URODYNAMIC EFFECTS OF BETA-ADRENOBLOCKERS: NEBIVOLOL ADVANTAGES

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M. P. Savenkov

2008-01-01

Full Text Available Aim. To compare urodynamic effects of beta-blockers with different selectivity (propranolol, metoprolol, nebivolol in patients with arterial hypertension (HT and concomitant benign prostatic hyperplasia (BPH.Material and methods. 32 patients (aged 67,5 y.o. in average with HT of 1-2 stages were involved in the study. All patients had BPH (prostate volume >40 sm3 , increase of residual urine volume with moderate or severe low urinary tract symptoms (IPSS 8-25 and reduction of maximum urine flow rate to 5-13 ml/s. The urodynamic effect of beta-blockers was estimated by changes of urination frequency and uroflowmetry indices after single taking and 14-day therapy.Results. Propranolol and metoprolol led to aggravation of urination disorders. Nebivolol resulted in soft urodilating and urostimulating effects. It led to urination improvement and reduced a risk of urodynamic disorders.Conclusion. Urodynamic effects of cardiovascular drugs should be considered by practitioners especially in treatment of elderly patients.

Experimental search for a heavy neutrino in the beta spectrum of 35S

International Nuclear Information System (INIS)

Altzitzoglou, T.; Calaprice, F.; Dewey, M.; Lowry, M.; Piilonen, L.; Brorson, J.; Hagen, S.; Loeser, F.

1985-01-01

We present results of an experimental study of the shape of the energy spectrum for the decay 35 S→ 35 Cl+e - +ν/sub e/. The measurements were performed to search for evidence of a beta-decay branch with a heavy neutrino. No evidence for heavy neutrinos is observed. In particular, our limit for the branch to a 17-keV neutrino is 0.4%, in serious disagreement with the 3% branch claimed by Simpson

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

Science.gov (United States)

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

2007-11-01

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

Luminal and parenteral TFF2 and TFF3 dimer and monomer in two models of experimental colitis in the rat

DEFF Research Database (Denmark)

Poulsen, Steen Seier; Kissow, Hannelouise; Hare, Kristine

2005-01-01

% dextran sodium sulphate in the drinking water or by one intraperitoneal injection of mitomycin C, 3.75 mg/kg. TFF peptides were administered as subcutaneous injections or directly into the lumen via a catheter placed in the proximal colon. Treatments were saline, TFF2, TFF3 monomer or TFF3 dimer 5 mg......2 had positive effect only in DSS-induced colitis. The TFF3 monomer was without any effects in both models. Treatment effect was most pronounced in the middle part of the colon, closest to the tip of the catheter. Injected TFF peptides, especially the TFF3 monomer, aggravated the colitis score...... in both colitis models. CONCLUSIONS: Intracolonic administration of TFF3 dimer and TFF2 improves experimentally induced colitis in rats. The TFF3 monomer has no effect. Parenteral administration of TFF peptides aggravates the colitis especially the TFF3 monomer....

Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

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Ken-Ichiro Inoue

2011-01-01

Full Text Available Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanoparticles on pulmonary inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS as a disease model in innate immunity, and demonstrate that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Second, we introduce the effects of nanoparticles on allergic pulmonary inflammation as a disease model in adaptive immunity, and show that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic inflammation, including adjuvant effects on Th2-milieu. Third, we show that very small nanoparticle exposure exacerbates emphysematous pulmonary inflammation, which is concomitant with enhanced lung expression of proinflammatory molecules (including those that are innate immunity related. Taken together, nanoparticle exposure may synergistically facilitate pathological pulmonary inflammation via both innate and adaptive immunological impairment.

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

[3H]-beta-endorphin binding in rat brain

International Nuclear Information System (INIS)

Houghten, R.A.; Johnson, N.; Pasternak, G.W.

1984-01-01

The binding of [ 3 H]-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the 3 H-ligand is binding to more than one class of site. A portion of [ 3 H]-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of [ 3 H]-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers [ 3 H]-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of [ 3 H]-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo

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....

Pregnancy aggravates proteinuria in subclinical glomerulonephritis in the rat

NARCIS (Netherlands)

Faas, MM; Bakker, WW; Poelman, RT; Schuiling, GA

Because subclinical renal disease may be aggravated during pregnancy-as reflected in the occurrence of proteinuria, for example-we investigated whether a subclinical glomerulonephritis (SG) in the non-pregnant rat (passive Heymann nephritis), a condition without proteinuria, is aggravated when the

Headache attributed to intracranial pressure alterations: applicability of the International Classification of Headache Disorders ICHD-3 beta version versus ICHD-2.

Science.gov (United States)

Curone, M; Peccarisi, C; Bussone, G

2015-05-01

The association between headache and changes in intracranial pressure is strong in clinical practice. Syndromes associated with abnormalities of cerebrospinal fluid (CSF) pressure include spontaneous intracranial hypotension (SIH) and idiopathic intracranial hypertension (IIH). In 2013, the Headache Classification Committee of the International Headache Society (IHS) published the third International Classification of Headache Disorders (ICHD-3 beta version). The aim of this study was to investigate applicability of the new ICHD-3 versus ICHD-2 criteria in a clinical sample of patients with intracranial pressure (ICP) alterations. Patients admitted at our Headache Center for headache evaluation in whom a diagnosis of ICP alterations was performed were reviewed. 71 consecutive patients were studied. 40 patients (Group A) were diagnosed as IIH, 22 (Group B) as SIH, 7 (Group C) and 2 (Group D), respectively, as symptomatic intracranial hypertension and symptomatic intracranial hypotension. Main headache features were: in Group A, daily or nearly-daily headache (100 %) with diffuse/non-pulsating pain (73 %), aggravated by coughing/straining (54 %) and migrainous-associated symptoms (43 %). In Group B, an orthostatic headache (100 %) with nausea (29 %), vomiting (24 %), hearing disturbance (33 %), neck pain (48 %), hypacusia (24 %), photophobia (22 %) was reported. In Group C, a diffuse non-pulsating headache was present in 95 % with vomiting (25 %), sixth nerve palsy (14 %) and tinnitus (29 %). In Group D, an orthostatic headache with neck stiffness was reported by 100 %. Regarding applicability of ICHD-2 criteria in Group A, 73 % of the patients fitted criterion A; 100 %, criterion B; 100 %, criterion C; and 75 %, criterion D; while applying ICHD-3 beta version criteria, 100 % fitted criterion A; 97.5 %, criterion B; 100 %, criterion C; and 100 %, criterion D. In Group B, application of ICHD-2 showed 91 % patients fitting criterion A; 100 %, criterion B; 100

Study of the neutron-rich nuclei with N=21, sup 3 sup 5 Si and sup 3 sup 3 Mg, by beta decay of sup 3 sup 5 Al and sup 3 sup 3 Na

CERN Document Server

Nummela, S; Caurier, E; Courtin, S; Dessagne, P; Holmlund, E; Jokinen, A; Knipper, A; Le Scornet, G; Mieh, C; Nowacki, F; Lyapin, L G; Oinonen, M; Poirier, E; Radivojevic, Z; Ramdhane, M; Trzaska, W H; Walter, G; Äystö, J

2002-01-01

The first information on the level structure of the N=21 nuclei, sup 3 sup 5 Si and sup 3 sup 3 Mg, has been obtained by the beta decay study of sup 3 sup 5 Al and sup 3 sup 3 Na, produced by fragmentation of an UC target with 1.4 GeV protons at CERN/ISOLDE. The experimental technique involved beta-gamma, beta-gamma-gamma, and beta-n-gamma coincidences, neutron spectra being obtained by time of flight measurements. Gamma detection was made either using large Ge counters or small BaF sub 2 scintillators (for lifetime measurements). In the case of the sup 3 sup 5 Al decay, (T sub 1 sub / sub 2 =41.6(2.2) ms), a simple structure has been found for the level scheme of sup 3 sup 5 Si (Z=14, N=21) which has been interpreted with the level sequence : 7/2 sup - , 3/2 sup - and 3/2 sup + corresponding respectively to the ground state and the states at 910 and 974 keV. The life-time of the 974 keV [T sub 1 sub / sub 2 =5.9(6) ns] is found consistent with the proposed level scheme and multipolarities. The investigation ...

High-pressure behavior of beta-Ga2O3 nanocrystals

DEFF Research Database (Denmark)

Wang, H.; He, Y.; Chen, W.

2010-01-01

that nanocrystalline monoclinic beta-Ga2O3 underwent a phase transition to rhombohedral alpha-Ga2O3. It was found that beta- to alpha-Ga2O3 transition began at about 13.6-16.4 GPa, and extended up to 39.2 GPa. At the highest pressure used, only alpha-Ga2O3 was present, which remained after pressure release. A Birch......-Murnaghan fit to the P-V data yielded a zero-pressure bulk modulus at fixed B-0(')=4: B-0=228(9) GPa and B-0=333(19) GPa for beta-Ga2O3 and alpha-Ga2O3 phases, respectively. We compared our results with bulk beta-Ga2O3, and concluded that the phase-transition pressure and bulk modulus of nanocrystalline beta...

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.

Measurement of the 2{nu}{beta}{beta} decay of {sup 100}Mo to the excited 0{sub 1}{sup +} state in the NEMO3 experiment

Energy Technology Data Exchange (ETDEWEB)

Vala, L

2003-09-01

The NEMO3 detector was designed for the study of double beta decay and in particular to search for the neutrinoless double beta decay process (0{nu}{beta}{beta}). The intended sensitivity in terms of a half-life limit for the 0{nu}{beta}{beta} decay is of the order of 10{sup 25} y which corresponds to an effective neutrino mass m{sub {nu}} on the level of (0.3 - 0.1) eV. The 0{nu}{beta}{beta} process is today the most promising test of the Majorana nature of the neutrino. The detector was constructed in the Modane Underground Laboratory (LSM) in France by an international collaboration including France, Russia, the Czech Republic, the USA, the UK, Finland, and Japan. The experiment has been taking data since May 2002. The quantity of {sup 100}Mo in the detector (7 kg) allows an efficient measurement of the two-neutrino double beta decay (2{nu}{beta}{beta}) of {sup 100}Mo to the excited 0{sub 1}{sup +} state (eeN{gamma} channel). Monte-Carlo simulations of the effect and of all the relative sources of background have been produced in order to define a set of appropriate selection criteria. Both Monte-Carlo simulations and special runs with sources of {sup 208}Tl and {sup 214}Bi showed that the only significant background in the eeN{gamma} channel comes from radon that penetrated inside the wire chamber of NEMO3. The experimental data acquired from May 2002 to May 2003 have been analysed in order to determine the signal from the 2{nu}{beta}{beta} decay of {sup 100}Mo to the excited 0{sub 1}{sup +} state and the corresponding background level. The physical result, which was obtained at the level of four standard deviations, is given in the form of an interval of half-life values at 95% confidence level: [5.84*10{sup 20}, 2.26*10{sup 21}] y for method A and [5.83*10{sup 20}, 1.71*10{sup 21}] y for method B. (author)

Sizeable beta-strength in ³¹Ar ^{(beta 3p) decay}

DEFF Research Database (Denmark)

T. Koldste, G.; Blank, B.; J. G. Borge, M.

2014-01-01

We present for the first time precise spectroscopic information on the recently discovered decay mode beta-delayed 3p-emission. The detection of the 3p events gives an increased sensitivity to the high energy part of the Gamow-Teller strength distribution from the decay of 31Ar revealing that as ...... that as much as 30% of the strength resides in the beta-3p decay mode. A simplified description of how the main decay modes evolve as the excitation energy increases in 31Cl is provided....

(/sup 3/H)-beta-endorphin binding in rat brain

Energy Technology Data Exchange (ETDEWEB)

Houghten, R.A.; Johnson, N.; Pasternak, G.W.

1984-10-01

The binding of (/sup 3/H)-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the /sup 3/H-ligand is binding to more than one class of site. A portion of (/sup 3/H)-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of (/sup 3/H)-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers (/sup 3/H)-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of (/sup 3/H)-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo.

Peroxisome proliferator-activated receptor alpha (PPARalpha) protects against oleate-induced INS-1E beta cell dysfunction by preserving carbohydrate metabolism

DEFF Research Database (Denmark)

Frigerio, F; Brun, T; Bartley, C

2009-01-01

and investigated key metabolic pathways and genes responsible for metabolism-secretion coupling during a culture period of 3 days in the presence of 0.4 mmol/l oleate. RESULTS: In INS-1E cells, the secretory dysfunction primarily induced by oleate was aggravated by silencing of PPARalpha. Conversely, PPARalpha...... enzyme pyruvate carboxylase. PPARalpha overproduction increased both beta-oxidation and fatty acid storage in the form of neutral triacylglycerol, revealing overall induction of lipid metabolism. These observations were substantiated by expression levels of associated genes. CONCLUSIONS....../INTERPRETATION: PPARalpha protected INS-1E beta cells from oleate-induced dysfunction, promoting both preservation of glucose metabolic pathways and fatty acid turnover....

Investigation of the causes of clinical symptom aggravation in process of intravenous thrombolysis with alteplase

Directory of Open Access Journals (Sweden)

LI Chen-hua

2013-04-01

Full Text Available Objective To explore the causes of aggravation of microcirculation disorders in the process of intravenous thrombolysis with alteplase and the clinical outcomes. Methods The clinical data of the aggravated signs and symptoms of 13 cases treated by alteplase were reported, and the onset characteristics and clinical outcomes were analysed to summarize emergency experiences. Results There were 13 patients with stenosis of intracranial large arteries occurred perforating branch infarctions caused by the blocking of carried arteries (8 cases in internal carotid system, 5 cases in vertebral-basilar system. In the process of thrombolytic therapy, main aggravated presentations including cortical ischemic symptom, quadriplegia, exacerbated disturbance of consciousness were seen. Imaging examinations showed multiple new petechial ischemic foci in cortex and watershed region or increasing of infarct foci in cerebellum and brain stem. The prognosis was favorable after expectant treatment. NIHSS score was 8.69 ± 3.42 at 24 h after treatment, and mRS score was 0.94 ±0.37 at 3 month-follow-up. Neurologic deficit and quality of life were evidently improved. Conclusion In the course of intravenous thrombolytic therapy with alteplase. Aggravated clinical signs and symptoms may be related to various factors. Emboli disintegration inducing microcirculation disorder is inferred to be the main cause. For patients presenting aggravated signs and symptoms in thrombolysis process, favorable outcomes may occur as long as intensive care and timely treatment are performed.

Comparisons of experimental beta-ray spectra important to decay heat predictions with ENSDF [Evaluated Nuclear Structure Data File] evaluations

International Nuclear Information System (INIS)

Dickens, J.K.

1990-03-01

Graphical comparisons of recently obtained experimental beta-ray spectra with predicted beta-ray spectra based on the Evaluated Nuclear Structure Data File are exhibited for 77 fission products having masses 79--99 and 130--146 and lifetimes between 0.17 and 23650 sec. The comparisons range from very poor to excellent. For beta decay of 47 nuclides, estimates are made of ground-state transition intensities. For 14 cases the value in ENSDF gives results in very good agreement with the experimental data. 12 refs., 77 figs., 1 tab

Increase of crevicular interleukin 1beta under academic stress at experimental gingivitis sites and at sites of perfect oral hygiene.

Science.gov (United States)

Deinzer, R; Förster, P; Fuck, L; Herforth, A; Stiller-Winkler, R; Idel, H

1999-01-01

This study analyses the effects of academic stress on crevicular interleukin-1beta(I1-1beta) both at experimental gingivitis sites and at sites of perfect oral hygiene. I1-1beta is thought to play a predominant role in periodontal tissue destruction. 13 medical students participating in a major medical exam (exam group) and 13 medical students not participating in any exam throughout the study period (control group) volunteered for the study. In a split-mouth-design, they refrained from any oral hygiene procedures in two opposite quadrants for 21 days (experimental gingivitis) while they maintained perfect hygiene levels at the remaining sites. Crevicular fluid was sampled for further I1-1beta analysis at teeth 5 and 6 of the upper jaw at days 1, 5, 8, 11, 14, 18 and 21 of the experimental gingivitis period. Exam students showed significantly higher I1-1beta levels than controls both at experimental gingivitis sites (area under the curve, exam group: 1240.64+/-140.07; control group: 697.61+/-111.30; p=0.004) and at sites of perfect oral hygiene (exam group: 290.42+/-63.19; control group: 143.98+/-42.71; p = 0.04). These results indicate that stress might affect periodontal health by increasing local I1-1beta levels especially when oral hygiene is neglected.

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.

Beta/gamma test problems for ITS

International Nuclear Information System (INIS)

Mei, G.T.

1993-01-01

The Integrated Tiger Series of Coupled Electron/Photon Monte Carlo Transport Codes (ITS 3.0, PC Version) was used at Oak Ridge National Laboratory (ORNL) to compare with and extend the experimental findings of the beta/gamma response of selected health physics instruments. In order to assure that ITS gives correct results, several beta/gamma problems have been tested. ITS was used to simulate these problems numerically, and results for each were compared to the problem's experimental or analytical results. ITS successfully predicted the experimental or analytical results of all tested problems within the statistical uncertainty inherent in the Monte Carlo method

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

Science.gov (United States)

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

2007-03-01

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

High-fat, carbohydrate-free diet markedly aggravates obesity but prevents beta-cell loss and diabetes in the obese, diabetes-susceptible db/db strain.

Science.gov (United States)

Mirhashemi, Farshad; Kluth, Oliver; Scherneck, Stephan; Vogel, Heike; Kluge, Reinhart; Schurmann, Annette; Joost, Hans-Georg; Neschen, Susanne

2008-01-01

We have previously reported that a high-fat, carbohydrate-free diet prevents diabetes and beta-cell destruction in the New Zealand Obese (NZO) mouse strain. Here we investigated the effect of diets with and without carbohydrates on obesity and development of beta-cell failure in a second mouse model of type 2 diabetes, the db/db mouse. When kept on a carbohydrate-containing standard (SD; with (w/w) 5.1, 58.3, and 17.6% fat, carbohydrates and protein, respectively) or high-fat diet (HFD; 14.6, 46.7 and 17.1%), db/db mice developed severe diabetes (blood glucose >20 mmol/l, weight loss, polydipsia and polyurea) associated with a selective loss of pancreatic beta-cells, reduced GLUT2 expression in the remaining beta-cells, and reduced plasma insulin levels. In contrast, db/db mice kept on a high-fat, carbohydrate-free diet (CFD; with 30.2 and 26.4% (w/w) fat or protein) did not develop diabetes and exhibited near-normal, hyperplastic islets in spite of a morbid obesity (fat content >60%) associated with hyperinsulinaemia. These data indicate that in genetically different mouse models of obesity-associated diabetes, obesity and dietary fat are not sufficient, and dietary carbohydrates are required, for beta-cell destruction.

Pediatric Aspects of Headache Classification in the International Classification of Headache Disorders-3 (ICHD-3 beta version).

Science.gov (United States)

McAbee, Gary N; Morse, Anne Marie; Assadi, Mitra

2016-01-01

This analysis looks at the applicability of the International Classification of Headache Disorders-3 beta (ICHD-3 beta) to various headache syndromes of children and adolescents. Areas of similarities and differences between adult and pediatric headaches are addressed as they relate to the ICHD-3 beta.

Hypoxia Aggravates Inactivity-Related Muscle Wasting

Directory of Open Access Journals (Sweden)

Tadej Debevec

2018-05-01

Full Text Available Poor musculoskeletal state is commonly observed in numerous clinical populations such as chronic obstructive pulmonary disease (COPD and heart failure patients. It, however, remains unresolved whether systemic hypoxemia, typically associated with such clinical conditions, directly contributes to muscle deterioration. We aimed to experimentally elucidate the effects of systemic environmental hypoxia upon inactivity-related muscle wasting. For this purpose, fourteen healthy, male participants underwent three 21-day long interventions in a randomized, cross-over designed manner: (i bed rest in normoxia (NBR; PiO2 = 133.1 ± 0.3 mmHg, (ii bed rest in normobaric hypoxia (HBR; PiO2 = 90.0 ± 0.4 mmHg and ambulatory confinement in normobaric hypoxia (HAmb; PiO2 = 90.0 ± 0.4 mmHg. Peripheral quantitative computed tomography and vastus lateralis muscle biopsies were performed before and after the interventions to obtain thigh and calf muscle cross-sectional areas and muscle fiber phenotype changes, respectively. A significant reduction of thigh muscle size following NBR (-6.9%, SE 0.8%; P < 0.001 was further aggravated following HBR (-9.7%, SE 1.2%; P = 0.027. Bed rest-induced muscle wasting in the calf was, by contrast, not exacerbated by hypoxic conditions (P = 0.47. Reductions in both thigh (-2.7%, SE 1.1%, P = 0.017 and calf (-3.3%, SE 0.7%, P < 0.001 muscle size were noted following HAmb. A significant and comparable increase in type 2× fiber percentage of the vastus lateralis muscle was noted following both bed rest interventions (NBR = +3.1%, SE 2.6%, HBR = +3.9%, SE 2.7%, P < 0.05. Collectively, these data indicate that hypoxia can exacerbate inactivity-related muscle wasting in healthy active participants and moreover suggest that the combination of both, hypoxemia and lack of activity, as seen in COPD patients, might be particularly harmful for muscle tissue.

A new alternative transcript encodes a 60 kDa truncated form of integrin beta 3.

Science.gov (United States)

Djaffar, I; Chen, Y P; Creminon, C; Maclouf, J; Cieutat, A M; Gayet, O; Rosa, J P

1994-05-15

A cDNA for integrin beta 3 isolated from a human erythroleukaemia (HEL) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta 3c, results from the use of a cryptic AG donor splice site in intron 8 of the beta 3 gene, and is different from a previously described alternative beta 3 mRNA. The predicted open reading frame of beta 3C stops at a TAG stop codon 69 bp downstream from position 1281. It starts with the signal peptide and the 404 N-terminal extracellular residues of beta 3, encompassing the ligand binding sites, followed by 23 C-terminal intron-derived residues, corresponding to a truncated form of beta 3 lacking the cysteine-rich, transmembrane and cytoplasmic domains. Expression of beta 3C mRNA was demonstrated in human platelets, megakaryocytes, endothelial cells and HEL cells by reverse transcriptase/PCR. The beta 3C transcript was also demonstrated in the mouse, suggesting its conservation through evolution. Finally, a 60 kDa polypeptide corresponding to the beta 3C alternative transcript was demonstrated in platelets by Western blotting using a polyclonal antibody raised against a synthetic peptide designed from the beta 3C intronic sequence. Taken together, these results suggest a biological role for beta 3C, the first alternative transcript showing an altered extracellular domain of a beta integrin.

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

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

2008-01-11

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

The effect of different classes of beta-antagonists on clinical and experimental hypertension.

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Fitzgerald, J D

1982-01-01

The reference beta adrenoceptor antagonist propranolol reduces blood pressure in about 60% of patients with essential hypertension. Pressure is reduced in the supine, and erect positions without postural hypotension as well as during exercise. The average extent of pressure reduction is approximately 26/16 mm.Hg. Though all clinically available beta antagonists reduce blood pressure, the profile may be modified by both adrenotropic and non-adrenotropic ancillary properties. Of the adrenotropic properties, potency influences dose frequency and total body burden of drug. Selective beta 1 antagonism may enhance safety without reducing efficacy in patients with obstructive airways disease. Selective beta 2 blockade does not reduce blood pressure in experimental models or normal subjects, but the response in patients is unknown. Partial agonism may reduce efficacy if the degree of stimulant activity is too great. Of the non-adrenotropic properties, membrane stabilising properties are of relevance only in so far as such agents undergo extensive biotransformation resulting in either reduced efficacy when drugs are used at fixed doses or the formation of biologically active metabolites. The additional properties of either alpha adrenergic blockade or inhibition of vascular smooth muscle tone modify both the speed of onset and the haemodynamic profile. The interaction of these ancillary pharmacological properties is evaluated in this review.

Involvement of beta 3-adrenoceptor in altered beta-adrenergic response in senescent heart: role of nitric oxide synthase 1-derived nitric oxide.

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Birenbaum, Aurélie; Tesse, Angela; Loyer, Xavier; Michelet, Pierre; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno; Amour, Julien

2008-12-01

In senescent heart, beta-adrenergic response is altered in parallel with beta1- and beta2-adrenoceptor down-regulation. A negative inotropic effect of beta3-adrenoceptor could be involved. In this study, the authors tested the hypothesis that beta3-adrenoceptor plays a role in beta-adrenergic dysfunction in senescent heart. beta-Adrenergic responses were investigated in vivo (echocardiography-dobutamine, electron paramagnetic resonance) and in vitro (isolated left ventricular papillary muscle, electron paramagnetic resonance) in young adult (3-month-old) and senescent (24-month-old) rats. Nitric oxide synthase (NOS) immunolabeling (confocal microscopy), nitric oxide production (electron paramagnetic resonance) and beta-adrenoceptor Western blots were performed in vitro. Data are mean percentages of baseline +/- SD. An impaired positive inotropic effect (isoproterenol) was confirmed in senescent hearts in vivo (117 +/- 23 vs. 162 +/- 16%; P < 0.05) and in vitro (127 +/- 10 vs. 179 +/- 15%; P < 0.05). In the young adult group, the positive inotropic effect was not significantly modified by the nonselective NOS inhibitor N-nitro-L-arginine methylester (L-NAME; 183 +/- 19%), the selective NOS1 inhibitor vinyl-L-N-5(1-imino-3-butenyl)-L-ornithine (L-VNIO; 172 +/- 13%), or the selective NOS2 inhibitor 1400W (183 +/- 19%). In the senescent group, in parallel with beta3-adrenoceptor up-regulation and increased nitric oxide production, the positive inotropic effect was partially restored by L-NAME (151 +/- 8%; P < 0.05) and L-VNIO (149 +/- 7%; P < 0.05) but not by 1400W (132 +/- 11%; not significant). The positive inotropic effect induced by dibutyryl-cyclic adenosine monophosphate was decreased in the senescent group with the specific beta3-adrenoceptor agonist BRL 37344 (167 +/- 10 vs. 142 +/- 10%; P < 0.05). NOS1 and NOS2 were significantly up-regulated in the senescent rat. In senescent cardiomyopathy, beta3-adrenoceptor overexpression plays an important role in the

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

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

2004-04-01

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

17 beta-hydroxysteroid dehydrogenase 3 deficiency in the Mediterranean population.

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Rosler, Ariel

2006-08-01

Eighty-five males with 17 beta-HSD3 were identified among a highly inbred Arab population in Israel and 57 studied over a period of 25 years. The founders of this defect originated in the mountainous regions of present Lebanon and Syria, but most of the families now live in Jerusalem, Hebron, the Tel-Aviv area and, in particular, in Gaza, where the frequency of affected males is estimated at 1 in 100 to 150. Affected individuals are born with ambiguity of the external genitalia and reared as females until puberty. Thereafter marked virilization occurs, leading in many cases to the spontaneous adoption of a male gender identity and role. Adults develop a male habitus with abundant body hair and beard and the phallus and testes enlarge to adult proportions. Gender reassignment in infancy was only possible when enough erectile tissue was present at birth and developed into a normal size penis with testosterone. 17 beta-HSD3 deficiency can be reliably diagnosed by endocrine evaluation and mutation analysis. In adults the defect is characterized by markedly increased concentrations of androstenedione (A) with borderline low to normal testosterone (T) levels and a high A/T ratio. 5a-dihydrotestosterone (DHT) concentrations are moderately decreased, normal or high and dehydroepiandrosterone (DHEA) levels are high. The estrogen pathway is also impaired, even though both estrone (E-1) and estradiol-17 beta (E-2) levels are high. Children have low basal levels of all androgens, but the defect may be demonstrated after prolonged stimulation with human chorionic gonadotropin (HCG). LH and FSH levels are very high after puberty and normal in childhood. 17 beta-HSD3 isozyme is encoded by the chromosome 9q22 17 beta-HSD3 gene and expressed exclusively in testes. A point mutation in exon 3, codon 80 of the 17 beta-HSD3 gene, R80Q, caused by a single base substitution from CGG ( arginine) to CAG ( glutamine) was identified in both alleles of 24 individuals from 9 extended Arab

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

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

Science.gov (United States)

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

2009-06-01

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

Structural and optical characterization of Eu3+ doped beta-Ga2O3 nanoparticles using a liquid-phase precursor method.

Science.gov (United States)

Kim, Moung-O; Kang, Bongkyun; Yoon, Daeho

2013-08-01

Eu3+ doped beta-Ga2O3 and non-doped beta-Ga2O3 nanoparticles were synthesized at 800 degrees C using a liquid-phase precursor (LPP) method, with different annealing times and Eu3+ ion concentrations. Eu3+ doped beta-Ga2O3 nanoparticles showed broad XRD peaks, revealing a second phase compared with the non-doped beta-Ga2O3 nanoparticles. The cathode luminescence (CL) spectra of beta-Ga2O3 and Eu3+ doped beta-Ga2O3 nanoparticles showed a broad band emission (300-500 nm) of imperfection and two component emissions. The luminescence quenching properties of Eu3+ dopant ion concentration appeared gradually beyond 5 mol% in our investigation.

Coexistence of beta 1- and beta 2-adrenoceptors in the rabbit heart: quantitative analysis of the regional distribution by (-)-/sup 3/H-dihydroalprenolol binding

Energy Technology Data Exchange (ETDEWEB)

Brodde, O.E.; Leifert, F.J.; Krehl, H.J.

1982-01-01

We determined the amount of beta 1- and beta 2-adrenoceptors in right and left atria and ventricles of rabbits. For this purpose inhibition of specific (-)-/sup 3/H-dihydroalprenolol ((-)-/sup 3/H-DHA) binding (5 nM) by beta 1-selective (practolol, metoprolol) and beta 2-selective (zinterol, IPS 339) adrenergic drugs was determined and analyzed by pseudo-Scatchard (Hofstee) plots. For both atria, inhibition of binding by the four selective beta-adrenergic drugs resulted in non-linear Hofstee plots, suggesting the coexistence of both beta-adrenoceptor subtypes. From these plots we calculated a beta 1:beta 2-adrenoceptor ratio of 72:28 for the right atrium and of 82:18 for the left. In contrast, only a very small amount of beta 2-adrenoceptors (approximately 5-7% of the total beta-adrenoceptor population) could be detected in the ventricles. For comparison we analyzed the inhibition of specific (-)-/sup 3/H-DHA binding in tissues with homogeneous population of beta-adrenoceptors (beta 1:guinea pig left ventricle; beta 2: cerebellum of mature rats). For both tissues the four selective beta-adrenergic drugs showed linear Hofstee plots, demonstrating that in tissues with homogeneous beta-receptor population interaction of each drug with the receptor followed simple mass-action kinetics. We conclude that beta 1- and beta 2-adrenoceptors coexist in rabbit atria while the ventricles are predominantly endowed the beta 1-adrenoceptors.

Anodic Aluminum Oxide Membrane-Assisted Fabrication of beta-In(2)S(3) Nanowires.

Science.gov (United States)

Shi, Jen-Bin; Chen, Chih-Jung; Lin, Ya-Ting; Hsu, Wen-Chia; Chen, Yu-Cheng; Wu, Po-Feng

2009-06-06

In this study, beta-In(2)S(3) nanowires were first synthesized by sulfurizing the pure Indium (In) nanowires in an AAO membrane. As FE-SEM results, beta-In(2)S(3) nanowires are highly ordered, arranged tightly corresponding to the high porosity of the AAO membrane used. The diameter of the beta-In(2)S(3) nanowires is about 60 nm with the length of about 6-8 mum. Moreover, the aspect ratio of beta-In(2)S(3) nanowires is up to 117. An EDS analysis revealed the beta-In(2)S(3) nanowires with an atomic ratio of nearly S/In = 1.5. X-ray diffraction and corresponding selected area electron diffraction patterns demonstrated that the beta-In(2)S(3) nanowire is tetragonal polycrystalline. The direct band gap energy (E(g)) is 2.40 eV from the optical measurement, and it is reasonable with literature.

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

Directory of Open Access Journals (Sweden)

Tetsuya Kimura

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

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

Science.gov (United States)

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

2004-04-01

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

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.

Inhibition of common cold-induced aggravation of childhood asthma by leukotriene receptor antagonists.

Science.gov (United States)

Yoshihara, Shigemi; Fukuda, Hironobu; Abe, Toshio; Nishida, Mitsuhiro; Yamada, Yumi; Kanno, Noriko; Arisaka, Osamu

2012-09-01

Virus infection is an important risk factor for aggravation of childhood asthma. The objective of this study was to examine the effect of drugs on aggravation of asthma induced by a common cold. Asthma control was examined in a survey of 1,014 Japanese pediatric patients with bronchial asthma. The occurrence of common cold, asthma control, and drugs used for asthma control were investigated using a modified Childhood Asthma Control Test (C-ACT) for patients aged cold and aggravation of asthma were significantly higher in patients aged cold-induced aggravation was significantly less effective in patients aged cold, asthma control was significantly more effective for those treated with leukotriene receptor antagonists (LTRAs) compared to treatment without LTRAs. Asthma control did not differ between patients who did or did not take inhaled corticosteroids or long-acting β2 stimulants. These findings showed a high prevalence of common cold in younger patients with childhood asthma and indicated that common cold can induce aggravation of asthma. LTRAs are useful for long-term asthma control in very young patients who develop an asthma attack due to a common cold.

Aggravation of dyspnea in stage I non-small cell lung cancer patients following stereotactic body radiotherapy

DEFF Research Database (Denmark)

Paludan, Merete; Traberg Hansen, Anders; Petersen, Jørgen

2006-01-01

the association of dose-volume histogram parameters with changes in dyspnea. The study concerns 28 medically inoperable stage I NSCLC patients that received SBRT at our department between 2000 and 2003. A central dose of 45 Gy/3 fractions was delivered in 5-8 days. WHO toxicity scoring of dyspnea...... consistent temporal variations of dyspnea after SBRT. We identified COPD as the factor showing the closest association with aggravation of dyspnea. The observed aggravation of dyspnea following SBRT reflects habitual exacerbations of COPD rather than treatment-related toxicity. Concern about pulmonary...

Field-testing of the ICHD-3 beta diagnostic criteria for classical trigeminal neuralgia

DEFF Research Database (Denmark)

Maarbjerg, Stine; Sørensen, Morten Togo; Gozalov, Aydin

2015-01-01

INTRODUCTION: We aimed to field-test the beta version of the third edition of the International Classification of Headache Disorders (ICHD-3 beta) diagnostic criteria for classical trigeminal neuralgia (TN). The proposed beta draft of the 11th version of the International Classification of Diseases...... (ICD-11 beta) is almost exclusively based on the ICHD-3 beta classification structure although slightly abbreviated. We compared sensitivity and specificity to ICHD-2 criteria, and evaluated the needs for revision. METHODS: Clinical characteristics were systematically and prospectively collected from...

Proposed experimental test of Bell's inequality in nuclear beta decay

International Nuclear Information System (INIS)

Skalsey, M.

1986-01-01

A β decay experiment is proposed for testing Bell's inequality, related to hidden-variables alternatives to quantum mechanics. The experiment uses Mott scattering for spin polarization analysis of internal conversion electrons. Beta-decay electrons, in cascade with the conversion electrons, are longitudinally polarized due to parity violation in the weak interaction. So simply detecting the β electron direction effectively measures the spin. A two-particle spin-spin correlation can thus be investigated and related, within certain assumptions, to Bell's inequality. The example of 203 Hg decay is used for a calculation of expected results. Specific problems related to nuclear structure and experimental inconsistencies are also discussed

Molecular cloning and characterization of a human beta-Gal-3'-sulfotransferase that acts on both type 1 and type 2 (Gal beta 1-3/1-4GlcNAc-R) oligosaccharides.

Science.gov (United States)

Honke, K; Tsuda, M; Koyota, S; Wada, Y; Iida-Tanaka, N; Ishizuka, I; Nakayama, J; Taniguchi, N

2001-01-05

A novel sulfotransferase gene (designated GP3ST) was identified on human chromosome 2q37.3 based on its similarity to the cerebroside 3'-sulfotransferase (CST) cDNA (Honke, K., Tsuda, M., Hirahara, Y., Ishii, A., Makita, A., and Wada, Y. (1997) J. Biol. Chem. 272, 4864-4868). A full-length cDNA was obtained by reverse transcription-polymerase chain reaction and 5'- and 3'-rapid amplification of cDNA ends analyses of human colon mRNA. The isolated cDNA clone predicts that the protein is a type II transmembrane protein composed of 398 amino acid residues. The amino acid sequence indicates 33% identity to the human CST sequence. A recombinant protein that is expressed in COS-1 cells showed no CST activity, but did show sulfotransferase activities toward oligosaccharides containing nonreducing beta-galactosides such as N-acetyllactosamine, lactose, lacto-N-tetraose (Lc4), lacto-N-neotetraose (nLc4), and Gal beta 1-3GalNAc alpha-benzyl (O-glycan core 1 oligosaccharide). To characterize the cloned sulfotransferase, a sulfotransferase assay method was developed that uses pyridylaminated (PA) Lc4 and nLc4 as enzyme substrates. The enzyme product using PA-Lc4 as an acceptor was identified as HSO(3)-3Gal beta 1-3GlcNAc beta 1-3Gal beta 1- 4Glc-PA by two-dimensional (1)H NMR. Kinetics studies suggested that GP3ST is able to act on both type 1 (Gal beta 1-3GlcNAc-R) and type 2 (Gal beta 1-4GlcNAc-R) chains with a similar efficiency. In situ hybridization demonstrated that the GP3ST gene is expressed in epithelial cells lining the lower to middle layer of the crypts in colonic mucosa, hepatocytes surrounding the central vein of the liver, extravillous cytotrophoblasts in the basal plate and septum of the placenta, renal tubules of the kidney, and neuronal cells of the cerebral cortex. The results of this study indicate the existence of a novel beta-Gal-3'-sulfotransferase gene family.

Genetics Home Reference: 3-beta-hydroxysteroid dehydrogenase deficiency

Science.gov (United States)

... for This Page Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana ... A, Copeland KC, Chang YT, Lutfallah C, Mason JI. Carriers for type II 3beta-hydroxysteroid dehydrogenase (HSD3B2) ...

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

Science.gov (United States)

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

2010-08-11

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

A new alternative transcript encodes a 60 kDa truncated form of integrin beta 3.

OpenAIRE

Djaffar, I; Chen, Y P; Creminon, C; Maclouf, J; Cieutat, A M; Gayet, O; Rosa, J P

1994-01-01

A cDNA for integrin beta 3 isolated from a human erythroleukaemia (HEL) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta 3c, results from the use of a cryptic AG donor splice site in intron 8 of the beta 3 gene, and is different from a previously described alternative beta 3 mRNA. The predicted open reading frame of beta 3C stops at a TAG stop codon 69 bp downstream from position 1281. It starts with the signal peptide and the 404 N-terminal extracellular residu...

A semiconductor beta ray spectrometer

International Nuclear Information System (INIS)

Bom, V.R.

1987-01-01

Measurement of energy spectra of beta particles emitted from nuclei in beta-decay processes provides information concerning the mass difference of these nuclei between initial and final state. Moreover, experimental beta spectra yield information on the feeding of the levels in the daughter nucleus. Such data are valuable in the construction and checking of the level schemes. This thesis describes the design, construction, testing and usage of a detector for the accurate measurement of the mentioned spectra. In ch. 2 the design and construction of the beta spectrometer, which uses a hyper-pure germanium crystal for energy determination, is described. A simple wire chamber is used to discriminate beta particles from gamma radiation. Disadvantages arise from the large amounts of scattered beta particles deforming the continua. A method is described to minimize the scattering. In ch. 3 some theoretical aspects of data analysis are described and the results of Monte-Carlo simulations of the summation of annihilation radiation are compared with experiments. Ch. 4 comprises the results of the measurements of the beta decay energies of 103-108 In. 87 refs.; 34 figs.; 7 tabs

Standardization of low energy beta and beta-gamma complex emitters by the tracer and the efficiency extrapolation methods

International Nuclear Information System (INIS)

Sahagia, M.

1978-01-01

The absolute standardization of radioactive solutions of low energy beta emitters and beta-gamma emitters with a high probability of disintegration to the ground state is described; the tracer and the efficiency extrapolation methods were used. Both types of radionuclides were mathematically and physically treated in an unified manner. The theoretical relations between different beta spectra were calculated according to Williams' model and experimentally verified for: 35 S + 60 Co, 35 S + 95 Nb, 147 Pm + 60 Co, 14 C + 95 Nb and two beta branches of 99 Mo. The optimum range of beta efficiency variation was indicated. The basic supposition that all beta efficieny tend to unity in the same time was experimentally verified, using two 192 Ir beta branches. Four computer programs, written in the FORTRAN IV language, were elaborated, for the adequate processing of the experimental data. Good precision coefficients according to international standards were obtained in the absolute standardization of 35 S, 147 Pm, 99 Mo solutions. (author)

GSK3 beta forms a tetrameric complex with endogenous PS1-CTF/NTF and beta-catenin. Effects of the D257/D385A and FAD-linked mutations.

