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Sample records for putative beta 3-adrenoceptors

  1. Differences between the third cardiac beta-adrenoceptor and the colonic beta 3-adrenoceptor in the rat.

    PubMed Central

    Kaumann, A. J.; Molenaar, P.

    1996-01-01

    1. The heart of several species including man contains atypical beta-adrenoceptors, in addition to coexisting beta 1- and beta 2-adrenoceptors. We now asked the question whether or not the third cardiac beta-adrenoceptor is identical to the putative beta 3-adrenoceptor. We compared the properties of the third cardiac beta-adrenoceptor with those of beta 3-adrenoceptors in isolated tissues of the rat. To study the third cardiac beta-adrenoceptor we used spontaneously beating right atria, paced left atria and paced left ventricular papillary muscles. As a likely model for putative beta 3-adrenoceptors we studied atypical beta-adrenoceptors of the colonic longitudinal muscle precontracted with 30 mM KCl. We used beta 3-adrenoceptor-selective agonists, antagonists and non-conventional partial agonists (ie high-affinity blockers of both beta 1- and beta 2-adrenoceptors know to exert also stimulant effects through beta 3-adrenoceptors). 2. The non-conventional partial agonist (-)-CGP 12177 caused positive chronotropic effects in right atria (pD2 = 7.3) and positive inotropic effects in left atria (pD2 = 7.5). The stimulant effects of (-)-CGP 12177 were resistant to blockade by 200 nM-2 microM (-)-propranolol and 3 microM ICI 118551 (a beta 2-selective antagonist) but antagonized by 1 microM (-)-bupranolol (pKB = 6.4-6.8), 3 microM CGP 20712A (a beta 1-selective antagonist) (pKB = 6.3-6.4) and 6.6 microM SR 59230A (a beta 3-selective antagonist, pKB = 5.1-5.4). 3. The non-conventional partial agonist cyanopindolol caused positive chronotropic effects in right atria (pD2 = 7.7) and positive inotropic effects in left atria (pD2 = 7.1). The stimulant effects of cyanopindolol were resistant to blockade by 200 nM (-)-propranolol but antagonized by 1 microM (-)-bupranolol (pKB = 6.8-7.1). 4. Neither (-)-CGP 12177 nor cyanopindolol caused stimulant effects in papillary muscles at concentrations between 0.2 nM and 20 microM. 5. In the presence of 200 nM (-)-propranolol the beta 3

  2. Demonstration of an in vivo functional beta 3-adrenoceptor in man.

    PubMed

    Enocksson, S; Shimizu, M; Lönnqvist, F; Nordenström, J; Arner, P

    1995-05-01

    Although it is well established in several mammalian species that beta 3-adrenoceptors play a major role in regulating lipolysis and thermogenesis in adipose tissue, the functional existence and role of this receptor subtype in man has been controversial. We investigated whether the beta 3-adrenoceptor functionally co-exists with beta 1- and beta 2-adrenoceptors in vivo in human adipose tissue. Subcutaneous abdominal adipose tissue of healthy non-obese subjects was microdialyzed with equimolar concentrations of dobutamine (selective beta 1-adrenoceptor agonist), terbutaline (selective beta 2-adrenoceptor agonist), or CGP 12177 (selective beta 3-adrenoceptor agonist). All three agents caused a rapid, sustained, concentration-dependent and significant elevation of the glycerol level in the microdialysate (lipolysis index). However, only terbutaline stimulated the nutritive blood flow in adipose tissue, as measured by an ethanol escape technique. Dobutamine and CGP 12177 was equally effective in elevating the glycerol level (maximum effect 150% above baseline). Terbutaline was significantly more effective than the other two beta-agonists (maximum effect 200% above baseline). When adipose tissue was pretreated with the beta 1/beta 2-selective adrenoceptor blocker propranolol the glycerol increasing effect of dobutamine or terbutaline was inhibited by 80-85% but the glycerol response to CGP 12177 was not influenced. It is concluded that a functional beta 3-adrenoceptor is present in vivo in man. It co-exists with beta 1- and beta 2-adrenoceptors in adipose tissue and may therefore play a role in lipolysis regulation. It appears, however, that the beta 2-adrenoceptor is the most important beta-adrenoceptor subtype for the mobilization of lipids from abdominal subcutaneous adipose tissue because of its concomitant stimulatory effect on lipolysis and blood flow. PMID:7738189

  3. Expression of beta 3-adrenoceptor mRNA in rat brain.

    PubMed Central

    Summers, R. J.; Papaioannou, M.; Harris, S.; Evans, B. A.

    1995-01-01

    The reverse transcription/polymerase chain reaction was used to demonstrate beta 3-adrenoceptor mRNA in rat brain regions. Levels were highest in hippocampus, cerebral cortex and striatum and lower in hypothalamus, brainstem and cerebellum. Images Figure 1 PMID:8590968

  4. The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors.

    PubMed

    Baker, Jillian G

    2005-02-01

    Beta-adrenoceptor antagonists ("beta-blockers") are one of the most widely used classes of drugs in cardiovascular medicine (hypertension, ischaemic heart disease and increasingly in heart failure) as well as in the management of anxiety, migraine and glaucoma. Where known, the mode of action in cardiovascular disease is from antagonism of endogenous catecholamine responses in the heart (mainly at beta1-adrenoceptors), while the worrisome side effects of bronchospasm result from airway beta2-adrenoceptor blockade. The aim of this study was to determine the selectivity of beta-antagonists for the human beta-adrenoceptor subtypes. (3)H-CGP 12177 whole cell-binding studies were undertaken in CHO cell lines stably expressing either the human beta1-, beta2- or the beta3-adrenoceptor in order to determine the affinity of ligands for each receptor subtype in the same cell background. In this study, the selectivity of well-known subtype-selective ligands was clearly demonstrated: thus, the selective beta1 antagonist CGP 20712A was 501-fold selective over beta2 and 4169-fold selective over beta3; the beta2-selective antagonist ICI 118551 was 550- and 661-fold selective over beta1 and beta3, respectively, and the selective beta3 compound CL 316243 was 10-fold selective over beta2 and more than 129-fold selective over beta1. Those beta2-adrenoceptor agonists used clinically for the treatment of asthma and COPD were beta2 selective: 29-, 61- and 2818-fold for salbutamol, terbutaline and salmeterol over beta1, respectively. There was little difference in the affinity of these ligands between beta1 and beta3 adrenoceptors. The clinically used beta-antagonists studied ranged from bisoprolol (14-fold beta1-selective) to timolol (26-fold beta2-selective). However, the majority showed little selectivity for the beta1- over the beta2-adrenoceptor, with many actually being more beta2-selective. This study shows that the beta1/beta2 selectivity of most clinically used beta-blockers is

  5. Pharmacological evidence for the presence of functional beta(3)-adrenoceptors in rat retinal blood vessels.

    PubMed

    Mori, Asami; Miwa, Tomoyo; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2010-08-01

    The aim of this study was to examine whether stimulation of beta(3)-adrenoceptors dilates rat retinal blood vessels and how diabetes affects the vasodilator responses. Images of ocular fundus were captured with an original high-resolution digital fundus camera in vivo. The retinal vascular responses were evaluated by measuring diameter of retinal blood vessels contained in the digital images. Both systemic blood pressure and heart rate (HR) were continuously recorded. The beta(3)-adrenoceptor agonist CL316243 (0.3-10 microg/kg/min, i.v.) increased diameter of retinal arterioles (at 10 microg/kg/min, a 31% increase) and decreased mean blood pressure (at 10 microg/kg/min, a 21% decrease) in a dose-dependent manner. CL316243 produced a small but significant increase in HR (at 10 microg/kg/min, a 9% increase). Both SR59230A (1 mg/kg, i.v.) and L-748337 (50 microg/kg, i.v.), beta(3)-adrenoceptor antagonists, significantly prevented CL316243-induced retinal vasodilator responses. Similar observations were made with another beta(3)-adrenoceptor agonist, BRL37344. The beta(2)-adrenoceptor agonist salbutamol also increased diameter of retinal arterioles (at 10 microg/kg/min, a 43% increase), whereas the drug produced greater decrease in blood pressure (at 10 microg/kg/min, a 46% decrease) and increase in HR (at 10 microg/kg/min, a 16% increase), compared with beta(3)-adrenoceptor agonists. The retinal vasodilator responses to CL316243 and BRL37344 observed under blockade of beta(1)/beta(2)-adrenoceptors with propranolol (2 mg/kg, i.v. bolus followed by 100 microg/kg/min infusion) were unaffected 2 weeks after induction of diabetes by the combination of streptozotocin treatment and D: -glucose feeding. On the other hand, the vasodilator responses to salbutamol of retinal arterioles were significantly reduced in diabetic rats. These results suggest that stimulation of beta(3)-adrenoceptors causes the vasodilation of retinal arterioles in vivo and the vasodilator responses are

  6. Modulation of beta2- and beta3-adrenoceptor-mediated relaxation of rat oesophagus smooth muscle by protein kinase C.

    PubMed

    Oostendorp, Jaap; Obels, Peter Ph; Terpstra, A Rene; Nelemans, S Adriaan; Zaagsma, Johan

    2004-07-01

    Although a prominent role for protein kinase C (PKC) in the cross-talk between the phosphoinositide pathway and beta2-adrenoceptor signalling has been indicated, modulation of beta3-adrenoceptor function by PKC has not been studied thus far. In the present study, we have compared the relative capacity of PKC in modulating beta2- and beta3-adrenoceptor-mediated relaxation of methacholine-contracted rat oesophagus smooth muscle. To this purpose the effects of the PKC-inhibitor GF 109203X (2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide) on relaxation induced by fenoterol, formoterol, (-)-noradrenaline, BRL 35135 (4-[2-[(2-hydroxy-2-(chlorophenyl)ethyl)amino]-propyl]-phenoxyacetic-acidmethylester) and IBMX (3-isobutyl-1-methyl-xanthine) were studied, in the absence and presence of the selective beta2-adrenoceptor antagonist ICI 118,551 (erythro-1(7-methylindan-4-yloxy)-3-(isopropylamin)-butan-2-ol). Our results show that inhibition of PKC resulted in differential augmentation of both beta2- and beta3-adrenoceptor-mediated relaxation. In contrast, relaxation induced by IBMX was not influenced at all by GF 109203X. The beta2-adrenoceptor bears phosphorylation sites for several kinases, including PKC. Since the beta3-adrenoceptor lacks these consensus sites, the results may also indicate that PKC-mediated Galphas phosphorylation is involved in the cross-talk between the muscarinic receptor-mediated phosphoinositide pathway and beta2- and, particularly, beta3-adrenoceptor signalling. PMID:15219823

  7. Obesity-related phenotypes and the beta3-adrenoceptor gene variant in postmenopausal women.

    PubMed

    Tchernof, A; Starling, R D; Walston, J D; Shuldiner, A R; Dvorak, R V; Silver, K; Matthews, D E; Poehlman, E T

    1999-07-01

    We examined the hypothesis that postmenopausal women with the beta3-adrenoceptor gene variant (Trp64Arg) have reduced total daily energy expenditure (TEE), altered free fatty acid kinetics, and increased intra-abdominal fat. A secondary objective was to examine whether the obese state masks the effect of the variant on resting metabolic rate (RMR). There were 23 obese heterozygous women with the genetic variant (age 58 +/- 6 years; BMI 36 +/- 7 kg/m2) who were compared with 19 homozygous obese women with the normal allele (age 56 +/- 4 years; BMI 36 +/- 3 kg/m2). Daily energy expenditure was determined from doubly labeled water and indirect calorimetry, lipolysis from infusion of [1-13C]palmitate, and body fat distribution from computed tomography. No significant differences were found in TEE, RMR, energy expenditure of physical activity, the thermic effect of a meal, fat oxidation as estimated by fasting and postprandial respiratory quotients (RQs), or rate of lipolysis. Similarly, no difference was found in visceral adipose tissue and abdominal subcutaneous fat areas. When RMR was compared between obese (n = 23) and never-obese women with the Trp64Arg variant (n = 16), we found a 317 kcal/day lower RMR in never-obese women after controlling for fat mass, fat-free mass, and age (P < 0.0017). These results do not support the hypothesis that already obese women with the Trp64Arg polymorphism of the beta3-adrenergic receptor gene have lower daily energy expenditure, altered lipolysis, and increased abdominal obesity. On the other hand, the lower RMR in never-obese women suggests that the obese state may mask a moderate effect of the Trp64Arg variant on energy expenditure. Although these results need to be confirmed in other populations, the obese state may have been a confounding factor in previous studies of the beta3-adrenoceptor Trp64Arg variant and energy expenditure. PMID:10389848

  8. Apparent lack of beta 3-adrenoceptors and of insulin regulation of glucose transport in brown adipose tissue of guinea pigs.

    PubMed

    Himms-Hagen, J; Triandafillou, J; Begin-Heick, N; Ghorbani, M; Kates, A L

    1995-01-01

    Norepinephrine-induced thermogenesis was substantial in adipocytes from brown adipose tissue (BAT) of cold-acclimated guinea pigs but absent in adipocytes from BAT of warm-acclimated guinea pigs. There was no thermogenic response to any beta 3-adrenergic agonist (CL-316,243, ZD-7114, BRL-28410, CGP-12177). The receptor was characterized as a beta 1-adrenoceptor. Adrenergic agonists stimulated adenylate cyclase in membranes from BAT of both warm- and cold-acclimated guinea pigs also via a beta 1-adrenoceptor; beta 3-adrenergic agonists had no effect. Glucose transport by brown adipocytes from warm-acclimated guinea pigs was not stimulated by either norepinephrine or insulin. Cold acclimation induced the appearance of stimulation of glucose transport by norepinephrine in association with the appearance of a large capacity for thermogenesis, but there was little improvement in response to insulin. GLUT4 was present in membranes from BAT of both warm- and cold-acclimated guinea pigs. Insulin is known to have an antilipolytic effect on both BAT and white adipose tissue of guinea pigs. Thus there is a selective lack of insulin-regulated glucose transport that is not improved by cold acclimation. Guinea pigs may have a mutated component of the translocation mechanism for GLUT4. beta 3-Adrenoceptors appear to be absent in brown adipocytes of adult guinea pigs, as in white adipocytes of guinea pigs, yet are known to be present in the gut. Tissue-specific expression of beta 3-adrenergic receptors in guinea pigs may differ from that in rats, in which receptors are expressed in the adipose tissues and gut. PMID:7840345

  9. In situ assessment of the role of the beta 1-, beta 2- and beta 3-adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue.

    PubMed Central

    Barbe, P.; Millet, L.; Galitzky, J.; Lafontan, M.; Berlan, M.

    1996-01-01

    1. The involvement of beta 1-, beta 2- and beta 3-adrenoceptors in the control of lipolysis and nutritive blood flow was investigated in abdominal subcutaneous adipose tissue of healthy young adults by use of an in situ microdialysis technique. 2. Dialysis probes were infused either with isoprenaline (non-selective beta-adrenoceptor agonist), CGP 12,177 (selective beta 3-adrenoceptor agonist having beta 1-/beta 2-antagonist properties), dobutamine (selective beta 1-adrenoceptor agonist) or terbutaline (selective beta 2-adrenoceptor agonist). The recovery of each probe used for perfusion was calculated by an in vivo calibration method. The local blood flow was estimated through the measurement of the escape of ethanol infused simultaneously with the drugs included in the probe. 3. Isoprenaline infusion at 0.01 microM had a weak effect while higher concentrations of isoprenaline (0.1 and 1 microM) caused a rapid, sustained and concentration-dependent increase of glycerol outflow; the maximum increase was 306 +/- 34% with 1 microM. Isoprenaline also increased the nutritive blood flow in adipose tissue; a significant effect appeared at 0.1 microM isoprenaline and was greater at 1 microM. 4. CGP 12,177 (10 and 100 microM) increased the glycerol concentration in the dialysate (128 +/- 8 and 149 +/- 12%, respectively) and nutritive blood flow. Terbutaline and dobutamine (100 microM) both provoked rapid and similar increases in glycerol outflow (252 +/- 18 and 249 +/- 18%, respectively). Both, terbutaline and dobutamine increased nutritive blood flow. 5. It is concluded that beta 1- and beta 2-adrenoceptor subtypes are both mainly involved in the mobilization of lipids and in the control of nutritive blood flow. beta 3-Adrenoceptors play a weaker role in the control of lipolysis and nutritive blood flow in human subcutaneous abdominal adipose tissue. PMID:8851509

  10. β3-adrenoceptors inhibit stimulated norepinephrine release in spontaneously hypertensive rats

    PubMed Central

    Berg, Torill

    2014-01-01

    Here, the influence of β3-adrenoceptors on catecholamine release in normotensive and spontaneously hypertensive rats was analyzed. Blood pressure was recorded through a femoral artery catheter, and cardiac output by ascending aorta flow. Time from onset of flow to maximum rise in flow indicated inotropy. Total peripheral vascular resistance (TPR) was calculated. Norepinephrine release was stimulated with tyramine, which allowed presynaptic release-control to be reflected as changes in the plasma norepinephrine concentration. β3-adrenoceptor agonist (BRL37344) reduced baseline vascular resistance, the tyramine-stimulated norepinephrine overflow and the positive inotropic response to tyramine in hypertensive but not normotensive rats. β3-adrenoceptor antagonist (SR59230A) reduced tyramine-stimulated norepinephrine release in both strains and the secretion of epinephrine in hypertensive rats. SR59230A reduced tyramine-induced tachycardia in normotensive rats, and prevented down-regulation of the tyramine-induced rise in resistance in hypertensive rats. It was concluded that the contradicting results obtained by agonist vs. antagonist, could be explained by their interaction with two different β-adrenoceptors: The BRL37344-dependent inhibition of stimulated norepinephrine release and positive inotropic response to tyramine was compatible with stimulation of β3-adrenoceptor coupling to inhibitory G-protein. This was observed only in hypertensive rats during stimulated, high levels of circulating catecholamines. The effect of BRL37344 on baseline vascular resistance was compatible with activation of β3-adrenoceptor coupling to endothelial nitric oxide synthase. The inhibitory effect of SR59230A on tyramine-stimulated norepinephrine release in both strains, the increased TPR-response to tyramine in hypertensive rats and tachycardia in normotensive rats may result from inhibition of the low-affinity-state β1-adrenoceptor, also known as the putative β4-adrenoceptor

  11. The odd sibling: features of β3-adrenoceptor pharmacology.

    PubMed

    Cernecka, Hana; Sand, Carsten; Michel, Martin C

    2014-11-01

    β3-Adrenoceptor agonists have recently been introduced for the treatment of overactive urinary bladder syndrome. Their target, the β3-adrenoceptor, was discovered much later than β1- and β2-adrenoceptors and exhibits unique properties which make extrapolation of findings from the other two subtypes difficult and the β3-adrenoceptor a less-understood subtype. This article discusses three aspects of β3-adrenoceptor pharmacology. First, the ligand-recognition profile of β3-adrenoceptors differs considerably from that of the other two subtypes, i.e., many antagonists considered as nonselective actually are β3-sparing, including propranolol or nadolol. Many agonists and antagonists classically considered as being β3-selective actually are not, including BRL 37,344 ((±)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy] acetic acid sodium hydrate) or SR 59,230 (3-(2-ethylphenoxy)-[(1S)-1,2,3,4-tetrahydronaphth-1-ylamino]-(2S)-2-propanol oxalate). Moreover, the binding pocket apparently differs between the human and rodent β3-adrenoceptor, yielding considerable species differences in potency. Second, the expression pattern of β3-adrenoceptors is more restricted than that of other subtypes, particularly in humans; this makes extrapolation of rodent findings to the human situation difficult, but it may result in a smaller potential for side effects. The role of β3-adrenoceptor gene polymorphisms has insufficiently been explored and may differ even between primate species. Third, β3-adrenoceptors lack the phosphorylation sites involved in agonist-induced desensitization of the other two subtypes. Thus, they exhibit downregulation and/or desensitization in some, but not other, cell types and tissues. When desensitization occurs, it most often is at the level of mRNA or signaling molecule expression. All three of these factors have implications for future studies to better understand the β3-adrenoceptor as a novel pharmacological target

  12. A Putatively Functional Haplotype in the Gene Encoding Transforming Growth Factor Beta-1 as a Potential Biomarker for Radiosensitivity

    SciTech Connect

    Schirmer, Markus A.; Brockmoeller, Juergen; Rave-Fraenk, Margret; Virsik, Patricia; Wilken, Barbara; Kuehnle, Elna; Campean, Radu; Hoffmann, Arne O.; Mueller, Katarina; Goetze, Robert G.; Neumann, Michael; Janke, Joerg H.; Nasser, Fatima; Wolff, Hendrik A.; Ghadimi, B. Michael; Schmidberger, Heinz; Hess, Clemens F.; Christiansen, Hans; Hille, Andrea

    2011-03-01

    Purpose: To determine whether genetic variability in TGFB1 is related to circulating transforming growth factor-{beta}1 (TGF-{beta}1) plasma concentrations after radiotherapy and to radiosensitivity of lymphoid cells. Patients and Methods: Transforming growth factor-{beta}1 plasma concentrations (n = 79) were measured in patients 1 year after radiotherapy and chromosomal aberrations (n = 71) ex vivo before therapy start. Furthermore, TGF-{beta}1 secretion and apoptosis were measured in isolated peripheral blood mononuclear cells of 55 healthy volunteers. These phenotypes were analyzed in relation to five germline polymorphisms in the 5' region of the TGFB1 gene. Because of high linkage disequilibrium, these five polymorphisms reflect frequent genetic variation in this region. A presumed impact of TGF-{beta}1 on DNA damage or repair was measured as micronucleus formation in 30 lymphoblastoid cell lines. Results: We identified a hypofunctional genetic haplotype termed H3 tagging the 5' region of the TGFB1 gene encoding TGF-{beta}1. H3 was associated with lower TGF-{beta}1 plasma concentrations in patients (p = 0.01) and reduced TGF-{beta}1 secretion in irradiated peripheral blood mononuclear cells (p = 0.003). Furthermore, cells with H3 were less prone to induction of chromosomal aberrations (p = 0.001) and apoptosis (p = 0.003) by irradiation. The hypothesis that high TGF-{beta}1 could sensitize cells to DNA damage was further supported by increased micronuclei formation in 30 lymphoblastoid cell lines when preincubated with TGF-{beta}1 before irradiation (p = 0.04). Conclusions: On the basis of TGF-{beta}1 plasma levels and radiation sensitivity of lymphoid cells, this study revealed a putatively hypofunctional TGFB1 haplotype. The significance of this haplotype and the suggested link between TGF-{beta}1 function and DNA integrity should be further explored in other cell types, as well as other experimental and clinical conditions.

