Marchiò, Luciano; Dallavalle, Francesco

2008-05-28

A complete thermodynamic study of the protonation and Cu(II) complex formation equilibria of a series of alpha- and beta-aminohydroxamic acids in aqueous solution was performed. The thermodynamic parameters obtained for the protonation of glycine-, (S)-alpha-alanine-, (R,S)-valine-, (S)-leucine-, beta-alanine- and (R)-aspartic-beta-hydroxamic acids were compared with those previously reported for gamma-amino- and (S)-glutamic-gamma-hydroxamic acids. The enthalpy/entropy parameters calculated for the protonation microequilibria of these three types of ligands are in very good agreement with the literature values for simple amines and hydroxamic acids. The pentanuclear complexes [Cu5L4H(-4)]2+ contain the ligands acting as (NH2,N-)-(O,O-) bridging bis-chelating and correspond to 12-metallacrown-4 (12-MC-4) which are formed by self-assembly between pH 4 and 6 with alpha-aminohydroxamates (HL), while those with beta- and gamma-derivatives exist in a wider pH range (4-11). The stability order of these metallomacrocycles is beta- > alpha- > gamma-aminohydroxamates. The formation of 12-MC-4 with alpha-aminohydroxamates is entropy-driven, and that with beta-derivatives is enthalpy-driven, while with gamma-GABAhydroxamate both effects occur. These results are interpreted on the basis of specific enthalpies or entropy contributions related to chelate ring dimensions, charge neutralization and solvation-desolvation effects. The enthalpy/entropy parameters of 12-MC-4 with alpha-aminohydroxamic acids considered are also dependent on the optical purity of the ligands. Actually, that with (R,S)-valinehydroxamic acid presents an higher entropy and a lower enthalpy value than those of enantiopure ligands, although the corresponding stabilities are almost equivalent. Moreover, DFT calculations are in agreement with a more exothermic enthalpy found for metallacrowns with enantiomerically pure ligands.

[3H]Ethynylbicycloorthobenzoate ([3H]EBOB) binding in recombinant GABAA receptors.

Science.gov (United States)

Yagle, Monica A; Martin, Michael W; de Fiebre, Christopher M; de Fiebre, NancyEllen C; Drewe, John A; Dillon, Glenn H

2003-12-01

Ethynylbicycloorthobenzoate (EBOB) is a recently developed ligand that binds to the convulsant site of the GABAA receptor. While a few studies have examined the binding of [3H]EBOB in vertebrate brain tissue and insect preparations, none have examined [3H]EBOB binding in preparations that express known configurations of the GABAA receptor. We have thus examined [3H]EBOB binding in HEK293 cells stably expressing human alpha1beta2gamma2 and alpha2beta2gamma2 GABAA receptors, and the effects of CNS convulsants on its binding. The ability of the CNS convulsants to displace the prototypical convulsant site ligand, [35S]TBPS, was also assessed. Saturation analysis revealed [3H]EBOB binding at a single site, with a K(d) of approximately 9 nM in alpha1beta2gamma2 and alpha2beta2gamma2 receptors. Binding of both [3H]EBOB and [35S]TBPS was inhibited by dieldrin, lindane, tert-butylbicycloorthobenzoate (TBOB), PTX, TBPS, and pentylenetetrazol (PTZ) at one site in a concentration-dependent fashion. Affinities were in the high nM to low microM range for all compounds except PTZ (low mM range), and the rank order of potency for these convulsants to displace [3H]EBOB and [35S]TBPS was the same. Low [GABA] stimulated [3H]EBOB binding, while higher [GABA] (greater than 10 microM) inhibited [3H]EBOB binding. Overall, our data demonstrate that [3H]EBOB binds to a single, high affinity site in alpha1beta2gamma2 and alpha2beta2gamma2 GABAA receptors, and modulation of its binding is similar to that seen with [35S]TBPS. [3H]EBOB has a number of desirable traits that may make it preferable to [35S]TBPS for analysis of the convulsant site of the GABAA receptor.