Science.gov (United States)

Tesco, G; Tanzi, R E

2000-01-01

We have previously shown that the endogenous C-terminal fragment of presenilin 1 co-immunoprecipitates with endogenous beta-catenin. Since PS1 has been suggested to be involved in beta-catenin stabilization, we further investigated whether GSK3 beta, responsible for beta-catenin phosphorylation and degradation, is part of the PS1/beta-catenin complex. In naïve H4 and CHO cells, PS1 co-immunoprecipitated with both endogenous beta-catenin and GSK3 beta. In addition, GSK3 beta endogenously binds to the PS1-CTF/NTF complex and beta-catenin in naïve CHO cells. GSK3 beta also co-immunoprecipitated with PS1 full length in CHO cell lines overexpressing PS1 wild type. Given that it has been recently shown that PS1 mutations of aspartate 257 or 385 result in prevention of PS1 endoproteolysis and inhibition of gamma-secretase activity, we also tested whether PS1 endoproteolysis is required for beta-catenin/GSK3 beta/PS1 binding and whether PS1 FAD-linked mutations affect GSK3 beta recruitment in the PS1/beta-catenin complex. GSK3 beta was detected in PS1 immunoprecipitates from H4 cell lines overexpressing PS1 wild type, delta E10, A286E, L246V and in CHO cell lines overexpressing aspartate or M146L mutations. The latter data show that the absence of PS1 endoproteolysis (D257A/D385A and delta E10) or the presence of PS1-FAD mutations does not interfere with beta-catenin/GSK3 beta/PS1 complex formation.

Expressão de galectina-3 e beta-catenina em lesões pré-malignas e carcinomatosas de língua de camundongos Galectin-3 and beta-catenin expression in premalignant and carcinomatous lesions in tongue of mice

Directory of Open Access Journals (Sweden)

Juliana Moreira de Almeida Sant'ana

2011-02-01

. Altered galectin-3 and beta-catenin expressions have been described in different tumors, however, there are no studies evaluating their expression in dysplasias and carcinomas induced in carcinogenic tongue models. OBJECTIVES: To study galectin-3 and beta-catenin expressions in dysplasias and carcinomas experimentally induced in mouse tongue. METHODS: Twenty C57Bl/6 male mice were treated with 4NQO in their drinking water for 16 weeks and sacrificed at weeks 16 and 32. Tongues were removed, routinely processed, and stained with hematoxylin and eosin to detect dysplasias and carcinomas. An immunohistochemical assay was performed to determine the level of positivity for galectin-3 and beta-catenin in these lesions as well as their correlation in carcinomas. RESULTS: The number of mice affected by carcinomas increased from week 16 to week 32 (22.2% vs. 88.9% and the number affected by dysplasias decreased (66.7% vs. 11.1%. There was an increase in non-membranous beta-catenin- and cytoplasmic galectin-3-positive cells in dysplasias and carcinomas, although this difference was not statiscally significant. Nonetheless, there was a significant increase of nuclear galectin-3-positive cells in the evolution from dysplasia to carcinoma (p = 0.04. There was no correlation between beta-catenin and galectin-3. CONCLUSION: Wnt signaling pathway is active in both dysplasias and carcinomas and the increase of nuclear galectin-3-positive cells in carcinomas suggests its influence on malignant transformation in the tongue epithelium.

Experiments close to the beta-limit in W7-AS

International Nuclear Information System (INIS)

Weller, A; Geiger, J; Werner, A; Zarnstorff, M C; Nuehrenberg, C; Sallander, E; Baldzuhn, J; Brakel, R; Burhenn, R; Dinklage, A; Fredrickson, E; Gadelmeier, F; Giannone, L; Grigull, P; Hartmann, D; Jaenicke, R; Klose, S; Knauer, J P; Koenies, A; Kolesnichenko, Ya I; Laqua, H P; Lutsenko, V V; McCormick, K; Monticello, D; Osakabe, M; Pasch, E; Reiman, A; Rust, N; Spong, D A; Wagner, F; Yakovenko, Yu V

2003-01-01

A major objective of the experimental program in the last phase of the W7-AS stellarator was to explore and demonstrate the high-beta performance of advanced stellarators. MHD-quiescent discharges at low impurity radiation levels with volume averaged beta-values of up to beta=3.4% have been achieved. A very important prerequisite was the attainment of the high density H-Mode (HDH) regime. This was made possible by the installation of extensive graphite plasma facing components designed for island divertor operation. The co-directed neutral beam injection provided increased absorbed heating power of up to 3.2 MW in high-beta plasmas with B<=1.25 T. The anticipated improved features concerning equilibrium and stability at high plasma beta could be verified experimentally by the comparison of x-ray data with free boundary equilibrium calculations. The maximum beta found in configurations with a rotational transform around t=0.5 is determined by the available heating power. No evidence of a stability limit has been found in the accessible configuration space, and the discharges are remarkably quiescent at maximum beta, most likely due the increase of the magnetic well depth. An increase in low m/n MHD activity is typically observed during the transition towards high beta. The beneficial stability properties of net-current-free configurations could be demonstrated by comparison with configurations where a significant inductive current drive was involved. Current driven instabilities such as tearing modes and soft disruptions can prevent access to beta-values as high as in the currentless case. The experimental results indicate that optimized stellarators such as W7-X can be considered as a viable option for an attractive stellarator fusion reactor

Disregarding Graduated Treatment: Why Transfer Aggravates Recidivism

Science.gov (United States)

Johnson, Kristin; Lanza-Kaduce, Lonn; Woolard, Jennifer

2011-01-01

These data merge correctional histories with official state and courthouse information for a sample of teenage offenders, some of whom had been transferred to the adult system. Previous research indicated that transfer aggravates recidivism after the age of 18. The correctional data allow the examination of the relationship between sanctions and…

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

Science.gov (United States)

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

1986-04-20

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

Experimental proof of quantum non-separability based on the transition of the atom in beta-decay

International Nuclear Information System (INIS)

Vatai, E.

1988-01-01

The basic non-local character of the quantum processes is a continuously discussed and doubted problem of quantum theory. Recent experimental proofs of the Bell inequalities are questioned in the literature, using local theories of hidden variables. Present paper shows a simple and direct proof of non-locality of quantum processes, analyzing the case of the beta decay. The hypothetical energy transfer between shell electrons and beta electron-neutrino system is proved to be superluminal but necessary for the energy balance of the process. This argumentation proves the nonseparability and nonlocality of quantum processes. (D.G.) 8 refs

Evaluation of TGF beta1 expression and comparison the thickness of different aorta layers in experimental diabetes.

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Cuce, G; Kalkan, S S; Esen, H H

2011-01-01

It was aimed to investigate the effects of experimental diabetes on TGF beta1 expression and tunica intima and media thickness in abdominal and thoracic aorta. Fourteen three months old female rats were divided into two groups, non-diabetic and streptozotocin (STZ) induced diabetic group. Hematoxylin-Eosin and Verhoeff's Van Gieson elastic staining and TGF beta1 immunohistochemistry staining were performed. Abdominal and thoracic intima and media thickness of aortas were measured with the oculometer. Evaluation of intima and media thickness measurements showed no significant statistical differences between non-diabetic and diabetic groups. TGF beta1 expression increased significantly in thoracic diabetic (TD) group. The 60 day duration of diabetes is not sufficiently enough time for the development of pathological changes that could lead to thickening in aortic intima-media layers. TGF beta1 expression was negative in the abdominal aorta that can predispose to the development of atherosclerosis, which could develop overtime. This finding may be interpreted as an appropriate basis for the development of atherosclerosis. In the thoracic aorta TGF beta1 may coordinate cellular events such as tissue repair (Fig. 5, Ref. 23).

Synthesis and characterization of f-element iodate architectures with variable dimensionality, alpha- and beta-Am(IO3)3.

Science.gov (United States)

Runde, Wolfgang; Bean, Amanda C; Brodnax, Lia F; Scott, Brian L

2006-03-20

Two americium(III) iodates, beta-Am(IO3)3 (I) and alpha-Am(IO3)3 (II), have been prepared from the aqueous reactions of Am(III) with KIO(4) at 180 degrees C and have been characterized by single-crystal X-ray diffraction, diffuse reflectance, and Raman spectroscopy. The alpha-form is consistent with the known structure type I of anhydrous lanthanide iodates. It consists of a three-dimensional network of pyramidal iodate groups bridging [AmO8] polyhedra where each of the americium ions are coordinated to eight iodate ligands. The beta-form reveals a novel architecture that is unknown within the f-element iodate series. beta-Am(IO3)3 exhibits a two-dimensional layered structure with nine-coordinate Am(III) atoms. Three crystallographically unique pyramidal iodate anions link the Am atoms into corrugated sheets that interact with one another through intermolecular IO3-...IO3- interactions forming dimeric I2O10 units. One of these anions utilizes all three O atoms to simultaneously bridge three Am atoms. The other two iodate ligands bridge only two Am atoms and have one terminal O atom. In contrast to alpha-Am(IO3)3, where the [IO3] ligands are solely corner-sharing with [AmO8] polyhedra, a complex arrangement of corner- and edge-sharing mu2- and mu3-[IO3] pyramids can be found in beta-Am(IO3)3. Crystallographic data: I, monoclinic, space group P2(1)/n, a = 8.871(3) A, b = 5.933(2) A, c = 15.315(4) A, beta = 96.948(4) degrees , V = 800.1(4) A(3), Z = 4; II, monoclinic, space group P2(1)/c, a = 7.243(2) A, b = 8.538(3) A, c = 13.513(5) A, beta = 100.123(6) degrees , V = 822.7(5) A(3), Z = 4.

Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

Science.gov (United States)

Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

2006-12-01

We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

Time reversal violation in radiative beta decay: experimental plans

Science.gov (United States)

Behr, J. A.; McNeil, J.; Anholm, M.; Gorelov, A.; Melconian, D.; Ashery, D.

2017-01-01

Some explanations for the excess of matter over antimatter in the universe involve sources of time reversal violation (TRV) in addition to the one known in the standard model of particle physics. We plan to search for TRV in a correlation between the momenta of the beta, neutrino, and the radiative gamma sometimes emitted in nuclear beta decay. Correlations involving three (out of four) momenta are sensitive at lowest order to different TRV physics than observables involving spin, such as electric dipole moments and spin-polarized beta decay correlations. Such experiments have been done in radiative kaon decay, but not in systems involving the lightest generation of quarks. An explicit low-energy physics model being tested produces TRV effects in the Fermi beta decay of the neutron, tritium, or some positron-decaying isotopes. We will present plans to measure the TRV asymmetry in radiative beta decay of laser-trapped 38mK at better than 0.01 sensitivity, including suppression of background from positron annihilation. Supported by NSERC, D.O.E., Israel Science Foundation. TRIUMF receives federal funding via a contribution agreement with the National Research Council of Canada.

Hiperbilirrubinemia neonatal agravada Aggravated neonatal hyperbilirubinemia

Directory of Open Access Journals (Sweden)

Ana Campo González

2010-09-01

Full Text Available INTRODUCCIÓN. La mayoría de las veces la ictericia en el recién nacido es un hecho fisiológico, causado por una hiperbilirrubinemia de predominio indirecto, secundario a inmadurez hepática e hiperproducción de bilirrubina. El objetivo de este estudio fue determinar el comportamiento de la hiperbilirrubinemia neonatal en el Hospital Docente Ginecoobstétrico de Guanabacoa en los años 2007 a 2009. MÉTODOS. Se realizó un estudio descriptivo y retrospectivo de 173 recién nacidos que ingresaron al Departamento de Neonatología con diagnóstico de hiperbilirrubinemia agravada. RESULTADOS. La incidencia de hiperbilirrubinemia neonatal agravada fue del 3,67 % y predominó en hermanos con antecedentes de ictericia (56,65 %. El tiempo de aparición fue de 48 a 72 h (76,87 % y entre los factores agravantes se hallaron el nacimiento pretérmino y el bajo peso al nacer. La mayoría de los pacientes fueron tratados con luminoterapia (90,17 %. CONCLUSIÓN. La hiperbilirrubinemia neonatal agravada constituye un problema de salud. Los factores agravantes son la prematuridad y el bajo peso al nacer. La luminoterapia es una medida terapéutica eficaz para su tratamiento.INTRODUCTION. Most of times jaundice in newborn is a physiological fact due to hyperbilirubinemia of indirect predominance, secondary to liver immaturity and to bilirubin hyperproduction. The aim of present of present study was to determine the behavior of neonatal hyperbilirubinemia in the Gynecology and Obstetrics Teaching Hospital of Guanabacoa municipality from 2007 to 2009. METHODS. A retrospective and descriptive study was conducted in 173 newborn patients admitted in the Neonatology Department diagnosed with severe hyperbilirubinemia. RESULTS. The incidence of severe neonatal hyperbilirubinemia was of 3,67% with predominance in brothers with a history of jaundice (56,65%. The time of appearance was of 48 to 72 hrs (76,87% and among the aggravating factors were the preterm birth and

Beta 3 and PDI proteins isolated from human platelets bind with ECwt rotavirus in vitro

International Nuclear Information System (INIS)

Mayorga, Diana; Rubio, Linda; Guerrero-Fonseca, Carlos A; Acosta-Losada, Orlando

2010-01-01

Commercial integrin Beta 3 is currently not available and commercial PDI is too expensive, which is making access difficult to these proteins needed for conducting experiments aimed at the establishment of possible interactions between integrin Beta 3 and PDI and wild type rotavirus strains. Objective. To explore a methodology allowing isolation of proteins Beta 3 and PDI from human platelets to be used as antigens in the generation of rabbit polyclonal antibodies useful in the assessment of interactions between these proteins and rotavirus ECwt. Materials and methods. Proteins Beta 3 and PDI from human platelet lysates were separated using preparative electrophoresis under reducing conditions and then eluted. Interactions of these proteins with rotavirus ECwt were analyzed using co-immunoprecipitation, Western blotting and capture ELISA. Results. Proteins from human platelet lysates were separated by preparative electrophoresis under reducing conditions. The identification of proteins Beta 3 and PDI present in a gel slice was performed through their reaction with commercial antibodies in a Western blotting analysis. Protein purity was established after electro elution from a gel slice. Polyclonal antibodies against protein Beta 3 were generated in rabbit. Incubation of eluted proteins Beta 3 and PDI with rotavirus ECwt showed in co-immunoprecipitation and ELISA assays that these proteins bound virus in vitro. The same binding was showed to occur when rotavirus was incubated with isolated small intestinal villi from suckling mice. Conclusions. Relatively high amounts of proteins Beta 3 and PDI were partially purified from human platelets by preparative electrophoresis. The isolation of these proteins allowed the generation of polyclonal antibodies against Beta 3 in addition to the establishment of the in vitro interaction of proteins Beta 3 and PDI with rotavirus ECwt. This interaction was also demonstrated in vivo after incubating the virus with isolated small

BETA (Bitter Electromagnet Testing Apparatus)

Science.gov (United States)

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

2017-10-01

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

Beyond Bullying: Aggravating Elements of Peer Victimization Episodes

Science.gov (United States)

Turner, Heather A.; Finkelhor, David; Shattuck, Anne; Hamby, Sherry; Mitchell, Kimberly

2015-01-01

This study sought to identify features of peer victimization that aggravate negative outcomes in children. The features that were assessed include "power imbalance," a commonly used criterion in defining bullying, and 5 other characteristics: injury, weapon involvement, Internet involvement, sexual content, and bias content. Three…

Development of biomarker specific of pancreatic beta cells (incretin radiolabelled) for image of beta functional mass in diabetic and obese: study in animal model

International Nuclear Information System (INIS)

Seo, Daniele

2017-01-01

Increased prevalence of obesity worldwide, has become a vast concern, stimulating investigations focusing prevention and therapy of this condition. The association of type 2 diabetes or insulin resistance aggravates the prognosis of obesity. Even patients successfully submitted to bariatric or metabolic surgery, may not be cured of diabetes, as improvement of circulating values of glucose and insulin not necessarily reflects recovery of pancreatic beta cell mass. There is no consensus about how to estimate beta cell mass in vivo. Available tools suffer from low sensitivity and specificity, often being as well cumbersome and expensive. Radiolabeled incretins, such as glucagon-like-peptide 1 (GLP-1) analogs, seem to be promising options for the measurement of beta cell mass in diabetes and insulinoma. The objective of this study was the development of two conjugates of GLP-1 analog, radiolabeled with 99m Technetium, as a noninvasive imaging method for the estimation of pancreatic beta cell mass, in the presence of obesity. Animal models were selected, including hyperlipidic diet-induced obesity, diet restricted obesity, and as controls, alloxan diabetes. Results indicated that both radiotracers achieved over 97% radiochemical yield. The most successful product was 99m Tc-HYNIC-βAla-Exendin-4. Low beta cell mass uptake occurred in diet-induced obesity. Diet-restricted obesity, with substantial shedding of excess body weight, was followed by remarkable decrease of fasting blood glucose, however beta cell mass uptake was only mildly improved. Future studies are recommended in obesity, type 2 diabetes, and dieting, including bariatric and metabolic operations. (author)

Spectrofluorimetric determination of stoichiometry and association constants of the complexes of harmane and harmine with beta-cyclodextrin and chemically modified beta-cyclodextrins.

Science.gov (United States)

Martín, L; León, A; Olives, A I; Del Castillo, B; Martín, M A

2003-06-13

The association characteristics of the inclusion complexes of the beta-carboline alkaloids harmane and harmine with beta-cyclodextrin (beta-CD) and chemically modified beta-cyclodextrins such as hydroxypropyl-beta-cyclodextrin (HPbeta-CD), 2,3-di-O-methyl-beta-cyclodextrin (DMbeta-CD) and 2,3,6-tri-O-methyl-beta-cyclodextrin (TMbeta-CD) are described. The association constants vary from 112 for harmine/DMbeta-CD to 418 for harmane/HPbeta-CD. The magnitude of the interactions between the host and the guest molecules depends on the chemical and geometrical characteristics of the guest molecules and therefore the association constants vary for the different cyclodextrin complexes. The steric hindrance is higher in the case of harmine due to the presence of methoxy group on the beta-carboline ring. The association obtained for the harmane complexes is stronger than the one observed for harmine complexes except in the case of harmine/TMbeta-CD. Important differences in the association constants were observed depending on the experimental variable used in the calculations (absolute value of fluorescence intensity or the ratio between the fluorescence intensities corresponding to the neutral and cationic forms). When fluorescence intensity values were considered, the association constants were higher than when the ratio of the emission intensity for the cationic and neutral species was used. These differences are a consequence of the co-existence of acid-base equilibria in the ground and in excited states together with the complexation equilibria. The existence of a proton transfer reaction in the excited states of harmane or harmine implies the need for the experimental dialysis procedure for separation of the complexes from free harmane or harmine. Such methodology allows quantitative results for stoichiometry determinations to be obtained, which show the existence of both 1:1 and 1:2 beta-carboline alkaloid:CD complexes with different solubility properties.

Selected aspects in the structure of beta-delayed particle spectra

International Nuclear Information System (INIS)

Honkanen, J.; Aeystoe, J.; Eskola, K.

1986-01-01

Some weak beta-delayed particle emitters in the T z =-3/2, -1, -1/2, +1/2 and +5/2 series are reviewed. Selected features of the delayed particle emission are discussed in terms of experimental delayed particle data and (p,γ), (p,p') and (p,n) reaction data. Experimental beta transition strengths are compared with the existing complete shell-model calculations for the sd-shell nuclei. The effect of the Gamow-Teller giant resonance on the structure of the delayed particle spectra is considered. The correlation between the widths of two decay channels, protons and alpha particles, and the preceeding beta decay is studied in the case of the 40 Sc decay. (orig.)

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.

Vitamin D depletion aggravates hypertension and target-organ damage

DEFF Research Database (Denmark)

Andersen, Louise Bjørkholt; Przybyl, Lukasz; Haase, Nadine

2015-01-01

BACKGROUND: We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin. METHODS AND RESULTS: Four-week-old double-transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (h......REN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P....6±3.3 versus 162.3±3.8 mm Hg, PVitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase-associated lipocalin, hREN, and r...

TGF-beta3 is expressed in taste buds and inhibits proliferation of primary cultured taste epithelial cells.

Science.gov (United States)

Nakamura, Shin-ichi; Kawai, Takayuki; Kamakura, Takashi; Ookura, Tetsuya

2010-01-01

Transforming growth factor-betas (TGF-betas), expressed in various tissues, play important roles in embryonic development and adult tissue homeostasis through their effects on cell proliferation, cell differentiation, cell death, and cell motility. However, expression of TGF-beta signaling components and their biological effect on taste epithelia has not been elucidated. We performed expression analysis of TGF-beta signaling components in taste epithelia and found that the TGF-beta3 mRNA was specifically expressed in taste buds. Type II TGF-betas receptor (TbetaR-II) mRNA was specifically expressed in the tongue epithelia including the taste epithelia. To elucidate the biological function of TGF-beta3 in taste epithelia, we performed proliferation assay with primary cultured taste epithelial cells. In the presence of TGF-beta3, percentage of BrdU-labeled cells decreased significantly, suggesting that the TGF-beta3 inhibited the proliferation of cultured taste epithelial cells through inhibiting cell-cycle entry into S phase. By quantitative reverse transcription-polymerase chain reaction assay, we found that the TGF-beta3 resulted in an increased level of expression of p15Ink4b and p21Cip1, suggesting that the TGF-beta3 inhibited the taste epithelial cell proliferation through inhibiting G1cyclin-Cdk complexes. Taken together, these results suggested that the TGF-beta3 may regulate taste epithelial cell homeostasis through controlling cell proliferation.

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

International Nuclear Information System (INIS)

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

1998-01-01

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

Preventive Effects of Beta-Hydroxy-Beta-Methyl Butyrate

OpenAIRE

N. Ravanbakhsh; N. Torabi; M. Foadoddini

2016-01-01

Aims: One of the major factors in sudden cardiac arrest is the initiation and continuation of deadly arrhythmias during ischemia. It is known that beta-hydroxy-beta-methylbutyrate (HMB) has useful effects such as anti-inflammatory and anti-apoptosis effects in the skeletal muscles. The aim of this study was to investigate the preventive effects of HMB on the ventricular arrhythmias due to the ischemia. Materials & Methods: In the experimental study, 30 Wistar male rats were randomly div...

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

DEFF Research Database (Denmark)

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

2004-01-01

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

Tables of double beta decay data

International Nuclear Information System (INIS)

Tretyak, V.I.

1995-01-01

A compilation of experimental data on double beta decay is presented. The tables contain the most stringent known experimental limits or positive results of 2β transitions of 69 natural nuclides to ground and excited states of daughter nuclei for different channels (2β - ; 2β + ; εβ + ; 2ε) and modes (0ν; 2ν; 0νM) of decay. (authors). 189 refs., 9 figs., 3 tabs

Beta and Gamma Gradients

DEFF Research Database (Denmark)

Løvborg, Leif; Gaffney, C. F.; Clark, P. A.

1985-01-01

Experimental and/or theoretical estimates are presented concerning, (i) attenuation within the sample of beta and gamma radiation from the soil, (ii) the gamma dose within the sample due to its own radioactivity, and (iii) the soil gamma dose in the proximity of boundaries between regions...... of differing radioactivity. It is confirmed that removal of the outer 2 mm of sample is adequate to remove influence from soil beta dose and estimates are made of the error introduced by non-removal. Other evaluations include variation of the soil gamma dose near the ground surface and it appears...... that the present practice of avoiding samples above a depth of 0.3 m may be over-cautious...

Diisononyl phthalate aggravates allergic dermatitis by activation of NF-kB.

Science.gov (United States)

Kang, Jun; Song, Jing; Shen, Shiping; Li, Baizhan; Yang, Xu; Chen, Mingqing

2016-12-20

Several epidemiological studies have suggested a possible link between exposure to Diisononyl phthalate (DINP) and the development of allergies. These findings remain controversial since there is insufficient scientific evidence to assess the ability of DINP to influence allergic immune responses. In addition, the mechanisms behind DINP-caused allergic diseases have not been fully elucidated. In this study, Balb/c mice were orally exposed to DINP for 3 weeks and were then sensitized with fluorescein isothiocyanate (FITC). We showed that oral exposure to DINP could aggravate allergic-dermatitis-like lesions, indicated by an increase in the number of mast cells, and in increased skin edema in FITC-induced contact hypersensitivity. This deterioration was concomitant with increased total serum immunoglobulin-E and Th2 cytokines. We determined the oxidative damage and the activation of nuclear factor-kb (NF-kB). The data demonstrated that DINP could promote oxidative damage and the activation of NF-kB in the skin. The expression of thymic stromal lymphopoietin and the activation of signal transducer and activator of transcriptions 3, 5 and 6 were enhanced concomitant with exacerbated allergic dermatitis effects and the activation of NF-kB induced by DINP. These effects were alleviated by pyrollidine dithiocarbamate, an inhibitor of NF-kB. The results suggest that oral exposure to DINP aggravated allergic contact dermatitis, which was positively regulated via NF-kB.

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

Science.gov (United States)

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

2007-06-07

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

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.

The neutrino mass from beta spectrum (ITEP-85)

International Nuclear Information System (INIS)

Lubimov, V.

1986-01-01

The new cycle of tritium beta spectrum measurements in valine with the ITEP spectrometer is discussed (ITEP-85). The detailed investigation of the total response function (TRF) has been performed. The special run of beta spectrum measurements carried out in a wide energy interval (3.4 KeV) has turned out to be a sensitive mode for the TRF experimental test. The results confirm the indication of the neutrino nonzero mass. 11 refs., 10 figs

On the nuclear double beta decay: microscopic description

International Nuclear Information System (INIS)

Civitarese, Osvaldo

1989-01-01

This paper is devoted to the discussion of some problems related with microscopic descriptions of the nuclear double beta decay. It has been organized in the following order: 1) Review of the experimental situation; 2) Brief discussion of the theoretical aspects related to the current algebra, weak interaction, neutrino and majoron's status and 3) Elements of the standard nuclear theory involved in the calculation of transition densities for the nuclear double beta decay. (Author) [es

Development of biomarker specific of pancreatic beta cells (incretin radiolabelled) for image of beta functional mass in diabetic and obese: study in animal model; Desenvolvimento de biomarcador específico de células beta pancreáticas (incretina radiomarcada) para imagem da massa beta funcional em diabéticos e obesos: estudo em modelo animal

Energy Technology Data Exchange (ETDEWEB)

Seo, Daniele

2017-07-01

Increased prevalence of obesity worldwide, has become a vast concern, stimulating investigations focusing prevention and therapy of this condition. The association of type 2 diabetes or insulin resistance aggravates the prognosis of obesity. Even patients successfully submitted to bariatric or metabolic surgery, may not be cured of diabetes, as improvement of circulating values of glucose and insulin not necessarily reflects recovery of pancreatic beta cell mass. There is no consensus about how to estimate beta cell mass in vivo. Available tools suffer from low sensitivity and specificity, often being as well cumbersome and expensive. Radiolabeled incretins, such as glucagon-like-peptide 1 (GLP-1) analogs, seem to be promising options for the measurement of beta cell mass in diabetes and insulinoma. The objective of this study was the development of two conjugates of GLP-1 analog, radiolabeled with {sup 99m} Technetium, as a noninvasive imaging method for the estimation of pancreatic beta cell mass, in the presence of obesity. Animal models were selected, including hyperlipidic diet-induced obesity, diet restricted obesity, and as controls, alloxan diabetes. Results indicated that both radiotracers achieved over 97% radiochemical yield. The most successful product was {sup 99m}Tc-HYNIC-βAla-Exendin-4. Low beta cell mass uptake occurred in diet-induced obesity. Diet-restricted obesity, with substantial shedding of excess body weight, was followed by remarkable decrease of fasting blood glucose, however beta cell mass uptake was only mildly improved. Future studies are recommended in obesity, type 2 diabetes, and dieting, including bariatric and metabolic operations. (author)

Headache characteristics of uncomplicated intracranial vertebral artery dissection and validation of ICHD-3 beta diagnostic criteria for headache attributed to intracranial artery dissection.

Science.gov (United States)

Kim, Jae-Gyum; Choi, Jeong-Yoon; Kim, Sung Un; Jung, Jin-Man; Kwon, Do-Young; Park, Moon Ho; Oh, Kyungmi

2015-05-01

Headache may be a warning sign of subsequent stroke in patients with vertebral artery dissection (VAD). Even though the headache characteristics of VAD have been described predominantly in patients with extracranial VAD and neurological complications, headache semiology is not well known in patients with uncomplicated intracranial vertebral artery dissection (ICVAD). In the present study, we attempt to identify the headache semiology that characterizes ICVAD and validate the revised version of the International Classification of Headache Disorders (ICHD-3 beta) criteria for headache attributed to intracranial artery dissection. Six patients with neurologically uncomplicated ICVAD presented at a participating medical center, and eight similar patients were reviewed in the literature. Combining these data, we analyzed headache characteristics of patients with uncomplicated ICVAD according to their pain onset and duration, nature, intensity, location, aggravating and relieving factors, associated symptoms, response to medication, and prognosis. Headache in uncomplicated ICVAD usually has an acute mode of onset (11/14) and persistent (10/14) temporal feature. Pain that has a throbbing quality (nine of 14) and severe intensity (13/14) on the ipsilesional (10/14) and occipitonuchal area (12/14) is a headache prototype in ICVAD. Additionally, headache was intensified by head flexion and rotation (three of six), and relieved by head extension and supine positioning (five of six). Headache of all patients in the present study fulfilled the ICHD-3 beta criteria. Headache semiology of uncomplicated ICVAD is mostly homogenous in the present study. These characteristics may be helpful in the diagnosis of uncomplicated ICVAD. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Iodine-123 labelled N-(2-fluoroethyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane for dopamine transporter imaging in the living human brain

Energy Technology Data Exchange (ETDEWEB)

Kuikka, J.T. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); AAkerman, K. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); Bergstroem, K.A. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); Karhu, J. [Dept. of Clinical Neurophysiology, Kuopio Univ. Hospital (Finland); Hiltunen, J. [MAP Medical Technologies Oy, Tikkakoski (Finland); Haukka, J. [MAP Medical Technologies Oy, Tikkakoski (Finland); Heikkinen, J. [Dept. of Clinical Physiology, Kuopio Univ. Hospital (Finland); Tiihonen, J. [Dept. of Forensic Psychiatry, Niuvanniemi Hospital, Kuopio (Finland); Wang, S. [Research Biochemical International (RBI), Natick, MA (United States); Neumeyer, J.L. [Research Biochemical International (RBI), Natick, MA (United States)

1995-07-01

Here we report a pilot comparison of [{sup 123}I]{beta}-CIT and [{sup 123}I]{beta}-CIT-FP with a new tropane derivative, [{sup 123}I]N-(2-fluoroethyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane ([{sup 123}I]{beta}-CIT-FE), using SPET imaging in four healthy male subjects. Peak uptake of [{sup 123}I]{beta}-CIT-FE into the basal ganglia occurred very rapidly (0.5 h after injection of tracer), after which the striatal washout obeyed a bi-exponential form. The specific DAT binding of [{sup 123}I]{beta}-CIT-FE into the basal ganglia was somewhat less (0.785{+-}0.117) than that of [{sup 123}I]{beta}-CIT (0.922{+-}0.004) or [{sup 123}I]{beta}-CIT-FP (0.813{+-}0.047). All these tracers have excellent imaging quality in healthy control subjects. However, the relatively fast washout of [{sup 123}I]{beta}-CIT-FE and low temporal resolution of older SPET cameras may limit the use of this tracer to the measurement of the DAT density. (orig./UG)

Rapid model building of beta-sheets in electron-density maps.

Science.gov (United States)

Terwilliger, Thomas C

2010-03-01

A method for rapidly building beta-sheets into electron-density maps is presented. beta-Strands are identified as tubes of high density adjacent to and nearly parallel to other tubes of density. The alignment and direction of each strand are identified from the pattern of high density corresponding to carbonyl and C(beta) atoms along the strand averaged over all repeats present in the strand. The beta-strands obtained are then assembled into a single atomic model of the beta-sheet regions. The method was tested on a set of 42 experimental electron-density maps at resolutions ranging from 1.5 to 3.8 A. The beta-sheet regions were nearly completely built in all but two cases, the exceptions being one structure at 2.5 A resolution in which a third of the residues in beta-sheets were built and a structure at 3.8 A in which under 10% were built. The overall average r.m.s.d. of main-chain atoms in the residues built using this method compared with refined models of the structures was 1.5 A.

Inducing and Aggravating Factors of Gastroesophageal Reflux Symptoms

Directory of Open Access Journals (Sweden)

Radhiyatam Mardhiyah

2016-12-01

Full Text Available Gastroesophageal reflux disease (subsequently abbreviated as GERD is a disease commonly found in the community. Several factors have been recognized as inducing and aggravating factors of GERD symptoms such as older age, female gender, obesity, smoking habit, alcohol consumption, certain diet and poor eating habit like eating fatty, spicy, and acid food.

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

Energy Technology Data Exchange (ETDEWEB)

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

2005-12-11

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

An experimental investigation of double beta decay of 100Mo

International Nuclear Information System (INIS)

Dougherty, B.L.

1988-01-01

New limits on half-lives for several double beta decay modes of 100 Mo were obtained with a novel experimental system which included thin source films interleaved with a coaxial array of windowless silicon detectors. Segmentation and timing information allowed backgrounds originating in the films to be studied in some detail. Dummy films containing 96 Mo were used to assess remaining backgrounds. With 0.1 mole years of 100 Mo data collected, the lower half-life limits at 90% confidence were 2.7 /times/ 10 18 years for decay via the two-neutrino mode, 5.2 /times/10 19 years for decay with the emission of a Majoron, and 1.6 /times/ 10 20 years and 2.2 /times/ 10 21 years for neutrinoless 0 + → 2 + and 0 + → 0 + transitions, respectively. 50 refs., 38 figs., 11 tabs

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

Science.gov (United States)

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

1966-02-01

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

Does gender activism aggravate the superiority of one gender over ...

African Journals Online (AJOL)

Does gender activism aggravate the superiority of one gender over the other? ... findings reveal that firstly, failure to value and embrace diversity by males, perpetuate gender discrimination. ... Keywords: Context, Culture, Structures, Systems ...

Aggravation by paroxetine, a selective serotonin reuptake inhibitor, of antral lesions generated by nonsteroidal anti-inflammatory drugs in rats.

Science.gov (United States)

Takeuchi, Koji; Tanaka, Akiko; Nukui, Kazuo; Kojo, Azusa; Gyenge, Melinda; Amagase, Kikuko

2011-09-01

Recent clinical studies have suggested a risk of adverse gastric reactions from the concomitant use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) with nonsteroidal anti-inflammatory drugs (NSAIDs). We examined the adverse effects of SSRIs on antral lesions produced by indomethacin in rats. Rats fasted for 24 h were refed for 1 h, then administered indomethacin (30 mg/kg s.c.) 1 h after the refeeding and killed 6 h later. Paroxetine (1-10 mg/kg) was given orally 30 min before indomethacin. Indomethacin caused antral lesions in refed rats. Paroxetine dose-dependently aggravated these lesions, despite provoking no damage by itself. Similar results were obtained when other NSAIDs such as diclofenac, flurbiprofen, and loxoprofen were coadministered with paroxetine or when indomethacin was coadministered with other antidepressants such as fluvoxamine and milnacipran, but not imipramine or maprotiline. Exogenous 5-HT also worsened the indomethacin-induced antral damage, whereas the aggravating effect of paroxetine was attenuated by ondansetron, a selective 5-HT(3) antagonist, but not antagonists for other 5-HT receptor subtypes. Indomethacin plus paroxetine had no effect on gastric secretion but significantly decreased mucosal superoxide dismutase (SOD) activity as well as GSH content. The antral damage induced by indomethacin plus paroxetine was significantly prevented by antisecretory (acid or pepsin) agents and mucosal protective agents as well as SOD and allopurinol. These results suggest that SSRIs aggravate NSAID-induced antral lesions, probably via the activation of 5HT(3) receptors, and the mechanism of aggravation may involve the corrosive action of acid/pepsin as well as an impaired antioxidative system.

Inhibition of Common Cold-Induced Aggravation of Childhood Asthma by Leukotriene Receptor Antagonists

OpenAIRE

Shigemi Yoshihara; Hironobu Fukuda; Toshio Abe; Mitsuhiro Nishida; Yumi Yamada; Noriko Kanno; Osamu Arisaka

2012-01-01

Background: : Virus infection is an important risk factor for aggravation of childhood asthma. The objective of this study was to examine the effect of drugs on aggravation of asthma induced by a common cold. Methods: : Asthma control was examined in a survey of 1,014 Japanese pediatric patients with bronchial asthma. The occurrence of common cold, asthma control, and drugs used for asthma control were investigated using a modified Childhood Asthma Control Test (C-ACT) for patients aged

Nuclear glycogen synthase kinase-3 {beta} (GSK-3) in Rhipicephalus (Boophilus) microplus tick embryogenesis

Energy Technology Data Exchange (ETDEWEB)

Mentzingen, Leticia; Andrade, Josiana G. de; Logullo, Carlos [Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF), Campos dos Goytacazes, RJ (Brazil). Centro de Biociencias e Biotecnologia. Lab. de Quimica e Funcao de Proteinas e Peptideos (LQFPP); Andrade, Caroline P. de; Vaz Junior, Itabajara [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil). Centro de Biotecnologia

2008-07-01

Full text: Glycogen synthase kinase-3 (GSK3) is recognized as a key component of a large number of cellular processes and diseases. Several mechanisms play a part in controlling the actions of GSK3, including phosphorylation, protein complex formation, and subcellular distribution. Recent observations point to functions for phosphorylases several transcription factors in the nucleus. Also, GSK3b participate of the canonical W nt signalling pathway, which has been studied intensively in embryonic and cancer cells. Like in many other signaling pathways, most components in W nt signal transduction were highly conserved during the evolution. More than 40 proteins have been reported to be phosphorylated by GSK3, including over a dozen transcription factors. Although the mechanisms regulating GSK3 are not fully understood, precise control appears to be achieved by a combination of phosphorylation, localization, and interactions with GSK3-binding proteins. Although GSK3 is traditionally considered a cytosolic protein, it is also present in nuclei. Nuclear GSK3 is particularly interesting because of the many transcription factors that it regulates enabling GSK3 to influence many signaling pathways that converge on these transcription factors, thereby regulating the expression of many genes. Our group identified that GSK-3 {beta} could be detected in different stage eggs of R. micro plus. In this work we detected the GSK-3 in isolated nuclear fraction from the egg homogenates of R. micro plus by western-blot analysis, using anti-GSK- 3 {beta} antibodies. The enzyme activity was also detected radiochemically throughout embryogenesis in same fraction. The GSK-3 activity was inhibiting by using SB 216763 (selective molecule inhibitors of GSK-3). Taken together our results suggest that GSK-3 {beta} isoform probably is involved in gene transcription factors during R. micro plus embryo development.

Deletion mutant defines DQ beta variants with DR4 positive DQw3 positive haplotypes

International Nuclear Information System (INIS)

Nepom, B.S.; Kim, S.J.; Nepom, G.T.

1986-01-01

We describe the production of an HLA deletion mutation by radiation mutagenesis of a DR4- and DQw3-homozygous, Dw4- and Dw14-heterozygous cell line designed to analyze polymorphisms associated with DR4 and DQw3. Southern blot analysis confirms a deletion of class I and class II genes on one haplotype. Variation in DQ beta alleles associated with DQw3 was previously described by characteristic RFLP patterns for a DQ beta bene. One pattern, which correlated precisely with A-10-83 monoclonal antibody reactivity (TA10), defined an allele which we call DQ''3.1''. The mutant cell line has lost the polymorphic bands on Southern blots corresponding to the DQ''3.1'' allele, while the intact Dw14 haplotype retains the alternate allele at DQ beta which is DQw-3 positive. TA10-negative. These data demonstrate the segregation of two DQw3 positive DQ beta allelic variants, both associated with DR4, which can be distinguished on the basis of both RFLP and monoclonal antibody reactivity

Calculation of {beta}-ray spectra. Odd-odd nuclei

Energy Technology Data Exchange (ETDEWEB)

Tachibana, Takahiro [Waseda Univ., Tokyo (Japan). Advanced Research Center for Science and Engineering

1996-05-01

In order to study {beta}-ray of atomic nucleus, it is natural to consider {beta}-ray data fundamental and important. In a recent experiment, Rudstam measured {beta}-ray spectra from short term nuclear fission product species in 1990. It is an important check point in theoretical study on {beta}-ray to investigate if these experimental data can be reproduced by any theoretical calculation. As there are several spectrum studies of {beta}-ray through decay heat for its various properties due to the general theory of the {beta}-decay, little descriptions can be found. In even such studies, spectra under high excitation state of daughter species difficult to measure and apt to short experimental results were treated with combination spectra composed of experimental and calculated values such as substitution of a part of the general theory with calculated value. In this paper, the {beta} spectra supposed by only the general theory was reported without using such data combination in order to confirm effectiveness of the theory. In particular, this report was described mainly on the results using recent modification of odd-odd nucleus species. (G.K.)

BetaShape: A new code for improved analytical calculations of beta spectra

Directory of Open Access Journals (Sweden)

Mougeot Xavier

2017-01-01

Full Text Available The new code BetaShape has been developed in order to improve the nuclear data related to beta decays. An analytical model was considered, except for the relativistic electron wave functions, for ensuring fast calculations. Output quantities are mean energies, log ft values and beta and neutrino spectra for single and multiple transitions. The uncertainties from the input parameters, read from an ENSDF file, are propagated. A database of experimental shape factors is included. A comparison over the entire ENSDF database with the standard code currently used in nuclear data evaluations shows consistent results for the vast majority of the transitions and highlights the improvements that can be expected with the use of BetaShape.

Selenium deficiency aggravates T-2 toxin-induced injury of primary neonatal rat cardiomyocytes through ER stress.