  13. Effects of β(3)-adrenoceptor activation on expression of pancreatic adrenoceptors and angiotensin II receptors in ApoE(-/-) mice.

    PubMed

    Song, Jun-Ying; Li, Yan-Fang; Jiang, Zhi-Li; Guo, Yan-Qing

    2015-10-01

    Hyperlipidemia can be harmful to the pancreas and β3-adrenoceptor agonist can improve lipid metabolism disorder. We aimed to study the effects of β3-adrenoceptor activation on glucose, insulin and the expression of pancreatic adrenoceptors and angiotensin II receptors. Ten C57BL/6J mice at the age of 10 weeks served as normal control, and forty age-matched apolipoprotein E knockout (ApoE(-/-)) mice were randomly divided into hyperlipidaemia model group, low-dose and high-dose β3-adrenoceptor agonist group and β3-adrenoceptor antagonist group. After 26 weeks of high-fat diet, treatments were given for 12 weeks. Serum glucose and insulin levels in 48 weeks old mice were measured using an automatic biochemical detector. Quantitative rt-PCR and Western blot were used to analyze the mRNA and protein expression of α1A-, α2A-, β2-, β3-adrenoceptors and angiotensin II type 1 and type 2 receptors in pancreas. We found that β3-adrenoceptor agonist could decrease serum glucose and insulin levels in aged ApoE(-/-) mice (P<0.01) and down-regulate the expression of α1A-adrenoceptor and angiotensin II type 1 receptor which were significantly increased in model mice (P<0.05, P<0.01). Compared with the model mice, α2A-, β2-, β3-adrenoceptor and angiotensin II type 2 receptor expression were up-regulated in β3-adrenoceptor agonist treat mice (P<0.05, P<0.01). These results suggest that chronic β3-adrenoceptor activation regulated the expression of adrenoceptors and angiontensin II receptors towards contrary direction, which indicates that there are interactions between β3-adrenoceptor and subtypes of adrenoceptor and angiotensin II receptor, and these interactions may play a protective role in pancreas and improve glucose metabolism disorders. PMID:26102566

  14. Role of β3-adrenoceptors in regulation of retinal vascular tone in rats.

    PubMed

    Mori, Asami; Nakahara, Tsutomu; Sakamoto, Kenji; Ishii, Kunio

    2011-12-01

    The aim of this study was to determine the role of β(3)-adrenoceptors in the action of endogenous catecholamines (adrenaline and noradrenaline) on rat retinal arterioles in vivo. Using an original high-resolution digital fundus camera, the rat ocular fundus images were captured. The diameter of retinal arterioles contained in the images was measured. Both systemic blood pressure and heart rate were recorded continuously. Adrenaline (0.3-5.0 μg/kg/min, i.v.) increased the diameter of retinal arterioles, mean blood pressure and heart rate in a dose-dependent manner. Under blockade of β(1)/β(2)-adrenoceptors with propranolol (2 mg/kg, i.v. bolus followed by 100 μg/kg/min infusion), adrenaline decreased the diameter of retinal arterioles. Similar observation was made under treatment with the β(3)-adrenoceptor antagonist L-748337 (50 μg/kg, i.v.). The pressor response to adrenaline was enhanced by propranolol, but not by L-748337. The positive chronotropic action of adrenaline was markedly prevented by propranolol, whereas it was unaffected by L-748337. Noradrenaline (0.03-1.0 μg/kg/min, i.v.) decreased the diameter of retinal arterioles but increased the mean blood pressure and heart rate. The effects of noradrenaline on retinal arteriolar diameter and blood pressure were unaffected by propranolol or L-748337. The positive chronotropic action of noradrenaline was almost completely abolished by propranolol. These results suggest that β(3)-adrenoceptors play crucial roles in vasodilator responses to adrenaline of retinal arterioles but have minor or no effect on noradrenaline-induced responses. The results also indicate that the functional role of β(3)-adrenoceptors may be more important than that in peripheral resistance vessels. PMID:21901314

  15. Identification of a putative yeast homolog of the mammalian beta chains of the clathrin-associated protein complexes.

    PubMed Central

    Kirchhausen, T

    1990-01-01

    The clathrin-associated protein complexes are heterotetrameric structures believed to interact with clathrin and with membrane components of mammalian coated pits and coated vesicles. I have identified a yeast homolog of the mammalian beta-type large chains, suggesting the existence in yeast cells of clathrin-associated protein complexes. A sequence comparison between the putative yeast beta-type chain and its mammalian counterparts shows that their amino-terminal domains are related over their entire length and that their carboxyl-terminal domains diverge completely. This observation is consistent with our earlier proposal (T. Kurchhausen et al., Proc. Natl. Acad. Sci. USA 86:2612-2616, 1989) for the bifunctional-domain organization of the large chains, in which the invariant amino-terminal region interacts with conserved proteins of the coat while the variable carboxyl-terminal domain interacts with different membrane components of coated pits and coated vesicles. PMID:2122239

  16. Effects of (−)-RO363 at human atrial β-adrenoceptor subtypes, the human cloned β3-adrenoceptor and rodent intestinal β3-adrenoceptors

    PubMed Central

    Molenaar, Peter; Sarsero, Doreen; Arch, Jonathan R S; Kelly, John; Henson, Sian M; Kaumann, Alberto J

    1997-01-01

    Chronic treatment of patients with β-blockers causes atrial inotropic hyperresponsiveness through β2-adrenoceptors, 5-HT4 receptors and H2-receptors but apparently not through β1-adrenoceptors despite data claiming an increased β1-adrenoceptor density from homogenate binding studies. We have addressed the question of β1-adrenoceptor sensitivity by determining the inotropic potency and intrinsic activity of the β1-adrenoceptor selective partial agonist (−)-RO363 and by carrying out both homogenate binding and quantitative β-adrenoceptor autoradiography in atria obtained from patients treated or not treated with β-blockers. In the course of the experiments it became apparent that (−)-RO363 also may cause agonistic effects through the third atrial β-adrenoceptor. To assess whether (−)-RO363 also caused agonistic effects through β3-adrenoceptors we studied its relaxant effects in rat colon and guinea-pig ileum, as well as receptor binding and adenylyl cyclase stimulation of chinese hamster ovary (CHO) cells expressing human β3-adrenoceptors. β-Adrenoceptors were labelled with (−)-[125I]-cyanopindolol. The density of both β1- and β2-adrenoceptors was unchanged in the 2 groups, as assessed with both quantitative receptor autoradiography and homogenate binding. The affinities of (−)-RO363 for β1-adrenoceptors (pKi=8.0–7.7) and β2-adrenoceptors (pKi=6.1–5.8) were not significantly different in the two groups. (−)-RO363 increased atrial force with a pEC50 of 8.2 (β-blocker treated) and 8.0 (non-β-blocker treated) and intrinsic activity with respect to (−)-isoprenaline of 0.80 (β-blocker treated) and 0.54 (non-β-blocker treated) (P<0.001) and with respect to Ca2+ (7 mM) of 0.65 (β-blocker treated) and 0.45 (non-β-blocker treated) (P<0.01). The effects of (−)-RO363 were resistant to antagonism by the β2-adrenoceptor antagonist, ICI 118,551 (50 nM). The effects of 0.3–10 nM (−)-RO363 were antagonized by 3–10 nM of the

  17. Repression of estrogen receptor {beta} function by putative tumor suppressor DBC1

    SciTech Connect

    Koyama, Satoshi; Wada-Hiraike, Osamu; Nakagawa, Shunsuke; Tanikawa, Michihiro; Hiraike, Haruko; Miyamoto, Yuichiro; Sone, Kenbun; Oda, Katsutoshi; Fukuhara, Hiroshi; Nakagawa, Keiichi; Kato, Shigeaki; Yano, Tetsu; Taketani, Yuji

    2010-02-12

    It has been well established that estrogen is involved in the pathophysiology of breast cancer. Estrogen receptor (ER) {alpha} appears to promote the proliferation of cancer tissues, while ER{beta} can protect against the mitogenic effect of estrogen in breast tissue. The expression status of ER{alpha} and ER{beta} may greatly influence on the development, treatment, and prognosis of breast cancer. Previous studies have indicated that the deleted in breast cancer 1 (DBC1/KIAA1967) gene product has roles in regulating functions of nuclear receptors. The gene encoding DBC1 is a candidate for tumor suppressor identified by genetic search for breast cancer. Caspase-dependent processing of DBC1 promotes apoptosis, and depletion of the endogenous DBC1 negatively regulates p53-dependent apoptosis through its specific inhibition of SIRT1. In addition, DBC1 modulates ER{alpha} expression and promotes breast cancer cell survival by binding to ER{alpha}. Here we report an ER{beta}-specific repressive function of DBC1. Immunoprecipitation and immunofluorescence studies show that ER{beta} and DBC1 interact in a ligand-independent manner similar to ER{alpha}. In vitro pull-down assays revealed a direct interaction between DBC1 amino-terminus and activation function-1/2 domain of ER{beta}. Although DBC1 shows no influence on the ligand-dependent transcriptional activation function of ER{alpha}, the expression of DBC1 negatively regulates the ligand-dependent transcriptional activation function of ER{beta}in vivo, and RNA interference-mediated depletion of DBC1 stimulates the transactivation function of ER{beta}. These results implicate the principal role of DBC1 in regulating ER{beta}-dependent gene expressions.

  18. Isolation and sequencing of a putative promoter region of the murine G protein beta 1 subunit (GNB1) gene.

    PubMed

    Kitanaka, Junichi; Kitanaka, Nobue; Takemura, Motohiko; Wang, Xiao-Bing; Hembree, Cambria M; Goodman, Nancy L; Uhl, George R

    2002-02-01

    The expression of the heterotrimeric GTP-binding protein beta 1 subunit gene (GNB1) is regulated by psychostimulants such as cocaine and amphetamines. Since the up-regulation appears to be one of the candidate processes of sensitization, it is necessary to elucidate the cellular and molecular mechanism of the GNB1 gene regulation for a better understanding the establishment of sensitization. In the present study, we describe the isolation and nucleotide sequence analysis of the GNB1 gene promoter region. We have isolated approximately 10 kb of the 5'-flanking region of the mouse of GNB1 gene and found potential elements involved in putative transcriptional control of the GNB1, such as AP1, AP2, Sp1, cyclic AMP response element, and nuclear factor kappa B recognition sites, within the sequences 0.3 kb upstream from the putative transcription start site. This region was highly rich in G + C content, but lacked TATA or CATT boxes. Comparing the nucleotide sequence of the cDNA clone with the human genome databases using the BLAST program a region containing putative exon 1 and promoter of the human GNB1 gene in chromosome 1 was found. The cloning and sequence analysis of an extensive portion of the 5'-flanking regulatory region of the GNB1 gene provides new insights into the factors involved in the regulation by psychostimulants of GNB1 expression. PMID:12180136

  19. Molecular and functional characteristics of β3-adrenoceptors in late pregnant mouse uterus: a comparison with β2-adrenoceptors.

    PubMed

    Parida, Subhashree; Uttam Singh, Thakur; Ravi Prakash, Vellanki; Mishra, Santosh K

    2013-01-30

    β(3)-adrenoceptor is a potential target for uterine relaxant drugs for the treatment of preterm labor. Mouse is an ideal experimental model for preterm labor. However, there is limited information on the molecular and functional characteristics of β(3)-adrenoceptors in mouse uterus. Therefore, the current study was undertaken to characterize the β(3)-adrenoceptors in late pregnant mouse uterus by molecular and functional experiments and to compare their expression and function with the β(2)-adrenoceptors. Using RT-PCR, we demonstrated the presence of β(3)-adrenoceptor mRNA in the mouse uterus. Accordingly, selective β(3)-adrenoceptor agonist SAR150640 (ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl)amino]cyclohexyl}benzoate hydrochloride) caused concentration-dependent relaxation of the isolated tissue. SR59230A (1 μM), a selective antagonist of β(3)-adrenoceptors, antagonized the relaxant response to SAR150640. Using real-time PCR we found that in comparison to β(3)-adrenoceptor mRNA, β(2)-adrenoceptor mRNA is predominantly expressed in the late pregnant mouse uterus. We then assessed the comparative efficiency of different β-adrenoceptor agonists, such as SAR150640, salbutamol and isoprenaline to relax the tissue. SAR150640 (pD(2) 6.64±0.21, E(max) 104.9±7.95), salbutamol (pD(2) 8.57±0.062, E(max) 103.1±3.22) and isoprenaline (pD(2) 9.48±0.084, E(max) 102.9±5.18) caused concentration-dependent inhibition of uterine rhythmic contractions. While the maximal relaxation to these agonists was comparable, the order of potency was isoprenaline>salbutamol>SAR. These results suggest that β(3)-adrenoceptor mRNA is present in the pregnant mouse uterus and is functionally active. The predominance of β(2)- over β(3)-adrenoceptor expression may explain variable potency amongst the β-adrenoceptor agonists. PMID:23219791

  20. Clinical use of the β3 adrenoceptor agonist mirabegron in patients with overactive bladder syndrome.

    PubMed

    Vij, Monika; Drake, Marcus J

    2015-10-01

    Mirabegron is a β3 adrenoceptor agonist licensed for the treatment of overactive bladder symptoms, such as urinary urgency or urgency incontinence. β3 adrenoceptor activation causes detrusor muscle relaxation, but mirabegron may also act by binding other targets in the bladder, and it may also reduce activity in sensory nerves. Phase III clinical trials (SCORPIO, ARIES, and CAPRICORN) evaluated mirabegron at various doses, demonstrating reduction from baseline to endpoint in mean incontinence episodes and mean number of micturitions per 24 h (coprimary endpoints), along with health-related quality of life and a range of secondary measures. Efficacy was seen in many patients who had previously discontinued antimuscarinic therapy on the grounds of lack of efficacy or poor tolerability. Treatment emergent adverse effects were documented in a long-term study (TAURUS), mostly being of mild or moderate severity. The most frequent adverse effects were hypertension, dry mouth, constipation, and headache, with a lower incidence of dry mouth than for the antimuscarinic active comparator. Efficacy and safety are not substantially different in older patients. A urodynamic safety study in men showed no consistent effect on voiding function, but a small increase in postvoid residual. Use of mirabegron in combination with α-adrenergic blockers does not appear to increase adverse effects. Dose reduction is needed in people with severe renal failure, or moderate hepatic failure. Dose adjustment is not needed in relation to food intake. Ongoing research is evaluating the potential for combination therapy with antimuscarinics. PMID:26425139

  1. Clinical use of the β3 adrenoceptor agonist mirabegron in patients with overactive bladder syndrome

    PubMed Central

    Vij, Monika

    2015-01-01

    Mirabegron is a β3 adrenoceptor agonist licensed for the treatment of overactive bladder symptoms, such as urinary urgency or urgency incontinence. β3 adrenoceptor activation causes detrusor muscle relaxation, but mirabegron may also act by binding other targets in the bladder, and it may also reduce activity in sensory nerves. Phase III clinical trials (SCORPIO, ARIES, and CAPRICORN) evaluated mirabegron at various doses, demonstrating reduction from baseline to endpoint in mean incontinence episodes and mean number of micturitions per 24 h (coprimary endpoints), along with health-related quality of life and a range of secondary measures. Efficacy was seen in many patients who had previously discontinued antimuscarinic therapy on the grounds of lack of efficacy or poor tolerability. Treatment emergent adverse effects were documented in a long-term study (TAURUS), mostly being of mild or moderate severity. The most frequent adverse effects were hypertension, dry mouth, constipation, and headache, with a lower incidence of dry mouth than for the antimuscarinic active comparator. Efficacy and safety are not substantially different in older patients. A urodynamic safety study in men showed no consistent effect on voiding function, but a small increase in postvoid residual. Use of mirabegron in combination with α-adrenergic blockers does not appear to increase adverse effects. Dose reduction is needed in people with severe renal failure, or moderate hepatic failure. Dose adjustment is not needed in relation to food intake. Ongoing research is evaluating the potential for combination therapy with antimuscarinics. PMID:26425139

  2. Nested Ty3-gypsy retrotransposons of a single Beta procumbens centromere contain a putative chromodomain.

    PubMed

    Weber, Beatrice; Schmidt, Thomas

    2009-01-01

    LTR retrotransposons belong to a major group of DNA sequences that are often localized in plant centromeres. Using BAC inserts originating from the centromere of a monosomic wild beet (Beta procumbens) chromosome fragment in Beta vulgaris, two complete LTR retrotransposons were identified. Both elements, designated Beetle1 and Beetle2, possess a coding region with genes in the order characteristic for Ty3-gypsy retrotransposons. Beetle1 and Beetle2 have a chromodomain in the C-terminus of the integrase gene and are highly similar to the centromeric retrotransposons (CRs) of rice, maize, and barley. Both retroelements were localized in the centromeric region of B. procumbens chromosomes by fluorescence in-situ hybridization. They can therefore be classified as centromere-specific chromoviruses. PCR analysis using RNA as template indicated that Beetle1 and Beetle2 are transcriptionally active. On the basis of the sequence diversity between the LTR sequences, it was estimated that Beetle1 and Beetle2 transposed within the last 60,000 years and 130,000 years, respectively. The centromeric localization of Beetle1 and Beetle2 and their transcriptional activity combined with high sequence conservation within each family play an important structural role in the centromeres of B. procumbens chromosomes. PMID:19322668

  3. Functional effects of β3-adrenoceptor on pacemaker activity in interstitial cells of Cajal from the mouse colon.

    PubMed

    Wu, Mei Jin; Shin, Dong Hoon; Kim, Man Yoo; Park, Chan Guk; Kim, Young Dae; Lee, Jun; Park, Il Koo; Choi, Seok; So, Insuk; Park, Jong Seong; Jun, Jae Yeoul

    2015-05-01

    We investigated the presence of β3-adrenoceptor and its functional effects on pacemaker potentials in colonic interstitial cells of Cajal (ICCs) from mice. The whole-cell patch clamp technique was used to record pacemaker potentials in cultured ICCs and reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the mRNA transcript levels β-adrenoceptors. The β3-adrenoceptor agonist, BRL37344, reduced the frequency of pacemaker potentials in a concentration-dependent manner. The inhibitory effects of BRL37344 were blocked by the pretreatment of propranolol, a nonspecific β-adrenoceptor antagonist, but not by the selective β1-adrenoceptor antagonist atenolol and the selective β2-adrenoceptor antagonist butoxamine. β3-adrenoceptor antagonists SR59230A and L748337 blocked the inhibitory effects of BRL37344. RT-PCR revealed mRNA transcripts of β1- and β3-adrenoceptor, but not β2-adrenoceptor, in c-kit- and Ano-1-positive colonic ICCs. The K(+) channel blockers tetraethylammonium, apamin, and glibenclamide did not block the effects of BRL37344. N(ω)-Nitro-l-arginine methyl ester hydrochloride (L-NAME), an NO synthase inhibitor, and chelerythrine, a protein kinase C inhibitor, also did not block the effects of BRL37344. Noradrenaline mimicked the effects of BRL37344 in colonic ICCs. However, the inhibitory effects of noradrenaline on pacemaker potentials were blocked only by pretreatment with atenolol but not by butoxamine, SR59230A, or L748337. In small intestinal ICCs, BRL37344 had no effect on pacemaker potentials and mRNA transcripts of β1-and β2-adrenoceptor, but not β3-adrenoceptor were detected. These results suggest that β3-adrenoceptors are present in colonic ICCs and may play a role in regulating gastrointestinal motility by the inhibition of pacemaker potentials. PMID:25725113

  4. Enhancement of 18F-Fluorodeoxyglucose Metabolism in Rat Brain Frontal Cortex Using a β3 Adrenoceptor Agonist

    PubMed Central

    Mirbolooki, M. Reza; Schade, Kimberly N.; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

    2014-01-01

    We report the use of β3-adrenergic receptor mediated activation of rat brain frontal cortex using mirabegron (a selective β3-adrenoceptor agonist), measured by 18F-FDG PET/CT. Another β3-agonis t, CL 316,243, did not have this effect due to impermeability through the blood brain barrier (BBB), while atomoxetine, a norepinephrine transporter blocker, did increase 18F-FDG uptake in the frontal cortex. Mirabegron exhibited a dose-dependent increase in frontal cortex 18F-FDG uptake. These findings suggest a possible use of selective β3-adrenoceptor agonists in reversing regional glucose hypometabolism in the brain. PMID:25347981

  5. Functional and molecular evidence for β1-, β2- and β3-adrenoceptors in human colon

    PubMed Central

    Roberts, S J; Papaioannou, M; Evans, B A; Summers, R J

    1997-01-01

    Relaxation of carbachol pre-contracted human colonic muscle to (–)-isoprenaline was examined in circular, longitudinal and taenia coli preparations to determine the β-adrenoceptor subtypes involved. β1-, β2- and β3-Adrenoceptor mRNAs were also measured in colonic muscle and mucosa.(–)-Isoprenaline caused relaxation of longitudinal smooth muscle preparations with pEC50=7.39±0.12, and this response was inhibited by both propranolol (0.1 μM, pKB 8.55±0.12) and the selective β1-antagonist, CGP 20712A (0.1 μM, pKB 8.80±0.20), while the selective β2-antagonist, ICI 118551 (0.1 μM) failed to inhibit isoprenaline relaxation consistently.(–)-Isoprenaline caused relaxation of taenia coli with a pEC50 of 6.70±0.17. Propranolol (0.1 μM), CGP 20712A (0.1 μM) and ICI 118551 (0.1 μM) inhibited the isoprenaline response with similar low affinities (pKB values 7.93, 7.71 and 7.54, respectively). Carbachol pre-contracted circular smooth muscle preparations failed to relax consistently to isoprenaline and these responses were not characterized.β1- and β2-Adrenoceptor mRNAs were present in circular/longitudinal muscle samples and taenia coli samples, and lower levels were detected in mucosa. β3-mRNA was also present in both muscle preparations but was not detected in human colonic mucosa.In summary, β1-adrenoceptors are the predominant subtype mediating isoprenaline-induced relaxation of the thin longitudinal smooth muscle of human colon, while β3-receptors do not appear to be involved in these responses. However, β3-adrenoceptors may play a role in relaxation of the taenia coli as conventional antagonist affinities are low. β3-Adrenoceptor mRNA was present in taenia coli and circular/longitudinal smooth muscle but absent from human colonic mucosa. PMID:9113375

  6. A wide variety of putative extremophiles and large beta-diversity at the Mars Desert Research Station (Utah)

    NASA Astrophysics Data System (ADS)

    Direito, Susana O. L.; Ehrenfreund, Pascale; Marees, Andries; Staats, Martijn; Foing, Bernard; Röling, Wilfred F. M.