PET imaging of {alpha}{sub v}{beta}{sub 3} integrin expression in tumours with {sup 68}Ga-labelled mono-, di- and tetrameric RGD peptides

Energy Technology Data Exchange (ETDEWEB)

Dijkgraaf, Ingrid; Franssen, Gerben M.; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, P.O. Box 9101, Nijmegen (Netherlands); Yim, Cheng-Bin [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, P.O. Box 9101, Nijmegen (Netherlands); Utrecht University, Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht (Netherlands); Schuit, Robert C. [VU University Medical Centre, Department of Nuclear Medicine and PET Research, P.O. Box 7057, Amsterdam (Netherlands); Luurtsema, Gert [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Hanzeplein 1, P.O. Box 30.001, Groningen (Netherlands); Liu, Shuang [Purdue University, School of Health Sciences, West Lafayette, IN (United States)

2011-01-15

Due to the restricted expression of {alpha}{sub v}{beta}{sub 3} in tumours, {alpha}{sub v}{beta}{sub 3} is considered a suitable receptor for tumour targeting. In this study the {alpha}{sub v}{beta}{sub 3}-binding characteristics of {sup 68}Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their {sup 111}In-labelled counterparts. A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)]{sub 2}) and a tetrameric (E{l_brace}E[c(RGDfK)]{sub 2}{r_brace}{sub 2}) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with {sup 68}Ga. In vitro {alpha}{sub v}{beta}{sub 3}-binding characteristics were determined in a competitive binding assay. In vivo {alpha}{sub v}{beta}{sub 3}-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner. The IC{sub 50} values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)]{sub 2} and DOTA-E{l_brace}E[c(RGDfK)]{sub 2}{r_brace}{sub 2} were 23.9 {+-} 1.22, 8.99 {+-} 1.20 and 1.74 {+-} 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 {+-} 1.15, 3.34 {+-} 1.16 and 1.80 {+-} 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the {sup 68}Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 {+-} 0.30, 5.24 {+-} 0.27 and 7.11 {+-} 0.67%ID/g, respectively) was comparable to that of their {sup 111}In-labelled counterparts (2.70 {+-} 0.29, 5.61 {+-} 0.85 and 7.32 {+-} 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised. The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The {sup 68}Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of {alpha}{sub v} {beta}{sub 3} expression with PET. (orig.)

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)

Peripheral blood IFN-gamma-secreting V alpha 24(+)V beta 11(+) NKT cell numbers are decreased in cancer patients independent of tumor type or tumor load

NARCIS (Netherlands)

Molling, JW; Kolgen, W; van der Vliet, HJJ; Boomsma, MF; Kruizenga, H; Smorenburg, CH; Molenkamp, BG; Langendijk, JA; Leemans, CR; von Blomberg, BME; Scheper, RJ; van den Eertwegh, AJM

2005-01-01

Natural killer T (NKT) cells are CDld-restricted lvmphoid cells and are characterized by an invariant T-cell receptor, which in humans consists of a V alpha 24 chain paired with a V beta 11 chain. These cells are known for their rapid production of large amounts of cytokines (e.g., IFN-gamma and

Characterization of the alpha and beta subunits of casein kinase 2 by far-UV CD spectroscopy

DEFF Research Database (Denmark)

Issinger, O G; Brockel, C; Boldyreff, B

1992-01-01

Although Chou-Fasman calculations of the secondary structure of recombinant casein kinase 2 subunits alpha and beta suggest they have a similar overall conformation, circular dichroism (CD) studies show that substantial differences in the conformation of the two subunits exist. In addition......, no changes in the far-UV CD spectrum of the alpha subunit are observed in the presence of casein or the synthetic decapeptide substrate RRRDDDSDDD. Furthermore, the alpha-helical structure of the alpha subunit (but not the beta subunit) can be increased in the presence of stoichiometric amounts of heparin...