Science.gov (United States)

Xu, Jing; Pan, Shengchi; Gan, Fang; Hao, Shu; Liu, Dandan; Xu, Haibin; Huang, Kehe

2018-04-01

Keshan disease is a potentially fatal cardiomyopathy in humans. Selenium deficiency, T-2 toxin, and myocarditis virus are thought to be the major factors contributing to Keshan disease. But the relationship among these three factors is poorly described. This study aims to explore whether selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury and its underlying mechanism. Cardiomyocytes were isolated from neonatal rat and cultured at the physiological (2.0 μM) or lower concentrations of selenium with different concentrations of T-2 toxin. Our results showed that selenium deficiencies aggravated T-2 toxin-induced cardiomyocyte injury in a concentration-dependent manner as demonstrated by MTT bioassay, LDH activity, reactive oxygen species levels and caspase 3 protein expressions. T-2 toxin treatment significantly increased mRNA expressions for stress proteins GRP78 and CHOP in cardiomyocytes compared with the control. Selenium deficiencies further promoted GRP78, CHOP and p-eIF2α expressions. Knockdown of CHOP by the specific small interfering RNA eliminated the effect of selenium deficiencies on T-2 toxin-induced injury. It could be concluded that selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury through initiating more aggressive endoplasmic reticulum stress. Copyright © 2018 Elsevier B.V. All rights reserved.

Experimental observations of MHD instabilities in the high-beta tokamak Torus-II

International Nuclear Information System (INIS)

Machida, M.

1982-01-01

The CO 2 laser scattering and interferometry diagnostics have been used to study the MHD instabilities in the high-beta tokamak Torus-II. Detailed measurements of the density and density fluctuation profiles have been performed. In order to measure density fluctuations with wavelengths longer than 2 cm, an interferometric like, phase matching technique has been developed. The toroidal and poloidal mode numbers have been measured using a double-beam, two-position technique. Working at high-beta values, average β greater than or equal to 10%, we have found parameters where the growing instabilities are created or suppressed. The plasma lifetime for both cases is seen to be about the same and the loss of the plasma appears to be caused by the decay in the external fields. The growing instability parameters are within the MHD regime, and it only grows at the outer edge of the plasma. This is in agreement with the theoretical Ballooning mode instability. The frequency and mode number measurements also agree with the Kinetic theory description of Ballooning modes. The comparison with possible other modes, such as Tearing and Drift instabilities, is performed and the Ballooning growth rate is shown to be the best fit to the experimental values

BETASCAN: probable beta-amyloids identified by pairwise probabilistic analysis.

Directory of Open Access Journals (Sweden)

Allen W Bryan

2009-03-01

Full Text Available Amyloids and prion proteins are clinically and biologically important beta-structures, whose supersecondary structures are difficult to determine by standard experimental or computational means. In addition, significant conformational heterogeneity is known or suspected to exist in many amyloid fibrils. Recent work has indicated the utility of pairwise probabilistic statistics in beta-structure prediction. We develop here a new strategy for beta-structure prediction, emphasizing the determination of beta-strands and pairs of beta-strands as fundamental units of beta-structure. Our program, BETASCAN, calculates likelihood scores for potential beta-strands and strand-pairs based on correlations observed in parallel beta-sheets. The program then determines the strands and pairs with the greatest local likelihood for all of the sequence's potential beta-structures. BETASCAN suggests multiple alternate folding patterns and assigns relative a priori probabilities based solely on amino acid sequence, probability tables, and pre-chosen parameters. The algorithm compares favorably with the results of previous algorithms (BETAPRO, PASTA, SALSA, TANGO, and Zyggregator in beta-structure prediction and amyloid propensity prediction. Accurate prediction is demonstrated for experimentally determined amyloid beta-structures, for a set of known beta-aggregates, and for the parallel beta-strands of beta-helices, amyloid-like globular proteins. BETASCAN is able both to detect beta-strands with higher sensitivity and to detect the edges of beta-strands in a richly beta-like sequence. For two proteins (Abeta and Het-s, there exist multiple sets of experimental data implying contradictory structures; BETASCAN is able to detect each competing structure as a potential structure variant. The ability to correlate multiple alternate beta-structures to experiment opens the possibility of computational investigation of prion strains and structural heterogeneity of amyloid

Radioresistance of experimentally-produced hybrid of Indian spinach (Beta palonga Basu and Mukherjee)

International Nuclear Information System (INIS)

Mukherjee, K.K.; Basu, R.K.

1975-01-01

An experimentally-produced hybrid between red and green plants of Beta palonga and the segregating population in F 2 showed more resistance to acute X-irradiation of seed than did their parents, as measured by seed germination, plant height, abnormal plant growth, chromosomal abnormality during meiosis and pollen grain sterility. In every measurement the F 2 plants were more sensitive than the F 1 hybrid. The radiosensitivity could not be interpreted in terms of average interphase chromosome volume. The resistance of the hybrid is suggested to be due to factors associated with heterozygosity and heterosis, although this has not been definately established. (author)

Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

DEFF Research Database (Denmark)

Holler, Jon G; Brandt, Christian T; Leib, Stephen L

2014-01-01

BACKGROUND: The hippocampus undergoes apoptosis in experimental pneumococcal meningitis leading to neurofunctional deficits in learning and memory function. The aim of the present study was 1) to investigate hippocampal apparent diffusion coefficient (ADC) and volume with MRI during the course...... and the volume and size of brain ventricles were positively correlated (Spearman Rank, p volume and the extent of apoptosis (p > 0.05). CONCLUSIONS: In experimental meningitis increase in volume and water diffusion of the hippocampus are significantly...... of experimental pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia on hippocampal water distribution and volume, 3) and to correlate these findings to the extent of apoptosis in the hippocampus. METHODS: Experimental meningitis in rats was induced by intracisternal injection of live...

Localisation of Neuregulin 1-{beta}3 to different sub-nuclear structures alters gene expression

Energy Technology Data Exchange (ETDEWEB)

Wang, Ming; Trim, Carol M.; Gullick, William J., E-mail: w.j.gullick@kent.ac.uk

2011-02-15

Neuregulins are growth factors that signal via the ErbB3 and ErbB4 receptors. Here we show using immunohistochemistry that they are often expressed in the nucleus of a range of tumour types including soft tissue and breast. The Neuregulin 1 type I-{beta}3 (NRG1-{beta}3) isoform localises to two sub-nuclear compartments in animal cells, nucleoli and spliceosomes. We used NRG1-{beta}3 tagged with photoactivatable GFP and demonstrated that this re-localised from nucleoli to spliceosomes over 90 min. Tyrosine kinase activity was not required for retaining the NRG1-{beta}3 within the nucleus. Mutation of the lysines 14 and 16 or 15 and 16 together prevented nucleolar uptake while four positively charged residues were identified which were required for spliceosome uptake. Molecular modelling suggests that three of these may form a binding site. We showed using a kinome array that NRG1-{beta}3 and a mutant exclusively localising to spliceosomes increased phosphorylation and/or expression of the HER4 and HER2 receptors. Using a transcriptomic analysis the same two constructs induced expression of several messenger RNAs and we confirmed the increased expression at the protein level of the most highly induced, Heat Shock Protein 70B'. These results suggest that Neuregulin activates receptor signalling in spliceosomes leading to altered gene expression.

Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice.

Science.gov (United States)

Jia, Yingli; He, Jinzhao; Wang, Liang; Su, Limin; Lei, Lei; Huang, Wei; Geng, Xiaoqiang; Zhang, Shun; Meng, Xiaolu; Zhou, Hong; Yang, Baoxue

2018-01-01

A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson's trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver. These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis. © 2018 The Author(s). Published by S. Karger AG, Basel.

Initial experience with single-photon emission tomography using iodine-123-labelled 2[beta]-carbomethoxy-3[beta](4-iodophnyl)tropane in human brain

Energy Technology Data Exchange (ETDEWEB)

Kuikka, J T [Kuopio Univ. Hospital (Finland). Dept. of Clinical Physiology; Bergstroem, K A [Kuopio Univ. Hospital (Finland). Dept. of Clinical Physiology; Vanninen, E [Kuopio Univ. Hospital (Finland). Dept. of Clinical Physiology; Laulumaa, V [Kuopio Univ. Hospital (Finland). Dept. of Neurology; Hartikainen, P [Kuopio Univ. Hospital (Finland). Dept. of Neurology; Laensimies, E [Kuopio Univ. Hospital (Finland). Dept. of Clinical Physiology

1993-09-01

The iodinated cocaine analogue 2[beta]-carbomethoxy-3[beta]-(4-iodophenyl)tropane ([sup 123]I[beta]-CIT), a new dopamine transporter, was preliminarily tested in human brain. Two normal volunteers and two patients with Parkinson's disease were imaged with a high-resolution single-photon emission tomography scanner. The specific binding of [sup 123]I[beta]-CIT in the basal ganglia and thalamus was high in normal volunteers. In addition, there was relatively intense uptake in the medial prefrontal area. Patients with Parkinson's disease who were older than controls showed significantly lower specific binding in the basal ganglia and thalamus and no uptake in the medial prefrontal cortex. This decrease in the dopamine transporter may be age related. (orig.)

Partial synthesis of (3R,6'R)-alpha-cryptoxanthin and (3R)-beta-cryptoxanthin from (3R,3'R,6'R)-lutein.

Science.gov (United States)

Khachik, Frederick; Chang, An-Ni; Gana, Audry; Mazzola, Eugene

2007-02-01

(3R,3'R,6'R)-Lutein (1), (3R,3'R)-zeaxanthin (2), (3R,6'R)-alpha-cryptoxanthin (3), and (3R)-beta-cryptoxanthin (4) are among dietary hydroxycarotenoids that have been identified in human serum, milk, and ocular tissues. While 1 containing 6% of 2 is commercially available, industrial production of optically active 3 and 4 has not yet been accomplished. Several processes have been developed that transform 1 into 3, 4, and minor quantities of (3R,5'RS,6'R)-3',4'-didehydro-5',6'-dihydro-beta,beta-caroten-3-ol (5) (a regioisomer of 3). In one process, lutein (1) was cleanly deoxygenated to 3 in the presence of trifluoroacetic acid (TFA) and Me3N.BH3 in CH2Cl2 at ambient temperature in nearly 90% yield. Reaction of lutein (1) with a Lewis acid (AlCl3, ZnBr2, ZnI2) and a hydride donor (Me3N.BH3, Na[BH3(OCOCF3)], NaCNBH3) in solvents such as CH2Cl2, THF, and TBME produced similar results. In a two-step process, high-temperature acid-catalyzed dehydration of 1 (propanol/water/acid, 90 degrees C) gave a mixture of anhydroluteins 6, 7, and 8 in 86% yield. In the second step, these dehydration products underwent ionic hydrogenation with TFA/Me3N.BH3 in CH2Cl2 to afford a mixture of 3 and 4 in nearly 80% yield that contained only 1% of 5.

A novel beta-adrenoceptor ligand for positron emission tomography : Evaluation in experimental animals

NARCIS (Netherlands)

van Waarde, A; Elsinga, PH; Doze, P; Heldoorn, M; Jaeggi, KA; Vaalburg, W

1998-01-01

Myocardial and pulmonary beta-adrenoceptors can be imaged and quantified with the antagonist (S)-4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-[C-11]-one (S-[C-11]CGP-12177). The synthesis of this ligand (based on the reaction of a precursor with [C-11]phosgene) is

Neuronal IFN-beta-induced PI3K/Akt-FoxA1 signalling is essential for generation of FoxA1(+)Treg cells

DEFF Research Database (Denmark)

Liu, Yawei; Marin, Andrea; Ejlerskov, Patrick

2017-01-01

Neurons reprogramme encephalitogenic T cells (Tenc) to regulatory T cells (Tregs), either FoxP3(+)Tregs or FoxA1(+)Tregs. We reported previously that neuronal ability to generate FoxA1(+)Tregs was central to preventing neuroinflammation in experimental autoimmune encephalomyelitis (EAE). Mice...... lacking interferon (IFN)-β were defective in generating FoxA1(+)Tregs in the brain. Here we show that lack of neuronal IFNβ signalling is associated with the absence of programme death ligand-1 (PDL1), which prevents their ability to reprogramme Tenc cells to FoxA1(+)Tregs. Passive transfer-EAE via IFNβ......-competent Tenc cells to mice lacking IFNβ and active induced-EAE in mice lacking its receptor, IFNAR, in the brain (Nes(Cre):Ifnar(fl/fl)) result in defective FoxA1(+)Tregs generation and aggravated neuroinflammation. IFNβ activates neuronal PI3K/Akt signalling and Akt binds to transcription factor FoxA1...

Identification of a novel group of putative Arabidopsis thaliana beta-(1,3)-galactosyltransferases

DEFF Research Database (Denmark)

Qu, Yongmei; Egelund, Jack; Gilson, Paul R

2008-01-01

To begin biochemical and molecular studies on the biosynthesis of the type II arabinogalactan chains on arabinogalactan-proteins (AGPs), we adopted a bioinformatic approach to identify and systematically characterise the putative galactosyltransferases (GalTs) responsible for synthesizing the beta......-(1,3)-Gal linkage from CAZy GT-family-31 from Arabidopsis thaliana. These analyses confirmed that 20 members of the GT-31 family contained domains/motifs typical of biochemically characterised beta-(1,3)-GTs from mammalian systems. Microarray data confirm that members of this family are expressed......,3)-GalT activity. This bioinformatic/molecular study of CAZy GT-family-31 was validated by the recent report of Strasser et al. (Plant Cell 19:2278-2292, 2007) that another member of this family (At1g26810; GALT1) encodes a beta-(1,3)-GalT involved in the biosynthesis of the Lewis a epitope of N...

Delayed diagnosis of congenital adrenal hyperplasia with salt wasting due to type II 3beta-hydroxysteroid dehydrogenase deficiency

DEFF Research Database (Denmark)

Johannsen, Trine H; Mallet, Delphine; Dige-Petersen, Harriet

2005-01-01

Classical 3beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency is a rare cause of congenital adrenal hyperplasia. We report two sisters presenting with delayed diagnoses of classical 3beta-HSD, despite salt wasting (SW) episodes in infancy. Sibling 1 was referred for premature pubarche, slig...

Enantioselective synthesis of the novel chiral sulfoxide derivative as a glycogen synthase kinase 3beta inhibitor.

Science.gov (United States)

Saitoh, Morihisa; Kunitomo, Jun; Kimura, Eiji; Yamano, Toru; Itoh, Fumio; Kori, Masakuni

2010-09-01

Glycogen synthase kinase 3beta (GSK-3beta) inhibitors are expected to be attractive therapeutic agents for the treatment of Alzheimer's disease (AD). Recently we discovered sulfoxides (S)-1 as a novel GSK-3beta inhibitor having in vivo efficacy. We investigated practical asymmetric preparation methods for the scale-up synthesis of (S)-1. The highly enantioselective synthesis of (S)-1 (94% ee) was achieved by titanium-mediated oxidation with D-(-)-diethyl tartrate on gram scale.

Residential characteristics aggravating infestation by Culex quinquefasciatus in a region of Northeastern Brazil

Directory of Open Access Journals (Sweden)

Juliana Cavalcanti Correia

2012-12-01

Full Text Available OBJECTIVE: Analyse how basic sanitation conditions, water supply and housing conditions affect the concentration of Culex quinquefasciatus METHODS: Populations of C. quinquefasciatus in 61 houses in the municipality of Olinda, PE, were monitored between October 2009 and October 2010. Observations were carried out in homes without the presence of preferred breeding sites in order to identify characteristics that may be aggravating factors for the development of the mosquito. Five aggravating factors were analysed: vegetation cover surrounding the home, number of residents/home, water storage, sewage drainage and water drainage. These characteristics were analysed in terms of presence or absence and as indicators of the degree of infestation, which was estimated through monitoring the concentration of eggs (oviposition traps - BR-OVT and adults (CDC light traps. RESULTS: Sewage drainage to a rudimentary septic tank or to the open air was the most frequent aggravating factor in the homes (91.8%, although the presence of vegetation was the only characteristic that significantly influenced the increase in the number of egg rafts (p = 0.02. The BR-OVT achieved positive results in 95.1% of the evaluations, with the presence of at least one egg raft per month. A total of 2,366 adults were caught, with a mosquito/room/night ratio of 32.9. No significant difference was found in the number of mosquitoes caught in the homes. CONCLUSIONS: Although the sanitation and water supply influence the population density of C. quinquefasciatus, residence features that are not usually considered in control measures can be aggravating factors in sustaining the mosquito population.

Dependence of the DIII-D beta limit on the current profile

Energy Technology Data Exchange (ETDEWEB)

Strait, E.J.; Chu, M.S.; Ferron, J.R.; Lao, L.L.; Osborne, T.H.; Taylor, T.S.; Turnbull, A.D. (General Atomics, San Diego, CA (United States)); Lazarus, E.A. (Oak Ridge National Lab., TN (United States))

1991-01-01

The maximum beta values achieved in DIII-D are not fully described by the simple scaling law [beta][sub max][proportional to]I/aB. There is, in addition, a dependence on the form of the current profile as parameterized by the safety factor q and internal inductance l[sub i]. The maximum experimentally achieved value of normalized beta [beta][sub N] = [beta]/(I/aB) varies from 3.5 at low safety factor q (q[sub 95]<3) to 5 at higher values of q. At low q, discharges are terminated by disruptions at high [beta][sub N] and at both the low and high l[sub i] boundaries of the stable range. These disruptions are attributed to external and global kink modes. At higher q, such disruptions are much less frequent, and beta is limited by slowly growing resistive modes, fishbones, and possibly by ballooning modes. At each value of q, the maximum beta tends to increase with internal inductance l[sub i]. A numerical study of kink mode stability has shown a similar trend for optimized pressure profiles. These observations have suggested a new scaling law for the operational beta limit: [beta][sub max]=4l[sub i](I/aB), which fits the DIII-D data well. (author) 13 refs., 4 figs.

Does simultaneous bilingualism aggravate children's specific language problems?

Science.gov (United States)

Korkman, Marit; Stenroos, Maria; Mickos, Annika; Westman, Martin; Ekholm, Pia; Byring, Roger

2012-09-01

There is little data on whether or not a bilingual upbringing may aggravate specific language problems in children. This study analysed whether there was an interaction of such problems and simultaneous bilingualism. Participants were 5- to 7-year-old children with specific language problems (LANG group, N = 56) or who were typically developing (CONTR group, N = 60). Seventy-three children were Swedish-Finnish bilingual and 43 were Swedish-speaking monolingual. Assessments (in Swedish) included tests of expressive language, comprehension, repetition and verbal memory. Per definition, the LANG group had lower scores than the CONTR group on all language tests. The bilingual group had lower scores than the monolingual group only on a test of body part naming. Importantly, the interaction of group (LANG or CONTR) and bilingualism was not significant on any of the language scores. Simultaneous bilingualism does not aggravate specific language problems but may result in a slower development of vocabulary both in children with and without specific language problems. Considering also advantages, a bilingual upbringing is an option also for children with specific language problems. In assessment, tests of vocabulary may be sensitive to bilingualism, instead tests assessing comprehension, syntax and nonword repetition may provide less biased methods. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

Status of double beta decay experiments using isotopes other than 136Xe

Science.gov (United States)

Pandola, L.

2014-09-01

Neutrinoless double beta decay is a lepton-number violating process predicted by many extensions of the standard model. It is actively searched for in several candidate isotopes within many experimental projects. The status of the experimental initiatives which are looking for the neutrinoless double beta decay in isotopes other than 136Xe is reviewed, with special emphasis given to the projects that passed the R&D phase. The results recently released by the experiment GERDA are also summarized and discussed. The GERDA data give no positive indication of neutrinoless double beta decay of 76Ge and disfavor in a model-independent way the long-standing observation claim on the same isotope. The lower limit reported by GERDA for the half-life of neutrinoless double beta decay of 76Ge is T1/20ν > 2.1 ṡ1025 yr (90% C.L.), or T1/20ν > 3.0 ṡ1025 yr, when combined with the results of other 76Ge predecessor experiments.

Influencia de la betarraga (Beta vulgaris var. cruenta en el aumento de leucocitos, en ratones

Directory of Open Access Journals (Sweden)

Jony Amaro

2014-01-01

Full Text Available Introducción: La betarraga es una planta oriunda del Mediterráneo utilizada para fines alimenticios y medicinales. Contiene flavonoides. Objetivos: Determinar la influencia del consumo del extracto de Beta vulgaris var. cruenta en el incremento de leucocitos, en el ratón albino. Diseño: Estudio experimental. Lugar: Bioterio de la Institución Educativa 1182. Material biológico: Veinte ratones albinos de la cepa balb/c, machos, de peso promedio 24 g. Intervenciones: Se formó dos grupos, experimental y control, cada uno de diez ratones. Al grupo experimental se le administró vía oral extracto de Beta vulgaris var. cruenta en dosis de 250 mg/kg, volumen de 2 mL, cada cinco horas durante una semana, alternando con nutrientes, y al grupo control solo se le administró nutrientes. Principales medidas de resultados: Recuento de leucocitos. Resultados: Dentro del periodo de acondicionamiento, se observó un ligero incremento en la media de leucocitos del grupo control (3 681 ± 431,1 frente al grupo experimental (3 579 ± 473,5, cuya diferencia no fue significativa. Luego de administrar al grupo experimental el extracto de Beta vulgaris var. cruenta, alternando con sus nutrientes respectivos, se observó diferencia significativa de la media (7 961 ± 275,4 frente al grupo control (3 693 ± 414,7 (t student p<0,05. Conclusiones: En condiciones experimentales, el consumo del extracto de Beta vulgaris var. cruenta incrementó significativamente el número de leucocitos.

Role of leucine in isoprenoid metabolism. Incorporation of (3-/sup 13/C)leucine and of (2-/sup 3/H,4-/sup 14/C)-. beta. ,. beta. -dimethyl-acrylic acid into phytosterols by tissue cultures of Andrographis paniculata

Energy Technology Data Exchange (ETDEWEB)

Anastasis, P; Freer, I; Overton, K; Rycroft, D; Singh, S B [Glasgow Univ. (UK). Dept. of Chemistry

1985-02-01

(3-/sup 13/C)Leucine is incorporated into phytosterols by tissue cultures of Andrographis paniculata by breakdown to acetyl-CoA and its subsequent incorporation via (3S)-3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) and mevalonic acid; (2-/sup 3/H,4-/sup 14/C)-..beta..,..beta..-dimethylacrylic acid also is not incorporated intact.

Beta adrenoreceptors in the rabbit bladder detrusor muscle

Energy Technology Data Exchange (ETDEWEB)

Anderson, G.F.; Marks, B.H.

1984-02-01

This study examines the beta adrenergic receptors of the rabbit detrusor smooth muscle, employing (/sup 125/I)iodocyanopindolol (ICYP) as a ligand for the binding of beta adrenergic receptors. Saturation binding experiments on the isolated membrane fraction yielded a KD for ICYP of 14.7 pM and a maximum binding of 147.6 fmol/mg of protein. Displacement of labeled ICYP by a series of beta adrenergic agents yielded the following KD values for the combined high and low affinity binding sites: I-propranolol, 0.76 nM; ICI 118,551, 1.7 nM; zinterol, 38.0 nM; metoprolol, 3.5 microM; and practolol, 61.4 microM. When these displacement experimental results were compared to KD values from other reported binding studies with ICYP for beta adrenoreceptors, both the order of potency and the KD values indicated primarily beta-2 adrenergic receptor subtypes. Computer program Scatfit analysis of the displacement curves indicated a single slope and affinity constant for all five beta adrenergic agents. Hofstee plots for zinterol, ICI 118,551 and metoprolol, however, were not linear and indicated that minor populations of beta-1 adrenoreceptors were also present as both high and low affinity binding sites could be defined. It is concluded that the primary receptor population is beta-2 and that this tissue is heterogenous with a small population of beta-1 adrenoreceptors representing approximately 13 to 23% of the total beta adrenoreceptor population.

Beta adrenoreceptors in the rabbit bladder detrusor muscle

International Nuclear Information System (INIS)

Anderson, G.F.; Marks, B.H.

1984-01-01

This study examines the beta adrenergic receptors of the rabbit detrusor smooth muscle, employing [ 125 I]iodocyanopindolol (ICYP) as a ligand for the binding of beta adrenergic receptors. Saturation binding experiments on the isolated membrane fraction yielded a KD for ICYP of 14.7 pM and a maximum binding of 147.6 fmol/mg of protein. Displacement of labeled ICYP by a series of beta adrenergic agents yielded the following KD values for the combined high and low affinity binding sites: I-propranolol, 0.76 nM; ICI 118,551, 1.7 nM; zinterol, 38.0 nM; metoprolol, 3.5 microM; and practolol, 61.4 microM. When these displacement experimental results were compared to KD values from other reported binding studies with ICYP for beta adrenoreceptors, both the order of potency and the KD values indicated primarily beta-2 adrenergic receptor subtypes. Computer program Scatfit analysis of the displacement curves indicated a single slope and affinity constant for all five beta adrenergic agents. Hofstee plots for zinterol, ICI 118,551 and metoprolol, however, were not linear and indicated that minor populations of beta-1 adrenoreceptors were also present as both high and low affinity binding sites could be defined. It is concluded that the primary receptor population is beta-2 and that this tissue is heterogenous with a small population of beta-1 adrenoreceptors representing approximately 13 to 23% of the total beta adrenoreceptor population

GSK-3β Inhibition Attenuates LPS-Induced Death but Aggravates Radiation-Induced Death via Down-Regulation of IL-6

Directory of Open Access Journals (Sweden)

Bailong Li

2013-12-01

Full Text Available Background: Exposure of high dose ionizing radiation is lethal. Signal pathways involved in radiation biology reaction still remain illdefined. Lipopolysaccharides (LPS, the ligands of Toll-like receptor 4(TLR4, could elicit strong immune responses. Glycogen synthase kinase-3β(GSK-3β promotes the production of inflammatory molecules and cell migration. Inhibition of GSK-3β provides protection against inflammation in animal models. The aim of the study was to investigate role of GSK-3β in LPS shock and ionizing radiation. Methods: WT or IL-6-/-mice or cells were pretreated with SB216763, a GSK-3β inhibitor, and survival of the mice was determined. Cell viability was assayed by Cell Counting Kit. Apoptosis was assayed by Annexin V-PI double staining. Serum concentrations of IL-6 and TNF-α were determined by ELISA. Results: SB216763 attenuated LPS induced mice or cell death but aggravated radiation induced mice or cell death. SB216763 reduced IL-6, but not TNF-α levels in vivo. IL-6-/- mice were more resistant to LPS-induced death but less resistant to radiation-induced death than wild type mice. Conclusions: Inhibition of GSK-3β conferred resistance to LPS shock but fostered death induced by ionizing radiation. Inhibition of GSK-3β was effective by reducing IL-6.

Design and production of sintered {beta}-tricalcium phosphate 3D scaffolds for bone tissue regeneration

Energy Technology Data Exchange (ETDEWEB)

Santos, Carlos F.L. [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Silva, Abilio P. [Centro de Ciencia e Tecnologia Aeroespaciais, Universidade da Beira Interior, Covilha (Portugal); Lopes, Luis [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Pires, Ines [Instituto de Engenharia Mecanica - Lisboa (IDMEC Lisboa/IST/UTL), Avenida Rovisco Pais, 1049-001 Lisboa (Portugal); Correia, Ilidio J., E-mail: icorreia@ubi.pt [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

2012-07-01

The characteristics of sintered {beta}-tricalcium phosphate ({beta}-TCP) scaffolds produced by 3D printing were studied by means of X-ray diffraction, Scanning Electron Microscopy, Fourier transform infrared spectroscopy, uniaxial compression tests and cytotoxicity tests, using human osteoblast cells. The results reported include details of the {beta}-TCP scaffolds' porosity, density, phase stability, mechanical behavior and cytotoxic profile. Collectively, these properties are fundamental for the future application of these scaffolds as bone substitutes for individualized therapy. Highlights: Black-Right-Pointing-Pointer {beta}-Tricalcium phosphate ({beta}-TCP) 3D scaffolds were produced by rapid prototyping. Black-Right-Pointing-Pointer Scaffold properties were assessed by SEM, FTIR, XRD and by mechanical tests. Black-Right-Pointing-Pointer The cytotoxic profile of the scaffolds was characterized by in vitro assays. Black-Right-Pointing-Pointer Scaffolds have good properties for its application as bone substitutes for individualized therapy.

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.

Preparation of [3beta-3H] labeled bile acids and bile alcohols

International Nuclear Information System (INIS)

Dayal, B.; Baga, E.; Tint, G.S.; Shefer, S.; Salen, G.

1979-01-01

[3beta-3H]-bile acids and bile alcohols may be useful for metabolic studies in man and animals because the 3-position is invulnerable to bacterial attack. A number of tritium labeled bile acids and bile alcohols were prepared by selective oxidation of the hydroxyl group at carbon-3 followed by reduction with NaBT4. In each case, the bile acids and bile alcohols epimeric at carbon-3 were resolved by analytical and preparative thin-layer chromatography and characterized by gas liquid chromatography. The average yield was 60 to 65% and specific activities of the final products were in the range of 7.4 x 10 7 dpm/mg

Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

Science.gov (United States)

Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A.; Ghosh, Partha Pratim; Mitra, Prasenjit

2016-06-01

Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation.

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

Science.gov (United States)

Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W.; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S.; Troncoso, Patricia; Maity, Sankar N.; Navone, Nora M.

2012-01-01

Purpose To study Wnt/beta-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the beta-catenin–androgen receptor (AR) interaction. Experimental Design We performed beta-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of beta-catenin–mediated transcription), and sequenced the beta-catenin gene in MDA PCa 118a, MDA PCa 118b, MDA PCa 2b, and PC-3 prostate cancer (PCa) cells. We knocked down beta-catenin in AR-negative MDA PCa 118b cells and performed comparative gene-array analysis. We also immunohistochemically analyzed beta-catenin and AR in 27 bone metastases of human CRPCs. Results Beta-catenin nuclear accumulation and TOP-flash reporter activity were high in MDA PCa 118b but not in MDA PCa 2b or PC-3 cells. MDA PCa 118a and 118b cells carry a mutated beta-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA PCa 118b cells with downregulated beta-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant beta-catenin. Finally, we found nuclear localization of beta-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher’s exact test), suggesting that reduced AR expression enables Wnt/beta-catenin signaling. Conclusion We identified a previously unknown downstream target of beta-catenin, HAS2, in PCa, and found that high beta-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone-metastatic PCa. These findings may guide physicians in managing these patients. PMID:22298898

Moderate alcohol consumption aggravates high fat-diet induced steatohepatitis in rats

Science.gov (United States)

Background: Nonalcoholic steatohepatitis (NASH) develops in the absence of chronic and excessive alcohol consumption. However, it remains unknown whether moderate alcohol consumption aggravates liver inflammation in pre-existing NASH condition. Methods: Sprague-Dawley rats were first fed ad libitum...

Tissue-specific and pathogen-induced regulation of a Nicotiana plumbaginifolia beta-1,3-glucanase gene.

Science.gov (United States)

Castresana, C; de Carvalho, F; Gheysen, G; Habets, M; Inzé, D; Van Montagu, M

1990-01-01

The Nicotiana plumbaginifolia gn1 gene encoding a beta-1,3-glucanase isoform has been characterized. The gn1 product represents an isoform distinct from the previously identified tobacco beta-1,3-glucanases. By expressing gn1 in Escherichia coli, we have determined directly that the encoded protein does, indeed, correspond to a beta-1,3-glucanase. In N. plumbaginifolia, gn1 was found to be expressed in roots and older leaves. Transgenic tobacco plants containing the 5'-noncoding region of gn1 fused to the beta-glucuronidase (GUS) reporter gene also showed maximum levels of GUS activity in roots and older leaves. No detectable activity was present in the upper part of the transgenic plants with the exception of stem cells at the bases of emerging shoots. The expression conferred by the gn1 promoter was differentially induced in response to specific plant stress treatments. Studies of three plant-bacteria interactions showed high levels of GUS activity when infection resulted in a hypersensitive reaction. Increased gene expression was confined to cells surrounding the necrotic lesions. The observed expression pattern suggests that the characterized beta-1,3-glucanase plays a role both in plant development and in the defense response against pathogen infection. PMID:2152158

Methodology to determine the efficiency of a beta emitter gases monitor; Metodologia para determinacao da eficiencia de um monitor de gases emissores de particulas beta

Energy Technology Data Exchange (ETDEWEB)

Carvalho, Marcos Rodrigues de

1995-07-01

This work presents a methodology developed to determinate the efficiency of air monitors used to measure the concentration of beta emitters noble gases in nuclear power stations. Efficiency values, obtained by means of theoretical computation are compared with experimental values. The experimental part of the work was performed using three different point beta source, to simulate small amounts of gas uniformly distributed in small volume. The comparison shows that theoretical an experimental values agree within 4,2 % for {sup 90}Sr + {sup 90}Y, {sup 204}Tl and {sup 45}Ca beta sources. (author)

Collagen V-induced nasal tolerance downregulates pulmonary collagen mRNA gene and TGF-beta expression in experimental systemic sclerosis

Directory of Open Access Journals (Sweden)

Parra Edwin R

2010-01-01

Full Text Available Abstract Background The purpose of this study was to evaluate collagen deposition, mRNA collagen synthesis and TGF-beta expression in the lung tissue in an experimental model of scleroderma after collagen V-induced nasal tolerance. Methods Female New Zealand rabbits (N = 12 were immunized with 1 mg/ml of collagen V in Freund's adjuvant (IM. After 150 days, six immunized animals were tolerated by nasal administration of collagen V (25 μg/day (IM-TOL daily for 60 days. The collagen content was determined by morphometry, and mRNA expressions of types I, III and V collagen were determined by Real-time PCR. The TGF-beta expression was evaluated by immunostaining and quantified by point counting methods. To statistic analysis ANOVA with Bonferroni test were employed for multiple comparison when appropriate and the level of significance was determined to be p Results IM-TOL, when compared to IM, showed significant reduction in total collagen content around the vessels (0.371 ± 0.118 vs. 0.874 ± 0.282, p p p = 0.026. The lung tissue of IM-TOL, when compared to IM, showed decreased immunostaining of types I, III and V collagen, reduced mRNA expression of types I (0.10 ± 0.07 vs. 1.0 ± 0.528, p = 0.002 and V (1.12 ± 0.42 vs. 4.74 ± 2.25, p = 0.009 collagen, in addition to decreased TGF-beta expression (p Conclusions Collagen V-induced nasal tolerance in the experimental model of SSc regulated the pulmonary remodeling process, inhibiting collagen deposition and collagen I and V mRNA synthesis. Additionally, it decreased TGF-beta expression, suggesting a promising therapeutic option for scleroderma treatment.

Experiments on double beta decay

Energy Technology Data Exchange (ETDEWEB)

Busto, J [Neuchatel Univ. (Switzerland). Inst. de Physique

1996-11-01

The Double Beta Decay, and especially ({beta}{beta}){sub 0{nu}} mode, is an excellent test of Standard Model as well as of neutrino physics. From experimental point of view, a very large number of different techniques are or have been used increasing the sensitivity of this experiments quite a lot (the factor of 10{sup 4} in the last 20 years). In future, in spite of several difficulties, the sensitivity would be increased further, keeping the interest of this very important process. (author) 4 figs., 5 tabs., 21 refs.

Estimation error algorithm at analysis of beta-spectra

International Nuclear Information System (INIS)

Bakovets, N.V.; Zhukovskij, A.I.; Zubarev, V.N.; Khadzhinov, E.M.

2005-01-01

This work describes the estimation error algorithm at the operations with beta-spectrums, as well as compares the theoretical and experimental errors by the processing of beta-channel's data. (authors)

Growth mechanism and elemental distribution of beta-Ga2O3 crystalline nanowires synthesized by cobalt-assisted chemical vapor deposition.

Science.gov (United States)

Wang, Hui; Lan, Yucheng; Zhang, Jiaming; Crimp, Martin A; Ren, Zhifeng

2012-04-01

Long beta-Ga2O3 crystalline nanowires are synthesized on patterned silicon substrates using chemical vapor deposition technique. Advanced electron microscopy indicates that the as-grown beta-Ga2O3 nanowires are consisted of poly-crystalline (Co, Ga)O tips and straight crystalline beta-Ga2O3 stems. The catalytic cobalt not only locates at the nanowire tips but diffuses into beta-Ga2O3 nanowire stems several ten nanometers. A solid diffusion growth mechanism is proposed based on the spatial elemental distribution along the beta-Ga2O3 nanowires at nanoscale.

Identification of a Glycogen Synthase Kinase-3[beta] Inhibitor that Attenuates Hyperactivity in CLOCK Mutant Mice

Energy Technology Data Exchange (ETDEWEB)

Kozikowski, Alan P.; Gunosewoyo, Hendra; Guo, Songpo; Gaisina, Irina N.; Walter, Richard L.; Ketcherside, Ariel; McClung, Colleen A.; Mesecar, Andrew D.; Caldarone, Barbara (Psychogenics); (Purdue); (UIC); (UTSMC)

2012-05-02

Bipolar disorder is characterized by a cycle of mania and depression, which affects approximately 5 million people in the United States. Current treatment regimes include the so-called 'mood-stabilizing drugs', such as lithium and valproate that are relatively dated drugs with various known side effects. Glycogen synthase kinase-3{beta} (GSK-3{beta}) plays a central role in regulating circadian rhythms, and lithium is known to be a direct inhibitor of GSK-3{beta}. We designed a series of second generation benzofuran-3-yl-(indol-3-yl)maleimides containing a piperidine ring that possess IC{sub 50} values in the range of 4 to 680 nM against human GSK-3{beta}. One of these compounds exhibits reasonable kinase selectivity and promising preliminary absorption, distribution, metabolism, and excretion (ADME) data. The administration of this compound at doses of 10 to 25 mg kg{sup -1} resulted in the attenuation of hyperactivity in amphetamine/chlordiazepoxide-induced manic-like mice together with enhancement of prepulse inhibition, similar to the effects found for valproate (400 mg kg{sup -1}) and the antipsychotic haloperidol (1 mg kg{sup -1}). We also tested this compound in mice carrying a mutation in the central transcriptional activator of molecular rhythms, the CLOCK gene, and found that the same compound attenuates locomotor hyperactivity in response to novelty. This study further demonstrates the use of inhibitors of GSK-3{beta} in the treatment of manic episodes of bipolar/mood disorders, thus further validating GSK-3{beta} as a relevant therapeutic target in the identification of new therapies for bipolar patients.

Phase I study of transforming growth factor-beta 3 mouthwashes for prevention of chemotherapy-induced mucositis

NARCIS (Netherlands)

Wymenga, ANM; van der Graaf, WTA; Hofstra, LS; Spijkervet, FKL; Timens, W; Timmer-Bosscha, H; Sluiter, WJ; van Buuren, AHJAW; Mulder, NH; de Vries, EGE

The purpose of this study was to establish the safety and tolerability of recombinant transforming growth factor-beta 3 (TGF-beta 3; CGP 46614) mouthwashes intended for prevention of chemotherapy-induced mucositis. Local effects were especially analyzed by objective and subjective measurements of

A {beta} - {gamma} coincidence; Metodo de coincidencias {beta} - {gamma}

Energy Technology Data Exchange (ETDEWEB)

Agullo, F

1960-07-01

A {beta} - {gamma} coincidence method for absolute counting is given. The fundamental principles are revised and the experimental part is detailed. The results from {sup 1}98 Au irradiated in the JEN 1 Swimming pool reactor are given. The maximal accuracy is 1 per cent. (Author) 11 refs.

Experimentation with a prototype incinerator for beta-gamma waste

International Nuclear Information System (INIS)

Farber, M.G.; Lewandowski, K.E.; Becker, G.W.

1982-01-01

A test facility for the incineration of suspect and low-level beta-gamma waste has been built and operated at the Savannah River Laboratory. The processing steps include waste feeding, incineration, ash residue packaging, and off-gas cleanup. Demonstration of the full-scale (180 kg/hr) facility with nonradioactive, simulated waste is currently in progress. At the present time, over nine metric tons of material including rubber, polyethylene, and cellulose have been incinerated during three burning campaigns. A comprehensive test program of solid and liquid waste incineration is being implemented. The data from the research program is providing the technical basis for a phase of testing with low-level beta-gamma waste generated at the Savannah River Plant

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

Science.gov (United States)

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

1987-04-01

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

Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3beta is implicated in the treatment of cervical carcinoma.

Science.gov (United States)

Zhang, Yuan; Shu, Yi Min; Wang, Shu Fang; Da, Bang Hong; Wang, Ze Hua; Li, Hua Bin

2010-02-23

PMS2 expression loss was reported in a variety of human. However, its importance has not been fully understood in cervical carcinoma. The aim of this study was to determine the expression of PMS2 in cervical carcinoma and evaluate the significance of mismatch repair gene PMS2 regulated by glycogen synthase kinase 3beta (GSK-3beta) in chemosensitivity. We examined PMS2 and phosphorylated GSK-3beta(s9) expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we detected PMS2 expression in HeLa cells and evaluate the interaction with GSK-3beta after transfection with GSK-3beta by small interference RNA (siRNA), co-immunoprecipitation and immunoblotting. We also evaluated the effect of PMS2 transfection on HeLa cells' chemosensitivity to cisplatin treatment. We found significant downregulation of PMS2 in cervical carcinoma, which was negatively associated with phosphorylated GSK-3beta (s9). Furthermore, we demonstrated GSK-3beta transfection was able to interact with PMS2 and enhance PMS2 production in HeLa cells, and increased PMS2 production was responsible for enhanced chemosensitivity. Our results provide the evidence that stabilization of PMS2 production by GSK-3beta was important to improve chemosensitization, indicating the significance of GSK-3beta-related PMS2 downregulation in the development of cervical carcinoma and in developing a potential strategy for chemotherapy.