    2011-07-01

    Humankind's innate curiosity makes us wonder whether life is or was present on other planetary bodies such as Mars. The EuroGeoMars 2009 campaign was organized at the Mars Desert Research Station (MDRS) to perform multidisciplinary astrobiology research. MDRS in southeast Utah is situated in a cold arid desert with mineralogy and erosion processes comparable to those on Mars. Insight into the microbial community composition of this terrestrial Mars analogue provides essential information for the search for life on Mars: including sampling and life detection methodology optimization and what kind of organisms to expect. Soil samples were collected from different locations. Culture-independent molecular analyses directed at ribosomal RNA genes revealed the presence of all three domains of life (Archaea, Bacteria and Eukarya), but these were not detected in all samples. Spiking experiments revealed that this appears to relate to low DNA recovery, due to adsorption or degradation. Bacteria were most frequently detected and showed high alpha- and beta-diversity. Members of the Actinobacteria, Proteobacteria, Bacteroidetes and Gemmatimonadetes phyla were found in the majority of samples. Archaea alpha- and beta-diversity was very low. For Eukarya, a diverse range of organisms was identified, such as fungi, green algae and several phyla of Protozoa. Phylogenetic analysis revealed an extraordinary variety of putative extremophiles, mainly Bacteria but also Archaea and Eukarya. These comprised radioresistant, endolithic, chasmolithic, xerophilic, hypolithic, thermophilic, thermoacidophilic, psychrophilic, halophilic, haloalkaliphilic and alkaliphilic micro-organisms. Overall, our data revealed large difference in occurrence and diversity over short distances, indicating the need for high-sampling frequency at similar sites. DNA extraction methods need to be optimized to improve extraction efficiencies.

  7. Protracted treatment with diazepam increases the turnover of putative endogenous ligands for the benzodiazepine/. beta. -carboline recognition site

    SciTech Connect

    Miyata, M.; Mocchetti, I.; Ferrarese, C.; Guidotti, A.; Costa, E.

    1987-03-01

    DBI (diazepam-binding inhibitor) is a putative neuromodulatory peptide isolated from rat brain that acts on ..gamma..-aminobutyric acid-benzodiazepine-Cl/sup -/ ionosphore receptor complex inducing ..beta..-carboline-like effects. The authors used a cDNA probe complementary to DBI mRNA and a specific antibody for rat DBI to study in rat brain how the dynamic state of DBI can be affected after protected (three times a day for 10 days) treatment with diazepam and chlordiazepoxide by oral gavage. Both the content of DBI and DBI mRNA increased in the cerebellum and cerebral cortex but failed to change in the hippocampus and striatum of rats receiving this protracted benzodiazepine treatment. Acute treatment with diazepam did not affect the dynamic state of brain DBI. An antibody was raised against a biologically active octadecaneuropeptide derived from the tryptic digestion of DBI. The combined HPLC/RIA analysis of rat cerebellar extracts carried out with this antibody showed that multiple molecular forms of the octadecaneuropeptide-like reactivity are present and all of them are increased in rats receiving repeated daily injections of diazepam. It is inferred that tolerance to benzodiazepines in associated with an increase in the turnover rate of DBI, which may be responsible for the ..gamma..-aminobutyric acid receptor desensitization that occurs after protracted benzodiazepine administration.

  8. The novel β3-adrenoceptor agonist mirabegron reduces carbachol-induced contractile activity in detrusor tissue from patients with bladder outflow obstruction with or without detrusor overactivity.

    PubMed

    Svalø, Julie; Nordling, Jørgen; Bouchelouche, Kirsten; Andersson, Karl-Erik; Korstanje, Cees; Bouchelouche, Pierre

    2013-01-15

    β(3)-Adrenoceptors are major players in detrusor relaxation and have been suggested as a new putative target for the treatment of overactive bladder syndrome. We determined the effects of mirabegron (YM178), a novel β(3)-adrenoceptor agonist, on carbachol-induced tone in isolated human detrusor preparations from patients with bladder outflow obstruction (BOO) with and without detrusor overactivity (DO), and from patients with normal bladder function. We compared the effects to those of isoprenaline, a non-selective β-adrenoceptor agonist. Detrusor specimens were obtained from patients with benign prostatic hyperplasia undergoing cystoscopy and from patients undergoing radical prostatectomy/cystectomy (in total 33 donors). Detrusor contractility was evaluated by organ bath studies and strips were incubated with carbachol (1μM) to induce and enhance tension. Both mirabegron and isoprenaline reduced carbachol-induced tone in tissues from all groups. Isoprenaline decreased tension with higher potency than mirabegron in normal, BOO and BOO+DO detrusor strips with pIC(50) values of 7.49 ± 0.16 vs. 6.23 ± 0.26 (P=0.0002), 6.89 ± 0.34 vs. 6.04 ± 0.31 (P=0.01), and 6.57 ± 0.20 vs. 5.41 ± 0.08 (P<0.0001, n=4), respectively. The maximal relaxant effect of isoprenaline and mirabegron in the normal, BOO and BOO+DO detrusor was 37.7 ± 14.4% and 36.1 ± 23.3%, 14.4 ± 12.2% vs. 33.4 ± 21.0% and 18.3 ± 10.0% vs. 28.3 ± 12.2% (n=4, P>0.05), respectively. Mirabegron and isoprenaline reduced carbachol-induced tone in both normal bladders and obstructed bladder with and without DO. Isoprenaline had higher potency than mirabegron, but the efficacy of mirabegron effect was the same as that of isoprenaline. PMID:23246623

  9. Characterization of the role of HCN channels in β3-adrenoceptor mediated rat bladder relaxation

    PubMed Central

    Kashyap, Mahendra; Yoshimura, Naoki; Smith, Phillip P.; Chancellor, Michael; Tyagi, Pradeep

    2015-01-01

    Objective The second messenger cAMP is involved in both β3 adrenoceptor (β3-AR) mediated detrusor relaxation and the kinetics of Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Here we characterized the effect HCN channel activation and possible interaction with β3-AR in bladder. Materials and Methods Bladder tissues from Sprague-Dawley rats and Human organ donors were obtained for studying species-specific expression of HCN channels by real-time qPCR and Western Blot. Effect of β3-agonist on rat bladder strips (0.5 × 0.5 × 7 mm in size) was studied during activation and blockade of HCN channels by Lamotrigine and ZD7288, respectively. Results Expression of all four genes encoding for HCN channels (HCN1-4) was detected separately in bladder mucosa and detrusor from human and rat bladders. Species based differences were evident from relatively higher expression of HCN4 isoform in human bladder and that of HCN1 in rat bladder. Western blot confirmed the findings at mRNA level. Cumulative application β3-AR agonist CL316,243 produced a concentration dependent decrease in resting tension of rat bladder strips expressed as integral of mechanical activity. Pre-incubation of HCN channel blocker ZD 7288 opposed the relaxant effect of CL316,243, whereas co-administration of lamotrigine with CL316,243 at equal molar concentrations caused an additive decrease in resting tension. Cumulative addition of ZD7288 and lamotrigine in absence of CL316,243 showed opposing effects on detrusor contractility. Conclusions Species-specific differences were noted in expression of HCN channels in bladder. Opposing effects ZD7288 and Lamotrigine in the action of β3-AR agonist demonstrate possible functional interaction of HCN channels and β3-AR in detrusor contractility. PMID:26709376

  10. Interaction with Caveolin-1 Modulates G Protein Coupling of Mouse β3-Adrenoceptor*

    PubMed Central

    Sato, Masaaki; Hutchinson, Dana S.; Halls, Michelle L.; Furness, Sebastian G. B.; Bengtsson, Tore; Evans, Bronwyn A.; Summers, Roger J.

    2012-01-01

    Caveolins act as scaffold proteins in multiprotein complexes and have been implicated in signaling by G protein-coupled receptors. Studies using knock-out mice suggest that β3-adrenoceptor (β3-AR) signaling is dependent on caveolin-1; however, it is not known whether caveolin-1 is associated with the β3-AR or solely with downstream signaling proteins. We have addressed this question by examining the impact of membrane rafts and caveolin-1 on the differential signaling of mouse β3a- and β3b-AR isoforms that diverge at the distal C terminus. Only the β3b-AR promotes pertussis toxin (PTX)-sensitive cAMP accumulation. When cells expressing the β3a-AR were treated with filipin III to disrupt membrane rafts or transfected with caveolin-1 siRNA, the cyclic AMP response to the β3-AR agonist CL316243 became PTX-sensitive, suggesting Gαi/o coupling. The β3a-AR C terminus, SP384PLNRF389DGY392EGARPF398PT, resembles a caveolin interaction motif. Mutant β3a-ARs (F389A/Y392A/F398A or P384S/F389A) promoted PTX-sensitive cAMP responses, and in situ proximity assays demonstrated an association between caveolin-1 and the wild type β3a-AR but not the mutant receptors. In membrane preparations, the β3b-AR activated Gαo and mediated PTX-sensitive cAMP responses, whereas the β3a-AR did not activate Gαi/o proteins. The endogenous β3a-AR displayed Gαi/o coupling in brown adipocytes from caveolin-1 knock-out mice or in wild type adipocytes treated with filipin III. Our studies indicate that interaction of the β3a-AR with caveolin inhibits coupling to Gαi/o proteins and suggest that signaling is modulated by a raft-enriched complex containing the β3a-AR, caveolin-1, Gαs, and adenylyl cyclase. PMID:22535965

  11. β3-Adrenoceptor agonists for overactive bladder syndrome: Role of translational pharmacology in a repositioning clinical drug development project.

    PubMed

    Michel, Martin C; Korstanje, Cees

    2016-03-01

    β3-Adrenoceptor agonists were originally considered as a promising drug class for the treatment of obesity and/or type 2 diabetes. When these development efforts failed, they were repositioned for the treatment of the overactive bladder syndrome. Based on the example of the β3-adrenoceptor agonist mirabegron, but also taking into consideration evidence obtained with ritobegron and solabegron, we discuss challenges facing a translational pharmacology program accompanying clinical drug development for a first-in-class molecule. Challenges included generic ones such as ligand selectivity, species differences and drug target gene polymorphisms. Challenges that are more specific included changing concepts of the underlying pathophysiology of the target condition while clinical development was under way; moreover, a paucity of public domain tools for the study of the drug target and aspects of receptor agonists as drugs had to be addressed. Nonetheless, a successful first-in-class launch was accomplished. Looking back at this translational pharmacology program, we conclude that a specifically tailored and highly flexible approach is required. However, several of the lessons learned may also be applicable to translational pharmacology programs in other indications. PMID:26808167

  12. Direct interaction of beta-amyloid with Na,K-ATPase as a putative regulator of the enzyme function.

    PubMed

    Petrushanko, Irina Yu; Mitkevich, Vladimir A; Anashkina, Anastasia A; Adzhubei, Alexei A; Burnysheva, Ksenia M; Lakunina, Valentina A; Kamanina, Yulia V; Dergousova, Elena A; Lopina, Olga D; Ogunshola, Omolara O; Bogdanova, Anna Yu; Makarov, Alexander A

    2016-01-01

    By maintaining the Na(+) and K(+) transmembrane gradient mammalian Na,K-ATPase acts as a key regulator of neuronal electrotonic properties. Na,K-ATPase has an important role in synaptic transmission and memory formation. Accumulation of beta-amyloid (Aβ) at the early stages of Alzheimer's disease is accompanied by reduction of Na,K-ATPase functional activity. The molecular mechanism behind this phenomenon is not known. Here we show that the monomeric Aβ(1-42) forms a tight (Kd of 3 μM), enthalpy-driven equimolar complex with α1β1 Na,K-ATPase. The complex formation results in dose-dependent inhibition of the enzyme hydrolytic activity. The binding site of Aβ(1-42) is localized in the "gap" between the alpha- and beta-subunits of Na,K-ATPase, disrupting the enzyme functionality by preventing the subunits from shifting towards each other. Interaction of Na,K-ATPase with exogenous Aβ(1-42) leads to a pronounced decrease of the enzyme transport and hydrolytic activity and Src-kinase activation in neuroblastoma cells SH-SY5Y. This interaction allows regulation of Na,K-ATPase activity by short-term increase of the Aβ(1-42) level. However prolonged increase of Aβ(1-42) level under pathological conditions could lead to chronical inhibition of Na,K-ATPase and disruption of neuronal function. Taken together, our data suggest the role of beta-amyloid as a novel physiological regulator of Na,K-ATPase. PMID:27296892

  13. Direct interaction of beta-amyloid with Na,K-ATPase as a putative regulator of the enzyme function

    PubMed Central

    Petrushanko, Irina Yu.; Mitkevich, Vladimir A.; Anashkina, Anastasia A.; Adzhubei, Alexei A.; Burnysheva, Ksenia M.; Lakunina, Valentina A.; Kamanina, Yulia V.; Dergousova, Elena A.; Lopina, Olga D.; Ogunshola, Omolara O.; Bogdanova, Anna Yu.; Makarov, Alexander A.

    2016-01-01

    By maintaining the Na+ and K+ transmembrane gradient mammalian Na,K-ATPase acts as a key regulator of neuronal electrotonic properties. Na,K-ATPase has an important role in synaptic transmission and memory formation. Accumulation of beta-amyloid (Aβ) at the early stages of Alzheimer’s disease is accompanied by reduction of Na,K-ATPase functional activity. The molecular mechanism behind this phenomenon is not known. Here we show that the monomeric Aβ(1-42) forms a tight (Kd of 3 μM), enthalpy-driven equimolar complex with α1β1 Na,K-ATPase. The complex formation results in dose-dependent inhibition of the enzyme hydrolytic activity. The binding site of Aβ(1-42) is localized in the “gap” between the alpha- and beta-subunits of Na,K-ATPase, disrupting the enzyme functionality by preventing the subunits from shifting towards each other. Interaction of Na,K-ATPase with exogenous Aβ(1-42) leads to a pronounced decrease of the enzyme transport and hydrolytic activity and Src-kinase activation in neuroblastoma cells SH-SY5Y. This interaction allows regulation of Na,K-ATPase activity by short-term increase of the Aβ(1-42) level. However prolonged increase of Aβ(1-42) level under pathological conditions could lead to chronical inhibition of Na,K-ATPase and disruption of neuronal function. Taken together, our data suggest the role of beta-amyloid as a novel physiological regulator of Na,K-ATPase. PMID:27296892

  14. Structure-based sequence alignment for the beta-trefoil subdomain of the clostridial neurotoxin family provides residue level information about the putative ganglioside binding site.

    PubMed

    Ginalski, K; Venclovas, C; Lesyng, B; Fidelis, K

    2000-09-29

    Clostridial neurotoxins embrace a family of extremely potent toxins comprised of tetanus toxin (TeNT) and seven different serotypes of botulinum toxin (BoNT/A-G). The beta-trefoil subdomain of the C-terminal part of the heavy chain (H(C)), responsible for ganglioside binding, is the most divergent region in clostridial neurotoxins with sequence identity as low as 15%. We re-examined the alignment between family sequences within this subdomain, since in this region all alignments published to date show obvious inconsistencies with the beta-trefoil fold. The final alignment was obtained by considering the general constraints imposed by this fold, and homology modeling studies based on the TeNT structure. Recently solved structures of BoNT/A confirm the validity of this structure-based approach. Taking into account biochemical data and crystal structures of TeNT and BoNT/A, we also re-examined the location of the putative ganglioside binding site and, using the new alignment, characterized this site in other BoNT serotypes. PMID:11018534

  15. The selectivity of β-adrenoceptor agonists at human β1-, β2- and β3-adrenoceptors

    PubMed Central

    Baker, Jillian G

    2010-01-01

    Background and purpose: There are two important properties of receptor–ligand interactions: affinity (the ability of the ligand to bind to the receptor) and efficacy (the ability of the receptor–ligand complex to induce a response). Ligands are classified as agonists or antagonists depending on whether or not they have efficacy. In theory, it is possible to develop selective agonists based on selective affinity, selective intrinsic efficacy or both. This study examined the affinity and intrinsic efficacy of 31 β-adrenoceptor agonists at the three human β-adrenoceptors to determine whether the current agonists are subtype selective because of affinity or intrinsic efficacy. Experimental approach: Stable clonal CHO-K1 cell lines, transfected with either the human β1, β2 or β3-adrenoceptor, were used, and whole-cell [3H]-CGP 12177 radioligand binding and [3H]-cAMP accumulation were measured. Key results: Several agonists were found to be highly subtype selective because of selective affinity (e.g. salmeterol and formoterol, for the β2-adrenoceptor over the β1 or β3), while others (e.g. isoprenaline) had little affinity–selectivity. However, the intrinsic efficacy of salmeterol, formoterol and isoprenaline was similar across all three receptor subtypes. Other ligands (e.g. denopamine for β1; clenbuterol, AZ 40140d, salbutamol for β2) were found to have subtype-selective intrinsic efficacy. Several ligands appeared to activate two agonist conformations of the β1- and β3-adrenoceptors. Conclusions and implications: There are agonists with subtype selectivity based upon both selective affinity and selective intrinsic efficacy. Therefore, there is scope to develop better selective agonists based upon both selective affinity and selective intrinsic efficacy. This article is commented on by Kenakin, pp. 1045–1047 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00764.x PMID:20590599

  16. Putative structure and functions of a poly-beta-hydroxybutyrate/calcium polyphosphate channel in bacterial plasma membranes.

    PubMed Central

    Reusch, R N; Sadoff, H L

    1988-01-01

    A poly-beta-hydroxybutyrate complex extracted from the plasma membranes of genetically competent Escherichia coli contained polyhydroxybutyrate:polyphosphate:calcium in molar ratios approximating 1:1:0.5. The chain length of the polyhydroxybutyrate was estimated as 120-200 subunits, and that of the polyphosphate was estimated as 130-170 subunits. The extracted complex, when incorporated into liposomes, exhibited a lipid phase transition in the same temperature range as that of the membrane complex in whole cells as well as the same properties of irreversibility, lability, and sensitivity to chelating buffers. Space-filling molecular models and molecular energy minimization methods (Charmm) were used to develop and evaluate a plausible structure for the complex. It is proposed that the polyhydroxybutyrate forms an exolipophilic-endopolarophilic helix around an inner framework helix of calcium polyphosphate. The calcium ions link the two polymers by forming ionic bonds with phosphoryl oxygens of the polyphosphate and ion-dipole bonds with the ester carbonyl oxygens of the polyhydroxybutyrate. This symmetrical structure forms a channel through the membrane and may play a role in the transport of calcium, phosphate, and DNA. Images PMID:2454464

  17. Effect of mirabegron, a novel β3-adrenoceptor agonist, on bladder function during storage phase in rats.

    PubMed

    Hatanaka, Toshiki; Ukai, Masashi; Watanabe, Mai; Someya, Akiyoshi; Ohtake, Akiyoshi; Suzuki, Masanori; Ueshima, Koji; Sato, Shuichi; Kaku, Seiji

    2013-01-01

    Mirabegron, a selective β(3)-adrenoceptor agonist, facilitates urine storage function by exerting a relaxing effect on bladder smooth muscle. Here, we investigated the effect of mirabegron on bladder function during the storage phase. We assessed the effect of mirabegron on the resting intravesical pressure in anesthetized rats and also tested antimuscarinics (oxybutynin and tolterodine) under the same experimental conditions. Mirabegron dose-dependently decreased the resting intravesical pressure, while oxybutynin and tolterodine showed no statistically significant effects on resting intravesical pressure. We also investigated the effect of mirabegron on bladder function using cystometry technique in conscious rats with bladder outlet obstruction. While mirabegron dose-dependently decreased the frequency of nonvoiding contractions, considered an index of abnormal response in bladder storage, no significant effects were noted on the amplitude of nonvoiding contractions, micturition pressure, threshold pressure, voided volume, residual volume, or bladder capacity. Neither oxybutynin nor tolterodine affected the frequency of nonvoiding contractions; however, oxybutynin increased residual volume and tended to decrease voided volume in a dose-dependent manner, and tolterodine dose-dependently decreased voided volume. Taken together, these results shed light on the suggestion of mirabegron as a therapeutic agent, compared with antimuscarinics, with its most prominent effect being the facilitation of bladder storage. PMID:23224420

  18. Comparative inter-strain sequence analysis of the putative regulatory region of murine psychostimulant-regulated gene GNB1 (G protein beta 1 subunit gene).

    PubMed

    Kitanaka, Nobue; Kitanaka, Junichi; Walther, Donna; Wang, Xiao-Bing; Uhl, George R

    2003-08-01

    We isolated a cDNA clone from a murine genomic library of C57BL/6 strain, carrying 13.8 kb of nucleotides including exon 1 of heterotrimeric GTP-binding protein beta 1 subunit gene (genetic symbol, GNB1) and 10.6 kb of the 5' flanking region. Sequence comparison with GNB1 gene locus from 129Sv strain revealed a 0.2% divergence in a 13.2 kb common region between these two strains. The divergence consisted of eight single nucleotide polymorphisms, three insertions and one deletion, with 129Sv used as the reference. The exon 1 and the putative regulation elements, such as cyclic AMP response element, AP1, AP2, Sp1 and nuclear factor-kappa B recognition sites, were perfectly conserved. The expression of GNB1 mRNA was significantly increased in mouse striatum 2 h after single methamphetamine administration with an approximately 150% expression level compared with the basal level. In contrast, no change in the expression level was observed in the cerebral cortex. After the chronic methamphetamine treatment regimen, the expression level of GNB1 mRNA did not change in any brain regions examined. These results suggest (1) that the 5' flanking nucleotide sequence of GNB1 gene was strictly conserved for its possible contribution to the same change in the expression level between the mouse strains in response to psychostimulants and (2) that the initial process of development of behavioral sensitization appeared to occur parallel to the significant increase in the expression level of GNB1 gene in the mouse striatum. PMID:14631649

  19. The onset of labor alters corticotropin-releasing hormone type 1 receptor variant expression in human myometrium: putative role of interleukin-1beta.