Structure of $^{191}$Pb from $\\alpha$- and $\\beta$-decay spectroscopy

CERN Document Server

Cocolios, T E; Van de Walle, J; Franchoo, S; Marsh, B A; Sjoedin, A M; Huyse, M; Zemlyanoy, S; Cocolios, T E; Bastin, B; Barzakh, A; Page, R D; Mane, E; Van Duppen, P; Darby, I G; Venhart, M; Kudryavtsev, Yu; Huber, G; Fedosseev, V N; Andreyev, A N; Keupers, M; Flanagan, K T; Stefan, I; Dexters, W; Koester, U; Antalic, S; Buscher, J; Molkanov, P; Fedorov, D V

2010-01-01

Complementary studies of $^{191}$Pb have been made in the $\\beta$- decay of $^{191}$Bi at LISOL (CRC) and in the $\\alpha$- decay of $^{195}$Po at ISOLDE (CERN). Fine structures in the $\\alpha$- decay of the low-spin and high-spin isomers of $^{195}$Po have been fully resolved. Identification of the parent state is made possible via isomer selection based on narrow-band laser frequency scanning. The $\\alpha$-particle and $\\gamma$-ray energies have been determined with greater precision. New $\\alpha$-particle and $\\gamma$-ray energies are identified. Branching ratios in the decay of $^{195}$Po and $^{191}$Pb have been examined.

Mid-aged and aged wild-type and progestin receptor knockout (PRKO) mice demonstrate rapid progesterone and 3alpha,5alpha-THP-facilitated lordosis.

Science.gov (United States)

Frye, C A; Sumida, K; Lydon, J P; O'Malley, B W; Pfaff, D W

2006-05-01

Progesterone (P) and its 5alpha-reduced metabolite, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP), facilitate sexual behavior of rodents via agonist-like actions at intracellular progestin receptors (PRs) and membrane GABA(A)/benzodiazepine receptor complexes (GBRs), respectively. Given that ovarian secretion of progestins declines with aging, whether or not senescent mice are responsive to progestins was of interest. Homozygous PR knockout (PRKO) or wild-type mice that were between 10-12 (mid-aged) or 20-24 (aged) months of age were administered P or 3alpha,5alpha-THP, and the effect on lordosis were examined. Effects of a progestin-priming regimen that enhances PR-mediated (experiment 1) or more rapid, PR-independent effects of progestins (experiments 2 and 3) on sexual behavior were examined. Levels of P, 3alpha,5alpha-THP, and muscimol binding were examined in tissues from aged mice (experiment 4). Wild-type, but not PRKO, mice were responsive when primed with 17beta-estradiol (E(2); 0.5 microg) and administered P (500 microg, subcutaneously). Mid-aged wild-type mice demonstrated greater increases in lordosis 6 h later compared to their pre-P, baseline test than did aged wild-type mice (experiment 1). Lordosis of younger and older wild-type, but not PRKO, mice was significantly increased within 5 min of intravenous (IV) administration of P (100 ng), compared with E(2)-priming alone (experiment 2). However, wild-type and PRKO mice demonstrated significant increases in lordosis 5 min after IV administration of 3alpha,5alpha-THP, an effect which was more pronounced in mid-aged than in aged animals (100 ng-experiment 3). In tissues from aged wild-type and PRKO mice, levels of P, 3alpha,5alpha-THP, and muscimol binding were increased by P administration (experiment 4). PR binding was lower in the cortex of PRKO than that of wild-type mice. Mid-aged and aged PRKO and wild-type mice demonstrated rapid P or 3alpha,5alpha-THP-facilitated lordosis that may be

EEG-neurofeedback training of beta band (12-22Hz) affects alpha and beta frequencies - A controlled study of a healthy population.