Involvment of cytosolic and mitochondrial GSK-3beta in mitochondrial dysfunction and neuronal cell death of MPTP/MPP-treated neurons.

Directory of Open Access Journals (Sweden)

Agnès Petit-Paitel

Full Text Available Aberrant mitochondrial function appears to play a central role in dopaminergic neuronal loss in Parkinson's disease (PD. 1-methyl-4-phenylpyridinium iodide (MPP(+, the active metabolite of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, is a selective inhibitor of mitochondrial complex I and is widely used in rodent and cell models to elicit neurochemical alterations associated with PD. Recent findings suggest that Glycogen Synthase Kinase-3beta (GSK-3beta, a critical activator of neuronal apoptosis, is involved in the dopaminergic cell death. In this study, the role of GSK-3beta in modulating MPP(+-induced mitochondrial dysfunction and neuronal death was examined in vivo, and in two neuronal cell models namely primary cultured and immortalized neurons. In both cell models, MPTP/MPP(+ treatment caused cell death associated with time- and concentration-dependent activation of GSK-3beta, evidenced by the increased level of the active form of the kinase, i.e. GSK-3beta phosphorylated at tyrosine 216 residue. Using immunocytochemistry and subcellular fractionation techniques, we showed that GSK-3beta partially localized within mitochondria in both neuronal cell models. Moreover, MPP(+ treatment induced a significant decrease of the specific phospho-Tyr216-GSK-3beta labeling in mitochondria concomitantly with an increase into the cytosol. Using two distinct fluorescent probes, we showed that MPP(+ induced cell death through the depolarization of mitochondrial membrane potential. Inhibition of GSK-3beta activity using well-characterized inhibitors, LiCl and kenpaullone, and RNA interference, prevented MPP(+-induced cell death by blocking mitochondrial membrane potential changes and subsequent caspase-9 and -3 activation. These results indicate that GSK-3beta is a critical mediator of MPTP/MPP(+-induced neurotoxicity through its ability to regulate mitochondrial functions. Inhibition of GSK-3beta activity might provide protection against

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

Science.gov (United States)

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

2017-03-01

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

Status of international benchmark experiment for effective delayed neutron fraction ({beta}eff)

Energy Technology Data Exchange (ETDEWEB)

Okajima, S.; Sakurai, T.; Mukaiyama, T. [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

1997-03-01

To improve the prediction accuracy of the {beta}eff, the program of the international benchmark experiment (Beta Effect Reactor Experiment for a New International Collaborative Evaluation: BERNICE) was planned. This program composed of two parts; BERNICE-MASURCA and BERNICE-FCA. The former one was carried out in the fast critical facility MASURCA of CEA, FRANCE between 1993 and 1994. The latter one started in the FCA, JAERI in 1995 and still is going. In these benchmark experiments, various experimental techniques have been applied for in-pile measurements of the {beta}eff. The accuracy of the measurements was better than 3%. (author)

Synthesis, radiolabeling and baboon SPECT imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl)tropane ([{sup 123}I]YP256) as a serotonin transporter radiotracer

Energy Technology Data Exchange (ETDEWEB)

Bois, Frederic; Baldwin, Ronald M.; Amici, Louis; Al-Tikriti, Mohammed S. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Kula, Nora; Baldessarini, Ross [Department of Psychiatry and Neuroscience Program, Harvard Medical School, Mailman Research Center McLean Division of Massachusetts General Hospital, Belmont, MA 02478 (United States); Innis, Robert B.; Staley, Julie K. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Tamagnan, Gilles D. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Institute for Neurodegenerative Disorders, New Haven, CT 06510 (United States)], E-mail: gtamagnan@indd.org

2008-01-15

To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson's disease, Alzheimer's disease and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl) tropane (YP256, ). The radiolabeling was performed by iododestannylation using sodium [{sup 123}I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo.

Measurement of high-beta tokamak pressure profiles with multipoint Thomson scattering

International Nuclear Information System (INIS)

Levinton, F.M.

1983-01-01

A multipoint Thomson-scattering system has been developed to obtain pressure profiles along the major radius of Torus II, a high-beta tokamak. The profiles obtained during the 20 to 25 μs lifetime of the discharge indicates that the plasma has a peak temperature of 80 eV and density of 1.0 x 10 15 cm - 3 . The profiles remain fairly constant during this time until the equilibrium is lost, after which the temperature and density decays to 10 eV and 10 14 cm - 3 very quickly (approx. 1 μs). Experimental results show Torus II has a high-beta ( approx. 10%) equilibrium, with a strong shift of the peak of the pressure profile towards the outside. Numerical results from a 2-D free boundary MHD equilibrium code have obtained equilibria which closely approximate the experimentally measured profiles

Methodology to determine the efficiency of a beta emitter gases monitor

International Nuclear Information System (INIS)

Carvalho, Marcos Rodrigues de

1995-01-01

This work presents a methodology developed to determinate the efficiency of air monitors used to measure the concentration of beta emitters noble gases in nuclear power stations. Efficiency values, obtained by means of theoretical computation are compared with experimental values. The experimental part of the work was performed using three different point beta source, to simulate small amounts of gas uniformly distributed in small volume. The comparison shows that theoretical an experimental values agree within 4,2 % for 90 Sr + 90 Y, 204 Tl and 45 Ca beta sources. (author)

Double Beta Decay Experiments

International Nuclear Information System (INIS)

Piepke, A.

2005-01-01

The experimental observation of neutrino oscillations and thus neutrino mass and mixing gives a first hint at new particle physics. The absolute values of the neutrino mass and the properties of neutrinos under CP-conjugation remain unknown. The experimental investigation of the nuclear double beta decay is one of the key techniques for solving these open problems

Effect of tissue-specific acetylcholinesterase inhibitor C-547 on alpha 3 beta 4 and alpha beta epsilon delta acetylcholine receptors in COS cells

Czech Academy of Sciences Publication Activity Database

Lindovský, Jiří; Petrov, K.; Krůšek, Jan; Reznik, V.S.; Nikolsky, E. E.; Vyskočil, František

2012-01-01

Roč. 688, 1-3 (2012), s. 22-26 ISSN 0014-2999 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA202/09/0806; GA AV ČR(CZ) IAA500110905; GA AV ČR(CZ) IAA100110501; GA AV ČR(CZ) IAA5011411 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : nicotinic ACh receptor * alpha 3 beta 4 * alpha beta epsilon delta * C-547 * anti-cholinesterase Subject RIV: ED - Physiology Impact factor: 2.592, year: 2012

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

Study of once and twice forbidden {beta} transitions; Contribution a l'etude de transitions {beta} une fois et deux fois interdites

Energy Technology Data Exchange (ETDEWEB)

Hocquenghem, J C [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

1967-09-01

The realisation of an experimental set up for directional angular correlation measurements allowed us to determine {beta} - {gamma} angular correlations. These measurements together with the determination of the {beta} shape-factor have been made for the following transitions: the first forbidden {beta}{sup -} transitions of 386 keV in the {sup 177}Lu disintegration and of 352 keV in the {sup 175}Yb disintegration. The experimental results have been compared with theoretical predictions of the Nilsson's model; the twice forbidden {beta}{sup -} transition of 473 keV in the {sup 94}Nb disintegration. The {beta} transition nuclear matrix elements have been extracted from the experimental results. Comparison have been made with the theoretical values calculated by taking for nuclear wavefunctions those obtained by diagonalization of the residual interaction and assuming that protons and neutrons outside the {sup 90}Zr core are respectively on the 1 g 9/2 and 2 d 5/2 orbits. (author) [French] La realisation d'un ensemble de mesures de correlations angulaires directionnelles nous a permis la mesure de correlations {beta} - {gamma} en fonction de l'energie. En completant celles-ci par la mesure du facteur de forme du spectre {beta}, nous avons pu etudier ainsi: d'une part, les transitions {beta}{sup -} une fois interdites de 386 keV de la desintegration de {sup 177}Lu et de 352 keV de la desintegration de {sup 175}Yb, Les resultats experimentaux ont ete compares aux valeurs calculees dans le modele de Nilsson; d'autre part, la transition {beta}- deux fois interdite de 473 keV de la desintegration de {sup 94}Nb. Les elements de matrice nucleaire de la transition {beta}, extraits des resultats experimentaux, ont ete compares aux valeurs theoriques calculees. Les fonctions d'ondes nucleaires utilisees ont ete obtenues par diagonalisation de l'interaction residuelle en supposant que les protons et les neutrons, en dehors du coeur forme par le {sup 90}Zr, sont respectivement

Microstructural stability and thermomechanical processing of boron modified beta titanium alloys

Science.gov (United States)

Cherukuri, Balakrishna

One of the main objectives during primary processing of titanium alloys is to reduce the prior beta grain size. Producing an ingot with smaller prior beta grain size could potentially eliminate some primary processing steps and thus reduce processing cost. Trace additions of boron have been shown to decrease the as-cast grain size in alpha + beta titanium alloys. The primary focus of this dissertation is to investigate the effect of boron on microstructural stability and thermomechanical processing in beta titanium alloys. Two metastable beta titanium alloys: Ti-15Mo-2.6Nb-3Al-0.2Si (Beta21S) and Ti-5Al-5V-5Mo-3Cr (Ti5553) with 0.1 wt% B and without boron additions were used in this investigation. Significant grain refinement of the as-cast microstructure and precipitation of TiB whiskers along the grain boundaries was observed with boron additions. Beta21S and Beta21S-0.1B alloys were annealed above the beta transus temperature for different times to investigate the effect of boron on grain size stability. The TiB precipitates were very effective in restricting the beta grain boundary mobility by Zener pinning. A model has been developed to predict the maximum grain size as a function of TiB size, orientation, and volume fraction. Good agreement was obtained between model predictions and experimental results. Beta21S alloys were solution treated and aged for different times at several temperatures below the beta transus to study the kinetics of alpha precipitation. Though the TiB phase did not provide any additional nucleation sites for alpha precipitation, the grain refinement obtained by boron additions resulted in accelerated aging. An investigation of the thermomechanical processing behavior showed different deformation mechanisms above the beta transus temperature. The non-boron containing alloys showed a non-uniform and fine recrystallized necklace structure at grain boundaries whereas uniform intragranular recrystallization was observed in boron containing

Turn stability in beta-hairpin peptides: Investigation of peptides containing 3:5 type I G1 bulge turns.

Science.gov (United States)

Blandl, Tamas; Cochran, Andrea G; Skelton, Nicholas J

2003-02-01

The turn-forming ability of a series of three-residue sequences was investigated by substituting them into a well-characterized beta-hairpin peptide. The starting scaffold, bhpW, is a disulfide-cyclized 10-residue peptide that folds into a stable beta-hairpin with two antiparallel strands connected by a two-residue reverse turn. Substitution of the central two residues with the three-residue test sequences leads to less stable hairpins, as judged by thiol-disulfide equilibrium measurements. However, analysis of NMR parameters indicated that each molecule retains a significant folded population, and that the type of turn adopted by the three-residue sequence is the same in all cases. The solution structure of a selected peptide with a PDG turn contained an antiparallel beta-hairpin with a 3:5 type I + G1 bulge turn. Analysis of the energetic contributions of individual turn residues in the series of peptides indicates that substitution effects have significant context dependence, limiting the predictive power of individual amino acid propensities for turn formation. The most stable and least stable sequences were also substituted into a more stable disulfide-cyclized scaffold and a linear beta-hairpin scaffold. The relative stabilities remained the same, suggesting that experimental measurements in the bhpW context are a useful way to evaluate turn stability for use in protein design projects. Moreover, these scaffolds are capable of displaying a diverse set of turns, which can be exploited for the mimicry of protein loops or for generating libraries of reverse turns.

Wall stabilization of high beta plasmas in DIII-D

International Nuclear Information System (INIS)

Taylor, T.S.; Strait, E.J.; Lao, L.L.; Turnbull, A.D.; Burrell, K.H.; Chu, M.S.; Ferron, J.R.; Groebner, R.J.; La Haye, R.J.; Mauel, M.

1995-02-01

Detailed analysis of recent high beta discharges in the DIII-D tokamak demonstrates that the resistive vacuum vessel can provide stabilization of low n magnetohydrodynamic (MHD) modes. The experimental beta values reaching up to β T = 12.6% are more than 30% larger than the maximum stable beta calculated with no wall stabilization. Plasma rotation is essential for stabilization. When the plasma rotation slows sufficiently, unstable modes with the characteristics of the predicted open-quotes resistive wallclose quotes mode are observed. Through slowing of the plasma rotation between the q = 2 and q = 3 surfaces with the application of a non-axisymmetric field, the authors have determined that the rotation at the outer rational surfaces is most important, and that the critical rotation frequency is of the order of Ω/2π = 1 kHz

Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3beta loop.

Directory of Open Access Journals (Sweden)

Gediminas Matulis

2010-06-01

Full Text Available Invariant Natural Killer T cells (iNKT are a versatile lymphocyte subset with important roles in both host defense and immunological tolerance. They express a highly conserved TCR which mediates recognition of the non-polymorphic, lipid-binding molecule CD1d. The structure of human iNKT TCRs is unique in that only one of the six complementarity determining region (CDR loops, CDR3beta, is hypervariable. The role of this loop for iNKT biology has been controversial, and it is unresolved whether it contributes to iNKT TCR:CD1d binding or antigen selectivity. On the one hand, the CDR3beta loop is dispensable for iNKT TCR binding to CD1d molecules presenting the xenobiotic alpha-galactosylceramide ligand KRN7000, which elicits a strong functional response from mouse and human iNKT cells. However, a role for CDR3beta in the recognition of CD1d molecules presenting less potent ligands, such as self-lipids, is suggested by the clonal distribution of iNKT autoreactivity. We demonstrate that the human iNKT repertoire comprises subsets of greatly differing TCR affinity to CD1d, and that these differences relate to their autoreactive functions. These functionally different iNKT subsets segregate in their ability to bind CD1d-tetramers loaded with the partial agonist alpha-linked glycolipid antigen OCH and structurally different endogenous beta-glycosylceramides. Using surface plasmon resonance with recombinant iNKT TCRs and different ligand-CD1d complexes, we demonstrate that the CDR3beta sequence strongly impacts on the iNKT TCR affinity to CD1d, independent of the loaded CD1d ligand. Collectively our data reveal a crucial role for CDR3beta for the function of human iNKT cells by tuning the overall affinity of the iNKT TCR to CD1d. This mechanism is relatively independent of the bound CD1d ligand and thus forms the basis of an inherent, CDR3beta dependent functional hierarchy of human iNKT cells.

Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) beta-carboline derivatives.

Science.gov (United States)

Formagio, Anelise S Nazari; Tonin, Lilian T Düsman; Foglio, Mary Ann; Madjarof, Christiana; de Carvalho, João Ernesto; da Costa, Willian Ferreira; Cardoso, Flávia P; Sarragiotto, Maria Helena

2008-11-15

Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50)<100 microM) for all eight different types of human cancer cell lines tested. The beta-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI(50) values lying in the nanomolar concentration range (GI(50)=10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents.

PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration

Directory of Open Access Journals (Sweden)

Yaxi Zhu

2017-11-01

Full Text Available Abstract Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1, Neurogenin-3 (NEUROG3, and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells. PDX1 also binds to the regulatory elements and increases insulin gene transcription. Likewise, MAFA binds to the enhancer/promoter region of the insulin gene and drives insulin expression in response to glucose. In addition to those natural roles in beta cell development and maturation, ectopic expression of PDX1, NEUROG3, and/or MAFA has been successfully used to reprogram various cell types into insulin-producing cells in vitro and in vivo, such as pancreatic exocrine cells, hepatocytes, and pluripotent stem cells. Here, we review biological properties of PDX1, NEUROG3, and MAFA, and their applications and limitations for beta cell regenerative approaches. The primary source literature for this review was acquired using a PubMed search for articles published between 1990 and 2017. Search terms include diabetes, insulin, trans-differentiation, stem cells, and regenerative medicine.

Identification of beta 2-adrenoceptors on guinea pig alveolar macrophages using (-)-3-[125I]iodocyanopindolol

International Nuclear Information System (INIS)

Leurs, R.; Beusenberg, F.D.; Bast, A.; Van Amsterdam, J.G.; Timmerman, H.

1990-01-01

The beta-adrenoceptor antagonist (-)-3-[ 125 I]iodocyanopindolol ([ 125 I]ICYP) binds with high affinity and in saturable way to membranes of guinea pig alveolar macrophages. The equilibrium dissociation constant for [ 125 I]ICYP is 24.3 +/- 1.2 pM, and the number of binding sites is 166.3 +/- 13.7 fmol/mg protein (N = 4, +/- SEM). Displacement studies with selective antagonists showed that [ 125 I]ICYP labels beta 2-adrenoceptors on guinea pig alveolar macrophages

Pannus invasion and cartilage degradation in rheumatoid arthritis: involvement of MMP-3 and interleukin-1beta.

Science.gov (United States)

Ainola, M M; Mandelin, J A; Liljeström, M P; Li, T F; Hukkanen, M V J; Konttinen, Y T

2005-01-01

Synovial inflammation in rheumatoid arthritis (RA) leads to pannus tissue invasion and destruction of cartilage/bone matrix by proteinases. Our intention was to analyze some of the key matrix metalloproteinases (MMPs) in pannus tissue overlying evolving cartilage erosions in RA. Frozen tissue samples of pannus and synovium from advanced RA and synovium from osteoarthritic patients were used for immunohistochemical, western blotting and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis of MMP-1, -3, -13 and -14. Synovial fibroblast cultures, stimulated with tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), were analyzed with enzyme-linked immunosorbent assays (ELISA) and quantitative RT-PCR. MMP-3 was highly expressed in pannus tissue compared with significantly lower expression levels of MMP-1, -13 and -14. In fibroblast cultures IL-1beta was a potent stimulus for MMP-3, whereas TNF-alpha was more potent for MMP-1. This is the first study to demonstrate quantitatively in real time that MMP-3 mRNA expression is clearly higher in advanced RA pannus tissue compared to parallel RA or osteoarthritic synovium. MMP-3 mRNA levels were also clearly overexpressed in RA pannus compared to MMP-1, -13 and -14. Advanced RA has previously been found to overexpress IL-1beta. The high expression of MMP-3 in pannus and IL-1beta, mediated stimulation of MMP-3 suggest that MMP-3 plays a significant role in the progression of erosions through the proteoglycan-rich cartilage matrix.

Majorana neutrinos and double beta-decay

International Nuclear Information System (INIS)

Shchepkin, M.G.

1986-01-01

Problem, related to neutrino mass and lepton charge L conservation is briefly discussed. A possibility to experimentally test L conservation in different processes and to produce limitations for neutrino mass in double beta-decay processes is considered. Planned experiments on studying the double neutrinoless (2β) beta-decays and searching 2β(2ν)-decays, permitted by the conservation laws, are discussed. It is stressed, that comparison of the existing theoretical predictions of 2β(2ν)-decay probability with experimental results will make it possible to choose the most adequate approach to the calculation of double β-transition nuclear amplitudes

V&V of MCNP 6.1.1 Beta Against Intermediate and High-Energy Experimental Data

Energy Technology Data Exchange (ETDEWEB)

Mashnik, Stepan G [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2014-09-08

This report presents a set of validation and verification (V&V) MCNP 6.1.1 beta results calculated in parallel, with MPI, obtained using its event generators at intermediate and high-energies compared against various experimental data. It also contains several examples of results using the models at energies below 150 MeV, down to 10 MeV, where data libraries are normally used. This report can be considered as the forth part of a set of MCNP6 Testing Primers, after its first, LA-UR-11-05129, and second, LA-UR-11-05627, and third, LA-UR-26944, publications, but is devoted to V&V with the latest, 1.1 beta version of MCNP6. The MCNP6 test-problems discussed here are presented in the /VALIDATION_CEM/and/VALIDATION_LAQGSM/subdirectories in the MCNP6/Testing/directory. README files that contain short descriptions of every input file, the experiment, the quantity of interest that the experiment measures and its description in the MCNP6 output files, and the publication reference of that experiment are presented for every test problem. Templates for plotting the corresponding results with xmgrace as well as pdf files with figures representing the final results of our V&V efforts are presented. Several technical “bugs” in MCNP 6.1.1 beta were discovered during our current V&V of MCNP6 while running it in parallel with MPI using its event generators. These “bugs” are to be fixed in the following version of MCNP6. Our results show that MCNP 6.1.1 beta using its CEM03.03, LAQGSM03.03, Bertini, and INCL+ABLA, event generators describes, as a rule, reasonably well different intermediate- and high-energy measured data. This primer isn’t meant to be read from cover to cover. Readers may skip some sections and go directly to any test problem in which they are interested.

Aggravation of Risk and Precautionary Measures in Non-Life Insurance: A Tricky Scope for the Insurer?

Directory of Open Access Journals (Sweden)

Olavi-Jüri Luik

2015-12-01

Full Text Available Aggravation of risk and failure to take precautionary measures are focal issues in non-life insurance in terms of potential partial or full release of the insurer from the duty to perform. Not infrequently, it is difficult to draw a line between the aggravation of risk on the one hand, and non-compliance with precautionary measures on the other, since a particular action by a policyholder may present both situations. At the same time, the legal remedies available to the insurer regarding these two situations are different in scope. The aggravation of risk and non-compliance with precautionary measures are precisely the bases on which insurers actually reduce indemnity or refuse to compensate for damages. This article explores the differences between insurance laws in the Baltic states—specifically, the Estonian Law of Obligations Act, the Latvian Insurance Contract Law and Lithuanian rules contained in the Civil Code and Insurance Law. The article explores the differences between the Baltic states’ insurance laws and the Principles of European Insurance Contract Law (PEICL with regard to a policyholder’s duty in relation to aggravation of risk and precautionary measures, as the rights and obligations of policyholders do change where the optional instrument is applied. The article also includes comparisons to German, Finnish and Russian insurance law.

Biochemical and kinetic analysis of the GH3 family beta-xylosidase from Aspergillus awamori X-100.

Science.gov (United States)

Eneyskaya, Elena V; Ivanen, Dina R; Bobrov, Kirill S; Isaeva-Ivanova, Lyudmila S; Shabalin, Konstantin A; Savel'ev, Andrew N; Golubev, Alexander M; Kulminskaya, Anna A

2007-01-15

The beta-xylosidase from Aspergillus awamori X-100 belonging to the family 3 glycoside hydrolase revealed a distinctive transglycosylating ability to produce xylooligosaccharides with degree of polymerization more than 7. In order to explain this fact, the enzyme has been subjected to the detailed biochemical study. The enzymatic hydrolysis of p-nitrophenyl beta-D-xylopyranoside was found to occur with overall retention of substrate anomeric configuration suggesting cleavage of xylosidic bonds through a double-displacement mechanism. Kinetic study with aryl beta-xylopyranosides substrates, in which leaving group pK(a)s were in the range of 3.96-10.32, revealed monotonic function of log(k(cat)) and no correlation of log(k(cat)/Km) versus pKa values indicating deglycosylation as a rate-limiting step for the enzymatic hydrolysis. The classical bell-shaped pH dependence of k(cat)/Km indicated two ionizable groups in the beta-xylosidase active site with apparent pKa values of 2.2 and 6.4. The kinetic parameters of hydrolysis, Km and k(cat), of p-nitrophenyl beta-D-1,4-xylooligosaccharides were very close to those for hydrolysis of p-nitrophenyl-beta-D-xylopyranoside. Increase of p-nitrophenyl-beta-D-xylopyranoside concentration up to 80 mM led to increasing of the reaction velocity resulting in k(cat)(app)=81 s(-1). Addition of alpha-methyl D-xylopyranoside to the reaction mixture at high concentration of p-nitrophenyl-beta-D-xylopyranoside (50 mM) caused an acceleration of the beta-xylosidase-catalyzed reactions and appearance of a new transglycosylation product, alpha-methyl D-xylopyranosyl-1,4-beta-D-xylopyranoside, that was identified by 1H NMR spectroscopy. The kinetic model suggested for the enzymatic reaction was consistent with the results obtained.

Testagem do 1 - beta - D - Ribofuranosil, 1.2.4 - triazole - 3 - carboxamide em pacientes com hepatite

Directory of Open Access Journals (Sweden)

Anastácio Ferreira Morgado

1976-02-01

Full Text Available Realizou-se estudo do tipo duplo anonimato em 18 pacientes com hepatite aguda benigna. O gruoo experimental foi testado com uma provável droga de ação antiviral: 1-BETA-D-RIBOFURANOSIL, 1,2,4-TRIAZOLE-3- CARBOXAMIDE. O grupo controle ingeriu um placebo de lactose. Teve-se especial cuidado na seleção de pacientes, incluindo apenas pacientes que preenchessem critérios bem estabelecidos. Os pacientes foram seguidos semanalmente, avaliando-os clínica e laboratorialmente. Os resultados não evidenciaram diferenças significativas entre os dois grupos, sugerindo-se estudos com casuística mais numerosa e em regime de internação hospitalar.

Monitoring total endotoxin and (1 --> 3)-beta-D-glucan at the air exhaust of concentrated animal feeding operations.

Science.gov (United States)

Yang, Xufei; Wang, Xinlei; Zhang, Yuanhui; Lee, Jongmin; Su, Jingwei; Gates, Richard S

2013-10-01

Mitigation of bioaerosol emissions from concentrated animal feeding operations (CAFOs) demands knowledge of bioaerosol concentrations feeding into an end-of-pipe air treatment process. The aim of this preliminary study was to measure total endotoxin and (1 --> 3)-beta-glucan concentrations at the air exhaust of 18 commercial CAFOs and to examine their variability with animal operation type (swine farrowing, swine gestation, swine weaning, swine finishing, manure belt laying hen, and tom turkey) and season (cold, mild, and hot). The measured airborne concentrations of total endotoxin ranged from 98 to 23,157 endotoxin units (EU)/m3, and the airborne concentrations of total (1 --> 3)-beta-D-glucan ranged from 2.4 to 537.9 ng/m3. Animal operation type in this study had a significant effect on airborne concentrations of total endotoxin and (1 --> 3)-beta-D-glucan but no significant effect on their concentrations in total suspended particulate (TSP). Both endotoxin and (1 --> 3)-beta-D-glucan attained their highest airborne concentrations in visited tom turkey buildings. Comparatively, season had no significant effect on airborne concentrations of total endotoxin or (1 --> 3)-beta-D-glucan. Endotoxin and (1 --> 3)-beta-glucan concentrations in TSP dust appeared to increase as the weather became warmer, and this seasonal effect was significant in swine buildings. Elevated indoor temperatures in the hot season were considered to facilitate the growth and propagation of bacteria and fungi, thus leading to higher biocomponent concentrations in TSP.

The SU(3) beta function from numerical stochastic perturbation theory

Energy Technology Data Exchange (ETDEWEB)

Horsley, R. [Edinburgh Univ. (United Kingdom). School of Physics and Astronomy; Perlt, H. [Leipzig Univ. (Germany). Inst. fuer Theoretische Physik; Bonn Univ. (Germany). Helmholtz Inst. fuer Strahlen- und Kernphysik; Rakow, P.E.L. [Liverpool Univ. (United Kingdom). Theoretical Physics Div.; Schierholz, G.; Schiller, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

2013-09-15

The SU(3) beta function is derived from Wilson loops computed to 20th order in numerical stochastic perturbation theory. An attempt is made to include massless fermions, whose contribution is known analytically to 4th order. The question whether the theory admits an infrared stable fixed point is addressed.

Beta-alanine/alpha-ketoglutarate aminotransferase for 3-hydroxypropionic acid production

Science.gov (United States)

Jessen, Holly Jean [Chanhassen, MN; Liao, Hans H [Eden Prairie, MN; Gort, Steven John [Apple Valley, MN; Selifonova, Olga V [Plymouth, MN

2011-10-04

The present disclosure provides novel beta-alanine/alpha ketoglutarate aminotransferase nucleic acid and protein sequences having increased biological activity. Also provided are cells containing such enzymes, as well as methods of their use, for example to produce malonyl semialdehyde and downstream products thereof, such as 3-hydroxypropionic acid and derivatives thereof.

Betting Against Beta

DEFF Research Database (Denmark)

Frazzini, Andrea; Heje Pedersen, Lasse

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

Microscopic beta and gamma data for decay-heat needs

International Nuclear Information System (INIS)

Dickens, J.K.

1983-01-01

Microscopic beta and gamma data for decay-heat needs are defined as absolute-intensity spectral distributions of beta and gamma rays following radioactive decay of radionuclides created by, or following, the fission process. Four well-known evaluated data files, namely the US ENDF/B-V, the UK UKFPDD-2, the French BDN (for fission products), and the Japanese JNDC Nuclear Data Library, are reviewed. Comments regarding the analyses of experimental data (particularly gamma-ray data) are given; the need for complete beta-ray spectral measurements is emphasized. Suggestions on goals for near-term future experimental measurements are presented. 34 references

Density functional calculations of backbone 15N shielding tensors in beta-sheet and turn residues of protein G

International Nuclear Information System (INIS)

Cai Ling; Kosov, Daniel S.; Fushman, David

2011-01-01

We performed density functional calculations of backbone 15 N shielding tensors in the regions of beta-sheet and turns of protein G. The calculations were carried out for all twenty-four beta-sheet residues and eight beta-turn residues in the protein GB3 and the results were compared with the available experimental data from solid-state and solution NMR measurements. Together with the alpha-helix data, our calculations cover 39 out of the 55 residues (or 71%) in GB3. The applicability of several computational models developed previously (Cai et al. in J Biomol NMR 45:245–253, 2009) to compute 15 N shielding tensors of alpha-helical residues is assessed. We show that the proposed quantum chemical computational model is capable of predicting isotropic 15 N chemical shifts for an entire protein that are in good correlation with experimental data. However, the individual components of the predicted 15 N shielding tensor agree with experiment less well: the computed values show much larger spread than the experimental data, and there is a profound difference in the behavior of the tensor components for alpha-helix/turns and beta-sheet residues. We discuss possible reasons for this.

The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells

DEFF Research Database (Denmark)

Rønn, Sif G; Hansen, Johnny A; Lindberg, Karen

2002-01-01

GH is an important regulator of cell growth and metabolism. In the pancreas, GH stimulates mitogenesis as well as insulin production in beta-cells. The cellular effects of GH are exerted mainly through activation of the Janus kinase-signal transducer and activator of transcription (STAT) pathway...... stable transfection of the beta-cell lines with plasmids expressing SOCS-3 under the control of an inducible promoter, a time- and dose-dependent expression of SOCS-3 in the cells was obtained. EMSA showed that SOCS-3 is able to inhibit GH-induced DNA binding of both STAT3 and STAT5 in RIN-5AH cells...

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-08-01

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

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

African Journals Online (AJOL)

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

Hb taradale [beta82(EF6)Lys-->Arg]: a novel mutation at a 2,3-diphosphoglycerate binding site.

Science.gov (United States)

Brennan, Stephen O; Sheen, Campbell; Chan, Tim; George, Peter M

2005-01-01

Hb Taradale [beta82(EF6)Lys-->Arg] was initially detected as a split Hb A0 peak on Hb A1c, monitoring. Red cell parameters, hemoglobin (Hb) electrophoresis and stability tests were normal. Mass spectrometry (ms) clearly identified a variant beta chain with a mass increase of 28 Da and peptide mapping located the mutation site to peptide betaT-9. DNA sequencing confirmed the presence of a novel beta82(EF6)Lys-->Arg mutation. This conservative substitution at a 2,3-diphosphoglycerate (2,3-DPG) binding site did not, however, appear to affect the P50 for oxygen binding.

Responses of a grassland arthropod community to chronic beta and gamma radiation

International Nuclear Information System (INIS)

Styron, C.E.; Dodson, G.J.; Beauchamp, J.J.; Miller, F.L. Jr.

1976-01-01

A long-term project was initiated in 1968 at Oak Ridge National Laboratory to assess effects of mixed beta and gamma radiation from simulated fallout on a grassland ecosystem. Beta and gamma radiation dose rates in microhabitats of the experimentally contaminated enclosure were measured with LiF thermoluminescent microdosimeters. Extensive statistical analyses of data on numbers of individuals collected for each of 76 arthropod and 2 molluscan taxa have identified no lasting significant changes in similarity or species diversity of experimental versus control communities as the result of the long-term irradiation at low dose rates. Natural fluctuations in community dynamics obscured any possible radiation effects. Thus, the apparent threshold for mixed beta and gamma radiation inducing changes in community structure must be above the exposure rate range of 2.3 to 13 rad/day delivered during the 5 yr of observation. Establishing such a threshold is of importance in assessing the impact of communities subjected to chronic, low level environmental exposure to ionizing radiation

Beta reduction factors for protective clothing at the Oak Ridge National Laboratory

International Nuclear Information System (INIS)

Franklin, G.L.; Gonzalez, P.L.

1998-01-01

Beta reduction factors (f β ) for protective clothing (PC) at the Oak Ridge National Laboratory (ORNL) have been determined for a variety of protective clothing combinations. Data was collected to determine the experimental f β for several combinations of PCs under laboratory conditions. Radiation dose rates were measured with an open window Bicron reg-sign RSO-5 ion chamber for two distinct beta energy groups (E max = 1.218 x 10 -13 J(0.860 MeV) and 3.653 x 10 -13 J (2.280 MeV)). Data points determined, as the ratio of unattenuated (no PCs) to attenuated (PCs), were used to derive a set of equations using the Microsoft reg-sign Excel Linet function. Field comparison tests were then conducted to determine the validity of these beta reduction factors. The f β from the field tests were significantly less than the experimental f β , indicating that these factors will yield conservative results

Smad signaling pathway is a pivotal component of tissue inhibitor of metalloproteinases-3 regulation by transforming growth factor beta in human chondrocytes.

Science.gov (United States)

Qureshi, Hamid Yaqoob; Ricci, Gemma; Zafarullah, Muhammad

2008-09-01

Transforming growth factor beta (TGF-beta1) promotes cartilage matrix synthesis and induces tissue inhibitor of metalloproteinases-3 (TIMP-3), which inhibits matrix metalloproteinases, aggrecanases and TNF-alpha-converting enzyme implicated in articular cartilage degradation and joint inflammation. TGF-beta1 activates Akt, ERK and Smad2 pathways in chondrocytes. Here we investigated previously unexplored roles of specific Smads in TGF-beta1 induction of TIMP-3 gene by pharmacological and genetic knockdown approaches. TGF-beta1-induced Smad2 phosphorylation and TIMP-3 protein expression could be inhibited by the Smad2/3 phosphorylation inhibitors, PD169316 and SB203580 and by Smad2-specific siRNA. Specific inhibitor of Smad3 (SIS3) and Smad3 siRNA abolished TGF-beta induction of TIMP-3. Smad2/3 siRNAs also down regulated TIMP-3 promoter-driven luciferase activities, suggesting transcriptional regulation. SiRNA-driven co-Smad4 knockdown abrogated TIMP-3 augmentation by TGF-beta. TIMP-3 promoter deletion analysis revealed that -828 deletion retains the original promoter activity while -333 and -167 deletions display somewhat reduced activity suggesting that most of the TGF-beta-responsive, cis-acting elements are found in the -333 fragment. Chromatin Immunoprecipitation (ChIP) analysis confirmed binding of Smad2 and Smad4 with the -940 and -333 promoter sequences. These results suggest that receptor-activated Smad2 and Smad3 and co-Smad4 critically mediate TGF-beta-stimulated TIMP-3 expression in human chondrocytes and TIMP-3 gene is a target of Smad signaling pathway.

Integral validation of the effective beta parameter for the MOX reactors and incinerators; Validation integrale des estimations du parametre beta effectif pour les reacteurs Mox et incinerateurs

Energy Technology Data Exchange (ETDEWEB)

Zammit-Averlant, V

1998-11-19

{beta}{sub eff}, which represents the effective delayed neutron fraction, is an important parameter for the reactor nominal working as well as for studies of its behaviour in accidental situation. In order to improve the safety of nuclear reactors, we propose here to validate its calculation by using the ERANOS code with ERALIB1 library and by taking into account all the fission process physics through the {nu} energy dependence. To validate the quality of this calculation formalism, we calculated uncertainties as precisely as possible. The experimental values of {beta}{sub eff}, as well their uncertainties, have also been re-evaluated for consistency, because these `experimental` values actually contain a calculated component. We therefore obtained an entirely coherent set of calculated and measured {beta}{sub eff}. The comparative study of the calculated and measured values pointed out that the JEF2.2 {nu}{sub d} are already sufficient because the (E-C)/C are inferior to 3 % in average and in their uncertainly bars. The experimental uncertainties, even if lightly superior to those previously edited, remain inferior to the uncertainties of the calculated values. This allowed us to fit {nu}{sub d} with {beta}{sub eff}. This adjustment has brought an additional improvement on the recommendations of the {nu}{sub d} average values, for the classical scheme (thermal energy, fast energy) and for the new scheme which explains the {nu}{sub d} energy dependence. {beta}{sub eff}, for MOX or UOX fuel assemblies in thermal or fast configurations, can therefore be obtained with an uncertainty due to the nuclear data of about 2.0 %. (author) 110 refs.

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

Science.gov (United States)

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

2010-06-02

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

Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide.

Science.gov (United States)

Amour, Julien; Loyer, Xavier; Le Guen, Morgan; Mabrouk, Nejma; David, Jean-Stéphane; Camors, Emmanuel; Carusio, Nunzia; Vivien, Benoît; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno

2007-09-01

In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l-NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic

The potential role of SOCS-3 in the interleukin-1beta-induced desensitization of insulin signaling in pancreatic beta-cells

DEFF Research Database (Denmark)

Emanuelli, Brice; Glondu, Murielle; Filloux, Chantal

2004-01-01

insulin signaling is required for the optimal beta-cell function, we assessed the effect of IL-1beta on the insulin pathway in a rat pancreatic beta-cell line. We show that IL-1beta decreases insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate (IRS...

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

Purification and properties of two /beta/-glucosidases isolated from Aspergillus niger

Energy Technology Data Exchange (ETDEWEB)

Witte, K.; Wartenberg, A.

1989-01-01

The cellulase complex of the fungus Aspergillus niger (strain CBS 554.65=ATCC 16 888) was fractionated by gel filtration yielding six pronounced peaks. Only proteins from the fraction corresponding to the first peak (96 kDa) showed /beta/-glucosidase activity vs. the substrate 4-nitrophenyl-/beta/-D-glucopyranoside (pNPG). These proteins have been fractionated by chromatofocusing, yielding two /beta/-glucosidases (I and II) which are shown to be homogeneous in isoelectric focusing experiments (pI=4.6 and 3.8, respectively). Kinetic experiments with pNPG, MU-glucopyranoside and cellobiose revealed that both types of /beta/-glucosidases behave like aryl-/beta/-glucosidases, /beta/-Glucosidase-I acting on pNPG exhibits a split kinetics characterized by high and low substrate-concentration kinetics which are differentiated by different values of V and of K/sub m/. In addition, /beta/-glucosidase-II is shown to be an exo-glucohydrolase as deduced from experiments with MU-cellobiopyranoside. Experimental features should be emphasized; usual soft-gel ion-exchange materials did not work in the chromatofocusing separation of the two /beta/-glucosidases, in contrast to the 10 /mu/-Si 500=DEAE exchange material (Serva) typically used in HPLC-experiments. Furthermore, protein content determinations based on different procedures yielded widely differing values. (orig.).

SME-3, a novel member of the Serratia marcescens SME family of carbapenem-hydrolyzing beta-lactamases.

Science.gov (United States)

Queenan, Anne Marie; Shang, Wenchi; Schreckenberger, Paul; Lolans, Karen; Bush, Karen; Quinn, John

2006-10-01

Imipenem-resistant Serratia marcescens isolates were cultured from a lung transplant patient given multiple antibiotics over several months. The strains expressed SME-3, a beta-lactamase of the rare SME carbapenem-hydrolyzing family. SME-3 differed from SME-1 by a single amino acid substitution of tyrosine for histidine at position 105, but the two beta-lactamases displayed similar hydrolytic profiles.

Individual Differences in Behavioural Despair Predict Brain GSK-3beta Expression in Mice: The Power of a Modified Swim Test.

Science.gov (United States)

Strekalova, Tatyana; Markova, Nataliia; Shevtsova, Elena; Zubareva, Olga; Bakhmet, Anastassia; Steinbusch, Harry M; Bachurin, Sergey; Lesch, Klaus-Peter

2016-01-01

While deficient brain plasticity is a well-established pathophysiologic feature of depression, little is known about disorder-associated enhanced cognitive processing. Here, we studied a novel mouse paradigm that potentially models augmented learning of adverse memories during development of a depressive-like state. We used a modification of the classic two-day protocol of a mouse Porsolt test with an additional session occurring on Day 5 following the initial exposure. Unexpectedly, floating behaviour and brain glycogen synthase kinase-3 beta (GSK-3beta) mRNA levels, a factor of synaptic plasticity as well as a marker of distress and depression, were increased during the additional swimming session that was prevented by imipramine. Observed increases of GSK-3beta mRNA in prefrontal cortex during delayed testing session correlated with individual parameters of behavioural despair that was not found in the classic Porsolt test. Repeated swim exposure was accompanied by a lower pGSK-3beta/GSK-3beta ratio. A replacement of the second or the final swim sessions with exposure to the context of testing resulted in increased GSK-3beta mRNA level similar to the effects of swimming, while exclusion of the second testing prevented these changes. Together, our findings implicate the activation of brain GSK-3beta expression in enhanced contextual conditioning of adverse memories, which is associated with an individual susceptibility to a depressive syndrome.