    PubMed

    Markovic, Danijela; Vatish, Manu; Gu, Mei; Slater, Donna; Newton, Rob; Lehnert, Hendrik; Grammatopoulos, Dimitris K

    2007-07-01

    CRH targets the human myometrium during pregnancy. The efficiency of CRH actions is determined by expression of functional receptors (CRH-R), which are dynamically regulated. Studies in myometrial tissue biopsies using quantitative RT-PCR demonstrated that the onset of labor, term or preterm, is associated with a significant 2- to 3-fold increase in CRH-R1 mRNA levels. Detailed analysis of myometrial CRH-R1 mRNA variants showed a decline of the pro-CRH-R1 mRNA encoding the CRH-R1beta variant during labor and increased mRNA levels of CRH-R1d mRNA. Studies in myometrial cells identified IL-1beta as an important regulator of myometrial CRH-R1 gene expression because prolonged treatment of myometrial cells with IL-1beta (1 ng/ml) for 18 h induced expression of CRH-R1 mRNA levels by 1.5- to 2-fold but significantly attenuated CRH-R1beta mRNA expression by 70%. In contrast, IL-1beta had no effect on CRH-R1d mRNA expression. Studies using specific inhibitors suggest that ERK1/2, p38 MAPK, and downstream nuclear translocation of nuclear factor-kappaB mediate IL-1beta effects on myometrial CRH-R1 gene. However, the increased CRH-R1 mRNA expression was associated with a dampening of the receptor efficacy to activate the adenylyl cyclase/cAMP signaling cascade. Thus, our findings suggest that IL-1beta is an important regulator of CRH-R1 expression and functional activity, and this interaction might play a role in the transition of the uterus from quiescence to active contractions necessary for the onset of parturition. PMID:17431005

  20. Two unrelated putative membrane-bound progestin receptors, progesterone membrane receptor component 1 (PGMRC1) and membrane progestin receptor (mPR) beta, are expressed in the rainbow trout oocyte and exhibit similar ovarian expression patterns

    PubMed Central

    Mourot, Brigitte; Nguyen, Thaovi; Fostier, Alexis; Bobe, Julien

    2006-01-01

    Background In lower vertebrates, steroid-induced oocyte maturation is considered to involve membrane-bound progestin receptors. Two totally distinct classes of putative membrane-bound progestin receptors have been reported in vertebrates. A first class of receptors, now termed progesterone membrane receptor component (PGMRC; subtypes 1 and 2) has been studied since 1996 but never studied in a fish species nor in the oocyte of any animal species. A second class of receptors, termed membrane progestin receptors (mPR; subtypes alpha, beta and gamma), was recently described in vertebrates and implicated in the progestin-initiated induction of oocyte maturation in fish. Methods In the present study, we report the characterization of the full coding sequence of rainbow trout PGMRC1 and mPR beta cDNAs, their tissue distribution, their ovarian expression profiles during oogenesis, their hormonal regulation in the full grown ovary and the in situ localization of PGMRC1 mRNA in the ovary. Results Our results clearly show, for the first time in any animal species, that rainbow trout PGMRC1 mRNA is present in the oocyte and has a strong expression in ovarian tissue. In addition, we show that both mPR beta and PGMRC1, two members of distinct membrane-bound progestin receptor classes, exhibit highly similar ovarian expression profiles during the reproductive cycle with maximum levels during vitellogenesis and a down-expression during late vitellogenesis. In addition, the mRNA abundance of both genes is not increased after in vitro hormonal stimulation of full grown follicles by maturation inducing hormones. Conclusion Together, our findings suggest that PGMRC1 is a new possible participant in the progestin-induced oocyte maturation in fish. However, its participation in the process of oocyte maturation, which remains to be confirmed, would occur at post-transcriptional levels. PMID:16457725

  1. A point mutation in the putative TATA box, detected in nondiseased individuals and patients with hereditary breast cancer, decreases promoter activity of the 17{beta}-hydroxysteroid dehydrogenase type 1 gene 2 (EDH17B2) in vitro

    SciTech Connect

    Peltoketo, H.; Piao, Y.; Isomaa, V.

    1994-09-01

    EDH17B2, the gene encoding 17{beta}-hydroxysteroid dehydrogenase type 1, has been suggested as a candidate for the familial breast cancer gene, BRCA1, located on 17q12-q21. We analyzed the promoter region of EDH17B2 in DNA from 20 control individuals and 40 patients with familial breast cancer. Two frequent (designated vI and vIII) and two rare (vII and vIV) nucleotide variations were present in both the breast cancer patients and the controls, except the alteration vII, which was found only in one patient. Although the data do not support the identification of EDH17B2 as the BRCA1 gene, it is of interest that point mutation vIV (A {yields} C) was located in the putative TATA box of the EDH17B2 gene. Reporter gene analysis showed that the mutation vIV decreases EDH17B2 promoter activity by an average of 45% in in vitro assays, suggesting that nucleotide A at position -27 is significant for efficient transcription. 12 refs., 2 figs., 1 tab.

  2. Venom gland EST analysis of the saw-scaled viper, Echis ocellatus, reveals novel alpha9beta1 integrin-binding motifs in venom metalloproteinases and a new group of putative toxins, renin-like aspartic proteases.

    PubMed

    Wagstaff, Simon C; Harrison, Robert A

    2006-08-01

    Echis ocellatus is the most medically important snake in West Africa. However, the composition of its venom and the differential contribution of these venom components to the severe haemorrhagic and coagulopathic pathology of envenoming are poorly understood. To address this situation we assembled a toxin transcriptome based upon 1000 expressed sequence tags (EST) from a cDNA library constructed from pooled venom glands of 10 individual E. ocellatus. We used a variety of bioinformatic tools to construct a fully annotated venom-toxin transcriptome that was interrogated with a combination of BLAST annotation, gene ontology cataloguing and disintegrin-motif searching. The results of these analyses revealed an unusually abundant and diverse expression of snake venom metalloproteinases (SVMP) and a broad toxin-expression profile including several distinct isoforms of bradykinin-potentiating peptides, phospholipase A(2), C-type lectins, serine proteinases and l-amino oxidases. Most significantly, we identified for the first time a conserved alpha(9)beta(1) integrin-binding motif in several SVMPs, and a new group of putative venom toxins, renin-like aspartic proteases. PMID:16713134

  3. Messenger RNAs encoding the beta subunits of guinea pig (Cavia porcellus) luteinizing hormone (gpLH) and putative chorionic gonadotropin (gpCG) are transcribed from a single-copy gpLH/CGbeta gene.

    PubMed

    Sherman, G B; Heilman, D F; Hoss, A J; Bunick, D; Lund, L A

    2001-06-01

    Neither gene locus nor gene sequence characterizations have been reported for the beta subunits of guinea pig (gp) LH and putative gp chorionic gonadotropin (CG). Descriptions of this locus would allow comparison with functionally relevant molecular genetic features of other species' homologous loci including the single-copy equid LH/CGbeta gene and the primate LHbeta-CGbeta gene cluster locus. Contiguous cDNA and genomic DNA fragments spanning the entire mature coding sequence of gpLHbeta mRNA, gpCGbeta mRNA and a homologous gpLH/CGbeta gene were amplified using PCR methodologies. With the exception of one silent mutation, the two cDNA and the genomic sequences were identical where they overlapped. Comparison of guinea pig coding sequence with LHbeta, CGbeta and LH/CGbeta sequences of other vertebrate species revealed the following order of similarity expressed as per cent coding sequence identity: rhinoceros LHbeta (83.6%)>pig LHbeta (81.8%)>donkey LH/CGbeta=bovine LHbeta (81.5%)> horse LH/CGbeta (80.6%)>dog LHbeta (79.7%)>human LHbeta (78.2%)>rat LHbeta (77.9%)>human CGbeta (75.8%)>turkey LHbeta (52.7%); values that are generally consistent with recently postulated phylogenetic relationships. Like the consensus mammalian LHbeta gene, the 5'-flanking region of the gpLH/CGbeta gene contains a single TATA sequence 37 bp upstream of the translation start codon. The first in-frame stop codon occurred at codon position +122 which is consistent with the 121 amino acid residue length of the consensus mammalian mature LHbeta peptide. To estimate gene copy number, full-length gpLHbeta cDNA was radiolabeled and hybridized to Southern blots of guinea pig genomic DNA digested with a panel of six restriction endonucleases. The resulting simple hybridization pattern strongly suggested that there is a single-copy gpLH/CGbeta gene. Northern analysis of total pituitary RNA using the same probe indicated that gpLHbeta transcript size is indistinguishable from that of consensus

  4. Beta-adrenoceptors in obstetrics and gynecology.

    PubMed

    Modzelewska, Beata

    2016-01-01

    One hundred and twenty years after the description of extracts from the adrenal medulla, the use of beta-blockers and beta-agonists evolved from antianginal drugs and tocolytics to ligand-directed signaling. Beta-blockers in the fields of obstetrics and gynecology have so far been limited to the consideration of continuing treatment of disorders of the cardiovascular system and other dysfunctions that started before pregnancy. Studies in recent years have shown that beta-adrenoceptor signaling might be crucial in carcinogenesis and metastasis, apoptosis and anoikis. On the other hand, the use of beta-adrenoceptor agonists in tocolysis is, as yet, the primary method for inhibiting premature uterine contractions. Unfortunately, the efficacy of current pharmacological treatment for the management of preterm labor is regularly questioned. Moreover, studies related to non-pregnant myometrium performed to date indicate that the rhythmic contractions of the uterus are required for menstruation and have an important role in human reproduction. In turn, abnormal uterine contractility has been linked to dysmenorrhea, a condition associated with painful uterine cramping. The benefits of the use of beta2-adrenoceptor agonists in dysmenorrhea are still unclear and should be balanced against a wide range of adverse effects recognized with this class of medication. The ideal tocolytic agent is one which is effective for the pregnant or non-pregnant woman but has no side effects on either the woman or the baby. Looking to the future with both caution and hope, the potential metamorphosis of beta3-adrenoceptor agonists from experimental tools into therapeutic drugs for tocolysis warrants attention. PMID:27442692

  5. Evidence for monoclonal expansion of synovial T cells bearing V alpha 2.1/V beta 5.5 gene segments and recognizing a synthetic peptide that shares homology with a number of putative autoantigens.

    PubMed Central

    Ostenstad, B; Dybwad, A; Lea, T; Førre, O; Vinje, O; Sioud, M

    1995-01-01

    A peptide of 15 amino acids derived from the cereal glycine-rich cell wall protein (GRP), sharing a significant homology with Epstein-Barr virus nuclear antigen-1 (EBNA-1), fibrillar and procollagen, stimulated synovial fluid (SF) T cells from juvenile (JRA) and adult (RA) rheumatoid arthritis patients. An overexpression of the V alpha 2 gene family was found in the SF from patients who responded significantly to the peptide. To investigate in more detail the SF T-cell responses to the GRP peptide, we established peptide-specific T-cell lines and clones from a DR8+ positive JRA patient with pauciarticular form. The T-cell clones were phenotyped as T-cell receptor (TCR)alpha beta+/CD4+ and their clonality was investigated by polymerase chain reaction (PCR) and flow cytometric analysis. TCR sequences from different clones demonstrated that the clones were identical and used the V alpha 2.1/J alpha 6 combined with V beta 5.5/J beta 2.7 gene segments. Interestingly, direct sequencing of the V alpha 2 family PCR product obtained from cDNA prepared from freshly isolated SF mononuclear cells identified the same TCR sequence as that used by the clones, suggesting the monoclonality of SF CD4+ T cells bearing V alpha 2.1/J alpha 6 gene products. The present data suggest a recruitment and expansion of a SF T-cell subpopulation, and also support the hypothesis that autoimmune diseases can be triggered by protein epitopes with crucial amino acids homologous to self-proteins. Images Figure 7 PMID:7490114

  6. Effects of ritobegron (KUC-7483), a novel β3-adrenoceptor agonist, on both rat bladder function following partial bladder outlet obstruction and on rat salivary secretion: a comparison with the effects of tolterodine.

    PubMed

    Maruyama, Itaru; Yonekubo, Saori; Tatemichi, Satoshi; Maruyama, Kazuyasu; Hoyano, Yuji; Yamazaki, Yoshinobu; Kusama, Hiroshi

    2012-01-01

    The objective of this study was to investigate the effects of the β3-adrenoceptor (AR) agonist ritobegron on rat bladder function following partial bladder outlet obstruction and on rat salivary secretion. In addition, the effects of ritobegron were compared with those of the anti-muscarinic agent tolterodine. After a 6-week partial bladder outlet obstruction (BOO), drug effects on bladder functions were evaluated using cystometrography. Effects on carbachol (CCh)-induced salivary secretion were evaluated in urethane-anesthetized rats. Ritobegron significantly decreased the frequency of non-voiding contractions (NVC), while both ritobegron and tolterodine each significantly decreased the amplitude of NVC. Ritobegron had no effect on either the micturition pressure (MP) or the residual volume (RV). In contrast, tolterodine dose-dependently decreased MP and increased RV. Ritobegron had no effect on CCh-induced salivary secretion, whereas tolterodine dose-dependently decreased it. Ritobegron decreased both the frequency and amplitude of NVC, which is similar to its effect on the contractions associated with detrusor overactivity (DO) in patients with an overactive bladder (OAB), without affecting MP, RV, or CCh-induced salivary secretion. Although tolterodine reduced the amplitude of NVC, it also markedly increased RV and significantly inhibited CCh-induced salivary secretion. These results suggest that use of ritobegron, a β3-AR agonist, is unlikely to lead to the residual urine and dry mouth symptoms that are associated with anti-muscarinic drugs, and that ritobegron may hold promise as a safe and effective agent for OAB treatment. PMID:23538508

  7. Proteomic profiling of Beta vulgaris leaves during rhizomania compatible interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rhizomania severely impacts sugarbeet (Beta vulgaris) production throughout the world, and is widely prevalent in most sugarbeet growing regions. Initial efforts to characterize proteome changes focused primarily on identifying putative host factors that elicit resistant interactions with Beet Necr...

  8. Beta experiment

    NASA Technical Reports Server (NTRS)

    1982-01-01

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

  9. [Functional exploration of brown adipose tissue using beta3 agonists].

    PubMed

    Bertin, R; de Marco, F; Blancher, G; Portet, R

    1994-06-01

    In view to utilize beta 3 adrenoceptor agonists for the investigation of body lipid metabolism, a study of the effects of BRL 37344 on the functional activity of the brown adipose tissue was performed in the Rat. It is known that this tissue is the principal site of heat production for nonshivering thermogenesis mainly due to the oxidation of fatty acids under the control of norepinephrine (NA) released from the sympathetic nervous system. In order to stimulate the activity of the tissue, rats were reared at 16 degrees C. When they were one month old, they were divided in two groups; one group received a surgical sympathectomy of the interscapular brown adipose tissue (TABI) (S group); the other group was sham-operated (T group). The resting metabolism was estimated by the continuous measurement of O2 consumption and CO2 release, at an ambient temperature of 25 degrees C. The animal capacity for nonshivering thermogenesis was determined by increased O2 consumption following i.p. administration of NA or BRL 37344. In the S group a large decrease in TABI NA content and a decrease in resting metabolism were observed. In both groups VO2 was increased by the two drugs; the increase was linearly related to the dose of BRL (between 2.5 to 10 micrograms/kg); but it was 3 times as high in the T group as in the S group. Moreover, the effect of BRL was 40 fold greater than the effect of NA. These results seem to indicate that, in cold reared rats, a part of nonshivering thermogenesis may be mediated by the beta 3 receptors of the brown fat. It may be concluded that the rats born in cold conditions are good models to study the role of beta 3 receptors in the energetic activity of this tissue very profuse in infant but not in adult man. PMID:7994586

  10. Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher respiratory quotient after aerobic exercise, but β3-adrenoceptor 64R allele does not affect lipolysis: a human model.

    PubMed

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise. PMID:24905907

  11. Carnitine Palmitoyltransferase 1B 531K Allele Carriers Sustain a Higher Respiratory Quotient after Aerobic Exercise, but β3-Adrenoceptor 64R Allele Does Not Affect Lipolysis: A Human Model

    PubMed Central

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise. PMID:24905907

  12. Beta cell adaptation in pregnancy: a tribute to Claes Hellerström

    PubMed Central

    2016-01-01

    Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin and growth hormone expressed in rodent beta cells. However, the beta cell expansion in human pregnancy seems to occur by neogenesis of beta cells from putative progenitor cells rather than by proliferation of existing beta cells. Claes Hellerström has pioneered the research on beta cell growth for decades, but the mechanisms involved are still not clarified. In this review the information obtained in previous studies is recapitulated together with some of the current attempts to resolve the controversy in the field: identification of the putative progenitor cells, identification of the factors involved in the expansion of the beta cell mass in human pregnancy, and the relative roles of endocrine factors and nutrients. PMID:27055631

  13. CRYSTAL STRUCTURE ANALYSIS OF A PUTATIVE OXIDOREDUCTASE FROM KLEBSIELLA PNEUMONIAE

    SciTech Connect

    Baig, M.; Brown, A.; Eswaramoorthy, S.; Swaminathan, S.

    2009-01-01

    Klebsiella pneumoniae, a gram-negative enteric bacterium, is found in nosocomial infections which are acquired during hospital stays for about 10% of hospital patients in the United States. The crystal structure of a putative oxidoreductase from K. pneumoniae has been determined. The structural information of this K. pneumoniae protein was used to understand its function. Crystals of the putative oxidoreductase enzyme were obtained by the sitting drop vapor diffusion method using Polyethylene glycol (PEG) 3350, Bis-Tris buffer, pH 5.5 as precipitant. These crystals were used to collect X-ray data at beam line X12C of the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory (BNL). The crystal structure was determined using the SHELX program and refi ned with CNS 1.1. This protein, which is involved in the catalysis of an oxidation-reduction (redox) reaction, has an alpha/beta structure. It utilizes nicotinamide adenine dinucleotide phosphate (NADP) or nicotine adenine dinucleotide (NAD) to perform its function. This structure could be used to determine the active and co-factor binding sites of the protein, information that could help pharmaceutical companies in drug design and in determining the protein’s relationship to disease treatment such as that for pneumonia and other related pathologies.

  14. Tuberculosis and nature's pharmacy of putative anti-tuberculosis agents.

    PubMed

    Chinsembu, Kazhila C

    2016-01-01

    Due to the growing problem of drug resistant Mycobacterium tuberculosis strains, coupled with the twinning of tuberculosis (TB) to human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), the burden of TB is now difficult to manage. Therefore, new antimycobacterial agents are being sought from natural sources. This review focuses on natural antimycobacterial agents from endophytes and medicinal plants of Africa, Europe, Asia, South America and Canada. In the countries mentioned in this review, numerous plant species display putative anti-TB activity. Several antimycobacterial chemical compounds have also been isolated, including: ellagitannin punicalagin, allicin, anthraquinone glycosides, iridoids, phenylpropanoids, beta-sitosterol, galanthimine, crinine, friedelin, gallic acid, ellagic acids, anthocyanidin, taraxerol, termilignan B, arjunic acid, glucopyranosides, 1-epicatechol, leucopelargonidol, hydroxybenzoic acids, benzophenanthridine alkaloids, neolignans, and decarine. These compounds may provide leads to novel and more efficacious drugs to lessen the global burden of TB and drug-resistant M. tuberculosis strains. If there is a long-term remedy for TB, it must lie in nature's pharmacy of putative antimycobacterial agents. PMID:26464047

  15. The Putative Son's Attractiveness Alters the Perceived Attractiveness of the Putative Father.

    PubMed

    Prokop, Pavol

    2015-08-01

    A body of literature has investigated female mate choice in the pre-mating context (pre-mating sexual selection). Humans, however, are long-living mammals forming pair-bonds which sequentially produce offspring. Post-mating evaluations of a partner's attractiveness may thus significantly influence the reproductive success of men and women. I tested herein the theory that the attractiveness of putative sons provides extra information about the genetic quality of fathers, thereby influencing fathers' attractiveness across three studies. As predicted, facially attractive boys were more frequently attributed to attractive putative fathers and vice versa (Study 1). Furthermore, priming with an attractive putative son increased the attractiveness of the putative father with the reverse being true for unattractive putative sons. When putative fathers were presented as stepfathers, the effect of the boy's attractiveness on the stepfather's attractiveness was lower and less consistent (Study 2). This suggests that the presence of an attractive boy has the strongest effect on the perceived attractiveness of putative fathers rather than on non-fathers. The generalized effect of priming with beautiful non-human objects also exists, but its effect is much weaker compared with the effects of putative biological sons (Study 3). Overall, this study highlighted the importance of post-mating sexual selection in humans and suggests that the heritable attractive traits of men are also evaluated by females after mating and/or may be used by females in mate poaching. PMID:25731909

  16. Toddlers' Duration of Attention toward Putative Threat

    ERIC Educational Resources Information Center

    Kiel, Elizabeth J.; Buss, Kristin A.

    2011-01-01

    Although individual differences in reactions to novelty in the toddler years have been consistently linked to risk of developing anxious behavior, toddlers' attention toward a novel, putatively threatening stimulus while in the presence of other enjoyable activities has rarely been examined as a precursor to such risk. The current study examined…

  17. The Putative Use of Lithium in Alzheimer's Disease.

    PubMed

    Morris, Gerwyn; Berk, Michael

    2016-01-01

    Alzheimer`s disease is a progressive neurodegenerative illness characterized by the invariant existence of β-amyloid plaques and neurofibrillary tangles. Presently approved pharmaceutical approaches offer only marginal efficacy and as yet there is no effective treatment which reverses or arrests the disease. Thus far, drugs targeting any single aspect of disease pathology have proved to be a failure or at best provided very slight clinical benefit. The consistent failure of drugs targeting aspects of the Aβ cascade has questioned the causal role of this pathway. There is a growing appreciation that the pathogenesis of the illness is multifactorial with Amyloid Beta, Phosphorylated Tau (ptau), inflammation, mitochondrial dysfunction, calcium dyshomeostasis, heavy metal imbalances, and GSK-3 interact in a highly complex manner to provoke a selfsustaining spiraling cascade of pathology, driving disease progression. In the light of such complex pathology, the failure of drugs aimed a targeting single molecules is not surprising as such approaches are usually ineffective against other complex diseases with a multifactorial pathogenesis. Combination therapies or multi target drugs might be more effective in controlling such illnesses. The putative neuroprotective effects of Lithium are achieved via the positive modulation of numerous homeostatic mechanisms regulating autophagy, oxidative stress, inflammation, and mitochondrial dysfunction likely achieved by inhibiting GSK-3 and inositol-145 triphosphate. Data regarding efficacy in human trials and animal models of AD are mixed, but recent data using "microdose" lithium in mild cognitive impairment is encouraging, hence lithium could be a putative multi target treatment in these patients. However, additional well designed long-term trials are needed to confirm its efficacy and safety, given that long term use is necessary to achieve reasonable therapeutic benefit. PMID:26892287

  18. Adhesin receptors of human oral bacteria and modeling of putative adhesin-binding domains.

    PubMed

    Cassels, F J; Hughes, C V; Nauss, J L

    1995-09-01

    Adherence by bacteria to a surface is critical to their survival in the human oral cavity. Many types of molecules are present in the saliva and serous exudates that form the acquired pellicle, a coating on the tooth surface, and serve as receptor molecules for adherent bacteria. The primary colonizing bacteria utilize adhesins to adhere to specific pellicle receptor molecules, then may adhere to other primary colonizers via adhesins, or may present receptor molecules to be utilized by secondary colonizing species. The most common primary colonizing bacteria are streptococci, and six streptococcal cell wall polysaccharide receptor molecules have been structurally characterized. A comparison of the putative adhesin disaccharide-binding regions of the six polysaccharides suggests three groups. A representative of each group was modeled in molecular dynamics simulations. In each case it was found that a loop formed between the galactofuranose beta (Galf beta) and an oxygen of the nearest phosphate group on the reducing side of the Galf beta, that this loop was stabilized by hydrogen bonds, and that within each loop resides the putative disaccharide-binding domain. PMID:8519475

  19. Magnetism and the putative early Martian life

    NASA Astrophysics Data System (ADS)

    Rochette, P.