Science.gov (United States)

Jurewicz, Katarzyna; Paluch, Katarzyna; Kublik, Ewa; Rogala, Jacek; Mikicin, Mirosław; Wróbel, Andrzej

2018-01-08

The frequency-function relation of various EEG bands has inspired EEG-neurofeedback procedures intending to improve cognitive abilities in numerous clinical groups. In this study, we administered EEG-neurofeedback (EEG-NFB) to a healthy population to determine the efficacy of this procedure. We evaluated feedback manipulation in the beta band (12-22Hz), known to be involved in visual attention processing. Two groups of healthy adults were trained to either up- or down-regulate beta band activity, thus providing mutual control. Up-regulation training induced increases in beta and alpha band (8-12Hz) amplitudes during the first three sessions. Group-independent increases in the activity of both bands were observed in the later phase of training. EEG changes were not matched by measured behavioural indices of attention. Parallel changes in the two bands challenge the idea of frequency-specific EEG-NFB protocols and suggest their interdependence. Our study exposes the possibility (i) that the alpha band is more prone to manipulation, and (ii) that changes in the bands' amplitudes are independent from specified training. We therefore encourage a more comprehensive approach to EEG-neurofeedback training embracing physiological and/or operational relations among various EEG bands. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improved synthesis with high yield and increased molecular weight of poly(alpha,beta-malic acid) by direct polycondensation.

Science.gov (United States)

Kajiyama, Tetsuto; Kobayashi, Hisatoshi; Taguchi, Tetsushi; Kataoka, Kazunori; Tanaka, Junzo

2004-01-01

The development of synthetic biodegradable polymers, such as poly(alpha-hydroxy acid), is particularly important for constructing medical devices, including scaffolds and sutures, and has attracted growing interest in the biomedical field. Here, we report a novel approach to preparing high molecular weight poly(malic acid) (HMW--PMA) as a biodegradable and bioabsorbable water-soluble polymer. We investigated in detail the reaction conditions for the simple direct polycondensation of l-malic acid, including the reaction times, temperatures, and catalysts. The molecular weight of synthesized alpha,beta-PMA is dependent on both the reaction temperature and time. The optimum reaction condition to obtain alpha,beta-PMA by direct polycondensation using tin(II) chloride as a catalyst was thus determined to be 110 degrees C for 45 h with a molecular weight of 5300. The method for alpha,beta-PMA synthesis established here will facilitate production of alpha,beta-PMA of various molecular weights, which may have a potential utility as biomaterials.

beta-Adrenergic and cholinergic receptors in hypertension-induced hypertrophy

International Nuclear Information System (INIS)

Vatner, D.E.; Kirby, D.A.; Homcy, C.J.; Vatner, S.F.

1985-01-01

Perinephritic hypertension was produced in dogs by wrapping one kidney with silk and removing the contralateral kidney 1 week later. Mean arterial pressure rose from 104 +/- 3 to 156 +/- 11 mm Hg, while left ventricular free wall weight, normalized for body weight, was increased by 49%. Muscarinic, cholinergic receptor density measured with [ 3 H]-quinuclidinyl benzilate, fell in hypertensive left ventricles (181 +/- 19 fmol/mg, n = 6; p less than 0.01) as compared with that found in normal left ventricles (272 +/- 16 fmol/mg, n = 8), while receptor affinity was not changed. The beta-adrenergic receptor density, measured by binding studies with [ 3 H]-dihydroalprenolol, rose in the hypertensive left ventricles (108 +/- 10 fmol/mg, n = 7; p less than 0.01) as compared with that found in normal left ventricles (68.6 +/- 5.2 fmol/mg, n = 15), while beta-adrenergic receptor affinity decreased in the hypertensive left ventricles (10.4 +/- 1.2 nM) compared with that found in the normal left ventricles (5.0 +/- 0.7 nM). Plasma norepinephrine levels were similar in the two groups, but myocardial norepinephrine levels were depressed (p less than 0.05) in dogs with hypertension. Moderate left ventricular hypertrophy induced by long-term aortic banding in dogs resulted in elevations in beta-adrenergic receptor density (115 +/- 14 fmol/mg) and decreases in affinity (10.4 +/- 2.2 nM) similar to those observed in the dogs with left ventricular hypertrophy induced by hypertension. Thus, these results suggest that perinephritic hypertension in the dog induces divergent effects on cholinergic and beta-adrenergic receptor density. The increased beta-adrenergic receptor density and decreased affinity may be a characteristic of left ventricular hypertrophy rather than hypertension