Modeling the mechanism of CLN025 beta-hairpin formation

Science.gov (United States)

McKiernan, Keri A.; Husic, Brooke E.; Pande, Vijay S.

2017-09-01

Beta-hairpins are substructures found in proteins that can lend insight into more complex systems. Furthermore, the folding of beta-hairpins is a valuable test case for benchmarking experimental and theoretical methods. Here, we simulate the folding of CLN025, a miniprotein with a beta-hairpin structure, at its experimental melting temperature using a range of state-of-the-art protein force fields. We construct Markov state models in order to examine the thermodynamics, kinetics, mechanism, and rate-determining step of folding. Mechanistically, we find the folding process is rate-limited by the formation of the turn region hydrogen bonds, which occurs following the downhill hydrophobic collapse of the extended denatured protein. These results are presented in the context of established and contradictory theories of the beta-hairpin folding process. Furthermore, our analysis suggests that the AMBER-FB15 force field, at this temperature, best describes the characteristics of the full experimental CLN025 conformational ensemble, while the AMBER ff99SB-ILDN and CHARMM22* force fields display a tendency to overstabilize the native state.

GSK3 inactivation is involved in mitochondrial complex IV defect in transforming growth factor (TGF) {beta}1-induced senescence

Energy Technology Data Exchange (ETDEWEB)

Byun, Hae-Ok; Jung, Hyun-Jung; Seo, Yong-Hak; Lee, Young-Kyoung [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721 (Korea, Republic of); Department of Molecular Science and Technology, The Graduate School, Ajou University, Suwon 443-721 (Korea, Republic of); Hwang, Sung-Chul [Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon 443-721 (Korea, Republic of); Seong Hwang, Eun [Department of Life Science, University of Seoul, Seoul 130-743 (Korea, Republic of); Yoon, Gyesoon, E-mail: ypeace@ajou.ac.kr [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721 (Korea, Republic of); Department of Molecular Science and Technology, The Graduate School, Ajou University, Suwon 443-721 (Korea, Republic of)

2012-09-10

Transforming growth factor {beta}1 (TGF {beta}1) induces Mv1Lu cell senescence by persistently producing mitochondrial reactive oxygen species (ROS) through decreased complex IV activity. Here, we investigated the molecular mechanism underlying the effect of TGF {beta}1 on mitochondrial complex IV activity. TGF {beta}1 progressively phosphorylated the negative regulatory sites of both glycogen synthase kinase 3 (GSK3) {alpha} and {beta}, corresponding well to the intracellular ROS generation profile. Pre-treatment of N-acetyl cysteine, an antioxidant, did not alter this GSK3 phosphorylation (inactivation), whereas pharmacological inhibition of GSK3 by SB415286 significantly increased mitochondrial ROS, implying that GSK3 phosphorylation is an upstream event of the ROS generation. GSK3 inhibition by SB415286 decreased complex IV activity and cellular O{sub 2} consumption rate and eventually induced senescence of Mv1Lu cell. Similar results were obtained with siRNA-mediated knockdown of GSK3. Moreover, we found that GSK3 not only exists in cytosol but also in mitochondria of Mv1Lu cell and the mitochondrial GSK3 binds complex IV subunit 6b which has no electron carrier and is topologically located in the mitochondrial intermembrane space. Involvement of subunit 6b in controlling complex IV activity and overall respiration rate was proved with siRNA-mediated knockdown of subunit 6b. Finally, TGF {beta}1 treatment decreased the binding of the subunit 6b to GSK3 and subunit 6b phosphorylation. Taken together, our results suggest that GSK3 inactivation is importantly involved in TGF {beta}1-induced complex IV defects through decreasing phosphorylation of the subunit 6b, thereby contributing to senescence-associated mitochondrial ROS generation.

Obesity does not aggravate vitrification injury in mouse embryos: a prospective study

Directory of Open Access Journals (Sweden)

Ma Wenhong

2012-08-01

Full Text Available Abstract Background Obesity is associated with poor reproductive outcomes, but few reports have examined thawed embryo transfer in obese women. Many studies have shown that increased lipid accumulation aggravates vitrification injury in porcine and bovine embryos, but oocytes of these species have high lipid contents (63 ng and 161 ng, respectively. Almost nothing is known about lipids in human oocytes except that these cells are anecdotally known to be relatively lipid poor. In this regard, human oocytes are considered to be similar to those of the mouse, which contain approximately 4 ng total lipids/oocyte. To date, no available data show the impact of obesity on vitrification in mouse embryos. The aim of this study was to establish a murine model of maternal diet-induced obesity and to characterize the effect of obesity on vitrification by investigating the survival rate and embryo developmental competence after thawing. Methods Prospective comparisons were performed between six–eight-cell embryos from obese and normal-weight mice and between fresh and vitrified embryos. Female C57BL/6 mice were fed standard rodent chow (normal-weight group or a high-fat diet (obese group for 6 weeks. The mice were mated, zygotes were collected from oviducts and cultured for 3 days, and six–eight-cell embryos were then selected to assess lipid content in fresh embryos and to evaluate differences in apoptosis, survival, and development rates in response to vitrification. Results In fresh embryos from obese mice, the lipid content (0.044 vs 0.030, Pvs.9.3%, Pvs. 93.1%, P Conclusions This study demonstrated that differences in survival and developmental rates between embryos from obese and normal-weight mice were eliminated after vitrification. Thus, maternal obesity does not aggravate vitrification injury, but obesity alone greatly impairs pre-implantation embryo survival and development.

Exposure to biohazards in wood dust: bacteria, fungi, endotoxins, and (1-->3)-beta-D-glucans.

Science.gov (United States)

Alwis, K U; Mandryk, J; Hocking, A D

1999-09-01

Personal exposure to fungi, bacteria, endotoxin, and (1-->3)-beta-D-glucan was determined at different woodworking sites--logging sites, sawmills, woodchipping sites, and joineries. Exposure levels to fungi at logging sites and sawmills were in the range of 10(3)-10(4) cfu/m3, at the woodchipping mill, 10(3)-10(5) cfu/m3, and at joineries, 10(2)-10(4) cfu/m3. Although mean endotoxin levels were lower than the suggested threshold value of 20 ng/m3, some personal exposures at sawmills and a joinery exceeded the standard. The geometric mean personal (1-->3)-beta-D-glucan exposure level at the woodchipping mill was 2.32 ng/m3, at sawmills, 1.37 ng/m3, at logging sites, 2.02 ng/m3, and at joineries, 0.43 ng/m3. Highly significant associations were found between mean personal inhalable endotoxin exposures and Gram-negative bacteria levels (p 3)-beta-D-glucan exposures and fungi levels (p = 0.0003). The prevalence of cough, phlegm, chronic bronchitis, nasal symptoms, frequent headaches, and eye and throat irritations was significantly higher among woodworkers than controls. Dose-response relationships were found between personal exposures and work-related symptoms among joinery workers and sawmill and chip mill workers.

Double beta radioactivity and physics of the neutrino. Study of the background noise at 3 MeV in the search of 100Mo beta beta decay

International Nuclear Information System (INIS)

Piquemal, F.

1994-05-01

Double beta decay without neutrino emission provides a test of the mass and nature of neutrinos (Majorana or Dirac). Experimental proof would be the observation of a peak at the transition energy in the spectrum of the two emitted electrons. The expected half-life of the process is extremely long (about 10 25 years for 100 Mo). So, being thus, it is very important to get a good knowledge of the origins and contributions of background noise in the region where the signal could occur. The main origins of the background noise in the region where the signal could occur. The main origins of the background noise are found to be e + - e - pairs induced by heavy energy gamma rays. These gamma rays follow the thermal neutron capture by the components of the detector. Another factor in the production of background noise is natural radio-activity. For example, the presence of Radon in the laboratory has been observed to produce deposits of 214 Bi on the sides of the detector. Data taken with the NEMO 2 prototype and an enriched molybdenum source foil indicates that the background limit reached is of the order of 1 event per year in the 3 MeV region. Results of this work have proven the necessity to have a magnetic field in NEMO 3 in order to reject e + - e - pairs. (author)

beta-Carotene in breast milk and serum is increased after a single beta-carotene dose.

Science.gov (United States)

Canfield, L M; Giuliano, A R; Neilson, E M; Yap, H H; Graver, E J; Cui, H A; Blashill, B M

1997-07-01

Normal lactating mothers were administered a single dose of 60 or 210 mg beta-carotene and changes in serum and milk retinol, alpha-tocopherol, and carotenoids were monitored for 8 d. Average serum beta-carotene concentrations increased 4.1- and 4.0-fold after the 60- and 210-mg doses, respectively. Milk beta-carotene concentrations increased 4.1- and 3.0-fold after the 60- and 210-mg doses, respectively. Maximum serum concentrations were reached 24 h after both supplements, although concentrations of milk beta-carotene continued to rise for 2-3 d. After 8 d, both serum and milk beta-carotene continued to rise for 2-3 d. After 8 d, both serum and milk beta-carotene concentrations remained about twofold higher than baseline concentrations. Increases in serum or milk beta-carotene concentrations were not dose-dependent. Initial serum and milk concentrations of beta-carotene predicted increases after supplementation, and increases in serum beta-carotene concentrations predicted those in milk. Concentrations of milk carotenoids were less than one-tenth their respective concentrations in serum. Lutein, beta-cryptoxanthin, lycopene, alpha-carotene, retinol, and alpha-tocopherol concentrations in serum or milk did not change significantly after beta-carotene supplementation. Retinol esters account for most of the retinol equivalents in the milk of well-nourished mothers. Initial and maximum concentrations of beta-carotene in serum and milk were strongly correlated for individual mothers. Collectively, the data showed that a single 60-mg supplement of beta-carotene sustained elevated beta-carotene concentrations in serum and milk for > 1 wk in normal mothers but did not affect concentrations of other major carotenoids, retinol, or alpha-tocopherol.

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

Main metabolites of 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl]-1-nitrosourea and 1-(2-chloroethyl)-3-(2',3', 4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea in rats

International Nuclear Information System (INIS)

Madelmont, J.C.; Moreau, M.F.; Godeneche, D.; Duprat, J.; Plagne, R.; Meyniel, G.

1982-01-01

The metabolism of two glycosylnitrosoureas, 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl]-1-nitrosourea (RFCNU) and 1-(2-chloroethyl)-3-(2',3',4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea (RPCNU), has been investigated in the rat. With the label on the carboxyl moiety of RFCNU, we have shown that hydrolysis of the 4-nitrobenzoyl ester occurred to a large extent in vivo; 4-nitrobenzoic acid and its glucuronide were the major urinary metabolites. Two other minor metabolites and their glucuronides were identified as 4-aminobenzoic acid and 4-acetamidobenzoic acid. With the label on the chloroethyl moieties of RFCNU and RPCNU, we have shown that chloroethanol was a major degradation product of this alkylating part of the molecule. The concentration of chloroethanol in plasma vs. time has been determined. In urine, four metabolites derived from alkylated glutathione, namely thiodiacetic acid and its sulfoxide, N-acetylcarboxymethylcysteine, and N-acetylhydroxyethylcysteine, have been identified

Ocean Acidification May Aggravate Social-Ecological Trade-Offs in Coastal Fisheries

Science.gov (United States)

Voss, Rudi; Quaas, Martin F.; Schmidt, Jörn O.; Kapaun, Ute

2015-01-01

Ocean Acidification (OA) will influence marine ecosystems by changing species abundance and composition. Major effects are described for calcifying organisms, which are significantly impacted by decreasing pH values. Direct effects on commercially important fish are less well studied. The early life stages of fish populations often lack internal regulatory mechanisms to withstand the effects of abnormal pH. Negative effects can be expected on growth, survival, and recruitment success. Here we study Norwegian coastal cod, one of the few stocks where such a negative effect was experimentally quantified, and develop a framework for coupling experimental data on OA effects to ecological-economic fisheries models. In this paper, we scale the observed physiological responses to the population level by using the experimentally determined mortality rates as part of the stock-recruitment relationship. We then use an ecological-economic optimization model, to explore the potential effect of rising CO2 concentration on ecological (stock size), economic (profits), consumer-related (harvest) and social (employment) indicators, with scenarios ranging from present day conditions up to extreme acidification. Under the assumptions of our model, yields and profits could largely be maintained under moderate OA by adapting future fishing mortality (and related effort) to changes owing to altered pH. This adaptation comes at the costs of reduced stock size and employment, however. Explicitly visualizing these ecological, economic and social tradeoffs will help in defining realistic future objectives. Our results can be generalized to any stressor (or stressor combination), which is decreasing recruitment success. The main findings of an aggravation of trade-offs will remain valid. This seems to be of special relevance for coastal stocks with limited options for migration to avoid unfavorable future conditions and subsequently for coastal fisheries, which are often small scale local

Ocean acidification may aggravate social-ecological trade-offs in coastal fisheries.

Science.gov (United States)

Voss, Rudi; Quaas, Martin F; Schmidt, Jörn O; Kapaun, Ute

2015-01-01

Ocean Acidification (OA) will influence marine ecosystems by changing species abundance and composition. Major effects are described for calcifying organisms, which are significantly impacted by decreasing pH values. Direct effects on commercially important fish are less well studied. The early life stages of fish populations often lack internal regulatory mechanisms to withstand the effects of abnormal pH. Negative effects can be expected on growth, survival, and recruitment success. Here we study Norwegian coastal cod, one of the few stocks where such a negative effect was experimentally quantified, and develop a framework for coupling experimental data on OA effects to ecological-economic fisheries models. In this paper, we scale the observed physiological responses to the population level by using the experimentally determined mortality rates as part of the stock-recruitment relationship. We then use an ecological-economic optimization model, to explore the potential effect of rising CO2 concentration on ecological (stock size), economic (profits), consumer-related (harvest) and social (employment) indicators, with scenarios ranging from present day conditions up to extreme acidification. Under the assumptions of our model, yields and profits could largely be maintained under moderate OA by adapting future fishing mortality (and related effort) to changes owing to altered pH. This adaptation comes at the costs of reduced stock size and employment, however. Explicitly visualizing these ecological, economic and social tradeoffs will help in defining realistic future objectives. Our results can be generalized to any stressor (or stressor combination), which is decreasing recruitment success. The main findings of an aggravation of trade-offs will remain valid. This seems to be of special relevance for coastal stocks with limited options for migration to avoid unfavorable future conditions and subsequently for coastal fisheries, which are often small scale local

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

IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

DEFF Research Database (Denmark)

Jacobsen, M L B; Rønn, S G; Bruun, C

2008-01-01

AIMS/HYPOTHESIS: Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1beta and IFN-gamma regulate...... the transcription of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine......-induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas m...

Double beta radioactivity and physics of the neutrino. Study of the background noise at 3 MeV in the search of {sup 100}Mo beta beta decay; Double radioactivite beta et physique du neutrino. Etude du bruit de fond a 3 MeV dans la recherche de la desintegration beta beta du {sup 100}Mo

Energy Technology Data Exchange (ETDEWEB)

Piquemal, F

1994-05-01

Double beta decay without neutrino emission provides a test of the mass and nature of neutrinos (Majorana or Dirac). Experimental proof would be the observation of a peak at the transition energy in the spectrum of the two emitted electrons. The expected half-life of the process is extremely long (about 10{sup 25} years for {sup 100}Mo). So, being thus, it is very important to get a good knowledge of the origins and contributions of background noise in the region where the signal could occur. The main origins of the background noise in the region where the signal could occur. The main origins of the background noise are found to be e{sup +} - e{sup -} pairs induced by heavy energy gamma rays. These gamma rays follow the thermal neutron capture by the components of the detector. Another factor in the production of background noise is natural radio-activity. For example, the presence of Radon in the laboratory has been observed to produce deposits of {sup 214}Bi on the sides of the detector. Data taken with the NEMO 2 prototype and an enriched molybdenum source foil indicates that the background limit reached is of the order of 1 event per year in the 3 MeV region. Results of this work have proven the necessity to have a magnetic field in NEMO 3 in order to reject e{sup +} - e{sup -}pairs. (author).

Impact Ionization in Monoclinic $\\beta-Ga_2O_3$

OpenAIRE

Ghosh, Krishnendu; Singisetti, Uttam

2017-01-01

We report a theoretical investigation of extremely high field transport in an emerging widebandgap material $\\beta-Ga_2O_3$ from first principles. The signature high-field effect explored here is impact ionization. Interaction between a ground-state electron and an excited electron is computed from the matrix elements of a screened Coulomb operator. Maximally localized Wannier functions (MLWF) are utilized in computing the electron-electron self-energy. A full-band Monte Carlo (FBMC) simulati...

SPL and Beta Beams to the Frejus

CERN Document Server

Mezzetto, M

2005-01-01

Physics potential of a conventional neutrino beam generated by the 2.2 GeV, 4MW, Superconducting Proton Linac and of a Beta Beam fired to a gigantic water Ccaronerenkov detector hosted below Frejus, 130 km away from CERN, are briefly summarized. theta/sub 13/ sensitivity could be improved by up to 3 orders of magnitude with respect to the present experimental limit and a first sensitive search for leptonic CP violation could be performed.

Selectivity of beta-adrenergic stimulating and blocking agents.

Science.gov (United States)

Löfdahl, C G; Svedmyr, N

1984-01-01

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

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...

Development and applications of beta and near beta titanium alloys

International Nuclear Information System (INIS)

Takemura, A.; Ohyama, H.; Nishimura, T.; Abumiya, T.

1993-01-01

In this report the authors introduced application of beta and near beta titanium alloys also development and processing of these alloys at Kobe Steel LTD. Ti-15Mo-5Zr-3Al is an alloy developed by Kobe Steel which has been applied for variety of sporting goods, also used as an erosion shield of steam turbine blades. Ti-15Mo-5Zr-3Al high strength wire for valve springs is under development. New beta alloys(Ti-V-Nb-Sn-Al) are under development which have lower flow stress at room temperature than Ti 15V-3Cr-3Sn-3Al, expected to improve productivity of cold forging. NNS forging and thermo mechanical treatment of Ti-10V-2Fe-3Al were studied. Ti-10V-2Fe3Al steam turbine blades and structural parts for aircraft were developed. Fine grain cold strips of Ti 15V-3Cr-3Sn-3Al are produced by annealing and pickling process. These cold strips are used for parts of a fishing rod

Individual Differences in Behavioural Despair Predict Brain GSK-3beta Expression in Mice: The Power of a Modified Swim Test

Directory of Open Access Journals (Sweden)

Tatyana Strekalova

2016-01-01

Full Text Available While deficient brain plasticity is a well-established pathophysiologic feature of depression, little is known about disorder-associated enhanced cognitive processing. Here, we studied a novel mouse paradigm that potentially models augmented learning of adverse memories during development of a depressive-like state. We used a modification of the classic two-day protocol of a mouse Porsolt test with an additional session occurring on Day 5 following the initial exposure. Unexpectedly, floating behaviour and brain glycogen synthase kinase-3 beta (GSK-3beta mRNA levels, a factor of synaptic plasticity as well as a marker of distress and depression, were increased during the additional swimming session that was prevented by imipramine. Observed increases of GSK-3beta mRNA in prefrontal cortex during delayed testing session correlated with individual parameters of behavioural despair that was not found in the classic Porsolt test. Repeated swim exposure was accompanied by a lower pGSK-3beta/GSK-3beta ratio. A replacement of the second or the final swim sessions with exposure to the context of testing resulted in increased GSK-3beta mRNA level similar to the effects of swimming, while exclusion of the second testing prevented these changes. Together, our findings implicate the activation of brain GSK-3beta expression in enhanced contextual conditioning of adverse memories, which is associated with an individual susceptibility to a depressive syndrome.

$\\beta$3$p$-spectroscopy and proton-$\\gamma$ width determination in the decay of $^{31}$Ar

CERN Multimedia

We propose to perform a detailed study of the $\\beta$-decay of the dripline nucleus $^{31}$Ar. This will allow a detailed study of the $\\beta$-delayed 3$p$-decay as well as provide important information on the resonances of $^{30}$S and $^{29}$P, in particular the ratio between the $p$- and $\\gamma$- partial widths relevant for astrophysics.

A plasmodesmata-associated beta-1,3-glucanase in Arabidopsis.

Science.gov (United States)

Levy, Amit; Erlanger, Michael; Rosenthal, Michal; Epel, Bernard L

2007-02-01

Plasmodesmal conductivity is regulated in part by callose turnover, which is hypothesized to be determined by beta-1,3-glucan synthase versus glucanase activities. A proteomic analysis of an Arabidopsis thaliana plasmodesmata (Pd)-rich fraction identified a beta-1,3-glucanase as present in this fraction. The protein encoded by the putative plasmodesmal associated protein (ppap) gene, termed AtBG_ppap, had previously been found to be a post-translationally modified glycosylphosphatidylinositol (GPI) lipid-anchored protein. When fused to green fluorescent protein (GFP) and expressed in tobacco (Nicotiana tabacum) or Nicotiana benthamiana epidermal cells, this protein displays fluorescence patterns in the endoplasmic reticulum (ER) membrane system, along the cell periphery and in a punctate pattern that co-localizes with aniline blue-stained callose present around the Pd. Plasma membrane localization was verified by co-localization of AtBG_ppap:GFP together with a plasma membrane marker N-[3-triethylammoniumpropyl]-4-[p-diethylaminophenylhexatrienyl] pyridinium dibromide (FM4-64) in plasmolysed cells. In Arabidopsis T-DNA insertion mutants that do not transcribe AtBG_ppap, functional studies showed that GFP cell-to-cell movement between epidermal cells is reduced, and the conductivity coefficient of Pd is lower. Measurements of callose levels around Pd after wounding revealed that callose accumulation in the mutant plants was higher. Taken together, we suggest that AtBG_ppap is a Pd-associated membrane protein involved in plasmodesmal callose degradation, and functions in the gating of Pd.

Platelet-derived growth factor-DD targeting arrests pathological angiogenesis by modulating glycogen synthase kinase-3beta phosphorylation.

Science.gov (United States)

Kumar, Anil; Hou, Xu; Lee, Chunsik; Li, Yang; Maminishkis, Arvydas; Tang, Zhongshu; Zhang, Fan; Langer, Harald F; Arjunan, Pachiappan; Dong, Lijin; Wu, Zhijian; Zhu, Linda Y; Wang, Lianchun; Min, Wang; Colosi, Peter; Chavakis, Triantafyllos; Li, Xuri

2010-05-14

Platelet-derived growth factor-DD (PDGF-DD) is a recently discovered member of the PDGF family. The role of PDGF-DD in pathological angiogenesis and the underlying cellular and molecular mechanisms remain largely unexplored. In this study, using different animal models, we showed that PDGF-DD expression was up-regulated during pathological angiogenesis, and inhibition of PDGF-DD suppressed both choroidal and retinal neovascularization. We also demonstrated a novel mechanism mediating the function of PDGF-DD. PDGF-DD induced glycogen synthase kinase-3beta (GSK3beta) Ser(9) phosphorylation and Tyr(216) dephosphorylation in vitro and in vivo, leading to increased cell survival. Consistently, GSK3beta activity was required for the antiangiogenic effect of PDGF-DD targeting. Moreover, PDGF-DD regulated the expression of GSK3beta and many other genes important for angiogenesis and apoptosis. Thus, we identified PDGF-DD as an important target gene for antiangiogenic therapy due to its pleiotropic effects on vascular and non-vascular cells. PDGF-DD inhibition may offer new therapeutic options to treat neovascular diseases.

Islet autoantibodies and residual beta cell function in type 1 diabetes children followed for 3-6 years

DEFF Research Database (Denmark)

Sørensen, Jesper Sand; Vaziri-Sani, Fariba; Maziarz, M

2012-01-01

To test if islet autoantibodies at diagnosis of type 1 diabetes (T1DM) and after 3-6 years with T1D predict residual beta-cell function (RBF) after 3-6 years with T1D.......To test if islet autoantibodies at diagnosis of type 1 diabetes (T1DM) and after 3-6 years with T1D predict residual beta-cell function (RBF) after 3-6 years with T1D....

Measurement of the two neutrino double beta decay half-life of Zr-96 with the NEMO-3 detector

Energy Technology Data Exchange (ETDEWEB)

Argyriades, J. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France); Arnold, R. [IPHC, Universite de Strasbourg, CNRS/IN2P3, F-67037 Strasbourg (France); Augier, C. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France); Baker, J. [INL, Idaho National Laboratory, 83415 Idaho Falls (United States); Barabash, A.S. [ITEP, Institute of Theoretical and Experimental Physics, 117259 Moscow (Russian Federation); Basharina-Freshville, A. [University College London, WC1E 6BT London (United Kingdom); Bongrand, M. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France); Broudin-Bay, G. [Universite Bordeaux, CENBG, UMR 5797, F-33175 Gradignan (France); CNRS/IN2P3, Centre d' Etudes Nucleaires de Bordeaux Gradignan, UMR5797, F-33175 Gradignan (France); Brudanin, V. [JINR, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation); Caffrey, A.J. [INL, Idaho National Laboratory, 83415 Idaho Falls (United States); Chapon, A. [LPC, ENSICAEN, Universite de Caen, CNRS/IN2P3, F-14032 Caen (France); Chauveau, E. [Universite Bordeaux, CENBG, UMR 5797, F-33175 Gradignan (France); CNRS/IN2P3, Centre d' Etudes Nucleaires de Bordeaux Gradignan, UMR5797, F-33175 Gradignan (France); Daraktchieva, Z. [University College London, WC1E 6BT London (United Kingdom); Durand, D. [LPC, ENSICAEN, Universite de Caen, CNRS/IN2P3, F-14032 Caen (France); Egorov, V. [JINR, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation); Fatemi-Ghomi, N. [University of Manchester, M13 9PL Manchester (United Kingdom); Flack, R. [University College London, WC1E 6BT London (United Kingdom); Guillon, B. [LPC, ENSICAEN, Universite de Caen, CNRS/IN2P3, F-14032 Caen (France); Hubert, Ph. [Universite Bordeaux, CENBG, UMR 5797, F-33175 Gradignan (France); CNRS/IN2P3, Centre d' Etudes Nucleaires de Bordeaux Gradignan, UMR5797, F-33175 Gradignan (France); Jullian, S. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France)

2010-12-08

Using 9.4 g of {sup 96}Zr isotope and 1221 days of data from the NEMO-3 detector corresponding to 0.031 kg y, the obtained 2{nu}{beta}{beta} decay half-life measurement is T{sub 1/2}{sup 2{nu}=}[2.35{+-}0.14(stat){+-}0.16(syst)]x10{sup 19} yr. Different characteristics of the final state electrons have been studied, such as the energy sum, individual electron energy, and angular distribution. The 2{nu} nuclear matrix element is extracted using the measured 2{nu}{beta}{beta} half-life and is M{sup 2{nu}=}0.049{+-}0.002. Constraints on 0{nu}{beta}{beta} decay have also been set.

Conformation, molecular packing and field effect mobility of regioregular beta,beta'-dihexylsexithiophiophene

DEFF Research Database (Denmark)

Kiriy, N.; Kiriy, A.; Bocharova, V.

2004-01-01

by the pulse-radiolysis time-resolved microwave conductivity (PR-TRMC) technique was found to be Sigmamu(min) = 3.9 x 10(-3) cm(2) V-1 s(-1), which is comparable with the PR-TRMC mobility found for alpha,omega-DH6T. The field-effect mobility (FEM) of beta,beta'-DH6T was found to be on the order of 10(-5) cm(2......) V-1 s(-1), which is considerably less than the FEM of alpha,omega-DH6T. To understand the reason for such poor macroscopic electrical properties, the conformation and the molecular packing of beta,beta'-DH6T were systematically studied by means of UV-vis spectroscopy, scanning electron microscopy...... less dense crystalline packing than alpha,omega-DH6T. In contrast to the almost upright orientation of alpha,omega-DH6T molecules against the substrate (tilt angle about 68), the long axis of beta,beta'-DH6T molecules and the surface plane form an angle of similar to20degrees. Thus, the crystalline...

Beta 1,3/1,6-glucan and vitamin C immunostimulate the non-specific immune response of white shrimp (Litopenaeus vannamei).

Science.gov (United States)

Wu, Yu-Sheng; Liau, Shu-Yu; Huang, Cheng-Ting; Nan, Fan-Hua

2016-10-01

This study mainly evaluated the effects of orally administered beta 1,3/1,6-glucan and vitamin C on the nonspecific immune responses of white shrimp (Litopenaeus vannamei). In this study, we found that the white shrimp oral administration with 1 g/kg of beta 1,3/1,6-glucan effectively enhanced O2(-) production and phenoloxidase and superoxide dismutase activity. Shrimp were oral administration with 0.2 g/kg of vitamin C presented beneficial nonspecific immune responses and enzyme activity and also observed in the beta 1,3/1,6-glucan treatment groups. Consequently, we compared the alterations in the immune activity between the beta 1,3/1,6-glucan and vitamin C groups and the evidence illustrated that combination of beta 1,3/1,6-glucan and vitamin C presented an additive effect on inducing the nonspecific immune responses of white shrimp. Copyright © 2016 Elsevier Ltd. All rights reserved.

Essential role of TGF-beta/Smad pathway on statin dependent vascular smooth muscle cell regulation.

Directory of Open Access Journals (Sweden)

Juan Rodríguez-Vita

Full Text Available BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII, and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs.

Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy.

Science.gov (United States)

Galán, María; Varona, Saray; Guadall, Anna; Orriols, Mar; Navas, Miquel; Aguiló, Silvia; de Diego, Alicia; Navarro, María A; García-Dorado, David; Rodríguez-Sinovas, Antonio; Martínez-González, José; Rodriguez, Cristina

2017-09-01

Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic LOX (TgLOX) mouse model with a strong cardiac expression of human LOX. TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H 2 O 2 production and with cardiofibroblast reprogramming. LOX overexpression promoted an age-associated concentric remodeling of the left ventricle and impaired diastolic function. Furthermore, LOX transgenesis aggravated angiotensin II (Ang II)-induced cardiac hypertrophy and dysfunction, which triggered a greater fibrotic response that was characterized by stronger collagen deposition and cross-linking and high expression of fibrotic markers. In addition, LOX transgenesis increased the Ang II-induced myocardial inflammatory infiltrate, exacerbated expression of proinflammatory markers, and decreased that of cardioprotective factors. Mechanistically, LOX overexpression enhanced oxidative stress and potentiated the Ang II-mediated cardiac activation of p38 MAPK while reducing AMPK activation. Our findings suggest that LOX induces an age-dependent disturbance of diastolic function and aggravates Ang II-induced hypertrophy, which provides novel insights into the role of LOX in cardiac performance.-Galán, M., Varona, S., Guadall, A., Orriols, M., Navas, M., Aguiló, S., de Diego, A., Navarro, M. A., García-Dorado, D., Rodríguez-Sinovas, A., Martínez-González, J., Rodriguez, C. Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy. © FASEB.

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.

High-fat diet aggravates 2,2′,4,4′-tetrabromodiphenyl ether-inhibited testosterone production via DAX-1 in Leydig cells in rats

International Nuclear Information System (INIS)

Zhang, Zhan; Yu, Yongquan; Xu, Hengsen; Wang, Chao; Ji, Minghui; Gu, Jun; Yang, Lu; Zhu, Jiansheng; Dong, Huibin; Wang, Shou-Lin

2017-01-01

Growing evidence has revealed that a high-fat diet (HFD) could lead to disorders of glycolipid metabolism and insulin-resistant states, and HFDs have been associated with the inhibition of testicular steroidogenesis. Our previous study demonstrated that 2,2′,4,4′-tetrabromodiphenyl ether (BDE47) could increase the risk of diabetes in humans and reduce testosterone production in rats. However, whether the HFD affects BDE47-inhibited testosterone production by elevating insulin levels and inducing related pathways remains unknown. In male rats treated with BDE47 by gavage for 12 weeks, the HFD significantly increased the BDE47 content of the liver and testis and increased the weight of the adipose tissue; increased macrovesicular steatosis in the liver and the levels of triglycerides, fasting glucose and insulin; further aggravated the disruption of the seminiferous epithelium; and lowered the level of testosterone, resulting in fewer sperm in the epididymis. Of note, the HFD enhanced BDE47-induced DAX-1 expression and decreased the expression levels of StAR and 3β-HSD in the testicular interstitial compartments in rats. In isolated primary Leydig cells from rats, BDE47 or insulin increased DAX-1 expression, decreased the expression of StAR and 3β-HSD, and reduced testosterone production, which was nearly reversed by knocking down DAX-1. These results indicated that the HFD aggravates BDE47-inhibited testosterone production through hyperinsulinemia, and the accumulation of testicular BDE47 that induces the up-regulation of DAX-1 and the subsequent down-regulation of steroidogenic proteins, i.e., StAR and 3β-HSD, in Leydig cells. - Highlights: • High-fat diet (HFD) aggravates the accumulation of BDE47 in liver and testis in rats. • HFD aggravates BDE47-inhibited testosterone production via DAX-1 in Leydig cells. • HFD enhances BDE47-induced the disorder of glycolipid metabolism and hyperinsulinemia. • Both hyperinsulinemia and accumulation of BDE47

High-fat diet aggravates 2,2′,4,4′-tetrabromodiphenyl ether-inhibited testosterone production via DAX-1 in Leydig cells in rats

Energy Technology Data Exchange (ETDEWEB)

Zhang, Zhan; Yu, Yongquan [State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Xu, Hengsen [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Wang, Chao [State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Ji, Minghui; Gu, Jun [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Yang, Lu; Zhu, Jiansheng [State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Dong, Huibin [Changzhou Center for Disease Control and Prevention, 203 Taishan Road, Changzhou 2013022 (China); Wang, Shou-Lin, E-mail: wangshl@njmu.edu.cn [State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China); Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166 (China)

2017-05-15

Growing evidence has revealed that a high-fat diet (HFD) could lead to disorders of glycolipid metabolism and insulin-resistant states, and HFDs have been associated with the inhibition of testicular steroidogenesis. Our previous study demonstrated that 2,2′,4,4′-tetrabromodiphenyl ether (BDE47) could increase the risk of diabetes in humans and reduce testosterone production in rats. However, whether the HFD affects BDE47-inhibited testosterone production by elevating insulin levels and inducing related pathways remains unknown. In male rats treated with BDE47 by gavage for 12 weeks, the HFD significantly increased the BDE47 content of the liver and testis and increased the weight of the adipose tissue; increased macrovesicular steatosis in the liver and the levels of triglycerides, fasting glucose and insulin; further aggravated the disruption of the seminiferous epithelium; and lowered the level of testosterone, resulting in fewer sperm in the epididymis. Of note, the HFD enhanced BDE47-induced DAX-1 expression and decreased the expression levels of StAR and 3β-HSD in the testicular interstitial compartments in rats. In isolated primary Leydig cells from rats, BDE47 or insulin increased DAX-1 expression, decreased the expression of StAR and 3β-HSD, and reduced testosterone production, which was nearly reversed by knocking down DAX-1. These results indicated that the HFD aggravates BDE47-inhibited testosterone production through hyperinsulinemia, and the accumulation of testicular BDE47 that induces the up-regulation of DAX-1 and the subsequent down-regulation of steroidogenic proteins, i.e., StAR and 3β-HSD, in Leydig cells. - Highlights: • High-fat diet (HFD) aggravates the accumulation of BDE47 in liver and testis in rats. • HFD aggravates BDE47-inhibited testosterone production via DAX-1 in Leydig cells. • HFD enhances BDE47-induced the disorder of glycolipid metabolism and hyperinsulinemia. • Both hyperinsulinemia and accumulation of BDE47

Rat beta-LPH, gamma-LPH and beta-endorphin biosynthesized by isolated cells of pars intermedia and pars distalis

International Nuclear Information System (INIS)

Gianoulakis, C.; Seidah, N.G.; Routhier, R.; Chretien, M.

1980-01-01

Rats pars intermedia cells were incubated for 3 h with the following amino-acids: a) 35 S-methionine and 3 H-phenylalamine; b) 3 H-valine; and c) 3 H-valine and 3 H-lysine. Radioactive gamma-lipotropin, beta-lipotropin and beta-endorphin were purified on carboxy- methyl-cellulose and characterized by polyacrylamide disc gel electrophoresis af pH 4.5, molecular weight estimation and microsequencing. Rat gamma-lipotropin was shown to differ slightly from ovine gamma-lipotropin in its NH 2 -terminal amino acid sequence, in containing no methionine and having phenylalanine at position 6, valine at positions 13 and 27, and lysine at position 20. The same variations were observed in the sequence of rat beta-lipotropin, while rat beta-endorphin was shown to be identical to the ovine beta-endorphin. Following a 3-h pulse of rat pars distalis, the cells were extracted with care to avoid beta-lipotropin degradation by proteolytic enzymes. A peptide was purified and identified to be rat beta-endorphin, thus demonstrating that beta-endorphin is biosynthesized in pars distalis and is not an extraction artifact. (author)

Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

Directory of Open Access Journals (Sweden)

Yihan Zhang

2016-01-01

Full Text Available Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R after high (25 mM or low (5.5 mM glucose culture. Cell viability, reactive oxygen species (ROS, and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2 and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

Beta activity of enriched uranium

International Nuclear Information System (INIS)

Nambiar, P.P.V.J.; Ramachandran, V.

1975-01-01

Use of enriched uranium as reactor fuel necessitates its handling in various forms. For purposes of planning and organising radiation protection measures in enriched uranium handling facilities, it is necessary to have a basic knowledge of the radiation status of enriched uranium systems. The theoretical variations in beta activity and energy with U 235 enrichment are presented. Depletion is considered separately. Beta activity build up is also studied for two specific enrichments, in respect of which experimental values for specific alpha activity are available. (author)

Study on adsorption of rhodamine B onto Beta zeolites by tuning SiO2/Al2O3 ratio.

Science.gov (United States)

Cheng, Zhi-Lin; Li, Yan-Xiang; Liu, Zan

2018-02-01

The exploration of the relationship between zeolite composition and adsorption performance favored to facilitate its better application in removal of the hazardous substances from water. The adsorption capacity of rhodamine B (RB) onto Beta zeolite from aqueous solution was reported. The relationship between SiO 2 /Al 2 O 3 ratio and adsorption capacity of Beta zeolite for RB was explored. The structure and physical properties of Beta zeolites with various SiO 2 /Al 2 O 3 ratios were determined by XRD, FTIR, TEM, BET, UV-vis and so on characterizations. The adsorption behavior of rhodamine B onto Beta zeolite matched to Langmuir adsorption isotherm and more suitable description for the adsorption kinetics was a pseudo-second-order reaction model. The maximum adsorption capacity of the as-prepared Beta zeolite with SiO 2 /Al 2 O 3 = 18.4 was up to 27.97mg/g. Copyright © 2017 Elsevier Inc. All rights reserved.

Immune-mediated beta-cell destruction in vitro and in vivo-A pivotal role for galectin-3

DEFF Research Database (Denmark)

Karlsen, Allan E; Størling, Zenia M; Sparre, Thomas

2006-01-01

Pro-apoptotic cytokines are toxic to the pancreatic beta-cells and have been associated with the pathogenesis of Type 1 diabetes (T1D). Proteome analysis of IL-1beta exposed isolated rat islets identified galectin-3 (gal-3) as the most up-regulated protein. Here analysis of human and rat islets a....... In summary, combined proteome-transcriptome-genome and functional analyses identify gal-3 as a candidate gene/protein in T1D susceptibility that may prove valuable in future intervention/prevention strategies....

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-12-16

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

Oral Candida as an aggravating factor of mucositis Induced by radiotherapy

International Nuclear Information System (INIS)

Simoes, Cristiane Araujo; Castro, Jurema Freire Lisboa de; Cazal, Claudia

2011-01-01

Antineoplastic treatment induces some undesirable consequences in head and neck cancer patients. Often, the emergence of major clinical manifestations, such as oral mucositis, results in temporary interruption of the treatment, decreasing the patients' quality of life, and increasing hospital costs. Radio-induced or chemo-induced oral mucositis is possibly aggravated by opportunist fungal infections, which turn the mucositis more resistant to the conventional treatments. Objective: this study aims to identify the presence of Candida sp. as a possible aggravating factor of oral mucositis in patients with head and neck cancer under antineoplastic treatment. Method: all patients with radio- or chemo-induced oral mucositis from the Cancer Hospital of Pernambuco, treated between October 2008 and April 2009, were selected for the study. The prevalence of Candida sp was measured through the cytological analysis of oral mucosa in patients with oral mucositis. The fungal presence was correlated with the mucositis severity. Results: the results showed a positive association between fungal colonization and more several lesions (degrees III and IV of mucositis). Conclusion: The outcomes shown may contribute to a solution for unconventional mucosites, which do not respond to the usual treatment. (author)

3D hand motion trajectory prediction from EEG mu and beta bandpower.