    2001-08-01

    A short critical review is provided on three questions linking magnetism and the putative early Mars life. Was there a large internal Martian magnetic field, during which period, and is it a requisite for life? What is the origin of the paleomagnetic signal of Martian meteorites, including ALH84001? What is the present credibility of the case for fossil bacterial magnetite grains in ALH84001?

  20. Generating Recombinant Antibodies against Putative Biomarkers of Retinal Injury

    PubMed Central

    Kierny, Michael R.; Cunningham, Thomas D.; Bouhenni, Rachida A.; Edward, Deepak P.; Kay, Brian K.

    2015-01-01

    Candidate biomarkers, indicative of disease or injury, are beginning to overwhelm the process of validation through immunological means. Recombinant antibodies developed through phage-display offer an alternative means of generating monoclonal antibodies faster than traditional immunization of animals. Peptide segments of putative biomarkers of laser induced injury in the rabbit, discovered through mass spectrometry, were used as targets for a selection against a library of phage-displayed human single-chain variable fragment (scFv) antibodies. Highly specific antibodies were isolated to four of these unique peptide sequences. One antibody against the retinal protein, Guanine Nucleotide-Binding Protein Beta 5 (GBB5), had a dissociation constant ~300 nM and recognized the full-length endogenous protein in retinal homogenates of three different animal species by western blot. Alanine scanning of the peptide target identified three charged and one hydrophobic amino acid as the critical binding residues for two different scFvs. To enhance the utility of the reagent, one scFv was dimerized through a Fragment-crystallizable hinge region (i.e., Fc) and expressed in HEK-293 cells. This dimeric reagent yielded a 25-fold lower detection limit in western blots. PMID:25902199

  1. The evolution of putative starch-binding domains.

    PubMed

    Machovic, Martin; Janecek, Stefan

    2006-11-27

    The present bioinformatics analysis was focused on the starch-binding domains (SBDs) and SBD-like motifs sequentially related to carbohydrate-binding module (CBM) families CBM20 and CBM21. Originally, these SBDs were known from microbial amylases only. At present homologous starch- and glycogen-binding domains (or putative SBD sequences) have been recognised in various plant and animal proteins. The sequence comparison clearly showed that the SBD-like sequences in genethonin-1, starch synthase III and glucan branching enzyme should possess the real SBD function since the two tryptophans (or at least two aromatics) of the typical starch-binding site 1 are conserved in their sequences. The same should apply also for the sequences corresponding with the so-called KIS-domain of plant AKINbetagamma protein that is a homologue of the animal AMP-activated protein kinase (AMPK). The evolutionary tree classified the compared SBDs into three distinct groups: (i) the family CBM20 (the motifs from genethonins, laforins, starch excess 4 protein, beta-subunits of the animal AMPK and all plant and yeast homologues, and eventually from amylopullulanases); (ii) the family CBM21 (the motifs from regulatory subunits of protein phosphatase 1 together with those from starch synthase III); and (iii) the (CBM20+CBM21)-related group (the motifs from the pullulanase subfamily consisting of pullulanase, branching enzyme, isoamylase and maltooligosyl trehalohydrolase). PMID:17084392

  2. Structure of inositol monophosphatase, the putative target of lithium therapy.

    PubMed Central

    Bone, R; Springer, J P; Atack, J R

    1992-01-01

    Inositol monophosphatase (EC 3.1.3.25), the putative molecular site of action of lithium therapy for manic-depressive illness, plays a key role in the phosphatidylinositol signaling pathway by catalyzing the hydrolysis of inositol monophosphates. To provide a structural basis from which to design better therapeutic agents for manic-depressive illness, the structure of human inositol monophosphatase has been determined to 2.1-A resolution by using x-ray crystallography. The enzyme exists as a dimer of identical subunits, each folded into a five-layered sandwich of three pairs of alpha-helices and two beta-sheets. Sulfate and an inhibitory lanthanide cation (Gd3+) are bound at identical sites on each subunit and establish the positions of the active sites. Each site is located in a large hydrophilic cavern that is at the base of the two central helices where several segments of secondary structure intersect. Comparison of the phosphatase aligned sequences of several diverse genes with the phosphatase structure suggests that the products of these genes and the phosphatase form a structural family with a conserved metal binding site. Images PMID:1332026

  3. Cereal beta-glucans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cereal beta-glucans occur predominantly in oats and barley, but can be found in other cereals. Beta-glucan structure is a mixture of single beta-1,3-linkages and consecutive beta-1,4-linkages, and cellotriosyl and cellotetraosyl units typically make up 90-95% of entire molecule. Lichenase can hydr...

  4. Putative Excitatory and Putative Inhibitory Inputs Localize to Different Dendritic Domains in a Drosophila Flight Motoneuron

    PubMed Central

    Kuehn, Claudia; Duch, Carsten

    2012-01-01

    Input-output computations of individual neurons may be affected by the three-dimensional structure of their dendrites and by the targeting of input synapses to specific parts of their dendrites. However, only few examples exist where dendritic architecture can be related to behaviorally relevant computations of a neuron. By combining genetic, immunohistochemical, and confocal laser scanning methods this study estimates the location of the spike initiating zone and the dendritic distribution patterns of putative synaptic inputs on an individually identified Drosophila flight motorneuron, MN5. MN5 is a monopolar neuron with more than 4000 dendritic branches. The site of spike initiation was estimated by mapping sodium channel immunolabel onto geometric reconstructions of MN5. Maps of putative excitatory cholinergic and of putative inhibitory GABAergic inputs on MN5 dendrites were created by charting tagged Dα7 nicotinic acetylcholine receptors and Rdl GABAA receptors onto MN5 dendritic surface reconstructions. Although these methods provided only an estimate of putative input synapse distributions, the data indicated that inhibitory and excitatory synapses were targeted preferentially to different dendritic domains of MN5, and thus, computed mostly separately. Most putative inhibitory inputs were close to spike initiation, which was consistent with sharp inhibition, as predicted previously based on recordings of motoneuron firing patterns during flight. By contrast, highest densities of putative excitatory inputs at more distant dendritic regions were consistent with the prediction that in response to different power demands during flight, tonic excitatory drive to flight motoneuron dendrites must be smoothly translated into different tonic firing frequencies. PMID:23279094

  5. Ten Putative Contributors to the Obesity Epidemic

    PubMed Central

    McAllister, Emily J.; Dhurandhar, Nikhil V.; Keith, Scott W.; Aronne, Louis J.; Barger, Jamie; Baskin, Monica; Benca, Ruth M.; Biggio, Joseph; Boggiano, Mary M.; Eisenmann, Joe C.; Elobeid, Mai; Fontaine, Kevin R.; Gluckman, Peter; Hanlon, Erin C.; Katzmarzyk, Peter; Pietrobelli, Angelo; Redden, David T.; Ruden, Douglas M.; Wang, Chenxi; Waterland, Robert A.; Wright, Suzanne M.; Allison, David B.

    2010-01-01

    The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects, as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic. PMID:19960394

  6. beta-Hexachlorocyclohexane (beta-HCH)

    Integrated Risk Information System (IRIS)

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

  7. A putative disease-associated haplotype within the SCN1A gene in Dravet syndrome.

    PubMed

    Fendri-Kriaa, Nourhène; Boujilbene, Salma; Kammoun, Fatma; Mkaouar-Rebai, Emna; Ben Mahmoud, Afif; Hsairi, Ines; Rebai, Ahmed; Triki, Chahnez; Fakhfakh, Faiza

    2011-05-20

    Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy, is one of the most severe forms of childhood epilepsy. DS is caused by a mutation in the neuronal voltage-gated sodium-channel alpha-subunit gene (SCN1A). However, 25-30% of patients with DS are negative for the SCN1A mutation screening, suggesting that other molecular mechanisms may account for these disorders. Recently, the first case of DS caused by a mutation in the neuronal voltage-gated sodium-channel beta-subunit gene (SCN1B) was also reported. In this report we aim to make the molecular analysis of the SCN1A and SCN1B genes in two Tunisian patients affected with DS. The SCN1A and SCN1B genes were tested for mutations by direct sequencing. No mutation was revealed in the SCN1A and SCN1B genes by sequencing analyses. On the other hand, 11 known single nucleotide polymorphisms were identified in the SCN1A gene and composed a putative disease-associated haplotype in patients with DS phenotype. One of the two patients with putative disease-associated haplotype in SCN1A had also one known single nucleotide polymorphism in the SCN1B gene. The sequencing analyses of the SCN1A gene revealed the presence of a putative disease-associated haplotype in two patients affected with Dravet syndrome. PMID:21531204

  8. Isolation and characterization of testis-specific cDNAs for luteinizing hormone beta-subunit in the rat.

    PubMed

    Zhang, F P; Rannikko, A; Huhtaniemi, I

    1995-05-25

    To study further the unexpected expression of the luteinizing hormone (LH) beta-subunit in the rat testis, we identified in a rat testicular cDNA library three LH beta clones with lengths of 3.2, 2.4 and 0.86 kb (TLH beta 1, TLH beta 2 and TLH beta 3). The clones were identified using a 32P-labeled cDNA probe complimentary to the known rat pituitary LH beta mRNA. Clone TLH beta 2 corresponds in size to the main LH beta mRNA species (2.7 kb) detected by Northern hybridization in the rat testis. Sequence analysis indicated that the different sizes of the three clones are due to alternative RNA splicing and differences at the 5' ends of transcripts. The sequence of one open reading frame deduced from TLH beta 1 is almost identical with the pituitary LH beta peptide, differing only in three amino acids in the putative signal peptide. It might encode a functional testis-specific LH beta peptide. Shorter transcripts from clones TLH beta 2 and TLH beta 3 may correspond to short testicular LH beta peptides. The present findings provide further evidence in the rat for expression of testis-specific mRNA variants of the LH beta gene. Their translation products may form a novel class of testicular para/autocrine factors. PMID:7763258

  9. A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure

    PubMed Central

    McMurray, John; Packer, Milton; Desai, Akshay; Gong, Jianjian; Greenlaw, Nicola; Lefkowitz, Martin; Rizkala, Adel; Shi, Victor; Rouleau, Jean; Solomon, Scott; Swedberg, Karl; Zile, Michael R.; Andersen, Karl; Arango, Juan Luis; Arnold, Malcolm; Be˘lohlávek, Jan; Böhm, Michael; Boytsov, Sergey; Burgess, Lesley; Cabrera, Walter; Chen, Chen-Huan; Erglis, Andrejs; Fu, Michael; Gomez, Efrain; Gonzalez, Angel; Hagege, Albert-Alain; Katova, Tzvetana; Kiatchoosakun, Songsak; Kim, Kee-Sik; Bayram, Edmundo; Martinez, Felipe; Merkely, Bela; Mendoza, Iván; Mosterd, Arend; Negrusz-Kawecka, Marta; Peuhkurinen, Keijo; Ramires, Felix; Refsgaard, Jens; Senni, Michele; Sibulo, Antonio S.; Silva-Cardoso, José; Squire, Iain; Starling, Randall C.; Vinereanu, Dragos; Teerlink, John R.; Wong, Raymond

    2015-01-01

    Aims Although active-controlled trials with renin–angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos. Methods and results We used the treatment-arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) as the reference trial for comparison of an ACE inhibitor to placebo and the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity-Alternative trial (CHARM-Alternative) as the reference trial for comparison of an ARB to placebo. The hazard ratio of LCZ696 vs. a putative placebo was estimated through the product of the hazard ratio of LCZ696 vs. enalapril (active-control) and that of the historical active-control (enalapril or candesartan) vs. placebo. For the primary composite outcome of cardiovascular death or heart failure hospitalization in PARADIGM-HF, the relative risk reduction with LCZ696 vs. a putative placebo from SOLVD-T was 43% (95%CI 34–50%; P < 0.0001) with similarly large effects on cardiovascular death (34%, 21–44%; P < 0.0001) and heart failure hospitalization (49%, 39–58%; P < 0.0001). For all-cause mortality, the reduction compared with a putative placebo was 28% (95%CI 15–39%; P < 0.0001). Putative placebo analyses based on CHARM-Alternative gave relative risk reductions of 39% (95%CI 27–48%; P < 0.0001) for the composite outcome of cardiovascular death or heart failure hospitalization, 32% (95%CI 16–45%; P < 0.0001) for cardiovascular death, 46% (33–56%; P < 0.0001) for heart failure hospitalization, and 26% (95%CI 11–39%; P < 0.0001) for all-cause mortality. Conclusion These indirect comparisons of LCZ696 with a putative placebo show that the strategy of combined angiotensin

  10. The Biogeography of Putative Microbial Antibiotic Production.

    PubMed

    Morlon, Hélène; O'Connor, Timothy K; Bryant, Jessica A; Charkoudian, Louise K; Docherty, Kathryn M; Jones, Evan; Kembel, Steven W; Green, Jessica L; Bohannan, Brendan J M

    2015-01-01

    Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics. PMID:26102275

  11. The Biogeography of Putative Microbial Antibiotic Production

    PubMed Central

    Bryant, Jessica A.; Charkoudian, Louise K.; Docherty, Kathryn M.; Jones, Evan; Kembel, Steven W.; Green, Jessica L.; Bohannan, Brendan J. M.

    2015-01-01

    Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics. PMID:26102275

  12. Magnetic Pulse Affects a Putative Magnetoreceptor Mechanism

    PubMed Central

    Davila, Alfonso F.; Winklhofer, Michael; Shcherbakov, Valera P.; Petersen, Nikolai

    2005-01-01

    Clusters of superparamagnetic (SP) magnetite crystals have recently been identified in free nerve endings in the upper-beak skin of homing pigeons and are interpreted as being part of a putative magnetoreceptor system. Motivated by these findings, we developed a physical model that accurately predicts the dynamics of interacting SP clusters in a magnetic field. The main predictions are: 1), under a magnetic field, a group of SP clusters self-assembles into a chain-like structure that behaves like a compass needle under slowly rotating fields; 2), in a frequently changing field as encountered by a moving bird, a stacked chain is a structurally more stable configuration than a single chain; 3), chain-like structures of SP clusters disrupt under strong fields applied at oblique angles; and 4), reassemble on a timescale of hours to days (assuming a viscosity of the cell plasma η ∼ 1 P). Our results offer a novel mechanism for magnetic field perception and are in agreement with the response of birds observed after magnetic-pulse treatments, which have been conducted in the past to specifically test if ferrimagnetic material is involved in magnetoreception, but which have defied explanation so far. Our theoretical results are supported by experiments on a technical SP model system using a high-speed camera. We also offer new predictions that can be tested experimentally. PMID:15863473

  13. Toddlers’ Duration of Attention towards Putative Threat

    PubMed Central

    Kiel, Elizabeth J.; Buss, Kristin A.

    2010-01-01

    Although individual differences in reactions to novelty in the toddler years have been consistently linked to risk for developing anxious behavior, toddlers’ attention towards a novel, putatively threatening stimulus while in the presence of other enjoyable activities has rarely been examined as a precursor to such risk. The current study examined how attention towards an angry-looking gorilla mask in a room with alternative opportunities for play in 24-month-old toddlers predicted social inhibition when children entered kindergarten. Analyses examined attention to threat above and beyond and in interaction with both proximity to the mask and fear of novelty observed in other situations. Attention to threat interacted with proximity to the mask to predict social inhibition, such that attention to threat most strongly predicted social inhibition when toddlers stayed furthest from the mask. This relation occurred above and beyond the predictive relation between fear of novelty and social inhibition. Results are discussed within the broader literature of anxiety development and attentional processes in young children. PMID:21373365

  14. Biogenic Origin for Earth's Oldest Putative Microfossils

    SciTech Connect

    De Gregorio, B.; Sharp, T; Flynn, G; Wirick, S; Hervig, R

    2009-01-01

    Carbonaceous microbe-like features preserved within a local chert unit of the 3.5 Ga old Apex Basalt in Western Australia may represent some of the oldest evidence of life on Earth. However, the biogenicity of these putative microfossils has been called into question, primarily because the sample collection locality is a black, carbon-rich, brecciated chert dike representing an Archean submarine hydrothermal spring, suggesting a formation via an abiotic organic synthesis mechanism. Here we describe the macromolecular hydrocarbon structure, carbon bonding, functional group chemistry, and biotic element abundance of carbonaceous matter associated with these filamentous features. These characteristics are similar to those of biogenic kerogen from the ca. 1.9 Ga old Gunflint Formation. Although an abiotic origin cannot be entirely ruled out, it is unlikely that known abiotic synthesis mechanisms could recreate both the structural and compositional complexity of this ancient carbonaceous matter. Thus, we find that a biogenic origin for this material is more likely, implying that the Apex microbe-like features represent authentic biogenic organic matter.

  15. The Leptospiral Antigen Lp49 is a Two-Domain Protein with Putative Protein Binding Function

    SciTech Connect

    Oliveira Giuseppe,P.; Oliveira Neves, F.; Nascimento, A.; Gomes Guimaraes, B.

    2008-01-01

    Pathogenic Leptospira is the etiological agent of leptospirosis, a life-threatening disease that affects populations worldwide. Currently available vaccines have limited effectiveness and therapeutic interventions are complicated by the difficulty in making an early diagnosis of leptospirosis. The genome of Leptospira interrogans was recently sequenced and comparative genomic analysis contributed to the identification of surface antigens, potential candidates for development of new vaccines and serodiagnosis. Lp49 is a membrane-associated protein recognized by antibodies present in sera from early and convalescent phases of leptospirosis patients. Its crystal structure was determined by single-wavelength anomalous diffraction using selenomethionine-labelled crystals and refined at 2.0 Angstroms resolution. Lp49 is composed of two domains and belongs to the all-beta-proteins class. The N-terminal domain folds in an immunoglobulin-like beta-sandwich structure, whereas the C-terminal domain presents a seven-bladed beta-propeller fold. Structural analysis of Lp49 indicates putative protein-protein binding sites, suggesting a role in Leptospira-host interaction. This is the first crystal structure of a leptospiral antigen described to date.

  16. Putative Lineage of Novel African Usutu Virus, Central Europe

    PubMed Central

    Cadar, Daniel; Bosch, Stefan; Jöst, Hanna; Börstler, Jessica; Garigliany, Mutien-Marie; Becker, Norbert

    2015-01-01

    We characterized the complete genome of a putative novel Usutu virus (USUV) strain (Usutu-BONN) detected in a dead blackbird from Germany. Genomic analysis revealed several unique amino acid substitutions among the polyprotein gene. Phylogenetic analyses demonstrated that Usutu-BONN constitutes a putative novel African USUV lineage, which was probably recently introduced to central Europe. PMID:26291923

  17. Identification of Putative Fallopian Tube Stem Cells

    PubMed Central

    Snegovskikh, Victoria; Mutlu, Levent; Massasa, Effi

    2014-01-01

    Stem cells are used to repair and regenerate multiple tissues in the adult. We have previously shown that stem cells play a significant role in mediating endometrial repair and tissue regeneration. We hypothesized that the oviduct may possess a similar population of stem cells that contribute to the maintenance of this tissue. Here we identify label-retaining cells (LRCs) in the murine oviduct which indicate the presence of a stem/progenitor cell population in this tissue as well. Two-day-old CD-1 mice were injected intraperitoneally with 5-bromo-2-deoxyuridine (BrdU) or vehicle control. Female animals (n = 36 for each group) were killed at 6 weeks post injection. Reproductive tracts were removed, specimens were embedded in paraffin, and 5-µ sections were prepared. Oviduct was identified by hematoxylin and eosin staining and morphology. Immunofluorescence studies were performed on serial sections tissues (n = 12 per animal) using antibodies against BrdU. Confocal microscopy was used to identify 4′,6-diamidino-2-phenylindole (DAPI)- and BrdU-stained nuclei. In the group of mice exposed to BrdU, we identified a population of LRCs in all specimens and not in controls. The putative stem cells are located at the base of each villi, suggesting the location of the stem cell niche. The number of DAPI-stained nuclei divided by the number of LRCs; LRCs constituted 0.5% of all nucleated cells. The oviduct contains a population of progenitor cells, likely used in the repair and regeneration of fallopian tube. Defective or insufficient stem cell reserve may underlie common tubal diseases, including hydrosalpinx and ectopic pregnancy. PMID:25305130

  18. Complete sequence of an HLA-dR beta chain deduced from a cDNA clone and identification of multiple non-allelic DR beta chain genes.

    PubMed Central

    Long, E O; Wake, C T; Gorski, J; Mach, B

    1983-01-01

    At least three polymorphic class II antigens are encoded in the human major histocompatibility complex (HLA): DR, DC and SB. cDNA clones encoding beta chains of HLA-DR antigen, derived from mRNA of a heterozygous B-cell line, were isolated and could be divided into four subsets, clearly distinct from cDNA clones encoding DC beta chains. Therefore, at least two non-allelic DR beta chain genes exist. The complete sequence of one of the DR beta chain cDNA clones is presented. It defines a putative signal sequence, two extracellular domains, a trans-membrane region and a cytoplasmic tail. Comparison with a DC beta chain cDNA clone revealed a homology of 70% between the two beta chains and that the two genes diverged under relatively little selective pressure. A set of amino acids conserved in immunoglobulin molecules was found to be identical in both DR and DC beta chains. Comparison of the DR beta chain sequence with the amino acid sequence of another DR beta chain revealed a homology of 87% and that most differences are single amino acid substitutions. Allelic polymorphism in DR beta chains has probably not arisen by changes in long blocks of sequence. PMID:11894954

  19. High Beta Tokamaks

    SciTech Connect

    Cowley, S.