Science.gov (United States)

Korik, A; Sosnik, R; Siddique, N; Coyle, D

2016-01-01

A motion trajectory prediction (MTP) - based brain-computer interface (BCI) aims to reconstruct the three-dimensional (3D) trajectory of upper limb movement using electroencephalography (EEG). The most common MTP BCI employs a time series of bandpass-filtered EEG potentials (referred to here as the potential time-series, PTS, model) for reconstructing the trajectory of a 3D limb movement using multiple linear regression. These studies report the best accuracy when a 0.5-2Hz bandpass filter is applied to the EEG. In the present study, we show that spatiotemporal power distribution of theta (4-8Hz), mu (8-12Hz), and beta (12-28Hz) bands are more robust for movement trajectory decoding when the standard PTS approach is replaced with time-varying bandpower values of a specified EEG band, ie, with a bandpower time-series (BTS) model. A comprehensive analysis comprising of three subjects performing pointing movements with the dominant right arm toward six targets is presented. Our results show that the BTS model produces significantly higher MTP accuracy (R~0.45) compared to the standard PTS model (R~0.2). In the case of the BTS model, the highest accuracy was achieved across the three subjects typically in the mu (8-12Hz) and low-beta (12-18Hz) bands. Additionally, we highlight a limitation of the commonly used PTS model and illustrate how this model may be suboptimal for decoding motion trajectory relevant information. Although our results, showing that the mu and beta bands are prominent for MTP, are not in line with other MTP studies, they are consistent with the extensive literature on classical multiclass sensorimotor rhythm-based BCI studies (classification of limbs as opposed to motion trajectory prediction), which report the best accuracy of imagined limb movement classification using power values of mu and beta frequency bands. The methods proposed here provide a positive step toward noninvasive decoding of imagined 3D hand movements for movement-free BCIs. �

17Beta-hydroxysteroid dehydrogenase-3 deficiency: diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations

NARCIS (Netherlands)

A.L.M. Boehmer (Annemie); D.J.J. Halley (Dicky); P.E. de Ruiter (Petra); M.F. Niermeijer (Martinus); S. Andersson (Stefan); F.H. de Jong (Frank); H.H. Bode (Hans); S.L.S. Drop (Stenvert); H. Kayserili (Hülya); M.A. de Vroede; C. Rodrigues (Cidade); B.J. Otten (Barto); B.B. Mendonça (Berenice); H.A. Delemarre-van de Waal (Henriette); C.W. Rouwé (Catrienus); A.O. Brinkmann (Albert); L.A. Sandkuijl (Lodewijk)

1999-01-01

textabstract17Beta-hydroxysteroid dehydrogenase-3 (17betaHSD3) deficiency is an autosomal recessive form of male pseudohermaphroditism caused by mutations in the HSD17B3 gene. In a nationwide study on male pseudohermaphroditism among all pediatric endocrinologists and

Batf3-dependent CD8α+ Dendritic Cells Aggravates Atherosclerosis via Th1 Cell Induction and Enhanced CCL5 Expression in Plaque Macrophages.

Science.gov (United States)

Li, Yalin; Liu, Xueyan; Duan, Wei; Tian, Hua; Zhu, Guangming; He, Hao; Yao, Shutong; Yi, Shuying; Song, Wengang; Tang, Hua

2017-04-01

Dendritic cells (DCs) play an important role in controlling T cell-mediated adaptive immunity in atherogenesis. However, the role of the basic leucine zipper transcription factor, ATF-like 3 (Batf3)-dependent CD8α + DC subset in atherogenesis remains unclear. Here we show that Batf3 -/- Apoe -/- mice, lacking CD8α + DCs, exhibited a significant reduction in atherogenesis and T help 1 (Th1) cells compared with Apoe -/- controls. Then, we found that CD8α + DCs preferentially induce Th1 cells via secreting interleukin-12 (IL-12), and that the expression of interferon-gamma (IFN-γ)or chemokine (C-C motif) ligand 5 (CCL5) in aorta were significantly decreased in Batf3 -/- Apoe -/- mice. We further demonstrated that macrophages were the major CCL5-expressing cells in the plaque, which was significantly reduced in Batf3 -/- Apoe -/- mice. Furthermore, we found CCL5 expression in macrophages was promoted by IFN-γ. Finally, we showed that Batf3 -/- Apoe -/- mice displayed decreased infiltration of leukocytes in the plaque. Thus, CD8α + DCs aggravated atherosclerosis, likely by inducing Th1 cell response, which promoted CCL5 expression in macrophages and increased infiltration of leukocytes and lesion inflammation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Lithium chloride increases the production of amyloid-beta peptide independently from its inhibition of glycogen synthase kinase 3.

Science.gov (United States)

Feyt, Christine; Kienlen-Campard, Pascal; Leroy, Karelle; N'Kuli, Francisca; Courtoy, Pierre J; Brion, Jean-Pierre; Octave, Jean-Noël

2005-09-30

Glycogen synthase kinase 3 (GSK3) is able to phosphorylate tau at many sites that are found to be phosphorylated in paired helical filaments in Alzheimer disease. Lithium chloride (LiCl) efficiently inhibits GSK3 and was recently reported to also decrease the production of amyloid-beta peptide (Abeta) from its precursor, the amyloid precursor protein. Therefore, lithium has been proposed as a combined therapeutic agent, inhibiting both the hyperphosphorylation of tau and the production of Abeta. Here, we demonstrate that the inhibition of GSK3 by LiCl induced the nuclear translocation of beta-catenin in Chinese hamster ovary cells and rat cultured neurons, in which a decrease in tau phosphorylation was observed. In both cellular models, a nontoxic concentration of LiCl increased the production of Abeta by increasing the beta-cleavage of amyloid precursor protein, generating more substrate for an unmodified gamma-secretase activity. SB415286, another GSK3 inhibitor, induced the nuclear translocation of beta-catenin and slightly decreased Abeta production. It is concluded that the LiCl-mediated increase in Abeta production is not related to GSK3 inhibition.

4 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT

Science.gov (United States)

2016-09-01

Award Number: W81XWH-15-1-0409 TITLE: 4 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-04094 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT 5c...testicular androgens, testosterone or dihydrotestosterone ( DHT ). Men diagnosed with advanced prostate cancer or failure potentially curative therapy are

Phase relationships in the area of the beta aluminate of the system K{sub 2}O-MgO-AL{sub 2}O{sub 3}; Phasenbeziehungen im Bereich der Beta-Aluminate des Systems K{sub 2}O-MgO-Al{sub 2}O{sub 3}

Energy Technology Data Exchange (ETDEWEB)

Kroon, P de

1996-12-01

The aim of this work was to be able to make statements about the thermodynamic stability of K-{beta}``-Al{sub 2}O{sub 3} in the pseudo-binary system K{sub 2}O-Al{sub 2}O{sub 3} and in the pseudo-ternary system K{sub 2}O-MgO-Al{sub 2}O{sub 3} relative to the adjacent phases of KAlO{sub 2} {alpha}-Al{sub 2}O{sub 3}, MgAl{sub 2}O{sub 4} and K-{beta}-Al{sub 2}O{sub 3}. (orig./MM) [Deutsch] Ziel dieser Arbeit war es, Aussagen ueber die thermodynamische Stabilitaet von K-{beta}``-Al{sub 2}O{sub 3} im pseudobinaeren System K{sub 2}O-Al{sub 2}O{sub 3} und im pseudoternaeren System K{sub 2}O-MgO-Al{sub 2}O{sub 3} relativ zu den benachbarten Phasen KAlO{sub 2}, {alpha}-Al{sub 2}O{sub 3}, MgAl{sub 2}O{sub 4} und K-{beta}-Al{sub 2}O{sub 3} machen zu koennen. (orig./MM)

Pituitary resistance to thyroid hormone associated with a base mutation in the hormone-binding domain of the human 3, 5,3[prime]-triiodothyronine receptor-[beta

Energy Technology Data Exchange (ETDEWEB)

Sasaki, Shigekazu; Nakamura, Hirotoshi; Tagami, Tetsuya; Miyoshi, Yohzi; Nogimori, Tsuyoshi; Mitsuma, Terunori; Imura, Hiroo (Kyoto Univ. School of Medicine, Aichi (Japan))

1993-05-01

Point mutations in the human T[sub 3] receptor-[beta] (TR[beta]) gene causing single amino acid substitutions have been identified in several different kindred with generalized resistance to thyroid hormone. Until now, no study has been reported on the TR gene in cases of pituitary resistance (PRTH). In the present study, the authors analyzed the TR[beta] gene in a 30-yr-old Japanese female with PRTH. She exhibited clinical features of hyperthyroidism, elevated serum thyroid hormone levels accompanied by inappropriately increased secretion of TSH, mildly elevated basal metabolic rate, and increased urinary excretion of hydroxyproline. No pituitary tumor was detected. DNA fragments of exons 3-8 of the geonomic TR[beta] gene were generated by the polymerase chain reaction and analyzed by a single stranded conformation polymorphism method. Exon 7 of the patient's TR[beta] gene showed an abnormal band, suggesting the existence of mutation(s). By subcloning and sequencing the DNA, a point mutation was identified in one allele at nucleotide 1297 (C to T), which altered the 333rd amino acid, arginine, to tryptophan. Neither of her apparently normal parents had any mutations of the TR[beta] gene. In vitro translation products of the mutant TR[beta] gene showed remarkably decreased T[sub 3]-binding activity (K[sub a], 2.1 [times] 10[sup 8] M[sup [minus]1]; normal TR[beta] K[sub a], 1.1 [times] 10[sup 10] M[sup [minus]1]). Since the molecular defect detected in a patient with PRTH is similar to that seen in subjects with generalized resistance to thyroid hormone, both types of the syndrome may represent a continuous spectrum of the same etiological defect with variable tissue resistance to thyroid hormone.

Human-specific SNP in obesity genes, adrenergic receptor beta2 (ADRB2, Beta3 (ADRB3, and PPAR γ2 (PPARG, during primate evolution.

Directory of Open Access Journals (Sweden)

Akiko Takenaka

Full Text Available UNLABELLED: Adrenergic-receptor beta2 (ADRB2 and beta3 (ADRB3 are obesity genes that play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. The Glu27 allele in ADRB2 and the Arg64 allele in ADRB3 are associated with abdominal obesity and early onset of non-insulin-dependent diabetes mellitus (NIDDM in many ethnic groups. Peroxisome proliferator-activated receptor γ (PPARG is required for adipocyte differentiation. Pro12Ala mutation decreases PPARG activity and resistance to NIDDM. In humans, energy-expense alleles, Gln27 in ADRB2 and Trp64 in ADRB3, are at higher frequencies than Glu27 and Arg64, respectively, but Ala12 in PPARG is at lower frequency than Pro12. Adaptation of humans for lipolysis, thermogenesis, and reduction of fat accumulation could be considered by examining which alleles in these genes are dominant in non-human primates (NHP. All NHP (P. troglodytes, G. gorilla, P. pygmaeus, H. agilis and macaques had energy-thrifty alleles, Gly16 and Glu27 in ADRB2, and Arg64 in ADRB3, but did not have energy-expense alleles, Arg16, Gln27 and Trp64 alleles. In PPARG gene, all NHP had large adipocyte accumulating type, the Pro12 allele. CONCLUSIONS: These results indicate that a tendency to produce much more heat through the energy-expense alleles developed only in humans, who left tropical rainforests for savanna and developed new features in their heat-regulation systems, such as reduction of body hair and increased evaporation of water, and might have helped the protection of entrails from cold at night, especially in glacial periods.

Characterization of the guinea pig 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4-isomerase expressed in the adrenal gland and gonads.

Science.gov (United States)

Durocher, Francine; Sanchez, Rocio; Ricketts, Marie-Louise; Labrie, Yvan; Laudet, Vincent; Simard, Jacques

2005-11-01

The guinea pig adrenal gland, analogous to the human, possesses the capacity to synthesize C(19) steroids. In order to further understand the control of guinea pig adrenal steroidogenesis we undertook the characterization of the guinea pig 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3beta-HSD) expressed in the adrenal gland. A cDNA clone encoding guinea pig 3beta-HSD isolated from a guinea pig adrenal library is predicted to encode a protein of 373 amino acid residues and 41,475Da. Ribonuclease protection assay suggests that this cDNA corresponds to the predominant, if not the sole, mRNA species detectable in total RNA from the guinea pig adrenal gland, ovary and testis. The guinea pig 3beta-HSD shows a similar affinity for both pregnenolone and dehydroepiandrosterone, and in addition, a 17beta-HSD type II-like activity was also observed. A phylogenetical analysis of the 3beta-HSD gene family demonstrates that the guinea pig is in a parallel branch to the myomorpha group supporting the hypothesis that the guinea pig lineage has branched off after the divergence among primates, artiodactyls and rodents, suggesting the paraphyly of the order rodentia.

A Behaviorally Specific, Empirical Alternative to Bullying: Aggravated Peer Victimization.

Science.gov (United States)

Finkelhor, David; Shattuck, Anne; Turner, Heather; Hamby, Sherry

2016-11-01

To test a behaviorally specific measure of serious peer victimization, called aggravated peer victimization (APV), using empirically derived aggravating elements of episodes (injury, weapon, bias content, sexual content, multiple perpetrators, and multiple contexts) and compare this measure with the conventional Olweus bullying (OB) measure, which uses repetition and power imbalance as its seriousness criteria. The data for this study come from The National Survey of Children's Exposure to Violence 2014, a study conducted via telephone interviews with a nationally representative sample. This analysis uses the 1,949 youth ages 10-17 from that survey. The APV measure identified twice as many youth with serious episodes involving injury, weapons, sexual assaults, and bias content as the OB measure. In terms of demographic and social characteristics, the groups were very similar. However, the APV explained significantly more of the variation in distress than the OB (R 2  = .19 vs. .12). An empirical approach to identifying the most serious incidents of peer victimization has advantages in identifying more of the youth suffering the effects of peer victimization. Moreover, its behaviorally specific criteria also bypass the difficult challenge of trying to reliably assess what is truly bullying with its ambiguous definitional element of power imbalance. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2017-01-01

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

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

Science.gov (United States)

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

2003-02-01

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

17 beta-hydroxysteroid dehydrogenase-3 deficiency : Diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations

NARCIS (Netherlands)

Boehmer, ALM; Brinkmann, AO; Sandkuijl, LA; Halley, DJJ; Niermeijer, MF; Andersson, S; de Jong, FH; Kayserili, H; de Vroede, MA; Otten, BJ; Rouwe, CW; Mendonca, BB; Rodrigues, C; Bode, HH; de Ruiter, PE; Delemarre-van de Waal, HA; Drop, SLS

1999-01-01

17 beta-Hydroxysteroid dehydrogenase-3 (17 beta HSD3) deficiency is an autosomal recessive form of male pseudohermaphroditism caused by mutations in the HSD17B3 gene. In a nationwide study on male pseudohermaphroditism among all pediatric endocrinologists and clinical geneticists in The Netherlands,

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-01-01

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

Development of beta reference radiations

International Nuclear Information System (INIS)

Wan Zhaoyong; Cai Shanyu; Li Yanbo; Yin Wei; Feng Jiamin; Sun Yuhua; Li Yongqiang

1997-09-01

A system of beta reference radiation has been developed, that is composed of 740 MBq 147 Pm beta source, 74 MBq and 740 MBq 90 Sr + 90 Y β sources, compensation filters, a source handling tool, a source jig, spacing bars, a shutter, a control unit and a beta dose meter calibration stand. For 740 MBq 147 Pm and 74 MBq 90 Sr + 90 Y beta reference radiations with compensation filters and 740 MBq 90 Sr + 90 Y beta reference radiation without compensation filter, at 20 cm, 30 cm and 30 cm distance separately; the residual energy of maximum is 0.14 MeV, 1.98 MeV and 2.18 MeV separately; the absorbed dose to tissue D (0.07) is 1.547 mGy/h (1996-05-20), 5.037 mGy/h (1996-05-10) and 93.57 mGy/h (1996-05-15) separately; the total uncertainty is 3.0%, 1.7% and 1.7% separately. For the first and the second beta reference radiation, the dose rate variability in the area of 18 cm diameter in the plane perpendicular to the beta-ray beam axis is within +-6% and +-3% separately. (3 refs., 2 tabs., 8 figs.)

A proportional chamber to measure the screening potential in sup 3 H beta decay

CERN Document Server

Paterson, D J; Batkin, I S

1999-01-01

A gas proportional chamber has been assembled to make precise observations of the low-energy region of the sup 3 H beta spectrum. Backgrounds have been measured and understood, and are maintained at approx 2% of the data rate. Wall effects have been simulated for this chamber and are predicted at <0.5% of events. Systematic effects which may introduce errors into the observed spectrum have been carefully measured at a level below approx 10 sup - sup 4 per ADC channel. This apparatus will be used to make precise measurements of the effects of screening of the nuclear charge by orbital electrons on the beta spectrum of sup 3 H, and to attempt to observe the effect of a hypothesized admixture of heavy neutrinos in the sup 3 H spectrum.

Leptin promotes osteoblast differentiation and mineralization of primary cultures of vascular smooth muscle cells by inhibiting glycogen synthase kinase (GSK)-3{beta}

Energy Technology Data Exchange (ETDEWEB)

Zeadin, Melec G.; Butcher, Martin K.; Shaughnessy, Stephen G. [Department of Medicine, McMaster University, Hamilton, ON (Canada); Thrombosis and Atherosclerosis Research Institute, Hamilton, ON (Canada); Werstuck, Geoff H., E-mail: Geoff.Werstuck@taari.ca [Department of Medicine, McMaster University, Hamilton, ON (Canada); Thrombosis and Atherosclerosis Research Institute, Hamilton, ON (Canada)

2012-09-07

Highlights: Black-Right-Pointing-Pointer Leptin promotes osteoblast differentiation of primary smooth muscle cells. Black-Right-Pointing-Pointer Leptin regulates the expression of genes involved in osteoblast differentiation. Black-Right-Pointing-Pointer Constitutively active GSK-3{beta} attenuates leptin-induced osteoblast differentiation. Black-Right-Pointing-Pointer This suggests that leptin signals through GSK-3{beta} to promote osteoblast differentiation. -- Abstract: In this study, we begin to investigate the underlying mechanism of leptin-induced vascular calcification. We found that treatment of cultured bovine aortic smooth muscle cells (BASMCs) with leptin (0.5-4 {mu}g/ml) induced osteoblast differentiation in a dose-dependent manner. Furthermore, we found that leptin significantly increased the mRNA expression of osteopontin and bone sialoprotein, while down-regulating matrix gla protein (MGP) expression in BASMCs. Key factors implicated in osteoblast differentiation, including members of the Wnt signaling pathway, were examined. Exposure to leptin enhanced phosphorylation of GSK-3{beta} on serine-9 thereby inhibiting activity and promoting the nuclear accumulation of {beta}-catenin. Transfection of BASMCs with an adenovirus that expressed constitutively active GSK-3{beta} (Ad-GSK-3{beta} S9A) resulted in a >2-fold increase in GSK-3{beta} activity and a significant decrease in leptin-induced alkaline phosphatase (ALP) activity. In addition, qRT-PCR analysis showed that GSK-3{beta} activation resulted in a significant decrease in the expression of osteopontin and bone sialoprotein, but a marked increase in MGP mRNA expression. When taken together, our results suggest a mechanism by which leptin promotes osteoblast differentiation and vascular calcification in vivo.

Beta limit of resistive plasma in Torsatron / Heliotron

International Nuclear Information System (INIS)

Itoh, K.; Ichiguchi, K.; Itoh, S.I.

1992-02-01

Stability against the interchange mode in the Torsatron / Heliotron device is investigated, taking into account the effects of the resistivity, current diffusivity, ion viscosity and thermal diffusivity. Critical beta for the low-mode-number stability is found at the finite beta value. For the range of plasma parameters of the present experiments, the resistive mode and current diffusive mode set comparable critical beta values, which are consistent with experimental observations. In future high temperature plasmas, the current diffusive mode determines the stability limit for the global mode. (author)

Non-redundant roles of phosphoinositide 3-kinase isoforms alpha and beta in glycoprotein VI-induced platelet signaling and thrombus formation.

Science.gov (United States)

Gilio, Karen; Munnix, Imke C A; Mangin, Pierre; Cosemans, Judith M E M; Feijge, Marion A H; van der Meijden, Paola E J; Olieslagers, Servé; Chrzanowska-Wodnicka, Magdalena B; Lillian, Rivka; Schoenwaelder, Simone; Koyasu, Shigeo; Sage, Stewart O; Jackson, Shaun P; Heemskerk, Johan W M

2009-12-04

Platelets are activated by adhesion to vascular collagen via the immunoglobulin receptor, glycoprotein VI (GPVI). This causes potent signaling toward activation of phospholipase Cgamma2, which bears similarity to the signaling pathway evoked by T- and B-cell receptors. Phosphoinositide 3-kinase (PI3K) plays an important role in collagen-induced platelet activation, because this activity modulates the autocrine effects of secreted ADP. Here, we identified the PI3K isoforms directly downstream of GPVI in human and mouse platelets and determined their role in GPVI-dependent thrombus formation. The targeting of platelet PI3Kalpha or -beta strongly and selectively suppressed GPVI-induced Ca(2+) mobilization and inositol 1,4,5-triphosphate production, thus demonstrating enhancement of phospholipase Cgamma2 by PI3Kalpha/beta. That PI3Kalpha and -beta have a non-redundant function in GPVI-induced platelet activation and thrombus formation was concluded from measurements of: (i) serine phosphorylation of Akt, (ii) dense granule secretion, (iii) intracellular Ca(2+) increases and surface expression of phosphatidylserine under flow, and (iv) thrombus formation, under conditions where PI3Kalpha/beta was blocked or p85alpha was deficient. In contrast, GPVI-induced platelet activation was insensitive to inhibition or deficiency of PI3Kdelta or -gamma. Furthermore, PI3Kalpha/beta, but not PI3Kgamma, contributed to GPVI-induced Rap1b activation and, surprisingly, also to Rap1b-independent platelet activation via GPVI. Together, these findings demonstrate that both PI3Kalpha and -beta isoforms are required for full GPVI-dependent platelet Ca(2+) signaling and thrombus formation, partly independently of Rap1b. This provides a new mechanistic explanation for the anti-thrombotic effect of PI3K inhibition and makes PI3Kalpha an interesting new target for anti-platelet therapy.

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

Science.gov (United States)

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

2014-04-29

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

Optimization of plastic scintillator thicknesses for online beta/gamma detection

Directory of Open Access Journals (Sweden)

Pourtangestani K.

2012-04-01

Full Text Available For efficient beta detection in a mixed beta gamma field, Monte Carlo simulation models have been built to optimize the thickness of a plastic scintillator, used in a whole body monitor. The simulation has been performed using the MCNP/X code for different thicknesses of plastic scintillator from 150 μm to 600 μm. The relationship between the thickness of the scintillator and the efficiency of the detector has been analyzed. For 150 μm thickness, an experimental investigation has been conducted with different beta sources at different positions on the scintillator and the counting efficiency of the unit has been measured. Evaluated data along with experimental ones have been discussed. A thickness of 300 μm to 500 μm has been found to be the optimum thickness for high efficiency beta detection in the presence of low energy gamma-rays.

Inhibition of Common Cold-Induced Aggravation of Childhood Asthma by Leukotriene Receptor Antagonists

Directory of Open Access Journals (Sweden)

Shigemi Yoshihara

2012-01-01

Conclusions: : These findings showed a high prevalence of common cold in younger patients with childhood asthma and indicated that common cold can induce aggravation of asthma. LTRAs are useful for long-term asthma control in very young patients who develop an asthma attack due to a common cold.

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

Science.gov (United States)

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

2006-04-01

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

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 adrenoceptors substitute the role of M(2) muscarinic receptor in coping with cold stress in the heart: evidence from M(2)KO mice.

Science.gov (United States)

Benes, Jan; Novakova, Martina; Rotkova, Jana; Farar, Vladimir; Kvetnansky, Richard; Riljak, Vladimir; Myslivecek, Jaromir

2012-07-01

We investigated the role of beta3-adrenoceptors (AR) in cold stress (1 or 7 days in cold) in animals lacking main cardioinhibitive receptors-M2 muscarinic receptors (M(2)KO). There was no change in receptor number in the right ventricles. In the left ventricles, there was decrease in binding to all cardiostimulative receptors (beta1-, and beta2-AR) and increase in cardiodepressive receptors (beta3-AR) in unstressed KO in comparison to WT. The cold stress in WT animals resulted in decrease in binding to beta1- and beta2-AR (to 37%/35% after 1 day in cold and to 27%/28% after 7 days in cold) while beta3-AR were increased (to 216% of control) when 7 days cold was applied. MR were reduced to 46% and 58%, respectively. Gene expression of M2 MR in WT was not changed due to stress, while M3 was changed. The reaction of beta1- and beta2-AR (binding) to cold was similar in KO and WT animals, and beta3-AR in stressed KO animals did not change. Adenylyl cyclase activity was affected by beta3-agonist CL316243 in cold stressed WT animals but CL316243 had almost no effects on adenylyl cyclase activity in stressed KO. Nitric oxide activity (NOS) was not affected by BRL37344 (beta3-agonist) both in WT and KO animals. Similarly, the stress had no effects on NOS activity in WT animals and in KO animals. We conclude that the function of M2 MR is substituted by beta3-AR and that these effects are mediated via adenylyl cyclase rather than NOS.

Meson-Exchange Enhancement of First-Forbidden $\\beta$-Transitions in the Lead Region

CERN Multimedia

Delaure, B J P; Severijns, N

2002-01-01

Both on-line and off-line low temperature nuclear orientation is used to measure the $\\beta$-asymmetry parameter for the first-forbidden g.s. $\\rightarrow$~g.s. $\\beta$-transitions of $^{205}$Hg, $^{207,209}$Tl, $^{209}$Pb and $^{213}$Bi. From this, the ratio of the rank-zero and the rank-one strengths in these decays can be deduced, with the rank of a $\\beta$-transition being defined as the total angular momentum of the lepton system. Combining this result with the experimental ${ft}$-values yields for the first time a purely experimental determination of the rank-zero contribution in these $\\Delta$ J = 0 first-forbidden transitions. This provides an independent check of the large enhancement (of about 100% over the impulse approximation) of the rank-zero matrix element of $\\gamma_{5} $, caused by meson exchange currents (MEC), which was recently obtained from a comparison of calculated first-forbidden $\\beta$-decay rates with experimentally observed values for nuclei in the lead region (A = 205-212). Measur...

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...

Reducing atelectasis attenuates bacterial growth and translocation in experimental pneumonia

NARCIS (Netherlands)

van Kaam, Anton H.; Lachmann, Robert A.; Herting, Egbert; de Jaegere, Anne; van Iwaarden, Freek; Noorduyn, L. Arnold; Kok, Joke H.; Haitsma, Jack J.; Lachmann, Burkhard

2004-01-01

Besides being one of the mechanisms responsible for ventilator-induced lung injury, atelectasis also seems to aggravate the course of experimental pneumonia. In this study, we examined the effect of reducing the degree of atelectasis by natural modified surfactant and/or open lung ventilation on

Influence of beetroot (Beta vulgaris var. cruenta) on mice leukocytes increase

OpenAIRE

Amaro, Jony

2014-01-01

Background: Beetroot is a flavonoid-containing Mediterranean plant used for food and medicinal purposes. Objectives: To determine the influence of Beta vulgaris var. cruenta extract consumption in increasing albino mice leukocytes. Design: Experimental study. Setting: School N° 1182 bioterium. Biologic material: Twenty male Balb/c albino mice weighing 24 g average. Interventions: Two groups of ten mice each were formed; the experimental group received Beta vulgaris var. cruenta extract at 250...

Blockade of rat alpha3beta4 nicotinic receptor function by methadone, its metabolites, and structural analogs.

Science.gov (United States)

Xiao, Y; Smith, R D; Caruso, F S; Kellar, K J

2001-10-01

The opioid agonist properties of (+/-)-methadone are ascribed almost entirely to the (-)-methadone enantiomer. To extend our knowledge of the pharmacological actions of methadone at ligand-gated ion channels, we investigated the effects of the two enantiomers of methadone and its metabolites R-(+)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium perchlorate (EDDP) and R-(+)-2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline hydrochloride (EMDP), as well as structural analogs of methadone, including (-)-alpha-acetylmethadol hydrochloride (LAAM) and (+)-alpha-propoxyphene, on rat alpha3beta4 neuronal nicotinic acetylcholine receptors (nAChRs) stably expressed in a human embryonic kidney 293 cell line, designated KXalpha3beta4R2. (+/-)-methadone inhibited nicotine-stimulated 86Rb+ efflux from the cells in a concentration-dependent manner with an IC50 value of 1.9 +/- 0.2 microM, indicating that it is a potent nAChR antagonist. The (-)- and (+)-enantiomers of methadone have similar inhibitory potencies on nicotine-stimulated 86Rb+ efflux, with IC50 values of approximately 2 microM. EDDP, the major metabolite of methadone, is even more potent, with an IC50 value of approximately 0.5 microM, making it one of the most potent nicotinic receptor blockers reported. In the presence of (+/-)-methadone, EDDP, or LAAM, the maximum nicotine-stimulated 86Rb+ efflux was markedly decreased, but the EC50 value for nicotine stimulation was altered only slightly, if at all, indicating that these compounds block alpha3beta4 nicotinic receptor function by a noncompetitive mechanism. Consistent with a noncompetitive mechanism, (+/-)-methadone, its metabolites, and structural analogs have very low affinity for nicotinic receptor agonist binding sites in membrane homogenates from KXalpha3beta4R2 cells. We conclude that both enantiomers of methadone and its metabolites as well as LAAM and (+)-alpha-propoxyphene are potent noncompetitive antagonists of alpha3beta4 nAChRs.

Chronic Exposure to Subtherapeutic Antibiotics Aggravates Ischemic Stroke Outcome in Mice

Directory of Open Access Journals (Sweden)

Xiao-Hui Dong

2017-10-01

Full Text Available Subtherapeutic antibiotics have been widely used in agriculture since the 1950s, which can be accumulated in human body through various approaches and may have long-term consequences. However, there is limited information about the link between chronic subtherapeutic antibiotic exposure and the outcome of ischemic brain injury. Here we showed that long-term treatment with subtherapeutic chlortetracycline, penicillin or vancomycin, which were widely used in agriculture approved by US Food and Drug Administration (FDA, could impair EPC functions, reduce ischemic brain angiogenesis and aggravate cerebral ischemic injury and long-term stroke outcomes in mice. In addition, transplantated EPCs from chronic antibiotic-treated mice showed a lower therapeutic effect on cerebral ischemic injury reduction and local angiogenesis promotion compared to those from control mice, and EPCs from the donor animals could integrate into the recipient ischemic brain in mice. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury reduction in mice, which could be impaired by chronic antibiotic exposure. In conclusion, chronic subtherapeutic antibiotic exposure aggravated cerebral ischemic injury in mice, which might be partly attributed to the impairment of both EPC-mediated angiogenesis and EPCs' paracrine effects. These findings reveal a previously unrecognized impact of chronic subtherapeutic antibiotic exposure on ischemic injury.

Beta decay of 22O

International Nuclear Information System (INIS)

Hubert, F.; Dufour, J.P.; Moral, R. del; Fleury, A.; Jean, D.; Pravikoff, M.S.; Delagrange, H.; Geissel, H.; Schmidt, K.H.; Hanelt, E.

1989-01-01

The beta-gamma spectroscopic study of 22 O is presented. This nucleus, produced as a projectile-like fragment from the interaction of a 60 MeV/n 40 Ar beam with a Be target, has been separated by the LISE spectrometer. Several gamma rays from 22 O decay have been observed, from which a half-life of (2.25±0.15) s has been determined. Accurate excitation energies have been deduced for several states in 22 F. A partial beta decay scheme of 22 O has been established. Experimental results have been compared with shell model calculations. (orig.)

[H-3]dihydroalprenolol binding to beta adrenergic receptors in multiple sclerosis brain

NARCIS (Netherlands)

Zeinstra, E; Wilczak, N; De Keyser, J

2000-01-01

By using immunocytochemistry we previously reported the absence of beta(2) adrenergic receptors on astrocytes in multiple sclerosis (MS) white matter. Here, we measured beta(1) and beta(2) adrenergic receptor concentrations in postmortem brain sections of six MS patients and six controls by using

High beta and confinement studies on TFTR

International Nuclear Information System (INIS)

Navratil, G.A.; Bhattacharjee, A.; Iacono, R.; Mauel, M.E.; Sabbagh, S.A.; Kesner, J.

1992-01-01

A new regime of high poloidal beta operation in TFTR was developed in the course of the first two years of this project (9/25/89 to 9/24/91). Our proposal to continue this successful collaboration between Columbia University and the Massachusetts Institute of Technology with the Princeton Plasma Physics Laboratory for a three year period (9/25/91 to 9/24/94) to continue to investigate improved confinement and tokamak performance in high poloidal beta plasmas in TFTR through the DT phase of operation was approved by the DOE and this is a report of our progress during the first 9 month budget period of the three year grant (9/25/91 to 6/24/92). During the approved three year project period we plan to (1) extend and apply the low current, high QDD discharges to the operation of TFTR using Deuterium and Tritium plasma; (2) continue the analysis and plan experiments on high poloidal beta phenomena in TFTR including: stability properties, enhanced global confinement, local transport, bootstrap current, and divertor formation; (3) plan and carry out experiments on TFTR which attempt to elevate the central q to values > 2 where entry to the second stability regime is predicted to occur; and (4) collaborate on high beta experiments using bean-shaped plasmas with a stabilizing conducting shell in PBX-M. In the seven month period covered by this report we have made progress in each of these four areas through the submission of 4 TFTR Experimental Proposals and the partial execution of 3 of these using a total of 4.5 run days during the August 1991 to February 1992 run

Why search for double beta decay?

International Nuclear Information System (INIS)

Kayser, B.

1988-01-01

Searching for neutrinoless double beta decay is the only known practical method for trying to determine whether neutrinos are their own antiparticles. The theoretical motivation for supposing that they may indeed be their own antiparticles is described. The reason that it is so difficult to ascertain experimentally whether they are or are not is explained, as is the special sensitivity of neutrinoless double beta decay. The potential implications of the observation of this reaction for neutrino mass and for the physics of neutrinos is discussed

Beta-decay of {sup 56}Cu

Energy Technology Data Exchange (ETDEWEB)

Ramdhane, M.; Baumann, P.; Knipper, A.; Walter, G. [Institute de Recherches Subatomiques, 67 - Strasbourg (France); Janas, Z.; Plochocki, A. [Warsaw Univ. (Poland). Inst. of Experimental Physics; Aeystoe, J.; Dendooven, P.; Jokinen, A.; Oinonen, M.; Pentilae, H. [Jyvaeskylae Univ. (Finland); Liu, W.; Grawe, H.; Hu, Z.; Kirchner, R.; Klepper, O.; Roeckl, E. [Gesellschaft fuer Schwerionenforschung mbH, Darmstadt (Germany); Gorska, M. [Warsaw Univ. (Poland). Inst. of Experimental Physics]|[Gesellschaft fuer Schwerionenforschung mbH, Darmstadt (Germany); Fujita, Y. [Osaka Univ. (Japan); Brown, B.A. [Michigan State Univ., East Lansing, MI (United States)

1998-02-01

By measuring positrons and {beta}-delayed {gamma}-rays emitted from mass-separated sources, the decay of {sup 56}Cu(4{sup +},T{sub z}=-1,T=1) to states in the doubly-magic nucleus {sup 56}Ni was studied for the first time. The half-life of {sup 56}Cu was measured to be 78(15) ms, and four {beta}-delayed {gamma}-rays were assigned to its decay. The resulting experimental data on Fermi and Gamow-Teller strength are compared with shell-model predictions. (orig.)

Cloning of gibberellin 3 beta-hydroxylase cDNA and analysis of endogenous gibberellins in the developing seeds in watermelon.

Science.gov (United States)

Kang, Hong-Gyu; Jun, Sung-Hoon; Kim, Joonyul; Kawaide, Hiroshi; Kamiya, Yuji; An, Gynheung

2002-02-01

We have isolated Cv3h, a cDNA clone from the developing seeds of watermelon, and have demonstrated significant amino acid homology with gibberellin (GA) 3 beta-hydroxylases. This cDNA clone was expressed in Escherichia coli as a fusion protein that oxidized GA(9) and GA(12) to GA(4) and GA(14), respectively. The Cv3h protein had the highest similarity with pumpkin GA 2 beta,3 beta-hydroxylase, but did not possess 2 beta-hydroxylation function. RNA blot analysis showed that the gene was expressed primarily in the inner parts of developing seeds, up to 10 d after pollination (DAP). In the parthenocarpic fruits induced by treatment with 1-(2-chloro-4-pyridyl)-3-phenylurea (CPPU), the embryo and endosperm of the seeds were undeveloped, whereas the integumental tissues, of maternal origin, showed nearly normal development. Cv3h mRNA was undetectable in the seeds of CPPU-treated fruits, indicating that the GA 3 beta-hydroxylase gene was expressed in zygotic cells. In our analysis of endogenous GAs from developing seeds, GA(9) and GA(4) were detected at high levels but those of GA(20) and GA(1) were very low. This demonstrates that GA biosynthesis in seeds prefers a non-13-hydroxylation pathway over an early 13-hydroxylation pathway. We also analyzed endogenous GAs from seeds of the parthenocarpic fruits. The level of bioactive GA(4 )was much lower there than in normal seeds, indicating that bioactive GAs, unconnected with Cv3h, exist in integumental tissues during early seed development.

Effect of dopamine-related drugs on duodenal ulcer induced by cysteamine or propionitrile: prevention and aggravation may not be mediated by gastrointestinal secretory changes in the rat

International Nuclear Information System (INIS)

Gallagher, G.; Brown, A.; Szabo, S.

1987-01-01

Dose- and time-response studies have been performed with dopamine agonists and antagonists using the cysteamine and propionitrile duodenal ulcer models in the rat. The experiments demonstrate that the chemically induced duodenal ulcer is prevented by bromocriptine, lergotrile and reduced by apomorphine or L-dopa. Aggravation of cysteamine-induced duodenal ulcer was seen especially after (-)-butaclamol, (-)-sulpiride, haloperidol and, less effectively, after other dopaminergic antagonists. The duodenal antiulcerogenic action of dopamine agonists was more prominent after chronic administration than after a single dose, whereas the opposite was found concerning the proulcerogenic effect of dopamine antagonists. In the chronic gastric fistula rat, both the antiulcerogens bromocriptine or lergotrile and the proulcerogens haloperidol, pimozide or (-)-N-(2-chlorethyl)-norapomorphine decreased the cysteamine- or propionitrile-induced gastric secretion. No correlation was apparent between the influence of these drugs on duodenal ulcer development and gastric and duodenal (pancreatic/biliary) secretions. In the chronic duodenal fistula rat, decreased acid content was measured in the proximal duodenum after haloperidol, and diminished duodenal pepsin exposure was recorded after bromocriptine. Furthermore, the aggravation by dopamine antagonists of experimental duodenal ulcer probably involves a peripheral component. The site of dopamine receptors and physiologic effects which modulate experimental duodenal ulcer remain to be identified, but their elucidation may prove to be an important element in the pathogenesis and treatment of duodenal ulcer

Immunohistochemical localization of integrin alpha V beta 3 and osteopontin suggests that they do not interact during embryo implantation in ruminants

Directory of Open Access Journals (Sweden)

MacLaren Leslie A

2004-04-01

Full Text Available Abstract Background It has been suggested that trophoblast attachment requires co-expression of integrin alpha V beta 3 and its ligand osteopontin at the fetal-maternal interface. Until now the expression patterns of integrin alpha V beta 3 and osteopontin in the pregnant bovine uterus were unknown. The objectives of this study were to localize integrin alpha V beta 3 and osteopontin in bovine and sheep endometrium during the periimplantation period and to compare the distribution patterns using antibodies that had not yet been tested in sheep. Methods Cell compartments within endometrial tissue sections were scored for immunohistochemical staining intensity and data were analyzed to determine the effects of day of pregnancy or cycle. Results In pregnant bovine endometrium, integrin alpha V beta 3 was detected in luminal epithelium, stroma, myometrium and smooth muscle. A strong band of immunoreactivity was observed in the subepithelial stroma of intercaruncular regions, but there was reduced reactivity in the caruncles and glands. Bovine trophoblast did not express integrin alpha V beta 3 at any stage of pregnancy. In ovine endometrium a different pattern of staining for integrin alpha V beta 3 was observed. Reactivity was not present in the luminal epithelium or trophoblast. There was strong staining of the deep glands and no reactivity in the superficial glands. Osteopontin distribution was similar for sheep and cattle. For both species, apical staining was present on the luminal epithelium and glands and on embryonic tissues. Conclusion In ruminants, integrin alpha V beta 3 and osteopontin do not co-localize at the fetal-maternal interface indicating that these proteins could not interact to facilitate embryo attachment as has been proposed in other species.

Receptor protection studies comparing recombinant and native nicotinic receptors: Evidence for a subpopulation of mecamylamine-sensitive native alpha3beta4* nicotinic receptors.

Science.gov (United States)

Free, R Benjamin; Kaser, Daniel J; Boyd, R Thomas; McKay, Dennis B

2006-01-09

Studies involving receptor protection have been used to define the functional involvement of specific receptor subtypes in tissues expressing multiple receptor subtypes. Previous functional studies from our laboratory demonstrate the feasibility of this approach when applied to neuronal tissues expressing multiple nicotinic acetylcholine receptors (nAChRs). In the current studies, the ability of a variety of nAChR agonists and antagonists to protect native and recombinant alpha3beta4 nAChRs from alkylation were investigated using nAChR binding techniques. Alkylation of native alpha3beta4* nAChRs from membrane preparations of bovine adrenal chromaffin cells resulted in a complete loss of specific [(3)H]epibatidine binding. This loss of binding to native nAChRs was preventable by pretreatment with the agonists, carbachol or nicotine. The partial agonist, cytisine, produced partial protection. Several nAChR antagonists were also tested for their ability to protect. Hexamethonium and decamethonium were without protective activity while mecamylamine and tubocurarine were partially effective. Addition protection studies were performed on recombinant alpha3beta4 nAChRs. As with native alpha3beta4* nAChRs, alkylation produced a complete loss of specific [(3)H]epibatidine binding to recombinant alpha3beta4 nAChRs which was preventable by pretreatment with nicotine. However, unlike native alpha3beta4* nAChRs, cytisine and mecamylamine, provide no protection for alkylation. These results highlight the differences between native alpha3beta4* nAChRs and recombinant alpha3beta4 nAChRs and support the use of protection assays to characterize native nAChR subpopulations.

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.

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.

Nuclear transparency and double beta decay of molybdenum 100

International Nuclear Information System (INIS)

Nicholson, H.W.

1992-08-01

Data taking is now complete on a double beta decay experiment which has been carried out with collaborators from the Lawrence Berkeley Laboratory, the University of New Mexico, and the Idaho National Engineering Laboratory, and work is continuing on a second collaborative experiment, AGS experiment 850 at the Brookhaven National Laboratory to study nuclear color transparency. In March, the experimental apparatus used to search for double beta decay in molybdenum 100 in the Consil silver mine in Osburn, Idaho was dismantled, and the data analysis is in its final stages. No evidence has been seen for the O + → O + mode of zero neutrino double beta decay collaborators with a 1σ lifetime limit of 3 x 10 22 years. This limit is 7.5 times greater than the limit we published previously in Physical Review Letters in 1989. Backgrounds have been simulated and fits are currently underway to a simulated O + → 2 + mode of zero neutrino double beta decay to improve on a very preliminary 1σ lifetime limit of 2.3 x 10 21 years presented at the April, 1992 meeting of the APS in Washington. A scintillating fiber detector with three Hamamatsu, H4140, 256 channel multianode phototubes has been built, instrumented, and tested in the May--July 1992 run in the EVA detector at Brookhaven Laboratory's AGS. Preliminary results from this detector have been disappointing. it is likely that the detector will have to be substantially redesigned before the 1993 AGS run

Aggravating andmitigating factors associated with cyclist injury severity in Denmark

DEFF Research Database (Denmark)

Kaplan, Sigal; Vavatsoulas,, Konstantinos; Prato, Carlo Giacomo

2014-01-01

severity on Danish roads by examining a comprehensive set of accidents involving a cyclist and a collision partner between 2007 and 2011. Method: This study estimates a generalized ordered logit model of the severity of cyclist injuries because of its ability to accommodate the ordered-response nature...... of severity while relaxing the proportional odds assumption. Results: Model estimates show that cyclist fragility (children under 10 years old and elderly cyclists over 60 years of age) and cyclist intoxication are aggravating individual factors,while helmet use is a mitigating factor. Speed limits above 70...

Thermoluminescence characterization of LiMgF3: DyF3 phosphors exposed to beta radiation

International Nuclear Information System (INIS)

Bernal, R.; Alday S, K.R.; Brown, F.; Cruz V, C.; Furetta, C.; Cruz Z, E.; Kitis, G.

2006-01-01

LiMgF 3 : DyF 3 phosphors were obtained as polycrystalline solids from the melting of component salts, with two DyF 3 concentrations, 2.02 % mol, and 4.04 % mol. In order to guarantee the homogeneity of composition, the samples were crushed and the resulting powder was pressed to form pellet-shaped phosphors, some of which were sintered at 700 C for 5 h under air atmosphere. Thermoluminescence measurements of beta irradiated samples show that these phosphors exhibit adequate properties to be considered for development of thermoluminescence dosimeters. Integrated thermoluminescence as a function of dose displays a linear dependence with dose for doses below 20.0 Gy. (Author)

Beta-glucosidase variants and polynucleotides encoding same

Science.gov (United States)

Wogulis, Mark; Harris, Paul; Osborn, David

2017-06-27

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

Phosphorylation events implicating p38 and PI3K mediate tungstate-effects in MIN6 beta cells

International Nuclear Information System (INIS)

Piquer, Sandra; Barcelo-Batllori, Silvia; Julia, Marta; Marzo, Nuria; Nadal, Belen; Guinovart, Joan J.; Gomis, Ramon

2007-01-01

Oral administration of sodium tungstate is an effective treatment for diabetes in animal models. Several lines of evidence indicate the pancreatic beta cell as one of the targets of tungstate action. Here, we examined the molecular mechanism by which this compound exerts its effects on the beta cell line MIN6. Tungstate treatment induced phosphorylation and subsequent activation of p38 and PI3K which in turn are implicated in tungstate PDX-1 nuclear localization and activation. Although no effect was observed in glucose-induced insulin secretion we found that tungstate activates basal insulin release, a process driven, at least in part, by activation of p38. These results show a direct involvement of p38 and PI3K phosphorylation in the mechanism of action of tungstate in the beta cell

Simulated progress in double-beta decay

International Nuclear Information System (INIS)

Miley, H.S.; Arthur, R.J.; Avignone, F.T.

1993-09-01

A Monte Carlo code has been developed to accurately simulate double-beta decay measurements. Coincident gamma rays, beta spectra, and angular correlations have been added to adequately simulate a complete 100 Mo nuclear decay and provide corrections to experimentally determined detector efficiencies. This code has been used to strip certain low-background spectra obtained in the Homestake gold mine in Lead, SD, for the purpose of extremely sensitive materials assay for the construction of new, large, enriched germanium detectors. Assays as low as 9 μBq/g of 210 Pb in lead shielding were obtained

Beta-gradient isochron dating of thin tooth enamel layers using ESR

International Nuclear Information System (INIS)

Marsh, R.E.Rebeccah E.; Rink, W.J.W. Jack

2000-01-01

The theoretical and experimental basis for the development of a new dating technique using beta-gradient isochrons and ESR is presented. For uranium-free portions of enamel adjacent to sediment, we can determine a beta-dose gradient due to sources in the nearest 2 mm layer of the sediment. If the equivalent dose to successive layers of enamel is plotted against the beta dose rate to each layer, an estimate of the age (equal to the slope of the line) that depends only on the environmental beta dose rate can be determined. Experimental methods and results for four teeth are discussed. The significance of this approach lies in its ability to isolate an age estimate that is independent of the uranium uptake model, since only portions of the enamel which are far away enough from internal sources of uranium, such as dentine, are used. In addition, this technique provides a time-averaged estimate of the actual gamma plus cosmic dose rate provided that a reasonable estimate of the average moisture content is used to calculate the environmental beta dose rate

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

Science.gov (United States)

Mega, T; Nishijima, T; Ikenaka, T

1990-04-01

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

Symbiont-derived beta-1,3-glucanases in a social insect: mutualism beyond nutrition

Directory of Open Access Journals (Sweden)

Rebeca B Rosengaus

2014-11-01

Full Text Available Termites have had a long co-evolutionary history with prokaryotic and eukaryotic gut microbes. Historically, the role of these anaerobic obligate symbionts has been attributed to the nutritional welfare of the host. We provide evidence that protozoa (and/or their associated bacteria colonizing the hindgut of the dampwood termite Zootermopsis angusticollis, synthesize multiple functional beta-1,3-glucanases, enzymes known for breaking down beta-1,3-glucans, the main component of fungal cell walls. These enzymes, we propose, may help in both digestion of ingested fungal hyphae and protection against invasion by fungal pathogens. This research points to an additional novel role for the mutualistic hindgut microbial consortia of termites, an association that may extend beyond ligno-cellulolytic activity and nitrogen fixation to include a reduction in the risks of mycosis at both the individual- and colony-levels while nesting in and feeding on microbial-rich decayed wood.

Scalar 3-point functions in CFT: renormalisation, beta functions and anomalies

Science.gov (United States)

Bzowski, Adam; McFadden, Paul; Skenderis, Kostas

2016-03-01

We present a comprehensive discussion of renormalisation of 3-point functions of scalar operators in conformal field theories in general dimension. We have previously shown that conformal symmetry uniquely determines the momentum-space 3-point functions in terms of certain integrals involving a product of three Bessel functions (triple- K integrals). The triple- K integrals diverge when the dimensions of operators satisfy certain relations and we discuss how to obtain renormalised 3-point functions in all cases. There are three different types of divergences: ultralocal, semilocal and nonlocal, and a given divergent triple- K integral may have any combination of them. Ultralocal divergences may be removed using local counterterms and this results in new conformal anomalies. Semilocal divergences may be removed by renormalising the sources, and this results in CFT correlators that satisfy Callan-Symanzik equations with beta functions. In the case of non-local divergences, it is the triple- K representation that is singular, not the 3-point function. Here, the CFT correlator is the coefficient of the leading nonlocal singularity, which satisfies all the expected conformal Ward identities. Such correlators exhibit enhanced symmetry: they are also invariant under dual conformal transformations where the momenta play the role of coordinates. When both anomalies and beta functions are present the correlators exhibit novel analytic structure containing products of logarithms of momenta. We illustrate our discussion with numerous examples, including free field realisations and AdS/CFT computations.

BETA digital beta radiometer

International Nuclear Information System (INIS)

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

1989-01-01

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

Synthesis, antitumor and antimicrobial activity of novel 1-substituted phenyl-3-[3-alkylamino(methyl)-2-thioxo-1,3,4-oxadiazole-5-yl] beta-carboline derivatives

Energy Technology Data Exchange (ETDEWEB)

Savariz, Franciele C.; Formagio, Anelise S. N.; Barbosa, Valeria A.; Sarragiotto, Maria Helena [Universidade Estadual de Maringa (UEM), PR (Brazil). Dept. de Quimica; Foglio, Mary Ann; Carvalho, Joao E. de; Duarte, Marta C.T. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Centro Pluridisciplinar de Pesquisas Quimicas, Biologicas e Agricolas; Dias Filho, Benedito P. [Universidade Estadual de Maringa (UEM), PR (Brazil). Dept. de Analises Clinicas

2010-07-01

With the purpose of activity enhancement of 1-substituted phenyl-3-(2-thioxo-1,3,4-oxadiazole-5-yl) beta-carbolines 1a-c, reported as potential antitumor agents in our previous study, herein we report the synthesis and antitumor activity evaluation of several novel Mannich bases 2-7(a-c), by the introduction of different alkylamino(methyl) groups in the 1,3,4-oxadiazole unity of 1a-c. The antimicrobial activities of 1a-c and of 2-7(a-c) were also evaluated. Additionally, an in silico study of the ADME properties of novel synthesized beta-carboline derivatives 2-7(a-c) was performed by evaluation of their Lipinski's parameters and topological polar surface area (TPSA) and percentage of absorption (% ABS) data. (author)

Pathways Involving Beta-3 Adrenergic Receptors Modulate Cold Stress-Induced Detrusor Overactivity in Conscious Rats.

Science.gov (United States)

Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Nishizawa, Osamu

2015-01-01

To investigate pathways involving beta-3 adrenergic receptors (ARs) in detrusor overactivity induced by cold stress, we determined if the beta-3 AR agonist CL316243 could modulate the cold stress-induced detrusor overactivity in normal rats. Two days prior to cystometric investigations, the bladders of 10-week-old female Sprague-Dawley rats were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were taken to estimate baseline values at room temperature (RT, 27 ± 2 °C) for 20 min. They were then intravenously administered vehicle, 0.1, or 1.0 mg/kg CL316243 (n = 6 in each group). Five minutes after the treatments, they were gently and quickly transferred to the low temperature (LT, 4 ± 2 °C) room for 40 min where the cystometric measurements were again made. Afterward, the rats were returned to RT for final cystometric measurements. The cystometric effects of CL316243 were also measured at RT (n = 6 in each group). At RT, both low and high dose of CL316243 decreased basal and micturition pressure while the high dose (1.0 mg/kg) significantly increased voiding interval and bladder capacity. During LT exposure, the high dose of CL316243 partially reduced cold stress-induced detrusor overactivity characterized by increased basal pressure and urinary frequency. The high drug dose also significantly inhibited the decreases of both voiding interval and bladder capacity compared to the vehicle- and low dose (0.1 mg/kg)-treated rats. A high dose of the beta-3 agonist CL316243 could modulate cold stress-induced detrusor overactivity. Therefore, one of the mechanisms in cold stress-induced detrusor overactivity includes a pathway involving beta-3 ARs. © 2014 Wiley Publishing Asia Pty Ltd.

LHCb: $2\\beta_s$ measurement at LHCb

CERN Multimedia

Conti, G

2009-01-01

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

Pain in Breast Cancer Treatment: Aggravating Factors and Coping Mechanisms

Directory of Open Access Journals (Sweden)

Maria de Fatima Guerreiro Godoy

2014-01-01

Full Text Available The objective of this study was to evaluate pain in women with breast cancer-related lymphedema and the characteristics of aggravating factors and coping mechanisms. The study was conducted in the Clinica Godoy, São Jose do Rio Preto, with a group of 46 women who had undergone surgery for the treatment of breast cancer. The following variables were evaluated: type and length of surgery; number of radiotherapy and chemotherapy sessions; continued feeling of the removed breast (phantom limb, infection, intensity of pain, and factors that improve and worsen the pain. The percentage of events was used for statistical analysis. About half the participants (52.1% performed modified radical surgery, with 91.3% removing only one breast; 82.6% of the participants did not perform breast reconstruction surgery. Insignificant pain was reported by 32.60% of the women and 67.3% said they suffered pain; it was mild in 28.8% of the cases (scale 1–5, moderate in 34.8% (scale 6–9, and severe in 4.3%. The main mechanisms used to cope with pain were painkillers in 41.30% of participants, rest in 21.73%, religious ceremonies in 17.39%, and chatting with friends in 8.69%. In conclusion, many mastectomized patients with lymphedema complain of pain, but pain is often underrecognized and undertreated.

Synthesis of mixed-valent {alpha}- and {beta}-NaFe{sub 2}O{sub 3} polymorphs under controlled partial oxygen pressure

Energy Technology Data Exchange (ETDEWEB)

Bruno, Shaun R.; Blakely, Colin K. [Department of Chemistry, Michigan State University, East Lansing, MI 48824 (United States); Poltavets, Viktor V., E-mail: poltavets@chemistry.msu.edu [Department of Chemistry, Michigan State University, East Lansing, MI 48824 (United States)

2012-08-15

Synthesis of mixed valent compounds, especially when multiple polymorphs exist, requires careful control of the preparation conditions. {alpha}- and {beta}-NaFe{sub 2}O{sub 3} polymorphs were synthesized under controlled partial oxygen pressure (pO{sub 2}). pO{sub 2} regions of stability at 850 Degree-Sign C were determined for both phases for the first time. A modified oxygen buffer method was developed for the facile preparation of mixed valent oxides under controlled pO{sub 2}. {beta}-NaFe{sub 2}O{sub 3} is the only known n=2 member of the AM{sub n}O{sub n+1} (A=alkali metal, M=3d metal) rock-salt related homolog series with layered cation ordering. The possibility of new members of the homolog series with other 3d metals is considered. - Graphical abstract: Schematic section of phase composition vs. partial O{sub 2} pressure diagram at 850 Degree-Sign C for Na/Fe=1/2 and structure models of {alpha}- and {beta}-NaFe{sub 2}O{sub 3}. Highlights: Black-Right-Pointing-Pointer {alpha}- and {beta}-NaFe{sub 2}O{sub 3} polymorphs were synthesized under controlled oxygen pressure. Black-Right-Pointing-Pointer {beta}-NaFe{sub 2}O{sub 3} has rock-salt related structure with layered cation ordering. Black-Right-Pointing-Pointer Existence of the rock-salt related homolog series AM{sub n}O{sub n+1} is discussed.

Optical spectroscopic elucidation of beta-turns in disulfide bridged cyclic tetrapeptides.

Science.gov (United States)

Borics, Attila; Murphy, Richard F; Lovas, Sándor

2007-01-01

Vibrational circular dichroism (VCD) spectroscopic features of type II beta-turns were characterized previously, but, criteria for differentiation between beta-turn types had not been established yet. Model tetrapeptides, cyclized through a disulfide bridge, were designed on the basis of previous experimental results and the observed incidence of amino acid residues in the i + 1 and i + 2 positions in beta-turns, to determine the features of VCD spectra of type I and II beta-turns. The results were correlated with electronic circular dichroism (ECD) spectra and VCD spectra calculated from conformational data obtained by molecular dynamics (MD) simulations. All cyclic tetrapeptides yielded VCD signals with a higher frequency negative and a lower frequency positive couplet with negative lobes overlapping. MD simulations confirmed the conformational homogeneity of these peptides in solution. Comparison with ECD spectroscopy, MD, and quantum chemical calculation results suggested that the low frequency component of VCD spectra originating from the tertiary amide vibrations could be used to distinguish between types of beta-turn structures. On the basis of this observation, VCD spectroscopic features of type II and VIII beta-turns and ECD spectroscopic properties of a type VIII beta-turn were suggested. The need for independent experimental as well as theoretical investigations to obtain decisive conformational information was recognized. Copyright 2006 Wiley Periodicals, Inc.

Proteasome inhibition-induced p38 MAPK/ERK signaling regulates autophagy and apoptosis through the dual phosphorylation of glycogen synthase kinase 3{beta}

Energy Technology Data Exchange (ETDEWEB)

Choi, Cheol-Hee [Research Center for Resistant Cells, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759 (Korea, Republic of); Department of Pharmacology, College of Medicine, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759 (Korea, Republic of); Lee, Byung-Hoon [College of Pharmacy and Multiscreening Center for Drug Development, Seoul National University, Seoul 151-742 (Korea, Republic of); Ahn, Sang-Gun [Department of Pathology, College of Dentistry, Chosun University, Gwangju 501-759 (Korea, Republic of); Oh, Seon-Hee, E-mail: oshccw@hanmail.net [Research Center for Resistant Cells, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759 (Korea, Republic of)

2012-02-24

Highlights: Black-Right-Pointing-Pointer MG132 induces the phosphorylation of GSK3{beta}{sup Ser9} and, to a lesser extent, of GSK3{beta}{sup Thr390}. Black-Right-Pointing-Pointer MG132 induces dephosphorylation of p70S6K{sup Thr389} and phosphorylation of p70S6K{sup Thr421/Ser424}. Black-Right-Pointing-Pointer Inactivation of p38 dephosphorylates GSK3{beta}{sup Ser9} and phosphorylates GSK3{beta}{sup Thr390}. Black-Right-Pointing-Pointer Inactivation of p38 phosphorylates p70S6K{sup Thr389} and increases the phosphorylation of p70S6K{sup Thr421/Ser424}. Black-Right-Pointing-Pointer Inactivation of p38 decreases autophagy and increases apoptosis induced by MG132. -- Abstract: Proteasome inhibition is a promising approach for cancer treatment; however, the underlying mechanisms involved have not been fully elucidated. Here, we show that proteasome inhibition-induced p38 mitogen-activated protein kinase regulates autophagy and apoptosis by modulating the phosphorylation status of glycogen synthase kinase 3{beta} (GSK3{beta}) and 70 kDa ribosomal S6 kinase (p70S6K). The treatment of MDA-MB-231 cells with MG132 induced endoplasmic reticulum stress through the induction of ATF6a, PERK phosphorylation, and CHOP, and apoptosis through the cleavage of Bax and procaspase-3. MG132 caused the phosphorylation of GSK3{beta} at Ser{sup 9} and, to a lesser extent, Thr{sup 390}, the dephosphorylation of p70S6K at Thr{sup 389}, and the phosphorylation of p70S6K at Thr{sup 421} and Ser{sup 424}. The specific p38 inhibitor SB203080 reduced the p-GSK3{beta}{sup Ser9} and autophagy through the phosphorylation of p70S6K{sup Thr389}; however, it augmented the levels of p-ERK, p-GSK3{beta}{sup Thr390}, and p-70S6K{sup Thr421/Ser424} induced by MG132, and increased apoptotic cell death. The GSK inhibitor SB216763, but not lithium, inhibited the MG132-induced phosphorylation of p38, and the downstream signaling pathway was consistent with that in SB203580-treated cells. Taken together, our

Constraint-based modeling and kinetic analysis of the Smad dependent TGF-beta signaling pathway.

Directory of Open Access Journals (Sweden)

Zhike Zi

Full Text Available BACKGROUND: Investigation of dynamics and regulation of the TGF-beta signaling pathway is central to the understanding of complex cellular processes such as growth, apoptosis, and differentiation. In this study, we aim at using systems biology approach to provide dynamic analysis on this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We proposed a constraint-based modeling method to build a comprehensive mathematical model for the Smad dependent TGF-beta signaling pathway by fitting the experimental data and incorporating the qualitative constraints from the experimental analysis. The performance of the model generated by constraint-based modeling method is significantly improved compared to the model obtained by only fitting the quantitative data. The model agrees well with the experimental analysis of TGF-beta pathway, such as the time course of nuclear phosphorylated Smad, the subcellular location of Smad and signal response of Smad phosphorylation to different doses of TGF-beta. CONCLUSIONS/SIGNIFICANCE: The simulation results indicate that the signal response to TGF-beta is regulated by the balance between clathrin dependent endocytosis and non-clathrin mediated endocytosis. This model is useful to be built upon as new precise experimental data are emerging. The constraint-based modeling method can also be applied to quantitative modeling of other signaling pathways.

Literature in Focus Beta Beams: Neutrino Beams

CERN Document Server

2009-01-01

By Mats Lindroos (CERN) and Mauro Mezzetto (INFN Padova, Italy) Imperial Press, 2009 The beta-beam concept for the generation of electron neutrino beams was first proposed by Piero Zucchelli in 2002. The idea created quite a stir, challenging the idea that intense neutrino beams only could be produced from the decay of pions or muons in classical neutrino beams facilities or in future neutrino factories. The concept initially struggled to make an impact but the hard work by many machine physicists, phenomenologists and theoreticians over the last five years has won the beta-beam a well-earned position as one of the frontrunners for a possible future world laboratory for high intensity neutrino oscillation physics. This is the first complete monograph on the beta-beam concept. The book describes both technical aspects and experimental aspects of the beta-beam, providing students and scientists with an insight into the possibilities o...

The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

Directory of Open Access Journals (Sweden)

Andreas Bayer

2017-01-01

Full Text Available Platelet-released growth factors (PRGF and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF® contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3 is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR. In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds.

The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

Science.gov (United States)

Lammel, Justus; Tohidnezhad, Mersedeh; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Cremer, Jochen; Jahr, Holger; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

2017-01-01

Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds. PMID:28811680

Imprecise methods may both obscure and aggravate a relation between fat and breast cancer

DEFF Research Database (Denmark)

Heitmann, B L; Frederiksen, Peder

2007-01-01

Bias in diet reporting may be both random and non-random, and may be found with simpler as well as more advanced dietary instruments. A random bias will contribute to obscure relations between diet and disease. A systematic bias may obscure or aggravate such associations. Underreporting of non-pr...

High beta and second stability region transport and stability analysis

International Nuclear Information System (INIS)

1990-01-01

This document summarizes progress made on the research of high beta and second region transport and stability. In the area second stability region studies we report on an investigation of the possibility of second region access in the center of TFTR ''supershots.'' The instabilities found may coincide with experimental observation. Significant progress has been made on the resistive stability properties of high beta poloidal ''supershot'' discharges. For these studies profiles were taken from the TRANSP transport analysis code which analyzes experimental data. Invoking flattening of the pressure profile on mode rational surfaces causes tearing modes to persist into the experimental range of interest. Further, the experimental observation of the modes seems to be consistent with the predictions of the MHD model. In addition, code development in several areas has proceeded

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

Science.gov (United States)

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

2000-09-15

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

Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

Directory of Open Access Journals (Sweden)

Jie Wu

Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

High-beta characteristics of first and second-stable spherical tokamaks in reconnection heating experiments of TS-3

International Nuclear Information System (INIS)

Ono, Y.

2002-01-01

Novel formations of ultra-high-beta Spherical Tokamak (ST) have been developed in the TS-3 device using high power heating of merging/ reconnection. In Type-A merging, two STs were merged together to build up the plasma beta. In Type-B merging, an oblate FRC was initially formed by merging of two spheromaks with opposing toroidal field B t and was transformed into an ultra-high-beta ST by applying external B t . Ballooning stability analyses confirmed formations of the first-stable STs by Type- A merging and the second-stable STs by Type-B merging and also the unstable STs by both mergings, revealing the ballooning stability window consistent with measured high-n instabilities. We made (1) those model analyses of the produced STs for the first time using the BALLOO stability code, revealing that hollowness/ broadness of current/pressure profiles widen significantly the window to the second-stable regime. This paper also addresses (2) normalized betas of the second-stable STs as large as 6-17 for comparison with the Troyon scaling and (3) a promising scaling of the reconnection heating energy. (author)

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

Science.gov (United States)

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

2017-01-01

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

Additional beta-delayed protons from the T/sub z/ = -3/2 nuclei 21Mg, 25Si, 29S, and 41Ti

International Nuclear Information System (INIS)

Zhou, Z.Y.; Schloemer, E.C.; Cable, M.D.; Ahmed, M.; Reiff, J.E.; Cerny, J.

1985-01-01

Beta-delayed proton emission has proven to be a useful tool for understanding nuclei far from stability. Most of the beta decay strength is concentrated at and below the isobaric analog state (IAS) of the parent nucleus (precursor) ground state. Identification of beta strength to states above the IAS is important not only because it provides additional tests of nuclear models of beta decay, but also because proton emission from such beta daughter nuclei frequently constitutes an important component of the background in searches for more exotic nuclei. Therefore the authors have re-measured the beta-delayed proton spectra of four T/sub z/ = -3/2 nuclei: 21 Mg, 25 Si, 29 S, and 41 Ti. Fourteen previously unreported proton groups were observed and beta decay branching ratios were derived for each

Regulation of pancreatic beta-cell mass and proliferation by SOCS-3

DEFF Research Database (Denmark)

Lindberg, K; Rønn, S G; Tornehave, D

2005-01-01

Growth hormone and prolactin are important growth factors for pancreatic beta-cells. The effects exerted by these hormones on proliferation and on insulin synthesis and secretion in beta-cells are largely mediated through the Janus kinase (JAK)/signal transducer and activator of transcription (ST...

Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2.

Science.gov (United States)

Huizing, Marjan; Scher, Charles D; Strovel, Erin; Fitzpatrick, Diana L; Hartnell, Lisa M; Anikster, Yair; Gahl, William A

2002-02-01

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disease consisting of oculocutaneous albinism and a storage pool deficiency resulting from absent platelet dense bodies. The disorder is genetically heterogeneous. The majority of patients, including members of a large genetic isolate in northwest Puerto Rico, have mutations in HPS1. Another gene, ADTB3A, was shown to cause HPS-2 in two brothers having compound heterozygous mutations that allowed for residual production of the gene product, the beta3A subunit of adaptor complex-3 (AP-3). This heterotetrameric complex serves as a coat protein-mediating formation of intracellular vesicles, e.g. the melanosome and platelet dense body, from membranes of the trans-Golgi network. We determined the genomic organization of the human ADTB3A gene, with intron/exon boundaries, and describe a third patient with beta3A deficiency. This 5-y-old boy has two nonsense mutations, C1578T (R-->X) and G2028T (E-->X), which produce no ADTB3A mRNA and no beta3A protein. The associated mu3 subunit of AP-3 is also entirely absent. In fibroblasts, the cell biologic concomitant of this deficiency is robust and aberrant trafficking through the plasma membrane of LAMP-3, an integral lysosomal membrane protein normally carried directly to the lysosome. The clinical concomitant is a severe, G-CSF-responsive neutropenia in addition to oculocutaneous albinism and platelet storage pool deficiency. Our findings expand the molecular, cellular, and clinical spectrum of HPS-2 and call for an increased index of suspicion for this diagnosis among patients with features of albinism, bleeding, and neutropenia.

Irf3 polymorphism alters induction of interferon beta in response to Listeria monocytogenes infection.

Directory of Open Access Journals (Sweden)

Oleg Garifulin

2007-09-01

Full Text Available Genetic makeup of the host plays a significant role in the course and outcome of infection. Inbred strains of mice display a wide range of sensitivities to Listeria monocytogenes infection and thus serve as a good model for analysis of the effect of genetic polymorphism. The outcome of L. monocytogenes infection in mice is influenced by the ability of this bacterium to induce expression of interferon beta mRNA, encoded in mouse by the Ifnb1 (interferon beta 1, fibroblast gene. Mouse strains that lack components of the IFN beta signaling pathway are substantially more resistant to infection. We found that macrophages from the ByJ substrain of the common C57BL/6 inbred strain of mice are impaired in their ability to induce Ifnb1 expression in response to bacterial and viral infections. We mapped the locus that controls differential expression of Ifnb1 to a region on Chromosome 7 that includes interferon regulatory factor 3 (Irf3, which encodes a transcription factor responsible for early induction of Ifnb1 expression. In C57BL/6ByJ mice, Irf3 mRNA was inefficiently spliced, with a significant proportion of the transcripts retaining intron 5. Analysis of the Irf3 locus identified a single base-pair polymorphism and revealed that intron 5 of Irf3 is spliced by the atypical U12-type spliceosome. We found that the polymorphism disrupts a U12-type branchpoint and has a profound effect on the efficiency of splicing of Irf3. We demonstrate that a naturally occurring change in the splicing control element has a dramatic effect on the resistance to L. monocytogenes infection. Thus, the C57BL/6ByJ mouse strain serves as an example of how a mammalian host can counter bacterial virulence strategies by introducing subtle alteration of noncoding sequences.

Obesogenic diet-induced gut barrier dysfunction and pathobiont expansion aggravate experimental colitis.

Directory of Open Access Journals (Sweden)

June-Chul Lee

Full Text Available Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.

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.)

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-03-16

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

The continuous monitoring of the artificial beta aerosol activity by measuring the alpha and beta activity in aerosol simultaneously

International Nuclear Information System (INIS)

Hayakawa, Hironobu; Oonishi, Masaki; Matsuura, Hiroyuki

1990-01-01

We have constructed the system to monitor the artificial beta aerosol activity around the nuclear power plants continuously in real time. The smaller releases of artificial radionuclides from the nuclear power plants can be lost in the fluctuations of the natural background of the beta aerosol activity, when only the beta activity of the aerosol is measured. This method to discriminate the artificial and the natural beta activity of the aerosol is based on the fact that the ratio of the natural alpha and beta activities of the aerosol is almost constant. The detection limit of this system is below 3 Bq/m 3 . (author)

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

Science.gov (United States)

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

1994-08-01

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

Beta decay of Cu-56

NARCIS (Netherlands)

Borcea, R; Aysto, J; Caurier, E; Dendooven, P; Doring, J; Gierlik, M; Gorska, M; Grawe, H; Hellstrom, M; Janas, Z; Jokinen, A; Karny, M; Kirchner, R; La Commara, M; Langanke, K; Martinez-Pinedo, G; Mayet, P; Nieminen, A; Nowacki, F; Penttila, H; Plochocki, A; Rejmund, M; Roeckl, E; Schlegel, C; Schmidt, K; Schwengner, R; Sawicka, M

2001-01-01

The proton-rich isotope Cu-56 was produced at the GSI On-Line Mass Separator by means of the Si-28(S-32, p3n) fusion-evaporation reaction. Its beta -decay properties were studied by detecting beta -delayed gamma rays and protons. A half-Life of 93 +/- 3 ms was determined for Cu-56. Compared to the

Beta decay heat following U-235, U-238 and Pu-239 neutron fission

Science.gov (United States)

Li, Shengjie

1997-09-01

This is an experimental study of beta-particle decay heat from 235U, 239Pu and 238U aggregate fission products over delay times 0.4-40,000 seconds. The experimental results below 2s for 235U and 239Pu, and below 20s for 238U, are the first such results reported. The experiments were conducted at the UMASS Lowell 5.5-MV Van de Graaff accelerator and 1-MW swimming-pool research reactor. Thermalized neutrons from the 7Li(p,n)7Be reaction induced fission in 238U and 239Pu, and fast neutrons produced in the reactor initiated fission in 238U. A helium-jet/tape-transport system rapidly transferred fission fragments from a fission chamber to a low background counting area. Delay times after fission were selected by varying the tape speed or the position of the spray point relative to the beta spectrometer that employed a thin-scintillator-disk gating technique to separate beta-particles from accompanying gamma-rays. Beta and gamma sources were both used in energy calibration. Based on low-energy(energies 0-10 MeV. Measured beta spectra were unfolded for their energy distributions by the program FERD, and then compared to other measurements and summation calculations based on ENDF/B-VI fission-product data performed on the LANL Cray computer. Measurements of the beta activity as a function of decay time furnished a relative normalization. Results for the beta decay heat are presented and compared with other experimental data and the summation calculations.

The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma.

Science.gov (United States)

Guillermet-Guibert, Julie; Bjorklof, Katja; Salpekar, Ashreena; Gonella, Cristiano; Ramadani, Faruk; Bilancio, Antonio; Meek, Stephen; Smith, Andrew J H; Okkenhaug, Klaus; Vanhaesebroeck, Bart

2008-06-17

The p110 isoforms of phosphoinositide 3-kinase (PI3K) are acutely regulated by extracellular stimuli. The class IA PI3K catalytic subunits (p110alpha, p110beta, and p110delta) occur in complex with a Src homology 2 (SH2) domain-containing p85 regulatory subunit, which has been shown to link p110alpha and p110delta to Tyr kinase signaling pathways. The p84/p101 regulatory subunits of the p110gamma class IB PI3K lack SH2 domains and instead couple p110gamma to G protein-coupled receptors (GPCRs). Here, we show, using small-molecule inhibitors with selectivity for p110beta and cells derived from a p110beta-deficient mouse line, that p110beta is not a major effector of Tyr kinase signaling but couples to GPCRs. In macrophages, both p110beta and p110gamma contributed to Akt activation induced by the GPCR agonist complement 5a, but not by the Tyr kinase ligand colony-stimulating factor-1. In fibroblasts, which express p110beta but not p110gamma, p110beta mediated Akt activation by the GPCR ligands stromal cell-derived factor, sphingosine-1-phosphate, and lysophosphatidic acid but not by the Tyr kinase ligands PDGF, insulin, and insulin-like growth factor 1. Introduction of p110gamma in these cells reduced the contribution of p110beta to GPCR signaling. Taken together, these data show that p110beta and p110gamma can couple redundantly to the same GPCR agonists. p110beta, which shows a much broader tissue distribution than the leukocyte-restricted p110gamma, could thus provide a conduit for GPCR-linked PI3K signaling in the many cell types where p110gamma expression is low or absent.

Gene-gun DNA vaccination aggravates respiratory syncytial virus-induced pneumonitis

DEFF Research Database (Denmark)

Bartholdy, Christina; Olszewska, Wieslawa; Stryhn, Anette

2004-01-01

elicited with recombinant vaccinia virus expressing the complete RSV M2 protein, but stronger than those induced by a similar DNA construct without the beta2m gene. DNA vaccination led to enhanced pulmonary disease after RSV challenge, with increased weight loss and cell recruitment to the lung. Depletion......A CD8+ T-cell memory response to respiratory syncytial virus (RSV) was generated by using a DNA vaccine construct encoding the dominant Kd-restricted epitope from the viral transcription anti-terminator protein M2 (M2(82-90)), linked covalently to human beta2-microglobulin (beta2m). Cutaneous gene...... of CD8+ T cells reduced, but did not abolish, enhancement of disease. Mice vaccinated with a construct encoding a class I-restricted lymphocytic choriomeningitis virus epitope and beta2m suffered more severe weight loss after RSV infection than unvaccinated RSV-infected mice, although RSV-specific CD8...

Experimental search for double beta decay of 100Mo

International Nuclear Information System (INIS)

Alston-Garnjost, M.; Dougherty, B.L.; Kenney, R.W.; Krivicich, J.M.; Tripp, R.D.; Nicholson, H.W.; Dieterle, B.D.; Leavitt, C.P.

1986-01-01

An experiment is proposed to search for double beta decay in 100 Mo using thin silicon solid state detectors. We expect to be sensitive to a half life limit of over 2 x 10 23 years for the neutrinoless mode and 2 x 10 20 years for the two-neutrino mode in one year's running. This is a substantial improvement in the measurement of the limits on electron neutrino mass and/or right-handed current admixtures over present 76 Ge experiments. 16 refs., 12 figs., 9 tabs

Optimization of Plastic Scintillator Thicknesses for Online Beta Detection in Mixed Fields

Energy Technology Data Exchange (ETDEWEB)

Pourtangestani, K.; Machrafi, R. [University of Ontario Institute of Technology, Oshawa, ON (Canada)

2013-07-15

For efficient beta detection in a mixed beta-gamma field, Monte Carlo simulation models have been developed to optimize the thickness of a plastic scintillator used in whole body monitor. The simulation has been performed using MCNP/X code and different thicknesses of plastic scintillators ranging from 150 to 600 {mu}m have been used. The relationship between the thickness of the scintillator and the efficiency of the detector has been analysed. For 150 {mu}m thickness, an experimental investigation has been conducted with different beta sources at different positions on the scintillator and the counting efficiency of the unit has been measured. Evaluated data along with experimental ones have been discussed. A thickness of 300 {mu}m to 500 {mu}m has been found to be an optimum thickness for better beta detection efficiency in the presence of low energy gamma ray. (author)

Weak interaction studies from nuclear beta decay

International Nuclear Information System (INIS)

Morita, M.

1981-01-01

The studies performed at the theoretical nuclear physics division of the Laboratory of Nuclear Studies, Osaka University, are reported. Electron spin density and internal conversion process, nuclear excitation by electron transition, beta decay, weak charged current, and beta-ray angular distributions in oriented nuclei have been studied. The relative intensity of internal conversion electrons for the case in which the radial wave functions of orbital electrons are different for electron spin up and down was calculated. The calculated value was in good agreement with the experimental one. The nuclear excitation following the transition of orbital electrons was studied. The calculated probability of the nuclear excitation of Os 189 was 1.4 x 10 - 7 in conformity with the experimental value 1.7 x 10 - 7 . The second class current and other problems on beta-decay have been extensively studied, and described elsewhere. Concerning weak charged current, the effects of all induced terms, the time component of main axial vector, all partial waves of leptons, Coulomb correction for the electrons in finite size nuclei, and radiative correction were studied. The beta-ray angular distribution for the 1 + -- 0 + transition in oriented B 12 and N 12 was investigated. In this connection, investigation on the weak magnetism to include all higher order corrections for the evaluation of the spectral shape factors was performed. Other works carried out by the author and his collaborators are also explained. (Kato, T.)

Kinematic shifts of beta -delayed particles as a probe of beta - nu angular correlations

CERN Document Server

Clifford, E T H; Evans, H C; Fästermann, T; Hagberg, E; Hardy, J C; Jackson, K P; Koslowsky, V T; Schmeing, H; Schrewe, U J

1981-01-01

Beta-delayed particles undergo a kinematic shift in energy due to recoil motion of the daughter nucleus following beta decay. A careful measurement of this energy shift can be used to establish the ratio of vector to axial vector components in beta transitions. Alpha-beta coincidence data for the beta-delayed alpha decay of /sup 20/Na have been obtained. Component ratios for 6 transitions including the superallowed branch are found. Limits on charge dependent mixing with the analogue state are deduced for 5 states in /sup 20/Ne*. For the superallowed branch the axial vector component is found; the polar vector component is deduced and establishes a value for the vector weak coupling constant of G/sub V/=(1.355+or-0.036)*10/sup -49/ erg cm /sup 3/. (13 refs).

Structure of the T cell receptor in a Ti alpha V beta 2, alpha V beta 8-positive T cell line

DEFF Research Database (Denmark)

Hou, X; Dietrich, J; Kuhlmann, J

1994-01-01

not known; however, it has been suggested that each TcR contains two Ti dimers. To gain insight into the structure of the TcR we constructed a Ti alpha V beta 2, alpha V beta 8-positive T cell line which expressed the endogenous human TiV beta 8 and the transfected mouse TiV beta 2 both in association......The T cell receptor (TcR) is composed of at least six different polypeptide chains consisting of the clonotypic Ti heterodimer (Ti alpha beta or Ti gamma delta) and the noncovalently associated CD3 chains (CD3 gamma delta epsilon zeta). The exact number of subunits constituting the TcR is still...... with the endogenous Ti alpha and CD3 chains at the cell surface. Preclearing experiments with radioiodinated cell lysate prepared with digitonin lysis buffer demonstrated that depleting the lysate of Ti alpha V beta 8 by immunoprecipitation with anti V beta 8 monoclonal antibody (mAb) did not reduce the amount of Ti...