    1998-11-14

    Perhaps the ideal tokamak would have high {beta} ({beta} {approx}> 1) and classical confinement. Such a tokamak has not been found, and we do not know if one does exist. We have searched for such a possibility, so far without success. In 1990, we obtained analytic equilibrium solutions for large aspect ratio tokamaks at {beta} {approx} {Omicron}(1) [1]. These solutions and the extension at high {beta} poloidal to finite aspect ratio [2] provided a basis for the study of high {beta} tokamaks. We have shown that these configurations can be stable to short scale MHD modes [3], and that they have reduced neoclassical transport [4]. Microinstabilities (such as the {del}T{sub i} mode) seem to be stabilized at high {beta} [5] - this is due to the large local shear [3] and the magnetic well. We have some concerns about modes associated with the compressional branch which may appear at high {beta}. Bill Dorland and Mike Kotschenreuther have studied this issue and our concerns may be unfounded. It is certainly tantalizing, especially given the lowered neoclassical transport values, that these configurations could have no microinstabilities and, one could assume, no anomalous transport. Unfortunately, while this work is encouraging, the key question for high {beta} tokamaks is the stability to large scale kink modes. The MHD {beta} limit (Troyon limit) for kink modes at large aspect ratio is problematically low. There is ample evidence from computations that the limit exists. However, it is not known if stable equilibria exist at much higher {beta}--none have been found. We have explored this question in the asymptotic high {beta} poloidal limit. Unfortunately, we are unable to find stable equilibrium and also unable to show that they don't exist. The results of these calculations will be published when a more definitive answer is found.

  20. Beta-Carotene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beta-carotene is a pigment that occurs naturally in many photosynthetic plants and organisms and one of the most abundant carotenoids found in human blood. The richest dietary sources of beta-carotene are yellow, orange, and leafy green fruits and vegetables, such as carrots, spinach, sweet potatoes...

  1. BETA GAUGE OPERATION MANUAL

    EPA Science Inventory

    This manual provides description and operating instructions for a redesigned Beta Gauge for measuring particles from vehicle exhaust. The improvements and a new control system including a control unit which is radically different from the prior unit, are described. Complete Beta ...

  2. Coordinate expression of beta1 integrins and their regulator, TGF beta2 at the floor plate of the medulla oblongata is correlated with the crossing of the fibers of olivocerebellar projection in mice.

    PubMed

    Ohyama, Kyoji; Kawamura, Koki

    2002-01-31

    During embryonic day 11 (E11) to E16, contact-dependent interacting molecules beta1 integrins and their putative regulator TGF beta2 are coordinately expressed at the floor plate in the caudal part of mouse myelencephalon. Their expression disappears at E18. Consistent with the peak of their expression (E13-E16), olivocerebellar fibers primarily cross the floor plate. These data indicate that spatiotemporal expression of beta1 integrins and TGF beta2 is correlated with the crossing of olivocerebellar fibers. PMID:11850066

  3. Characterization and expression of the beta-N-acetylglucosaminidase gene family of Tribolium castaneum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enzymes belonging to the Beta-N-acetylglucosaminidase (NAG) family cleave chitin oligosaccharides produced by the action of chitinases on chitin into the constituent N-acetylglucosamine monomer. Four genes encoding putative NAGs in the red flour beetle, Tribolium castaneum, namely TcNAG1, TcFDL, Tc...

  4. Rapid synthesis of beta zeolites

    SciTech Connect

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

    2015-08-18

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

  5. Putative Isotocin Distributions in Sonic Fish: Relationship to Vasotocin and Vocal-Acoustic Circuitry

    PubMed Central

    Goodson, James L.; Evans, Andrew K.; Bass, Andrew H.

    2008-01-01

    Recent neurophysiological evidence in the plainfin midshipman fish (Porichthys notatus) demonstrates that isotocin (IT) and arginine vasotocin (AVT) modulate fictive vocalizations divergently between three reproductive morphs. In order to provide an anatomical framework for the modulation of vocalization by IT, and to foster comparisons with the distributions of the IT homologues mesotocin (MT) and oxytocin (OT) in other vertebrate groups, we here describe putative IT distributions in the midshipman and the closely related gulf toadfish, Opsanus beta. Double-label fluorescent histochemistry was used for IT and AVT (using antibodies for MT, OT and the mammalian AVT homologue, arginine vasopressin, AVP). MT/OT-like immunoreactive (MT/OT-lir) cell groups are found in the anterior parvocellular, posterior parvocellular and magnocellular preoptic nuclei. MT/OT-lir fibers and putative terminals densely innervate the ventral telencephalon and numerous areas in the hypothalamus and brainstem. These distributions include all sites of vocal-acoustic integration recently identified for the forebrain and midbrain, as well as diencephalic components of the ascending auditory pathway. Results were qualitatively comparable across morphs, species and seasons. In contrast to the widespread distribution of MT/OT-lir, AVP-lir somata, fibers and putative terminals are almost completely restricted to vocal-acoustic regions. These data parallel earlier descriptions of AVT-ir in these species, although the present methods reveal a previously undescribed, seasonally variable AVP-lir cell group in the anterior tuberal hypothalamus, a vocally active site and a component of the ascending auditory pathway. These findings provide anatomical support for the role of IT and AVT in the modulation of vocal behavior at multiple levels of the central vocal-acoustic circuitry. PMID:12761820

  6. Identification of genes encoding putative nucleoporins and transport factors in the fission yeast Schizosaccharomyces pombe: a deletion analysis.

    PubMed

    Chen, Xue Qin; Du, Xianming; Liu, Jianhua; Balasubramanian, Mohan K; Balasundaram, David

    2004-04-30

    In a systematic approach to study genes that are related to nucleocytoplasmic trafficking in the fission yeast Schizosaccharomyces pombe, the open reading frames (ORFs) of 26 putative nucleoporins and transport factors were deleted. Here we report the initial characterization of these deletion mutants. Of the 26 putative genes deleted, 14 were found to be essential for viability. Null mutations of essential genes resulted in failure to either complete one round or to sustain cell division. Four of the 14 essential genes, SPBC582.11c, SPBC17G9.04c, SPBC3B9.16c and SPCC162.08c, encode putative nucleoporins and a myosin-like protein with homologues NUP84, NUP85, NUP120 and MLP1, respectively, that are not required for viability in Saccharomyces cerevisiae, suggesting that their gene products perform critical functions in Sz. pombe. On the basis of combined drug sensitivity assays and genetic analysis we have identified five non-essential null mutants that were hypersensitive to the microtubule depolymerizing drug thiabendazole (TBZ) and exhibited a cut phenotype upon TBZ treatment, suggesting possible involvement in microtubule function. Three of the corresponding ORFs, SPCC18B5.07c, nup40 and SPAC1805.04, encode putative nucleoporins with low similarity to the S. cerevisiae nucleoporins NUP2p, NUP53p and NUP133p, respectively. Further genetic analysis revealed that one of the nucleoporin genes, nup40, and another gene, SPCC1322.06, encoding a putative importin-beta/Cse1p superfamily protein may have a spindle checkpoint function. PMID:15116432

  7. Beta experiment flight report

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A focused laser Doppler velocimeter system was developed for the measurement of atmospheric backscatter (beta) from aerosols at infrared wavelengths. The system was flight tested at several different locations and the results of these tests are summarized.

  8. Beta-carotene

    MedlinePlus

    ... brain in people who drink alcohol. Preventing abdominal aortic aneurysm, or the enlargement of a large vessel running ... years does not reduce the occurrence of abdominal aortic aneurysm in male smokers. Cancer. Beta-carotene does not ...

  9. Beta-carotene

    MedlinePlus

    ... blindness during pregnancy, as well as diarrhea and fever after giving birth. Some people who sunburn easily, ... seems to reduce the incidence of diarrhea and fever post-childbirth. Pregnancy-related complications. Taking beta-carotene ...

  10. High beta multipoles

    SciTech Connect

    Prager, S C

    1982-05-01

    Multipoles are being employed as devices to study fusion issues and plasma phenomena at high values of beta (plasma pressure/magnetic pressure) in a controlled manner. Due to their large volume, low magnetic field (low synchrotron radiation) region, they are also under consideration as potential steady state advanced fuel (low neutron yield) reactors. Present experiments are investigating neoclassical (bootstrap and Pfirsch-Schlueter) currents and plasma stability at extremely high beta.

  11. CREST - a large and diverse superfamily of putative transmembrane hydrolases

    PubMed Central

    2011-01-01

    Background A number of membrane-spanning proteins possess enzymatic activity and catalyze important reactions involving proteins, lipids or other substrates located within or near lipid bilayers. Alkaline ceramidases are seven-transmembrane proteins that hydrolyze the amide bond in ceramide to form sphingosine. Recently, a group of putative transmembrane receptors called progestin and adipoQ receptors (PAQRs) were found to be distantly related to alkaline ceramidases, raising the possibility that they may also function as membrane enzymes. Results Using sensitive similarity search methods, we identified statistically significant sequence similarities among several transmembrane protein families including alkaline ceramidases and PAQRs. They were unified into a large and diverse superfamily of putative membrane-bound hydrolases called CREST (alkaline ceramidase, PAQR receptor, Per1, SID-1 and TMEM8). The CREST superfamily embraces a plethora of cellular functions and biochemical activities, including putative lipid-modifying enzymes such as ceramidases and the Per1 family of putative phospholipases involved in lipid remodeling of GPI-anchored proteins, putative hormone receptors, bacterial hemolysins, the TMEM8 family of putative tumor suppressors, and the SID-1 family of putative double-stranded RNA transporters involved in RNA interference. Extensive similarity searches and clustering analysis also revealed several groups of proteins with unknown function in the CREST superfamily. Members of the CREST superfamily share seven predicted core transmembrane segments with several conserved sequence motifs. Conclusions Universal conservation of a set of histidine and aspartate residues across all groups in the CREST superfamily, coupled with independent discoveries of hydrolase activities in alkaline ceramidases and the Per1 family as well as results from previous mutational studies of Per1, suggests that the majority of CREST members are metal-dependent hydrolases

  12. A putative hybrid swarm within Oonopsis foliosa (Asteraceae: Astereae)

    USGS Publications Warehouse

    Hughes, J.F.; Brown, G.K.

    2004-01-01

    Oo??nopsis foliosa var. foliosa and var. monocephala are endemic to short-grass steppe of southeastern Colorado and until recently were considered geographically disjunct. The only known qualitative feature separating these 2 varieties is floral head type; var. foliosa has radiate heads, whereas var. monocephala heads are discoid. Sympatry between these varieties is restricted to a small area in which a range of parental types and intermediate head morphologies is observed. We used distribution mapping, morphometric analyses, chromosome cytology, and pollen stainability to characterize the sympatric zone. Morphometrics confirms that the only discrete difference between var. foliosa and var. monocephala is radiate versus discoid heads, respectively. The outer florets of putative hybrid individuals ranged from conspicuously elongated yet radially symmetric disc-floret corollas, to elongated radially asymmetric bilabiate- or deeply cleft corollas, to stunted ray florets with appendages remnant of corolla lobes. Chromosome cytology of pollen mother cells from both putative parental varieties and a series of intermediate morphological types collected at the sympatric zone reveal evidence of translocation heterozygosity. Pollen stainability shows no significant differences in viability between the parental varieties and putative hybrids. The restricted distribution of putative hybrids to a narrow zone of sympatry between the parental types and the presence of meiotic chromosome-pairing anomalies in these intermediate plants are consistent with a hybrid origin. The high stainability of putative-hybrid pollen adds to a growing body of evidence that hybrids are not universally unfit.

  13. Homology modeling of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABA receptor channels and Surflex-docking of fipronil.

    PubMed

    Cheng, Jin; Ju, Xiu-Lian; Chen, Xiang-Yang; Liu, Gen-Yan

    2009-09-01

    To further explore the mechanism of selective binding of the representative gamma-aminobutyric acid receptors (GABARs) noncompetitive antagonist (NCA) fipronil to insect over mammalian GABARs, three-dimensional models of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABAR were generated by homology modeling, using the cryo-electron microscopy structure of the nicotinic acetylcholine receptor (nAChR) of Torpedo marmorata as a template. Fipronil was docked into the putative binding site of the human alpha 1 beta 2 gamma 2 and house fly beta 3 receptors by Surflex-docking, and the calculated docking energies are in agreement with experimental results. The GABA receptor antagonist fipronil exhibited higher potency with house fly beta 3 GABAR than with human alpha 1 beta 2 gamma 2 GABAR. Furthermore, analyses of Surflex-docking suggest that the H-bond interaction of fipronil with Ala2 and Thr6 in the second transmembrane segment (TM2) of these GABARs plays a relatively important role in ligand selective binding. The different subunit assemblies of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABARs may result in differential selectivity for fipronil. PMID:19238461

  14. Inhaled beta agonists.

    PubMed

    Op't Holt, Timothy B

    2007-07-01

    The beta(2) adrenoreceptor is a large molecule of some 413 amino acids. The duration of stimulation of this receptor depends on where and for how long a beta(2) adrenergic drug attaches itself to the beta(2) adrenoreceptor. beta(2) adrenergic drugs have been used for over 5,000 years, but only recently have we had the advantage of adrenergic drugs specific to the beta(2) adrenoreceptor. The short-acting beta(2) adrenergic drugs most frequently used include albuterol, pirbuterol, and levalbuterol. Levalbuterol, the R enantiomer of albuterol, has been described by some as a more effective bronchodilator than racemic albuterol, because it contains none of the S enantiomer. Some contend that the S isomer has pro-inflammatory properties. The 2 long-acting beta(2) adrenergic drugs are salmeterol and formoterol. These drugs have a duration of 12 h and reportedly improve forced expiratory volume in the first second, quality of life, and symptoms. Some recent reports indicate that these drugs are associated with higher mortality, but several authors have registered the opinion that it is not the bronchodilator that should be questioned, but instead that the fault lies in the patient recruitment in those studies. Regardless, if these long-acting drugs are effective for a given patient, it would seem inadvisable to withdraw them, given the current state of evidence. Arformoterol tartrate, the R enantiomer of formoterol, was approved by the U.S. Food and Drug Administration in October 2006; it is available as a nebulizer solution, to be administered every 12 h. Several other long-acting R isomers and RR isomers are in the approval pipeline. PMID:17594727

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

    SciTech Connect

    Zhang, L.; Sakkal-Alkaddour, S.; Chang, Ying T.; Yang, Xiaojiang; Songya Pang

    1996-01-01

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

  16. Beta 8 integrins mediate interactions of chick sensory neurons with laminin-1, collagen IV, and fibronectin.

    PubMed Central

    Venstrom, K; Reichardt, L

    1995-01-01

    Integrins are major receptors used by cells to interact with extracellular matrices. In this paper, we identify the first ligands for the beta 8 family of integrins, presenting evidence that integrin heterodimers containing the beta 8 subunit mediate interactions of chick sensory neurons with laminin-1, collagen IV, and fibronectin. A polyclonal antibody, anti-beta 8-Ex, was prepared to a bacterial fusion protein expressing an extracellular portion of the chicken beta 8 subunit. In nonreducing conditions, this antibody immunoprecipitated from surface-labeled embryonic dorsal root ganglia neurons a M(r) 100 k protein, the expected M(r) of the beta 8 subunit, and putative alpha subunit(s) of M(r) 120 k. Affinity-purified anti-beta 8-Ex strongly inhibited sensory neurite outgrowth on laminin-1, collagen IV, and fibronectin-coated substrata. Binding sites were identified in a heat-resistant domain in laminin-1 and in the carboxyl terminal, 40-kDa fibronectin fragment. On substrates coated with the carboxyl terminal fragment of fibronectin, antibodies to beta 1 and beta 8 were only partially effective alone, but were completely effective in combination, at inhibiting neurite outgrowth. Results thus indicate that the integrin beta 8 subunit in association with one or more alpha subunits forms an important set of extracellular matrix receptors on sensory neurons. Images PMID:7542940

  17. Boosted Beta Regression

    PubMed Central

    Schmid, Matthias; Wickler, Florian; Maloney, Kelly O.; Mitchell, Richard; Fenske, Nora; Mayr, Andreas

    2013-01-01

    Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1). Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures. PMID:23626706

  18. IO SUBSYSTEM 1 BETA

    SciTech Connect

    Sjaardema, Greg

    2002-08-21

    "IO Subsystem Ver. 1.0 Beta" uses standard object-oriented principles to minimize dependencies between the underlying input or output database format and the client code (i.e., Sierra) using the io subsystem. The interface and priciples are simolar to the Facade pattern described in the "Design Patterns" book by Gamma, et.al. The software uses data authentication algorithms to ensure data input/output is consistent with model being defined. "IO Subsystem Ver. 1.0 Beta" is a database independent input/output library for finite element analysis, preprocessing, post processing, and translation programs.

  19. IO SUBSYSTEM 1 BETA

    Energy Science and Technology Software Center (ESTSC)

    2002-08-21

    "IO Subsystem Ver. 1.0 Beta" uses standard object-oriented principles to minimize dependencies between the underlying input or output database format and the client code (i.e., Sierra) using the io subsystem. The interface and priciples are simolar to the Facade pattern described in the "Design Patterns" book by Gamma, et.al. The software uses data authentication algorithms to ensure data input/output is consistent with model being defined. "IO Subsystem Ver. 1.0 Beta" is a database independent input/outputmore » library for finite element analysis, preprocessing, post processing, and translation programs.« less

  20. Putative excitatory and putative inhibitory inputs are localised in different dendritic domains in a Drosophila flight motoneuron.

    PubMed

    Kuehn, Claudia; Duch, Carsten

    2013-03-01

    Input-output computations of individual neurons may be affected by the three-dimensional structure of their dendrites and by the location of input synapses on specific parts of their dendrites. However, only a few examples exist of dendritic architecture which can be related to behaviorally relevant computations of a neuron. By combining genetic, immunohistochemical and confocal laser scanning methods this study estimates the location of the spike-initiating zone and the dendritic distribution patterns of putative synaptic inputs on an individually identified Drosophila flight motorneuron, MN5. MN5 is a monopolar neuron with > 4,000 dendritic branches. The site of spike initiation was estimated by mapping sodium channel immunolabel onto geometric reconstructions of MN5. Maps of putative excitatory cholinergic and of putative inhibitory GABAergic inputs on MN5 dendrites were created by charting tagged Dα7 nicotinic acetylcholine receptors and Rdl GABAA receptors onto MN5 dendritic surface reconstructions. Although these methods provide only an estimate of putative input synapse distributions, the data indicate that inhibitory and excitatory synapses were located preferentially on different dendritic domains of MN5 and, thus, computed mostly separately. Most putative inhibitory inputs were close to spike initiation, which was consistent with sharp inhibition, as predicted previously based on recordings of motoneuron firing patterns during flight. By contrast, highest densities of putative excitatory inputs at more distant dendritic regions were consistent with the prediction that, in response to different power demands during flight, tonic excitatory drive to flight motoneuron dendrites must be smoothly translated into different tonic firing frequencies. PMID:23279094

  1. Bartonella henselae AS A PUTATIVE CAUSE OF CONGENITAL CHOLESTASIS

    PubMed Central

    VELHO, Paulo Eduardo Neves Ferreira; BELLOMO-BRANDÃO, Maria Ângela; DRUMMOND, Marina Rovani; MAGALHÃES, Renata Ferreira; HESSEL, Gabriel; BARJAS-CASTRO, Maria de Lourdes; ESCANHOELA, Cecília Amélia Fazzio; NEGRO, Gilda Maria Barbaro DEL; OKAY, Thelma Suely

    2016-01-01

    SUMMARY Severe anemia and cholestatic hepatitis are associated with bartonella infections. A putative vertical Bartonella henselae infection was defined on the basis of ultrastructural and molecular analyses in a three-year-old child with anemia, jaundice and hepatosplenomegaly since birth. Physicians should consider bartonellosis in patients with anemia and hepatitis of unknown origin. PMID:27410916

  2. DIFFERENTIAL GENE EXPRESSION OF PUTATIVE VIRULENCE GENES IN Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A shot-gun genomic library of the Flavobacterium columnare ALG-530 virulent strain has been constructed and more than 3,000 clones have been sequenced to date (800 contigs). Based on sequence identity with putative known virulence genes from related species, seven genes were selected for differentia...

  3. Developing putative AOPs from high content dataDeveloping putative AOPs from high content dataDeveloping putative AOPs from high content dataDeveloping putative AOPs from high content data

    EPA Science Inventory

    Developing putative AOPs from high content data Shannon M. Bell1,2, Stephen W. Edwards2 1 Oak Ridge Institute for Science and Education 2 Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development,...

  4. Sulfur Isotope Composition of Putative Primary Troilite in Chondrules

    NASA Technical Reports Server (NTRS)

    Tachibana, Shogo; Huss, Gary R.

    2002-01-01

    Sulfur isotope compositions of putative primary troilites in chondrules from Bishunpur were measured by ion probe. These primary troilites have the same S isotope compositions as matrix troilites and thus appear to be isotopically unfractionated. Additional information is contained in the original extended abstract.

  5. Applied Beta Dosimetry

    SciTech Connect

    Rich, B.L.

    1986-01-01

    Measurements of beta and/or nonpenetrating exposure results is complicated and past techniques and capabilities have resulted in significant inaccuracies in recorded results. Current developments have resulted in increased capabilities which make the results more accurate and should result in less total exposure to the work force. Continued development of works in progress should provide equivalent future improvements.

  6. beta-Chloronaphthalene

    Integrated Risk Information System (IRIS)

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

  7. beta-Propiolactone

    Integrated Risk Information System (IRIS)

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

  8. Putative glycoprotein and glycolipid polymorphonuclear leukocyte receptors for the Actinomyces naeslundii WVU45 fimbrial lectin.