Fabrication and characterization of new LiF: Eu{sup 3+} sintered phosphors exposed to beta particles

Energy Technology Data Exchange (ETDEWEB)

Garcia H, A.R.; Cruz V, C. [Depto. de Investigacion en Polimeros y Materiales de la Universidad de Sonora, A.P. 130, 83000 Hermosillo, Sonora (Mexico); Bernal, R.; Barboza F, M. [Universidad de Sonora, A.P. 5-088, 83190 Hermosillo, Sonora (Mexico); Kitis, G. [Nuclear Physics Laboratory, Aristotle University of Thessaloniki, 54124 (Greece); Castano, V.M. [IFUNAM, A.P. 1-1010, 76000 Queretaro (Mexico)

2006-07-01

Pellet-shaped LiF:Eu{sup 3+} phosphors were synthesized by sintering. To improve their thermoluminescence characteristics, different growth conditions were used. Thermal annealing at 750 C during 5 h under air atmosphere provided the samples with highest sensitivity. Characteristic glow curves exhibit an absolute maximum centered at 203 C, and another less intense peak between 250 and 300 C. The first peak has a position very suitable for dosimetry applications. Beta irradiated samples displayed a thermoluminescence response that increases as the radiation dose increased in the 0.16 - 42.0 Gy range. A fast fading of less than 20 % occurs in the first 10 s after irradiation, followed by a remarkable stability at room temperature. Computerized glow curve deconvolution of experimental data obtained applying the McKeever method to resolve the individual peaks revealed that the glow curves fits to nine individual peaks. Activation energies were computed by using the initial rise method. (Author)

Czochralski growth and characterization of {beta}-Ga{sub 2}O{sub 3} single crystals

Energy Technology Data Exchange (ETDEWEB)

Galazka, Z.; Uecker, R.; Irmscher, K.; Albrecht, M.; Klimm, D.; Pietsch, M.; Bruetzam, M.; Bertram, R.; Ganschow, S.; Fornari, R. [Leibniz Institute for Crystal Growth, Max-Born-Str. 2, 12489 Berlin (Germany)

2010-12-15

Transparent semiconducting {beta}-Ga{sub 2}O{sub 3} single crystals were grown by the Czochralski method from an iridium crucible under a dynamic protective atmosphere to control partial pressures of volatile species of Ga{sub 2}O{sub 3}. Thermodynamic calculations on different atmospheres containing CO{sub 2}, Ar and O{sub 2} reveal that CO{sub 2} growth atmosphere combined with overpressure significantly decreases evaporation of volatile Ga{sub 2}O{sub 3} species without any harm to iridium crucible. It has been found that CO{sub 2}, besides providing high oxygen concentration at high temperatures, is also acting as a minor reducing agent for Ga{sub 2}O{sub 3}. Different coloration of obtained crystals as well as optical and electrical properties are directly correlated with growth conditions (atmosphere, pressure and temperature gradients), but not with residual impurities. Typical electrical properties of the n-type {beta}-Ga{sub 2}O{sub 3} crystals at room temperature are: {rho} = 0.1 - 0.3 {omega}cm, {mu}{sub n,Hall} = 110 - 150 cm{sup 2}V{sup -1}s{sup -1}, n{sub Hall} = 2 - 6 x 10{sup 17} cm{sup -3} and E{sub Ionisation} = 30 - 40 meV. A decrease of transmission in the IR-region is directly correlated with the free carrier concentration and can be effectively modulated by the dynamic growth atmosphere. Electron paramagnetic resonance (EPR) spectra exhibit an isotropic shallow donor level and anisotropic defect level. According to differential thermal analysis (DTA) measurements, there is substantially no mass change of {beta}-Ga{sub 2}O{sub 3} crystals below 1200 C (i.e. no decomposition) under oxidizing or neutral atmosphere, while the mass gradually decreases with temperature above 1200 C. High resolution transmission electron microscopy (HRTEM) images at atomic resolution show the presence of vacancies, which can be attributed to Ga or O sites, and interstitials, which can likely be attributed to Ga atoms. (copyright 2010 WILEY-VCH Verlag GmbH and Co. KGa

5-Androstene-3{beta},17{beta}-diol Promotes Recovery of Immature Hematopoietic Cells Following Myelosuppressive Radiation and Synergizes With Thrombopoietin

Energy Technology Data Exchange (ETDEWEB)

Aerts-Kaya, Fatima S.F.; Visser, Trudi P.; Arshad, Shazia [Department of Hematology, Erasmus University Medical Center, Rotterdam (Netherlands); Frincke, James; Stickney, Dwight R.; Reading, Chris L. [Harbor Therapeutics, Inc, San Diego, California (United States); Wagemaker, Gerard, E-mail: g.wagemaker@erasmusmc.nl [Department of Hematology, Erasmus University Medical Center, Rotterdam (Netherlands)

2012-11-01

Purpose: 5-Androstene-3{beta},17{beta}-diol (5-AED) stimulates recovery of hematopoiesis after exposure to radiation. To elucidate its cellular targets, the effects of 5-AED alone and in combination with (pegylated) granulocyte colony-stimulating factor and thrombopoietin (TPO) on immature hematopoietic progenitor cells were evaluated following total body irradiation. Methods and Materials: BALB/c mice were exposed to radiation delivered as a single or as a fractionated dose, and recovery of bone marrow progenitors and peripheral blood parameters was assessed. Results: BALB/c mice treated with 5-AED displayed accelerated multilineage blood cell recovery and elevated bone marrow (BM) cellularity and numbers of progenitor cells. The spleen colony-forming unit (CFU-S) assay, representing the life-saving short-term repopulating cells in BM of irradiated donor mice revealed that combined treatment with 5-AED plus TPO resulted in a 20.1-fold increase in CFU-S relative to that of placebo controls, and a 3.7 and 3.1-fold increase in comparison to 5-AED and TPO, whereas no effect was seen of Peg-G-CSF with or without 5-AED. Contrary to TPO, 5-AED also stimulated reconstitution of the more immature marrow repopulating (MRA) cells. Conclusions: 5-AED potently counteracts the hematopoietic effects of radiation-induced myelosuppression and promotes multilineage reconstitution by stimulating immature bone marrow cells in a pattern distinct from, but synergistic with TPO.

Messenger RNAs from the Scutellum and Aleurone of Germinating Barley Encode (1-->3,1-->4)-beta-d-Glucanase, alpha-Amylase and Carboxypeptidase

DEFF Research Database (Denmark)

Mundy, John; Brandt, Anders; Fincher, Geoffrey B

1985-01-01

Polyclonal antibodies raised against barley (1-->3,1-->4)-beta-d-glucanase, alpha-amylase and carboxypeptidase were used to detect precursor polypeptides of these hydrolytic enzymes among the in vitro translation products of mRNA isolated from the scutellum and aleurone of germinating barley....... In the scutellum, mRNA encoding carboxypeptidase appeared to be relatively more abundant than that encoding alpha-amylase or (1-->3,1-->4)-beta-d-glucanase, while in the aleurone alpha-amylase and (1-->3,1-->4)-beta-d-glucanase mRNAs predominated. The apparent molecular weights of the precursors for (1......-->3,1-->4)-beta-d-glucanase, alpha-amylase, and carboxypeptidase were 33,000, 44,000, and 35,000, respectively. In each case these are slightly higher (1,500-5,000) than molecular weights of the mature enzymes. Molecular weights of precursors immunoprecipitated from aleurone and scutellum mRNA translation...

Calibration of TLD cards to beta ray spectra of 32P

International Nuclear Information System (INIS)

Ben-Shachar, B.; German, U.; Naim, E.

1994-01-01

The results of the evaluation of TLD chips are received in nC, and we need to transform these values to mGy, in order to obtain the penetrating and the non-penetrating dose. The calibration factors were determined experimentally by irradiation the TLD chips with an uranium source. Beta rays having other spectra can cause incorrect values when estimating the non-penetrating dose. If the spectrum of the beta source is known, a specific evaluation of the calibration factor can be performed. In this report, the estimation of the calibration factor for a 32 P source is presented. LiF:Ti,Mg TLD cards were irradiated calibrated source of 90 Sr/ 90 Y and 204 Tl and non-calibrated source of 32 P, in order to find the beta correction factor for the spectrum of 32 P. Calculations of the beta correction factor were performed too, by applying the Loevinger equations to the geometry of the TLD chips used in our routine measurements. The calculated values of the beta correction factors are lower than the experimental ones. When comparing the ratios, between the beta factors of 32 P and 90 Sr/ 90 Y received from the experiments and from the calculation, we found them to be constant up to ±5%. (authors) 15 refs, 2 figs, 6 tabs

New technique to determine beta half-lives in complex background conditions

International Nuclear Information System (INIS)

Kurtukian-Nieto, T.; Benlliure, J.; Casarejos, E.; Cortina-Gil, D.; Fernandez-Ordonez, M.; Pereira, J.; Schmidt, K.H.; Becker, F.; Henzlova, D.; Yordanov, O.; Audouin, L.; Blank, B.; Giovinazzo, J.; Jurado, B.; Rejmund, F.

2008-01-01

Very neutron-rich nuclei near the A = 195 r-process waiting point were produced as projectile fragments from a 208 Pb primary beam at GSI, Darmstadt, by cold fragmentation. After in-flight separation, the fragments were implanted in an active catcher, and time correlations to the subsequent beta-decay were established. Due to the periodic operation cycles of the synchrotron, providing the primary beam, the background shows a complex time structure, which prevents applying well established analytical methods to extract the half-life information. A new mathematical analysis method has been developed, which is based on a Monte Carlo code, simulating the time sequence of implantation and beta detection according to the experimental conditions, leaving the beta lifetimes and the beta detection efficiency as free parameters. In addition, both the analysis of the experimental data and the simulation were performed in time-reversed sequence. The ratio of forward/backward time spectra contains the information of the 'true' fragment-beta correlations. Half-lives were obtained from two-dimensional fits of the measured and simulated ratios of time correlations in forward- and backward-time direction by the least-squares method, being the lifetime and the beta-detection efficiency the two fitting parameters. Half-lives of 8 heavy neutron-rich nuclei approaching the r-process waiting point A = 195 have been determined. (authors)

Beta measurement evaluation and upgrade

International Nuclear Information System (INIS)

Swinth, K.L.; Rathbun, L.A.; Roberson, P.L.; Endres, G.W.R.

1986-01-01

This program focuses on the resolution of problems associated with the field measurement of the beta dose component at Department of Energy (DOE) facilities. The change in DOE programs, including increased efforts in improved waste management and decontamination and decommissioning (D and D) of facilities, coupled with beta measurement problems identified at Three Mile Island has increased the need to improve beta measurements. In FY 1982, work was initiated to provide a continuing effort to identify problems associated with beta dose assessment at DOE facilities. The problems identified resulted in the development of this program. The investigation includes (1) an assessment of measurement systems now in use, (2) development of improved calibration systems and procedures, (3) application of innovative beta dosimetry concepts, (4) investigation of new instruments or concepts for monitoring and spectroscopy, and (5) development of recommendations to assure an adequate beta measurement program within DOE facilities

Acute patellofemoral pain: aggravating activities, clinical examination, MRI and ultrasound findings

DEFF Research Database (Denmark)

Brushoj, C.; Holmich, P.; Nielsen, M.B.

2008-01-01

Objective: To investigate acute anterior knee pain caused by overuse in terms of pain location, aggravating activities, findings on clinical examination and ultrasound/MRI examination. To determine if acute anterior knee pain caused by overuse should be classified as a subgroup of patellofemoral......%)), but other synovial covered structures including the fat pad of Hoffa (12 patients (40%)), the medial plica and the joint line (12 patients (40%)) were also involved. Only eight patients (27%) experienced pain on the patellofemoral compression test. Only discrete changes was detected on MRI...

Tevatron B0 low beta tuning report

International Nuclear Information System (INIS)

Johnson, D.E.

1982-01-01

A detailed study of the low beta insertion for the B0 experimental area has been carried out and is described below. This insertion is similar to the Type C low beta previously report, anti p Note 169, although some changes have been made to the quadrupole lengths and positions. This insertion is designated Type E. The purpose of the study was to see if it is possible to turn the insertion on in a smooth and continuous manner and tune the insertion to a value of β* of less than one meter while maintaining the overall tune of the j Tevatron to a constant value. This was found to be possible. An examination of chromaticity corrections for the Tevatron with the low beta insertion on in various configurations was also undertaken

Recent Insights into Clostridium perfringens Beta-Toxin

Directory of Open Access Journals (Sweden)

Masahiro Nagahama

2015-02-01

Full Text Available Clostridium perfringens beta-toxin is a key mediator of necrotizing enterocolitis and enterotoxemia. It is a pore-forming toxin (PFT that exerts cytotoxic effect. Experimental investigation using piglet and rabbit intestinal loop models and a mouse infection model apparently showed that beta-toxin is the important pathogenic factor of the organisms. The toxin caused the swelling and disruption of HL-60 cells and formed a functional pore in the lipid raft microdomains of sensitive cells. These findings represent significant progress in the characterization of the toxin with knowledge on its biological features, mechanism of action and structure-function having been accumulated. Our aims here are to review the current progresses in our comprehension of the virulence of C. perfringens type C and the character, biological feature and structure-function of beta-toxin.

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

Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries.

Science.gov (United States)

Schuster, Daniela; Nashev, Lyubomir G; Kirchmair, Johannes; Laggner, Christian; Wolber, Gerhard; Langer, Thierry; Odermatt, Alex

2008-07-24

17Beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) plays a pivotal role in the local synthesis of the most potent estrogen estradiol. Its expression is a prognostic marker for the outcome of patients with breast cancer and inhibition of 17beta-HSD1 is currently under consideration for breast cancer prevention and treatment. We aimed to identify nonsteroidal 17beta-HSD1 inhibitor scaffolds by virtual screening with pharmacophore models built from crystal structures containing steroidal compounds. The most promising model was validated by comparing predicted and experimentally determined inhibitory activities of several flavonoids. Subsequently, a virtual library of nonsteroidal compounds was screened against the 3D pharmacophore. Analysis of 14 selected compounds yielded four that inhibited the activity of human 17beta-HSD1 (IC 50 below 50 microM). Specificity assessment of identified 17beta-HSD1 inhibitors emphasized the importance of including related short-chain dehydrogenase/reductase (SDR) members to analyze off-target effects. Compound 29 displayed at least 10-fold selectivity over the related SDR enzymes tested.

Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

Directory of Open Access Journals (Sweden)

Anja Kafka

2014-06-01

Full Text Available The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1, Dishevelled-3 (DVL3, E-cadherin (CDH1 and beta-catenin (CTNNB1. Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR/loss of heterozygosity (LOH. Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001. Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC were significantly associated to CDH1 LOH (p = 0.001. Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins.

Science.gov (United States)

Seong, Hyun-A; Jung, Haiyoung; Kim, Kyong-Tai; Ha, Hyunjung

2007-04-20

We have reported previously that PDK1 physically interacts with STRAP, a transforming growth factor-beta (TGF-beta) receptor-interacting protein, and enhances STRAP-induced inhibition of TGF-beta signaling. In this study we show that PDK1 coimmunoprecipitates with Smad proteins, including Smad2, Smad3, Smad4, and Smad7, and that this association is mediated by the pleckstrin homology domain of PDK1. The association between PDK1 and Smad proteins is increased by insulin treatment but decreased by TGF-beta treatment. Analysis of the interacting proteins shows that Smad proteins enhance PDK1 kinase activity by removing 14-3-3, a negative regulator of PDK1, from the PDK1-14-3-3 complex. Knockdown of endogenous Smad proteins, including Smad3 and Smad7, by transfection with small interfering RNA produced the opposite trend and decreased PDK1 activity, protein kinase B/Akt phosphorylation, and Bad phosphorylation. Moreover, coexpression of Smad proteins and wild-type PDK1 inhibits TGF-beta-induced transcription, as well as TGF-beta-mediated biological functions, such as apoptosis and cell growth arrest. Inhibition was dose-dependent on PDK1, but no inhibition was observed in the presence of an inactive kinase-dead PDK1 mutant. In addition, confocal microscopy showed that wild-type PDK1 prevents translocation of Smad3 and Smad4 from the cytoplasm to the nucleus, as well as the redistribution of Smad7 from the nucleus to the cytoplasm in response to TGF-beta. Taken together, our results suggest that PDK1 negatively regulates TGF-beta-mediated signaling in a PDK1 kinase-dependent manner via a direct physical interaction with Smad proteins and that Smad proteins can act as potential positive regulators of PDK1.

Dose point kernels for beta-emitting radioisotopes

International Nuclear Information System (INIS)

Prestwich, W.V.; Chan, L.B.; Kwok, C.S.; Wilson, B.

1986-01-01

Knowledge of the dose point kernel corresponding to a specific radionuclide is required to calculate the spatial dose distribution produced in a homogeneous medium by a distributed source. Dose point kernels for commonly used radionuclides have been calculated previously using as a basis monoenergetic dose point kernels derived by numerical integration of a model transport equation. The treatment neglects fluctuations in energy deposition, an effect which has been later incorporated in dose point kernels calculated using Monte Carlo methods. This work describes new calculations of dose point kernels using the Monte Carlo results as a basis. An analytic representation of the monoenergetic dose point kernels has been developed. This provides a convenient method both for calculating the dose point kernel associated with a given beta spectrum and for incorporating the effect of internal conversion. An algebraic expression for allowed beta spectra has been accomplished through an extension of the Bethe-Bacher approximation, and tested against the exact expression. Simplified expression for first-forbidden shape factors have also been developed. A comparison of the calculated dose point kernel for 32 P with experimental data indicates good agreement with a significant improvement over the earlier results in this respect. An analytic representation of the dose point kernel associated with the spectrum of a single beta group has been formulated. 9 references, 16 figures, 3 tables

Large-scale calculations of the beta-decay rates and r-process nucleosynthesis

Energy Technology Data Exchange (ETDEWEB)

Borzov, I N; Goriely, S [Inst. d` Astronomie et d` Astrophysique, Univ. Libre de Bruxelles, Campus Plaine, Bruxelles (Belgium); Pearson, J M [Inst. d` Astronomie et d` Astrophysique, Univ. Libre de Bruxelles, Campus Plaine, Bruxelles (Belgium); [Lab. de Physique Nucleaire, Univ. de Montreal, Montreal (Canada)

1998-06-01

An approximation to a self-consistent model of the ground state and {beta}-decay properties of neutron-rich nuclei is outlined. The structure of the {beta}-strength functions in stable and short-lived nuclei is discussed. The results of large-scale calculations of the {beta}-decay rates for spherical and slightly deformed nuclides of relevance to the r-process are analysed and compared with the results of existing global calculations and recent experimental data. (orig.)

Methodology development for dosimetry of 90Sr + 90Y beta therapy applicators

International Nuclear Information System (INIS)

Coelho, T.S.; Yoriyaz, H.; Fernandes, M.A.R.

2009-01-01

The 9 0Sr+ 9 0Y applicators, used in beta therapy for prevention of keloids and pterigio, are imported and its dosimetric features are only illustrated by the manufacturers. The exhaustive routine of the medical physicists in the clinic do not make possible the accomplishment of procedures for the confirmation of these parameters. This work presents a methodology development for dosimetry in two 9 0Sr+ 9 0Y beta therapy applicators of the Amersham brand. The Monte Carlo code MCNP 4 C was used for the simulation of the percentage depth dose curves. The experimental measurements of the radiation attenuation had been done with a mini-extrapolation chamber. The results of the experimental measures had been compared with the simulated values. Both percentage deep dose curves, the theoretical and the experimental ones, had presented similar behavior, which may validate the use of the MCNP 4 C for these simulations, strengthening the usage of this method at procedures of dosimetry of these beta radiation sources. (author)

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

Science.gov (United States)

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

2010-04-20

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

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

Science.gov (United States)

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

2005-02-01

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

Studies of metal-biomolecule systems in liquids with beta-detected NMR

CERN Document Server

Walczak, Michal

2017-01-01

My internship took place within a small research team funded via the European Research Council (ERC Starting Grant: Beta-Drop NMR) at ISOLDE. It was devoted to laser spin-polarization and beta-detected NMR techniques and their future applications in chemistry and biology. I was involved in the design and tests of the beta-NMR spectrometer which will be used in the upcoming experiments. In this way I have been exposed to many topics in physics (atomic and nuclear physics), experimental techniques (vacuum technology, lasers, beta detectors, electronics, DAQ software), as well as chemistry and biology (NMR on metal ions, metal ion binding to biomolecules, quantum chemistry calculations).

Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice.

Science.gov (United States)

Seys, Leen J M; Verhamme, Fien M; Dupont, Lisa L; Desauter, Elke; Duerr, Julia; Seyhan Agircan, Ayca; Conickx, Griet; Joos, Guy F; Brusselle, Guy G; Mall, Marcus A; Bracke, Ken R

2015-01-01

Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown. We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na⁺ channel (βENaC). βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured. Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements. We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.

Crystal Structures of KPC-2[beta]-Lactamase in Complex with 3-Nitrophenyl Boronic Acid and the Penam Sulfone PSR-3-226

Energy Technology Data Exchange (ETDEWEB)

Ke, Wei; Bethel, Christopher R.; Papp-Wallace, Krisztina M.; Pagadala, Sundar Ram Reddy; Nottingham, Micheal; Fernandez, Daniel; Buynak, John D.; Bonomo, Robert A.; van den Akker, Focco (Case Western); (Stokes); (SMU)

2012-08-01

Class A carbapenemases are a major threat to the potency of carbapenem antibiotics. A widespread carbapenemase, KPC-2, is not easily inhibited by {beta}-lactamase inhibitors (i.e., clavulanic acid, sulbactam, and tazobactam). To explore different mechanisms of inhibition of KPC-2, we determined the crystal structures of KPC-2 with two {beta}-lactamase inhibitors that follow different inactivation pathways and kinetics. The first complex is that of a small boronic acid compound, 3-nitrophenyl boronic acid (3-NPBA), bound to KPC-2 with 1.62-{angstrom} resolution. 3-NPBA demonstrated a Km value of 1.0 {+-} 0.1 {micro}M (mean {+-} standard error) for KPC-2 and blocks the active site by making a reversible covalent interaction with the catalytic S70 residue. The two boron hydroxyl atoms of 3-NPBA are positioned in the oxyanion hole and the deacylation water pocket, respectively. In addition, the aromatic ring of 3-NPBA provides an edge-to-face interaction with W105 in the active site. The structure of KPC-2 with the penam sulfone PSR-3-226 was determined at 1.26-{angstrom} resolution. PSR-3-226 displayed a K{sub m} value of 3.8 {+-} 0.4 {micro}M for KPC-2, and the inactivation rate constant (kinact) was 0.034 {+-} 0.003 s{sup -1}. When covalently bound to S70, PSR-3-226 forms a trans-enamine intermediate in the KPC-2 active site. The predominant active site interactions are generated via the carbonyl oxygen, which resides in the oxyanion hole, and the carboxyl moiety of PSR-3-226, which interacts with N132, N170, and E166. 3-NPBA and PSR-3-226 are the first {beta}-lactamase inhibitors to be trapped as an acyl-enzyme complex with KPC-2. The structural and inhibitory insights gained here could aid in the design of potent KPC-2 inhibitors.

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

DEFF Research Database (Denmark)

Wang, Hengzhuang; Ciofu, Oana; Yang, Liang

2013-01-01

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

Study of the {rho}-bar, {beta}-bar and {lambda} parameters of a light-water reactor; Etude des parametres {rho}-bar, {beta}-bar et {lambda} d'une pile a eau legere

Energy Technology Data Exchange (ETDEWEB)

Riche, R [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

1965-09-01

The kinetic and perturbation equations are derived from the time-dependent transport equation. Kinetic equations depend only on the ratios a = {rho}-bar/{beta}-bar and b = {beta}-bar/{lambda}, which are definite, while the reactivity {rho}-bar, the delayed neutron fraction ({beta}-bar and the generation time {lambda} are expressed in terms of an arbitrary function I. The 'static' definitions of these parameters, which reduce kinetic problems to a set of purely term dependent equations, introduce the effective fraction {beta}-bar. One way of determining experimentally the ratio b is presented; it consists in analysing the power transient after a rapid variation of the reactivity, caused by the implosion of an empty glass-bull. A simple interpretation is proposed. The apparatus can be transformed easily into a reactimeter. The value of the effective delayed neutron fraction {beta}-bar has been determined by averaging the reactivity effects of a copper sheet through out the reactor core. Experimental results: b = {beta}-bar/{lambda} = 129 s{sup -1} and {beta}-bar 795.10{sup -5}, have been determined on a light-water moderated, enriched-uranium fuelled reactor. The calculated values of the effectiveness of delayed neutrons {gamma} {beta}-bar/{beta} 1.23 and the generation time {lambda} 59.10{sup -6}s agrees fairly well with the experimental results. (author) [French] Les equations de la cinetique et de la perturbation sont deduites de la theorie du transport, par l'intermediaire de la 'notion' d'importance des neutrons. La cinetique ne depend que des rapports a = {rho}-bar/{beta}-bar et b = {beta}-bar/{lambda}, qui sont parfaitement definis; par contre, la reactivite {rho}-bar, la proportion de neutrons retardes {beta}-bar et le temps de generation des neutrons prompts {lambda} s'expriment a l'aide d'une meme fonction arbitraire I. Les definitions 'statiques' de ces parametres, qui permettent de rendre compte de la cinetique par des equations dependant purement du

Experimental program based on a High Beta Q Machine. Final report, 1 May 1978-30 September 1980

International Nuclear Information System (INIS)

Ribe, F.L.

1980-07-01

This report summarizes work done in designing and constructing the High Beta Q Machine from the inception of the work in May 1978 until the present time. It is a 3-m long, low-compression theta pinch with a 22-cm-diameter segmented compression coil with a minimum axial periodicity length of 10 cm. This capability of driving the machine as a simple, low-density theta pinch, and also of independently applying periodic magnetic fields before or after formation of the plasma column, gives the device considerable flexibility. Reported here is the construction and testing of the machine, development of its diagnostics and initial measurements of the plasma at early times in the duration of the crowbarred magnetic field. The experimental effort has been paralleled by theoretical work to model the diffuse profile, collisionless plasma in its response to the periodic RF magnetic fields. The model chosen is the Freidberg-Pearlstein Vlasov-fluid model which provides an MHD-like description but with accounting of ion kinetic effects over diffuse equilibrium profiles. A computer code has been developed to accurately calculate the resistive response of the plasma column, giving the power absorption by ion Landau damping and more recently, ion-cyclotron damping

Solubility of {beta}-carotene in ethanol- and triolein-modified CO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Araus, Karina A. [Departamento de Ingenieria Quimica y Bioprocesos, Pontificia Universidad Catolica de Chile, Avda. Vicuna Mackenna 4860, Macul, Santiago (Chile); Canales, Roberto I. [Departamento de Ingenieria Quimica y Ambiental, Universidad Tecnica Federico Santa Maria, Avda. Espana 1680, Valparaiso (Chile); Valle, Jose M. del [Departamento de Ingenieria Quimica y Bioprocesos, Pontificia Universidad Catolica de Chile, Avda. Vicuna Mackenna 4860, Macul, Santiago (Chile); Fuente, Juan C. de la, E-mail: juan.delafuente@usm.cl [Departamento de Ingenieria Quimica y Ambiental, Universidad Tecnica Federico Santa Maria, Avda. Espana 1680, Valparaiso (Chile); Centro Regional de Estudios en Alimentos Saludables, Blanco 1623, Valparaiso (Chile)

2011-12-15

Highlights: > We measure solubility of {beta}-carotene in pure CO{sub 2}, and with ethanol and triolein as co-solvents. > We model the solubility of {beta}-carotene in pure CO{sub 2}, and with co-solvents. > The co-solvent effect of triolein over solubility of {beta}-carotene in CO{sub 2} was higher than ethanol. - Abstract: Modification of an experimental device and methodology improved speed and reproducibility of measurement of solubility of {beta}-carotene in pure and modified SuperCritical (SC) CO{sub 2} at (313 to 333) K. Solubilities of {beta}-carotene in pure CO{sub 2} at (17 to 34) MPa ranged (0.17 to 1.06) {mu}mol/mol and agreed with values reported in literature. The solubility of {beta}-carotene in CO{sub 2} modified with (1.2 to 1.6) % mol ethanol increased by a factor of 1.7 to 3.0 as compared to its solubility in pure CO{sub 2} under equivalent conditions. The concentration of triolein in equilibrated ternary (CO{sub 2} + {beta}-carotene + triolein) mixtures having excess triolein reached values (0.01 to 0.39) mmol/mol corresponding to its solubility in pure SC CO{sub 2} under equivalent conditions. Under these conditions, the solubility of {beta}-carotene in triolein-modified CO{sub 2} increased by a factor of up to 4.0 in relation with its solubility in pure CO{sub 2} at comparable system temperature and pressure, reaching an uppermost value of 3.3 {mu}mol/mol at 333 K and 32 MPa. Unlike in the case of ethanol, where enhancements in solubility where relatively independent on system conditions, solubility enhancements using triolein as co-solvent increased markedly with system pressure, being larger than using (1.2 to 1.6) % mol ethanol at about (24 to 28) MPa, depending on system temperature. The increase in the solubility {beta}-carotene in SC CO{sub 2} as a result of using ethanol or triolein as co-solvent apparently does not depend on the increase in density associated with the dissolution of the co-solvent in CO{sub 2}. Enhancements may be due

The P1approximation in the transport of beta rays

International Nuclear Information System (INIS)

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

1994-01-01

A validation test for the p1 approximation to the linear transport of electrons in planar geometry has been performed. The p1 approximation is shown to be a good option for the description of the transport of beta rays with endpoint energies between 400kev and 3.5Mev through aluminium foils . This approximation together with the use of only elastic interactions of electrons with atoms has found good agreement with experimental results . A calculation has been made of the fraction of transmitted electrons through foils, solving the transport equation for planar geometry in the p1 approximation and assuming that only elastic scattering processes take place. The boundary condition at the entrance of the foil was a collimated beta source, while at the end of the foil has been adopted a vaccum boundary condition.Sources considered are those for which experimental and calculated spectrum shapes are known to agree. The calculated fractional transmission through different absorber thicknesses is found to have an exponential shape . Besides this fact the attenuation coefficients found ,when compared with those empirically obtained, agree to within 5%. 1 fig.; 4 refs. (author)

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.

The role of beta-endorphin in the pathophysiology of major depression.

Science.gov (United States)

Hegadoren, K M; O'Donnell, T; Lanius, R; Coupland, N J; Lacaze-Masmonteil, N

2009-10-01

A role for beta-endorphin (beta-END) in the pathophysiology of major depressive disorder (MDD) is suggested by both animal research and studies examining clinical populations. The major etiological theories of depression include brain regions and neural systems that interact with opioid systems and beta-END. Recent preclinical data have demonstrated multiple roles for beta-END in the regulation of complex homeostatic and behavioural processes that are affected during a depressive episode. Additionally, beta-END inputs to regulatory pathways involving feeding behaviours, motivation, and specific types of motor activity have important implications in defining the biological foundations for specific depressive symptoms. Early research linking beta-END to MDD did so in the context of the hypothalamic-pituitary-adrenal (HPA) axis activity, where it was suggested that HPA axis dysregulation may account for depressive symptoms in some individuals. The primary aims of this paper are to use both preclinical and clinical research (a) to critically review data that explores potential roles for beta-END in the pathophysiology of MDD and (b) to highlight gaps in the literature that limit further development of etiological theories of depression and testable hypotheses. In addition to examining methodological and theoretical challenges of past clinical studies, we summarize studies that have investigated basal beta-END levels in MDD and that have used challenge tests to examine beta-END responses to a variety of experimental paradigms. A brief description of the synthesis, location in the CNS and behavioural pharmacology of this neuropeptide is also provided to frame this discussion. Given the lack of clinical improvement observed with currently available antidepressants in a significant proportion of depressed individuals, it is imperative that novel mechanisms be investigated for antidepressant potential. We conclude that the renewed interest in elucidating the role of beta

Cloning and characterization of human liver cytosolic beta-glycosidase

NARCIS (Netherlands)

De Graaf, M; Van Veen, IC; Van Der Meulen-Muileman, IH; Gerritsen, WR; Pinedo, HM; Haisma, HJ

2001-01-01

Cytosolic beta -glucosidase (EC 3.2.1.21) from mammalian liver is a member of the family 1 glycoside hydrolases and is known for its ability to hydrolyse a range of beta -D-glycosides. including beta -D-glucoside acid beta -D-galactoside. We therefore refer to this enzyme as cytosolic beta

An X11alpha/FSBP complex represses transcription of the GSK3beta gene promoter.

LENUS (Irish Health Repository)

Lau, Kwok-Fai

2010-08-04

X11alpha is a neuronal adaptor protein that interacts with the amyloid precursor protein (APP) through a centrally located phosphotyrosine binding domain to inhibit the production of Abeta peptide that is deposited in Alzheimer\\'s disease brains. X11alpha also contains two C-terminal postsynaptic density-95, large discs, zona occludens 1 (PDZ) domains, and we show here that through its PDZ domains, X11alpha interacts with a novel transcription factor, fibrinogen silencer binding protein. Moreover, we show that an X11alpha\\/fibrinogen silencer binding protein complex signals to the nucleus to repress glycogen synthase kinase-3beta promoter activity. Glycogen synthase kinase-3beta is a favoured candidate kinase for phosphorylating tau in Alzheimer\\'s disease. Our findings show a new function for X11alpha that may impact on Alzheimer\\'s disease pathogenesis.

The first-in-man randomized trial of a beta3 adrenoceptor agonist in chronic heart failure

DEFF Research Database (Denmark)

Bundgaard, Henning; Axelsson, Anna; Hartvig Thomsen, Jakob

2017-01-01

AIMS: The third isotype of beta adrenergic receptors (β3 ARs) has distinctly different effects on cardiomyocytes compared with β1 and β2 ARs. Stimulation of β3 ARs may reduce cardiomyocyte Na+overload and reduce oxidative stress in heart failure (HF). We examined if treatment with the β3 AR agoni...

Trichoderma .beta.-glucosidase

Science.gov (United States)

Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian

2006-01-03

The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl3, and the corresponding BGL3 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL3, recombinant BGL3 proteins and methods for producing the same.

Chromosomal mapping and mutational analysis of the coding region of the glycogen synthase kinase-3alpha and beta isoforms in patients with NIDDM

DEFF Research Database (Denmark)

Hansen, L; Arden, K C; Rasmussen, S B

1997-01-01

isoforms of GSK-3alpha and GSK-3beta in 72 NIDDM patients and 12 control subjects. No structural changes were detected apart from a few silent mutations. Mapping of the GSK-3alpha to chromosome 19q13.1-13.2 and the GSK-3beta to chromosome 3q13.3-q21 outside known genetic loci linked to NIDDM further makes...

High beta and second stability region transport and stability analysis

International Nuclear Information System (INIS)

1991-01-01

This document describes ideal and resistive MHD studies of high-beta plasmas and of the second stability region. Significant progress is reported on the resistive stability properties of high beta poloidal ''supershot'' discharges. For these studies initial profiles were taken from the TRANSP code which is used extensively to analyze experimental data. When an ad hoc method of removing the finite pressure stabilization of tearing modes is implemented it is shown that there is substantial agreement between MHD stability computation and experiment. In particular, the mode structures observed experimentally are consistent with the predictions of the resistive MHD model. We also report on resistive stability near the transition to the second region in TFTR. Tearing modes associated with a nearby infernal mode may explain the increase in MHD activity seen in high beta supershots and which impede the realization of Q∼1. We also report on a collaborative study with PPPL involving sawtooth stabilization with ICRF

Work aggravated asthma in Great Britain: a cross-sectional postal survey.

Science.gov (United States)

Bradshaw, Lisa; Sumner, Jade; Delic, Julian; Henneberger, Paul; Fishwick, David

2018-04-12

Work aggravated asthma (WAA), asthma made worse by but not caused by workplace exposures, can have a negative impact on personal, social, financial and societal costs. There is limited data on prevalence levels of WAA in Great Britain (GB). The objective of this study was to estimate the prevalence of WAA in GB, and to assess its potential causes.Materials and methodsA cross-sectional postal questionnaire study was carried out. A total of 1620 questionnaires were sent to three populations of adults with asthma. The questionnaire recorded; demographic details, current job, self-reported health status, presence of asthma and respiratory symptoms, duration and severity of symptoms and medication requirements. Questions relating to work environment and employers' actions were included, and each participant completed an assessment of health-related quality of life using the EuroQol Research Foundation EQ-5D. There were 207 completed questionnaires; response rates were 6% primary care, 45% secondary care and 71% Asthma UK. This represented a 13% overall response rate. Self-reported prevalence of WAA was 33% (95% CI 24.4-41.6%). In all, 19% of workers had changed their job because of breathing problems. Workers with WAA reported higher levels of work-related stress. Quality of life using the EQ-5D utility index was lower in those with WAA. WAA is a common problem in asthmatics in GB. This result is in keeping with international prevalence rates. Further research could assist the understanding of the most significant aggravants to asthma at work and help define appropriate interventions by workplaces.

Beta-lipotropin is the major component of the plasma opioid response to surgical stress in humans

Energy Technology Data Exchange (ETDEWEB)

Porro, C.A.; Facchinetti, F.; Bertellini, E.; Petraglia, F.; Stacca, R.; Barbieri, G.C.; Genazzani, A.R.

1987-12-07

There is growing experimental evidence that beta-endorphin immunoreactivity is raised by surgical stress in patients undergoing general anesthesia. As the assay methods employed to date did not allow to fully discriminate between beta-endorphin and its immediate precursor, beta-lipotropin, the authors have investigated in the present study plasma levels of these two peptides by separating them by chromatography on plasma extracts prior to radioimmunoassay. Beta-lipotropin, but not beta-endorphin, plasma levels were found to be significantly elevated during surgery in the general anesthesia group, while no change was found in either peptide concentration in the spinal one. Cortisol plasma levels also increased significantly 90 minutes after the beginning of surgery. Although the sampling time they adopted may have prevented them from detecting an early peak of beta-endorphin during the first 30 minutes of surgery, the major component of the pituitary opioid response to surgical stress appears to be related to beta-lipotropin. This is in agreement with results of experimental work on various kinds of stress in animals and humans and seems to rule out a role for plasma beta-endorphin in post-operative analgesia. 38 references, 1 figure, 1 table.

On the coherent behavior of pancreatic beta cell clusters

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-12

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

Astrocytic expression of the Alzheimer's disease beta-secretase (BACE1) is stimulus-dependent

DEFF Research Database (Denmark)

Hartlage-Rübsamen, Maike; Zeitschel, Ulrike; Apelt, Jenny

2003-01-01

The beta-site APP-cleaving enzyme (BACE1) is a prerequisite for the generation of beta-amyloid peptides, which give rise to cerebrovascular and parenchymal beta-amyloid deposits in the brain of Alzheimer's disease patients. BACE1 is neuronally expressed in the brains of humans and experimental...... paradigms studied. In contrast, BACE1 expression by reactive astrocytes was evident in chronic but not in acute models of gliosis. Additionally, we observed BACE1-immunoreactive astrocytes in proximity to beta-amyloid plaques in the brains of aged Tg2576 mice and Alzheimer's disease patients....

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

Science.gov (United States)

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

2003-01-01

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

Integrin beta3 Leu33Pro polymorphism and risk of hip fracture: 25 years follow-up of 9233 adults from the general population

DEFF Research Database (Denmark)

Tofteng, Charlotte L; Bach-Mortensen, Pernille; Bojesen, Stig E

2007-01-01

for the integrin beta3 Leu33Pro polymorphism have a two-fold risk of hip fracture, mainly confined to postmenopausal women. Integrin beta3 Leu33Pro homozygosity could prove a useful marker for risk of future hip fracture and may contribute to pharmacogenetic variation in effects of integrin alphavbeta3 antagonists....

Structural policy in the context of international competition aggravation

Directory of Open Access Journals (Sweden)

Volodymyr Bodrov

2014-09-01

Full Text Available This article researches the essence and peculiarities of the structural policy, performs classification of its models and determines possibilities of their use in the context of increasing international competition. It discovers the main components of the economic structure and trends of the state policy regarding their modernization. Measures on improvement of state regulation instruments are offered, factors of influence upon improvement of the Ukrainian economy structure are analyzed and priority goals are systematized which require urgent implementation in the terms of competitive struggle aggravation at the global markets. The article also researches the matter of importance of performing a complex of state functional and selective measures in the form of matrix policy for the purpose of protecting national interests of the country in the context of global challenges

Pressure effect on the electrical conductivity and superconductivity of beta-(BDA-TTP)2I3.

Science.gov (United States)

Yamada, Jun-Ichi; Fujimoto, Kazuya; Akutsu, Hiroki; Nakatsuji, Shin'ichi; Miyazaki, Akira; Aimatsu, Masashi; Kudo, Satoshi; Enoki, Toshiaki; Kikuchi, Koichi

2006-03-28

The pressure-induced electrical conductivity properties of beta-(BDA-TTP)2I3 have been investigated; the salt exhibits a dramatic change in the conductivity behaviour above ca. 10 kbar and undergoes a superconducting transition with an onset near 10 K.

Beta-energy averaging and beta spectra

International Nuclear Information System (INIS)

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

1976-07-01

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

Co-ordinate regulation of the cytoskeleton in 3T3 cells overexpressing thymosin-beta4.

Science.gov (United States)

Golla, R; Philp, N; Safer, D; Chintapalli, J; Hoffman, R; Collins, L; Nachmias, V T

1997-01-01

In several cell types, short-term increases in the concentration of the G-actin-sequestering peptide thymosin-beta4 (Tbeta4) cause the disassembly of F-actin bundles. To determine the extent of cell adaptability to these reductions in F-actin, we overexpressed Tbeta4 in NIH 3T3 cells. In cell lines with Tbeta4 levels twice those of vector controls, G-actin increased approximately twofold as expected. However, F-actin did not decrease as in short-term experiments but rather also increased approximately twofold so that the G-F ratio remained constant. Surprisingly, the cytoskeletal proteins myosin IIA, alpha-actinin, and tropomyosin also increased nearly twofold. These increases were specific; DNA, total protein, lactic dehydrogenase, profilin, and actin depolymerizing factor levels were unchanged in the overexpressing cells. The Tbeta4 lines spread more fully and adhered to the dish more strongly than vector controls; this altered phenotype correlated with a twofold increase in talin and alpha5-integrin and a nearly threefold increase in vinculin. Focal adhesions, detected by indirect immunofluorescence with antivinculin, were increased in size over the controls. Northern blotting showed that mRNAs for both beta-actin and vinculin were increased twofold in the overexpressing lines. We conclude that 1) NIH 3T3 cells adapt to increased levels of G-actin sequestered by increased Tbeta4 by increasing their total actin so that the F-actin/G-actin ratio remains constant; 2) these cells coordinately increase several cytoskeletal and adhesion plaque proteins; and 3) at least for actin and vinculin, this regulation is at the transcriptional level. We therefore propose that the proteins of this multimember interacting complex making up the actin-based cytoskeleton, are coordinately regulated by factors that control the expression of several proteins. The mechanism may bear similarities to the control of synthesis of another multimember interacting complex, the myofibril of