    PubMed Central

    Sandberg, A L; Ruhl, S; Joralmon, R A; Brennan, M J; Sutphin, M J; Cisar, J O

    1995-01-01

    Recognition of receptors on sialidase-treated polymorphonuclear leukocytes (PMNs) by the Gal/GalNAc lectin associated with the type 2 fimbriae of certain strains of actinomyces results in activation of the PMNs, phagocytosis, and destruction of the bacteria. In the present study, plant lectins were utilized as probes to identify putative PMN receptors for the actinomyces lectin. The Gal-reactive lectin from Ricinus communis (RCAI), the Gal/GalNAc-reactive lectins from R. communis (RCAII) and Bauhinia purpurea (BPA), as well as the Gal beta 1-3GalNAc-specific lectins from Arachis hypogaea (PNA) and Agaricus bisporus (ABA) inhibited killing of Actinomyces naeslundii WVU45 by sialidase-treated PMNs. These five lectins detected a 130-kDa surface-labeled glycoprotein on nitrocellulose transfers of PMN extracts separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This glycoprotein was revealed only after treatment of the transfers with sialidase, a condition analogous to the sialidase dependence of the lectin-mediated biological responses of the PMNs to the actinomyces. The mannose-reactive lectin concanavalin A did not inhibit killing of the actinomyces and failed to detect the 130-kDa glycoprotein but did block PMN-dependent killing of Escherichia coli B, a bacterium that possesses mannose-sensitive fimbriae. Therefore, the PMN glycoprotein receptor for A. naeslundii is clearly distinct from those recognized by E. coli. Two major putative glycolipid receptors were also identified by actinomyces and RCAI overlays on sialidase-treated thin-layer chromatograms of PMN gangliosides. Thus, both a 130-kDa glycoprotein and certain gangliosides are implicated in the attachment of the actinomyces to PMNs. PMID:7790078

  9. Beta-2 Microglobulin Tumor Marker

    MedlinePlus

    ... limited. Home Visit Global Sites Search Help? Beta-2 Microglobulin Tumor Marker Share this page: Was this page helpful? Also known as: B2M; B 2 M; β2-Microglobulin; Thymotaxin Formal name: Beta 2 ...

  10. Beta-D-Allose inhibits fruiting body formation and sporulation in Myxococcus xanthus.

    PubMed

    Chavira, Marielena; Cao, Nga; Le, Karen; Riar, Tanveer; Moradshahi, Navid; McBride, Melinda; Lux, Renate; Shi, Wenyuan

    2007-01-01

    Myxococcus xanthus, a gram-negative soil bacterium, responds to amino acid starvation by entering a process of multicellular development which culminates in the assembly of spore-filled fruiting bodies. Previous studies utilizing developmental inhibitors (such as methionine, lysine, or threonine) have revealed important clues about the mechanisms involved in fruiting body formation. We used Biolog phenotype microarrays to screen 384 chemicals for complete inhibition of fruiting body development in M. xanthus. Here, we report the identification of a novel inhibitor of fruiting body formation and sporulation, beta-d-allose. beta-d-Allose, a rare sugar, is a member of the aldohexose family and a C3 epimer of glucose. Our studies show that beta-d-allose does not affect cell growth, viability, agglutination, or motility. However, beta-galactosidase reporters demonstrate that genes activated between 4 and 14 h of development show significantly lower expression levels in the presence of beta-d-allose. Furthermore, inhibition of fruiting body formation occurs only when beta-d-allose is added to submerged cultures before 12 h of development. In competition studies, high concentrations of galactose and xylose antagonize the nonfruiting response to beta-d-allose, while glucose is capable of partial antagonism. Finally, a magellan-4 transposon mutagenesis screen identified glcK, a putative glucokinase gene, required for beta-d-allose-mediated inhibition of fruiting body formation. Subsequent glucokinase activity assays of the glcK mutant further supported the role of this protein in glucose phosphorylation. PMID:17056749

  11. Misleading Betas: An Educational Example

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  12. The progression and topographic distribution of interleukin-1beta expression after permanent middle cerebral artery occlusion in the rat.

    PubMed

    Davies, C A; Loddick, S A; Toulmond, S; Stroemer, R P; Hunt, J; Rothwell, N J

    1999-01-01

    The cytokine interleukin-1 (IL-1) has been implicated in the exacerbation of ischemic damage in the brains of rodents. This study has ascertained the cellular localization and chronologic and topographic distribution of pro/mature interleukin-1beta (IL-1beta) protein 0.5, 1, 2, 6, 24, and 48 hours after ischemia by subjecting rats to permanent unilateral occlusion of the middle cerebral artery. Interleukin-1beta was localized immunocytochemically in vibratome sections of perfusion-fixed brains. The cells that expressed IL-1beta had the morphologic features of microglia and macrophages. Interleukin-1beta was first detected 1 hour after occlusion in ipsilateral meningeal macrophage-like cells. By 6 hours, pro/mature IL-1beta-immunoreactive (IL-1(beta)ir) putative microglia were present in the ischemic cerebral cortex, corpus callosum, caudoputamen, and surrounding tissue. By 24 and 48 hours after ischemia, the number and spread of IL-1(beta)ir cells increased greatly, including those resembling activated microglia and macrophages, as the core of the infarct became infiltrated. Interleukin-1(beta)ir cells also were present in apparently undamaged tissue, adjacent to the lesion ipsilaterally, and contralaterally in the cerebral cortex, dorsal corpus callosum, dorsal caudoputamen, and hippocampus. These results support the functional role of IL-1 in ischemic brain damage and reveal a distinct temporal and spatial expression of IL-1beta protein in cells believed to be microglia and macrophages. PMID:9886359

  13. Identification of a novel ovine LH-beta promoter region, which dramatically enhances its promoter activity.

    PubMed

    Aherrahrou, Redouane; Aherrahrou, Zouhair; Erdmann, Jeanette; Moumni, Mohieddine

    2015-01-01

    The luteinizing hormone beta subunit (LH-beta) gene plays a critical role in reproduction. In order to characterize and analyze the promoter region of LH-beta in sheep, a genomic library was constructed in phage lambda gt 10 and screened. A novel region of 1,224 bp upstream from the targeted LH-beta gene was identified. Blasting this sequence showed a perfect homology for the first 721 bp sequence with an upstream ovine LH-beta sequence in the database. However, the remaining 5'-503 bp showed no sequence matching. DNA from Moroccan breeds was isolated and the whole region was amplified and confirmed by sequencing. To further confirm the promoter activity of this region, an in vitro analysis using a luciferase assay was carried out. An increase in the promoter activity of the whole region was demonstrated compared to the empty vector. More interestingly, the unpublished region significantly enhanced the promoter activity compared to the known region alone. To predict putative transcription factor binding-sites (TFBSs), an in silico analysis was performed using the TFSEARCH program. The region features many TFBSs and contains two palindrome sequences of 17- and 18-bp. Taken together, a novel region was identified and confirmed in sheep which contained a promoter activity rich with binding sites for a putative regulatory element as shown in silico. PMID:26355566

  14. A Drosophila gene encoding a protein resembling the human. beta. -amyloid protein precursor

    SciTech Connect

    Rosen, D.R.; Martin-Morris, L.; Luo, L.; White, K. )

    1989-04-01

    The authors have isolated genomic and cDNA clones for a Drosophila gene resembling the human {beta}-amyloid precursor protein (APP). This gene produces a nervous system-enriched 6.5-kilobase transcript. Sequencing of cDNAs derived from the 6.5-kilobase transcript predicts an 886-amino acid polypeptide. This polypeptide contains a putative transmembrane domain and exhibits strong sequence similarity to cytoplasmic and extracellular regions of the human {beta}-amyloid precursor protein. There is a high probability that this Drosophila gene corresponds to the essential Drosophila locus vnd, a gene required for embryonic nervous system development.

  15. NF-{kappa}B p65 represses {beta}-catenin-activated transcription of cyclin D1

    SciTech Connect

    Hwang, Injoo; Choi, Yong Seok; Jeon, Mi-Ya; Jeong, Sunjoo

    2010-12-03

    Research highlights: {yields} Cyclin D1 transcription is directly activated by {beta}-catenin; however, {beta}-catenin-induced cyclin D1 transcription is reduced by NF-{kappa}B p65. {yields} Protein-protein interaction between NF-{kappa}B p65 and {beta}-catenin might be responsible for p65-mediated repression of cyclin D1. {yields} One of five putative binding sites, located further upstream of other sites, is the major {beta}-catenin binding site in the cyclin D1 promoter. {yields} NF-{kappa}B binding site in cyclin D1 is occupied not only by p65 but also by {beta}-catenin, which is dynamically regulated by the signal. -- Abstract: Signaling crosstalk between the {beta}-catenin and NF-{kappa}B pathways represents a functional network. To test whether the crosstalk also occurs on their common target genes, the cyclin D1 promoter was used as a model because it contains binding sites for both proteins. {beta}-catenin activated transcription from the cyclin D1 promoter, while co-expression of NF-{kappa}B p65 reduced {beta}-catenin-induced transcription. Chromatin immunoprecipitation revealed lithium chloride-induced binding of {beta}-catenin on one of the T-cell activating factor binding sites. More interestingly, {beta}-catenin binding was greatly reduced by NF-{kappa}B p65, possibly by the protein-protein interaction between the two proteins. Such a dynamic and complex binding of {beta}-catenin and NF-{kappa}B on promoters might contribute to the regulated expression of their target genes.

  16. Beta-thalassemia.

    PubMed

    Galanello, Renzo; Origa, Raffaella

    2010-01-01

    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  17. Beta-thalassemia

    PubMed Central

    2010-01-01

    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  18. Analysis of plausible downstream target genes of Hoxc8 in F9 teratocarcinoma cells. Putative downstream target genes of Hoxc8.

    PubMed

    Kwon, Yunjeong; Ko, Jeong Heon; Byung-Gyu, Kim; Kim, Myoung Hee; Kim, Byungkyu

    2003-09-01

    Although Hox genes are known to mediate developmental decisions involved in pattern formation during embryogenesis, it is still not well understood what Hox regulates. In order to analyze Hoxc8 downstream target genes, a stable cell line overexpressing Hoxc8 was established using F9 murine teratocarcinoma cells, proteom samples were analyzed by 2-DE, and compared with controls. The protein spots having differences more than 4 fold in intensity were selected, analyzed by MALDI-TOF, and grouped in terms of putative function; cytoskeleton and motility (vimentin, gamma-actin, tropomyosin, and tubulin beta-5 chain); folding, modification and degradation of protein (GRP78, proteasome subunit alpha type 5, 26S proteasome regulatory subunit p27 protein, and PDIR); metabolism (ATP synthase beta subunit, Pgam1, and CAII); transcription/translation factors and general nucleic acid binding proteins (RbAp46, PCNA, eEF-1-beta, and nucleophosmin). Although it may not be significant, 50% of the genes were located on chromosomes 2 and 3, suggesting the possibility of a non-random distribution of Hox downstream genes. Almost 50% of the genes analyzed showed some relation with Hox protein directly or indirectly; i.e., tubulin beta 5, EF-1 beta and PCNA have been reported to contain putative Hox binding regulatory sites and genes like vimentin, pgam1 and nucleophosmin to be regulated by RA, a potent modulator of Hox expression. These results altogether imply that proteom analysis could be a possible tool for the analysis of the potent Hox realizator genes, which provides a new insight into the function of Hox on pattern formation during embryogenesis. PMID:12974468

  19. Measurement of $\\beta_s$ at CDF

    SciTech Connect

    Oakes, Louise; /Oxford U.

    2011-02-01

    The latest results for the measurement of the CP violating phase {beta}{sub s} in B{sub s}{sup 0} {yields} J/{Psi}{phi} decays, from 5.2 fb{sup -1} integrated luminosity of CDF data are presented. For the first time, this measurement includes the contribution of B{sub s}{sup 0} {yields} J/{Psi}K{sup +}K{sup -} or B{sub s}{sup 0} {yields} J/{Psi}f{sub 0} events to the signal sample, where the f{sub 0} and non-resonant K{sup +}K{sup -} are S-wave states. Additional improvements to the analysis include more than doubling the signal sample, improved selection and particle ID, and fully calibrated flavour tagging for the full dataset. Additionally, the world's most precise single measurements of the B{sub s}{sup 0} lifetime, {tau}{sub s}, and width difference, {Delta}{Gamma}{sub s} are given.

  20. Thermophilic Beta-Glycosidase

    NASA Technical Reports Server (NTRS)

    Grogan, Dennis W.

    1992-01-01

    Report describes identification of thermophilic Beta-glycosidase enzyme from isolate of Sulfolobus solfataricus, sulfur-metabolizing archaebacteria growing aerobically and heterotrophically to relatively high cell yields. Enzyme useful in enzymatic conversion of cellulose to D-glucose and important in recycling of biomass. Used for removal of lactose from milk products. Offers promise as model substance for elucidation of basic principles of structural stabilization of proteins.

  1. Putative melatonin receptors in a human biological clock

    SciTech Connect

    Reppert, S.M.; Weaver, D.R.; Rivkees, S.A.; Stopa, E.G.

    1988-10-07

    In vitro autoradiography with /sup 125/I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific /sup 125/I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific /sup 125/I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific /sup 125/I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.

  2. Isolation, characterization, and expression of the gene encoding the beta subunit of the mitochondrial processing peptidase from Blastocladiella emersonii.

    PubMed

    Costa Rocha, C R; Lopes Gomes, S

    1998-08-01

    A 2.3-kb BamHI-KpnI fragment was isolated from a partial genomic library and shown by nucleotide sequence analysis to contain the entire coding region of the gene encoding the beta subunit of the Blastocladiella mitochondrial processing peptidase (beta-MPP). The predicted beta-MPP protein has 465 amino acids and a calculated molecular mass of 50.8 kDa. S1 nuclease protection assays revealed an intron, 209 bp in size, interrupting the coding region between the putative signal sequence and the mature protein. Northern blot analysis showed that beta-MPP mRNA levels decrease significantly during B. emersonii sporulation, reaching basal levels in the zoospore stage. The amount of beta-MPP protein, determined in Western blots, unlike its mRNA, does not vary significantly throughout the fungal life cycle. PMID:9683495

  3. Structural identification of putative USPs in Catharanthus roseus.

    PubMed

    Bahieldin, Ahmed; Atef, Ahmed; Shokry, Ahmed M; Al-Karim, Saleh; Al Attas, Sanaa G; Gadallah, Nour O; Edris, Sherif; Al-Kordy, Magdy A; Omer, Abdulkader M Shaikh; Sabir, Jamal S M; Ramadan, Ahmed M; Al-Hajar, Abdulrahman S M; Makki, Rania M; Hassan, Sabah M; El-Domyati, Fotouh M

    2015-10-01

    Nucleotide sequences of the C. roseus SRA database were assembled and translated in order to detect putative universal stress proteins (USPs). Based on the known conserved USPA domain, 24 Pfam putative USPA proteins in C. roseus were detected and arranged in six architectures. The USPA-like domain was detected in all architectures, while the protein kinase-like (or PK-like), (tyr)PK-like and/or U-box domains are shown downstream it. Three other domains were also shown to coexist with the USPA domain in C. roseus putative USPA sequences. These domains are tetratricopeptide repeat (or TPR), apolipophorin III (or apoLp-III) and Hsp90 co-chaperone Cdc37. Subsequent analysis divided USPA-like domains based on the ability to bind ATP. The multiple sequence alignment indicated the occurrence of eight C. roseus residues of known features of the bacterial 1MJH secondary structure. The data of the phylogenetic tree indicated several distinct groups of USPA-like domains confirming the presence of high level of sequence conservation between the plant and bacterial USPA-like sequences. PMID:26318047

  4. Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas.

    PubMed Central

    Eder, I. E.; Stenzl, A.; Hobisch, A.; Cronauer, M. V.; Bartsch, G.; Klocker, H.

    1997-01-01

    We previously detected elevated transforming growth factor beta-1 (TGF-beta1) serum levels in patients with invasive bladder carcinomas. In this study, we therefore investigated whether elevated serum levels correlate with enhanced TGF-beta expression in human bladder tumours. mRNA levels of TGF-beta1, -beta2 and -beta3 were reduced in bladder tumour tissue to 86%, 68% and 56%, respectively, of the levels in normal urothelium. On the other hand, TGF-beta1 protein levels were found to be higher in superficial tumours (Ta-T1) (mean level of 0.153 ng mg(-1)) and in invasive T2/T3 tumours (mean level of 0.104 ng mg(-1)) compared with normal urothelium (mean level of 0.065 ng mg(-1)). Invasive T4 tumours, however, contained only low amounts of TGF-beta1 (mean level of 0.02 ng mg(-1)). Neither in mean nor in individual patients were serum and tissue TGF-beta levels correlated with each other. Cell culture experiments on primary bladder cells revealed a 57% decrease in TGF-beta1 mRNA levels in tumour compared with normal epithelial cells. Tumour epithelial cells contained about two times higher levels of TGF-beta2 and TGF-beta3 mRNA than normal epithelial cells. Fibroblasts expressed about the same amount of TGF-beta1 or TGF-beta2 as epithelial cells. Yet, fibroblasts released only 19% and 13% of the amount secreted by tumour epithelial cells into the supernatant. TGF-beta3, on the other hand, was expressed by fibroblasts with higher levels than by epithelial cells. TGF-beta1 was the predominent isoform in bladder tissue and cells at protein as well as on mRNA levels indicating that TGFs-beta2 and -beta3 are of minor importance in bladder cancer. In summary, there is a lack of correlation between TGF-beta serum levels and TGF-beta expression in tumour tissue in bladder cancer. Images Figure 1 PMID:9192977

  5. Molecular tectonic model of virus structural transitions: the putative cell entry states of poliovirus.

    PubMed

    Belnap, D M; Filman, D J; Trus, B L; Cheng, N; Booy, F P; Conway, J F; Curry, S; Hiremath, C N; Tsang, S K; Steven, A C; Hogle, J M

    2000-02-01

    Upon interacting with its receptor, poliovirus undergoes conformational changes that are implicated in cell entry, including the externalization of the viral protein VP4 and the N terminus of VP1. We have determined the structures of native virions and of two putative cell entry intermediates, the 135S and 80S particles, at approximately 22-A resolution by cryo-electron microscopy. The 135S and 80S particles are both approximately 4% larger than the virion. Pseudoatomic models were constructed by adjusting the beta-barrel domains of the three capsid proteins VP1, VP2, and VP3 from their known positions in the virion to fit the 135S and 80S reconstructions. Domain movements of up to 9 A were detected, analogous to the shifting of tectonic plates. These movements create gaps between adjacent subunits. The gaps at the sites where VP1, VP2, and VP3 subunits meet are plausible candidates for the emergence of VP4 and the N terminus of VP1. The implications of these observations are discussed for models in which the externalized components form a transmembrane pore through which viral RNA enters the infected cell. PMID:10627545

  6. Synthesis on accumulation of putative neurotransmitters by cultured neural crest cells

    SciTech Connect

    Maxwell, G.D.; Sietz, P.D.; Rafford, C.E.

    1982-07-01

    The events mediating the differentiation of embryonic neural crest cells into several types of neurons are incompletely understood. In order to probe one aspect of this differentiation, we have examined the capacity of cultured quail trunk neural crest cells to synthesize, from radioactive precursors, and store several putative neurotransmitter compounds. These neural crest cultures develop the capacity to synthesize and accumulate acetylcholine and the catecholamines norepinephrine and dopamine. In contrast, detectable but relatively little synthesis and accumulation of 5-hydroxytryptamine gamma-aminobutyric acid, or octopamine from the appropriate radiolabeled precursors were observed. The capacity for synthesis and accumulation of radiolabeled acetylcholine and catecholamines is very low or absent at 2 days in vitro. Between 3 and 7 days in vitro, there is a marked rise in both catecholamine and acetylcholine accumulation in the cultures. These findings suggest that, under the particular conditions used in these experiments, the development of neurotransmitter biosynthesis in trunk neural crest cells ijs restricted and resembles, at least partially, the pattern observed in vivo. The development of this capacity to synthesize and store radiolabeled acetylcholine and catecholamines from the appropriate radioactive precursors coincides closely with the development of the activities of the synthetic enzymes choline acetyltransferase and dopamine beta-hydroxylase reported by others.

  7. Molecular Tectonic Model of Virus Structural Transitions: the Putative Cell Entry States of Poliovirus

    PubMed Central

    Belnap, David M.; Filman, David J.; Trus, Benes L.; Cheng, Naiqian; Booy, Frank P.; Conway, James F.; Curry, Stephen; Hiremath, Chaitanya N.; Tsang, Simon K.; Steven, Alasdair C.; Hogle, James M.

    2000-01-01

    Upon interacting with its receptor, poliovirus undergoes conformational changes that are implicated in cell entry, including the externalization of the viral protein VP4 and the N terminus of VP1. We have determined the structures of native virions and of two putative cell entry intermediates, the 135S and 80S particles, at ∼22-Å resolution by cryo-electron microscopy. The 135S and 80S particles are both ∼4% larger than the virion. Pseudoatomic models were constructed by adjusting the beta-barrel domains of the three capsid proteins VP1, VP2, and VP3 from their known positions in the virion to fit the 135S and 80S reconstructions. Domain movements of up to 9 Å were detected, analogous to the shifting of tectonic plates. These movements create gaps between adjacent subunits. The gaps at the sites where VP1, VP2, and VP3 subunits meet are plausible candidates for the emergence of VP4 and the N terminus of VP1. The implications of these observations are discussed for models in which the externalized components form a transmembrane pore through which viral RNA enters the infected cell. PMID:10627545

  8. Beta* and beta-waist measurement and control at RHIC

    SciTech Connect

    Ptitsyn,V.; Della Penna, A.; Litvinenko, V.N.; Malitsky, N.; Satogata, T.

    2009-05-04

    During the course of last RHIC runs the beta-functions at the collision points ({beta}*) have been reduced gradually to 0.7m. In order to maximize the collision luminosity and ensure the agreement of the actual machine optics with the design one, more precise measurements and control of {beta}* value and {beta}-waist location became necessary. The paper presents the results of the implementation of the technique applied in last two RHIC runs. The technique is based on well-known relation between the tune shift and the beta function and involves precise betatron tune measurements using BBQ system as well as specially developed knobs for {beta}-waist location control.

  9. In Vitro and In Vivo Effects of Natural Putative Secretagogues of Glucagon-Like Peptide-1 (GLP-1)

    PubMed Central

    Rafferty, Eamon P.; Wylie, Alastair R.; Elliott, Chris T.; Chevallier, Olivier P.; Grieve, David J.; Green, Brian D.

    2011-01-01

    Glucagon-like peptide-1 (GLP-1) is an intestinal hormone with well-established glucose-lowering activity. The in vitro and in vivo actions of natural putative secretagogues of GLP-1 were investigated. The acute GLP-1 releasing activity of olive leaf extract (OLE), glutamine (GLN), alpha casein (ACAS), beta casein (BCAS) and chlorogenic acid (CGA) were assessed in STC-1 cells and C57BL/6 mice. All compounds except ACAS significantly increased acute in vitro GLP-1 secretion (66–386%; P<0.05–0.001). Oral gavage of OLE and GLN modestly increased plasma GLP-1 concentrations (48% and 41%, respectively), but did not lower glycaemic excursions. OLE and GLN are potent stimulators of GLP-1 secretion both in vitro and in vivo and chronic studies should assess their suitability as nutritional therapies for type 2 diabetes. PMID:21886907

  10. Structural and functional analysis of Rv0554 from Mycobacterium tuberculosis: testing a putative role in menaquinone biosynthesis.

    PubMed

    Johnston, Jodie M; Jiang, Ming; Guo, Zhihong; Baker, Edward N

    2010-08-01

    Mycobacterium tuberculosis, the cause of tuberculosis, is a devastating human pathogen against which new drugs are urgently needed. Enzymes from the biosynthetic pathway for menaquinone are considered to be valid drug targets. The protein encoded by the open reading frame Rv0554 has been expressed, purified and subjected to structural and functional analysis to test for a putative role in menaquinone biosynthesis. The crystal structure of Rv0554 has been solved and refined in two different space groups at 2.35 and 1.9 A resolution. The protein is dimeric, with an alpha/beta-hydrolase monomer fold. In each monomer, a large cavity adjacent to the catalytic triad is enclosed by a helical lid. Dimerization is mediated by the lid regions. Small-molecule additives used in crystallization bind in the active site, but no binding of ligands related to menaquinone biosynthesis could be detected and functional assays failed to support possible roles in menaquinone biosynthesis. PMID:20693690

  11. Covisualization in living onion cells of putative integrin, putative spectrin, actin, putative intermediate filaments, and other proteins at the cell membrane and in an endomembrane sheath

    NASA Technical Reports Server (NTRS)

    Reuzeau, C.; Doolittle, K. W.; McNally, J. G.; Pickard, B. G.; Evans, M. L. (Principal Investigator)

    1997-01-01

    Covisualizations with wide-field computational optical-sectioning microscopy of living epidermal cells of the onion bulb scale have evidenced two major new cellular features. First, a sheath of cytoskeletal elements clads the endomembrane system. Similar elements clad the inner faces of punctate plasmalemmal sites interpreted as plasmalemmal control centers. One component of the endomembrane sheath and plasmalemmal control center cladding is anti-genicity-recognized by two injected antibodies against animal spectrin. Immunoblots of separated epidermal protein also showed bands recognized by these antibodies. Injected phalloidin identified F-actin with the same cellular distribution pattern, as did antibodies against intermediate-filament protein and other cytoskeletal elements known from animal cells. Injection of general protein stains demonstrated the abundance of endomembrane sheath protein. Second, the endomembrane system, like the plasmalemmal puncta, contains antigen recognized by an anti-beta 1 integrin injected into the cytoplasm. Previously, immunoblots of separated epidermal protein were shown to have a major band recognized both by this antibody prepared against a peptide representing the cytosolic region of beta 1 integrin and an antibody against the matrix region of beta 1 integrin. The latter antiboby also identified puncta at the external face of protoplasts. It is proposed that integrin and associated transmembrane proteins secure the endomembrane sheath and transmit signals between it and the lumen or matrix of the endoplasmic reticulum and organellar matrices. This function is comparable to that proposed for such transmembrane linkers in the plasmalemmal control centers, which also appear to bind cytoskeleton and a host of related molecules and transmit signals between them and the wall matrix. It is at the plasmalemmal control centers that the endoplasmic reticulum, a major component of the endomembrane system, attaches to the plasma membrane.

  12. [Beta blockers in migraine prophylaxis].

    PubMed

    Shimizu, Toshihiko

    2009-10-01

    Beta blockers (beta-adrenoceptor blockers) are known to be used for the prophylactic treatment of migraine. The improvement of migraine in the patients who recieved propranolol for angina pectoris revealed the effectiveness of propranolol in migraine prophylaxis. Many clinical trials have confirmed that propranolol is effective in the prophylactic treatment of migraine. Other beta-blocking drugs, namely nadolol, metoprolol, atenolol, timolol and bisoprolol, have also been demonstrated to be effective in the prophylaxis of migraine. In contrast, several beta blockers with intrinsic sympathetic activity (ISA), such as alprenolol, oxprenolol, pindolol and acebutolol, have not been demonstrated to be effective in migraine prophylaxis. In this review, we have descrived the pharmacologic background and pharmacokinetics of the beta blockers that demonstrated a prophylactic effect for migraine will be described. We have also reviewed the results of clinical trials of beta-blocking drugs for migraine. PMID:19882938

  13. An ABC transporter from Bacillus thuringiensis is essential for beta-exotoxin I production.

    PubMed

    Espinasse, Sylvain; Gohar, Michel; Lereclus, Didier; Sanchis, Vincent

    2002-11-01

    beta-Exotoxin I is a nonspecific insecticidal metabolite secreted by some Bacillus thuringiensis strains. Several studies of B. thuringiensis strains that have lost the capacity to produce beta-exotoxin I have suggested that there is a strong correlation between high levels of beta-exotoxin I production and the ability to synthesize crystal proteins. In this study, we showed that a mutant strain, B. thuringiensis 407-1(Cry(-))(Pig(+)), with no crystal gene, produced considerable amounts of beta-exotoxin I together with a soluble brown melanin pigment. Therefore, beta-exotoxin I production can take place after a strain has lost the plasmids bearing the cry genes, which suggests that these curable plasmids probably contain determinants involved in the regulation of beta-exotoxin I production. Using a mini-Tn10 transposon, we constructed a library of strain 407-1(Cry(-))(Pig(+)) mutants. We screened for nonpigmented mutants with impaired beta-exotoxin I production and identified a genetic locus harboring two genes (berA and berB) essential for beta-exotoxin I production. The deduced amino acid sequence of the berA gene displayed significant similarity to the ATP-binding domains of the DRI (drug resistance and immunity) family of ATP-binding cassette (ABC) proteins involved in drug resistance and immunity to bacteriocins and lantibiotics. The berB gene encodes a protein with six putative transmembrane helices, which probably constitutes the integral membrane component of the transporter. The demonstration that berAB is required for beta-exotoxin I production and/or resistance in B. thuringiensis adds an adenine nucleotide analog to the wide range of substrates of the superfamily of ABC proteins. We suggest that berAB confers beta-exotoxin I immunity in B. thuringiensis, through active efflux of the molecule. PMID:12374817

  14. Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy.

    PubMed

    Kawakami, Kazunobu; Nagatomo, Toshihisa; Abe, Haruhiko; Kikuchi, Kan; Takemasa, Hiroko; Anson, Blake D; Delisle, Brian P; January, Craig T; Nakashima, Yasuhide

    2006-03-01

    beta-Blockers are widely used in the treatment of cardiovascular diseases. However, their effects on HERG channels at comparable conditions remain to be defined. We investigated the direct acute effects of beta-blockers on HERG current and the molecular basis of drug binding to HERG channels with mutations of putative common binding site (Y652A and F656C). beta-Blockers were selected based on the receptor subtype. Wild-type, Y652A and F656C mutants of HERG channel were stably expressed in HEK293 cells, and the current was recorded by using whole-cell patch-clamp technique (23 degrees C). Carvedilol (nonselective), propranolol (nonselective) and ICI 118551 (beta(2)-selective) inhibited HERG current in a concentration-dependent manner (IC(50) 0.51, 3.9 and 9.2 microM, respectively). The IC(50) value for carvedilol was a clinically relevant concentration. High metoprolol (beta(1)-selective) concentrations were required for blockade (IC(50) 145 microM), and atenolol (beta(1)-selective) did not inhibit the HERG current. Inhibition of HERG current by carvedilol, propranolol and ICI 118551 was partially but significantly attenuated in Y652A and F656C mutant channels. Affinities of metoprolol to Y652A and F656C mutant channels were not different compared with the wild-type. HERG current block by all beta-blockers was not frequency-dependent. Drug affinities to HERG channels were different in beta-blockers. Our results provide additional strategies for clinical usage of beta-blockers. Atenolol and metoprolol may be preferable for patients with type 1 and 2 long QT syndrome. Carvedilol has a class III antiarrhythmic effect, which may provide the rationale for a favourable clinical outcome compared with other beta-blockers as suggested in the recent COMET (Carvedilol Or Metoprolol European Trial) substudy. PMID:16314852

  15. Solergy (Beta Version 1)

    Energy Science and Technology Software Center (ESTSC)

    2009-03-30

    SOLERGY simulates the operation and power output of a user-defined solar central receiver power plant for a time period of up to one year. SOLERGY utilizes recorded or simulated weather data and plant component performance models to calculate the power flowing through each part of the solar plant. A plant control subroutine monitors these powers and determines when to operate the various plant subsystems. The original version of the code was released in May 1987,more » within SAND86-8060 and was widely distributed. The Beta Version 1 to be released in 2009, includes some relatively small modifications to the original code.« less

  16. TCFL4: a gene at 17q21.1 encoding a putative basic helix-loop-helix leucine-zipper transcription factor.

    PubMed

    Bjerknes, M; Cheng, H

    1996-11-28

    TCFL4 (transcription factor like 4) is the HGMW-approved symbol for the gene of a widely expressed putative basic helix-loop-helix leucine-zipper (bHLH-zip) transcription factor which is located 3' to HSD17B1 (17-beta-hydroxysteroid dehydrogenase gene) at 17q21.1, centromeric to the BRCA1 (a gene implicated in familial breast cancer) locus. We report the human gene structure and the murine cDNA sequence of two variants, about 1.5 and 2.2 kb in size. The deduced protein is highly conserved between mouse and man. PMID:8973301

  17. Simultaneous beta and gamma spectroscopy

    DOEpatents

    Farsoni, Abdollah T.; Hamby, David M.

    2010-03-23

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

  18. Hundreds of putatively functional small open reading frames in Drosophila

    PubMed Central

    2011-01-01

    Background The relationship between DNA sequence and encoded information is still an unsolved puzzle. The number of protein-coding genes in higher eukaryotes identified by genome projects is lower than was expected, while a considerable amount of putatively non-coding transcription has been detected. Functional small open reading frames (smORFs) are known to exist in several organisms. However, coding sequence detection methods are biased against detecting such very short open reading frames. Thus, a substantial number of non-canonical coding regions encoding short peptides might await characterization. Results Using bio-informatics methods, we have searched for smORFs of less than 100 amino acids in the putatively non-coding euchromatic DNA of Drosophila melanogaster, and initially identified nearly 600,000 of them. We have studied the pattern of conservation of these smORFs as coding entities between D. melanogaster and Drosophila pseudoobscura, their presence in syntenic and in transcribed regions of the genome, and their ratio of conservative versus non-conservative nucleotide changes. For negative controls, we compared the results with those obtained using random short sequences, while a positive control was provided by smORFs validated by proteomics data. Conclusions The combination of these analyses led us to postulate the existence of at least 401 functional smORFs in Drosophila, with the possibility that as many as 4,561 such functional smORFs may exist. PMID:22118156

  19. Categorization of Putative Factors Against Rhopalosiphum padi (L.) (Heteroptera: Aphididae).

    PubMed

    Zeb, Qamar; Rondon, Silvia I; Naeem, Mohammad; Khan, Shah Alam; Goyer, Aymeric; Vleet, Steve Van; Corp, Mary K

    2016-02-01

    The bird cherry-oat aphid, Rhopalosiphum padi (L.) (Heteroptera: Aphididae), causes heavy losses to wheat crops worldwide by direct damage and virus transmission. This study was conducted to identify putative resistance mechanisms in four wheat varieties (Bobtail, Ladd, Stephens, and Skiles) and one advanced line (YS434)where R. padi was subjected to choice and no-choice tests. Antixenosis, antibiosis and tolerance studies were conducted in controlled environmental conditions at temperature of 20±5°C, 50–65% RH, and a photoperiod of 14:10 (L:D) h. Based on the antixenosis test, the variety Skiles was found susceptible to R. padi, while the line YS434 showed a significant level of resistance; the varieties Bobtail, Ladd, and Stephens showed intermediate response. In the antibiosis experiment, R. padi produced less progeny on the variety Skiles as compared with other varieties, but the developmental time for nymphs was also significantly shorter on Skiles and recorded higher intrinsic rate of natural increase (r(m)) values as compared with the varieties YS434, Bobtail, and Ladd. In the tolerance tests, the variety Ladd showed significantly lower tolerance index value than YS434, followed by Skiles, Bobtail, and Stephens. The plant resistance index value was greater for the variety Ladd, followed by Stephens, YS434, and Bobtail. In conclusion, this study provides baseline information that will contribute to the identification of putative resistance factors for a future breeding program against this aphid. PMID:26568060

  20. Evidence for a putative biomarker for substance dependence.

    PubMed

    Taylor, Jeanette; James, Lisa M

    2009-09-01

    Electrodermal response modulation (ERM) reflects the reduction in skin conductance response to an aversive stimulus that is temporally predictable relative to when it is unpredictable. Poor ERM is associated with substance dependence (SD). It was hypothesized that ERM is a putative biomarker for SD rather than for externalizing disorders generally. Participants included 83 controls (no SD, antisocial personality disorder [PD] or borderline PD), 52 participants with SD only (SD and no PD), 12 with PD only (antisocial and/or borderline PD and no SD), and 35 comorbid (having SD and PD). Diagnoses at definite and probable certainty levels were used and were determined by semistructured clinical interviews. ERM was calculated from skin conductance responses to predictable and unpredictable 2-s 110-dB white noise blasts. As expected, the SD-only and comorbid groups had significantly lower ERM scores than the control group, which did not differ significantly from the PD-only group. Results provide preliminary evidence that ERM is a putative biomarker for SD. Future research should examine cognitive correlates of ERM in an effort to understand why it relates to SD. PMID:19769433

  1. Brain response to putative pheromones in homosexual men.

    PubMed

    Savic, Ivanka; Berglund, Hans; Lindström, Per

    2005-05-17

    The testosterone derivative 4,16-androstadien-3-one (AND) and the estrogen-like steroid estra-1,3,5(10),16-tetraen-3-ol (EST) are candidate compounds for human pheromones. AND is detected primarily in male sweat, whereas EST has been found in female urine. In a previous positron emission tomography study, we found that smelling AND and EST activated regions covering sexually dimorphic nuclei of the anterior hypothalamus, and that this activation was differentiated with respect to sex and compound. In the present study, the pattern of activation induced by AND and EST was compared among homosexual men, heterosexual men, and heterosexual women. In contrast to heterosexual men, and in congruence with heterosexual women, homosexual men displayed hypothalamic activation in response to AND. Maximal activation was observed in the medial preoptic area/anterior hypothalamus, which, according to animal studies, is highly involved in sexual behavior. As opposed to putative pheromones, common odors were processed similarly in all three groups of subjects and engaged only the olfactory brain (amygdala, piriform, orbitofrontal, and insular cortex). These findings show that our brain reacts differently to the two putative pheromones compared with common odors, and suggest a link between sexual orientation and hypothalamic neuronal processes. PMID:15883379

  2. Chloroplast diversity in a putative hybrid swarm of Ponderosae (Pinaceae).

    PubMed

    Epperson, Bryan K; Telewski, Frank W; Willyard, Ann

    2009-03-01

    The Ponderosae subsection of the genus Pinus contains numerous taxa in disjunct mountain ranges of southern Arizona and New Mexico, differing for several leaf and cone traits, key among which is the number of leaf needles per fascicle. Trees with three needles are often found together with trees having five needles and mixed numbers. One taxonomic hypothesis is that there are swarms of hybrids between P. ponderosa and P. arizonica. A second hypothesis is that there are spatial mixtures of two separate taxa, five-needle P. arizonica and a "taxon X" containing three needle and mixed needle trees. We genotyped chloroplasts in one putative hybrid swarm on Mt. Lemmon using microsatellite markers and show that cpDNA is almost completely differentiated between two separate morphotypes corresponding to P. arizonica and "taxon X." Little if any introgression has occurred on Mt. Lemmon, and the simplest explanation is that little or no effective hybridization has occurred. Further results indicate that not only is taxon X not of hybrid origin, it is more closely related to nonregional Ponderosae other than P. ponderosa and P. arizonica. The results further suggest that other putative hybrid swarms in the region are also spatial mixtures of distinct taxa. PMID:21628225

  3. Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?

    PubMed

    Barber, Robert C; Phillips, Nicole R; Tilson, Jeffrey L; Huebinger, Ryan M; Shewale, Shantanu J; Koenig, Jessica L; Mitchel, Jeffrey S; O'Bryant, Sid E; Waring, Stephen C; Diaz-Arrastia, Ramon; Chasse, Scott; Wilhelmsen, Kirk C

    2015-01-01

    Although 24 Alzheimer's disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10(-7). Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel

  4. Amyloid Beta Mediates Memory Formation

    ERIC Educational Resources Information Center

    Garcia-Osta, Ana; Alberini, Cristina M.

    2009-01-01

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

  5. Transcriptional Regulation of the Beta-Synuclein 5′-Promoter Metal Response Element by Metal Transcription Factor-1

    PubMed Central

    McHugh, Patrick C.; Wright, Josephine A.; Brown, David R.

    2011-01-01

    The progression of many human neurodegenerative disorders is associated with an accumulation of alpha-synuclein. Alpha-synuclein belongs to the homologous synuclein family, which includes beta-synuclein. It has been proposed that beta-synuclein may be a natural regulator of alpha-synuclein. Therefore controlling beta-synuclein expression may control the accumulation of alpha-synuclein and ultimately prevent disease progression. The regulation of synucleins is poorly understood. We investigated the transcriptional regulation of beta-synuclein, with the aim of identifying molecules that differentially control beta-synuclein expression levels. To investigate transcriptional regulation of beta-synuclein, we used reporter gene assays and bioinformatics. We identified a region −1.1/−0.6 kb upstream of the beta-synuclein translational start site to be a key regulatory region of beta-synuclein 5′-promoter activity in human dopaminergic cells (SH-SY5Y). Within this key promoter region we identified a metal response element pertaining to a putative Metal Transcription Factor-1 (MTF-1) binding site. We demonstrated that MTF-1 binds to this 5′-promoter region using EMSA analysis. Moreover, we showed that MTF-1 differentially regulates beta-synuclein promoter binding site, as well as beta-synuclein mRNA and protein expression. This effect of MTF-1 on expression was found to be specific to beta-synuclein when compared to alpha-synuclein. Understanding the regulation of synucleins and how they interact may point to molecular targets that could be manipulated for therapeutic benefit. In this study we showed that MTF-1 differentially controls the expression of beta-synuclein when compared to its homolog alpha-synuclein. This could potentially provide a novel targets or pathways for therapeutic intervention and/or treatment of synucleinopathies. PMID:21386983

  6. Neutrinoless Double Beta Decay

    NASA Astrophysics Data System (ADS)

    Cremonesi, Oliviero

    2016-05-01

    After more than 3/4 of century from its proposal, Neutrinoless Double Beta Decay (NLDBD) is still missing observation and continues to represent the only practical method for investigating the Dirac/Majorana nature of neutrinos. In case neutrinos would be Majorana particles, NLDBD would provide unique informations on their properties (absolute mass scale and Majorana phases). Boosted by the discovery of neutrino oscillations, a number of experiments with improved sensitivity have been proposed in the past decade. Some of them have recently started operation and others are ready to start. They will push the experimental sensitivity on the decay halflife beyond 1026 year, starting to analyze the region of the inverted mass hierarchy. The status and perspectives of the ongoing experimental effort are reviewed. Uncertainties coming from the calculation othe decay nuclear matrix elements (NME) as well as the recently suggested possibility of a relevant quenching of the axial coupling constant are also discussed.

  7. Beta systems error analysis

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The atmospheric backscatter coefficient, beta, measured with an airborne CO Laser Doppler Velocimeter (LDV) system operating in a continuous wave, focussed model is discussed. The Single Particle Mode (SPM) algorithm, was developed from concept through analysis of an extensive amount of data obtained with the system on board a NASA aircraft. The SPM algorithm is intended to be employed in situations where one particle at a time appears in the sensitive volume of the LDV. In addition to giving the backscatter coefficient, the SPM algorithm also produces as intermediate results the aerosol density and the aerosol backscatter cross section distribution. A second method, which measures only the atmospheric backscatter coefficient, is called the Volume Mode (VM) and was simultaneously employed. The results of these two methods differed by slightly less than an order of magnitude. The measurement uncertainties or other errors in the results of the two methods are examined.

  8. Predicting neutrinoless double beta decay

    SciTech Connect

    Hirsch, M.; Villanova del Moral, A.; Valle, J.W.F.

    2005-11-01

    We give predictions for the neutrinoless double beta decay rate in a simple variant of the A{sub 4} family symmetry model. We show that there is a lower bound for the {beta}{beta}{sub 0{nu}} amplitude even in the case of normal hierarchical neutrino masses, corresponding to an effective mass parameter vertical bar m{sub ee} vertical bar {>=}0.17{radical}({delta}m{sub ATM}{sup 2}). This result holds both for the CP conserving and CP violating cases. In the latter case we show explicitly that the lower bound on vertical bar m{sub ee} vertical bar is sensitive to the value of the Majorana phase. We conclude therefore that in our scheme, {beta}{beta}{sub 0{nu}} may be accessible to the next generation of high sensitivity experiments.

  9. Exceptional error minimization in putative primordial genetic codes

    PubMed Central

    2009-01-01

    Background The standard genetic code is redundant and has a highly non-random structure. Codons for the same amino acids typically differ only by the nucleotide in the third position, whereas similar amino acids are encoded, mostly, by codon series that differ by a single base substitution in the third or the first position. As a result, the code is highly albeit not optimally robust to errors of translation, a property that has been interpreted either as a product of selection directed at the minimization of errors or as a non-adaptive by-product of evolution of the code driven by other forces. Results We investigated the error-minimization properties of putative primordial codes that consisted of 16 supercodons, with the third base being completely redundant, using a previously derived cost function and the error minimization percentage as the measure of a code's robustness to mistranslation. It is shown that, when the 16-supercodon table is populated with 10 putative primordial amino acids, inferred from the results of abiotic synthesis experiments and other evidence independent of the code's evolution, and with minimal assumptions used to assign the remaining supercodons, the resulting 2-letter codes are nearly optimal in terms of the error minimization level. Conclusion The results of the computational experiments with putative primordial genetic codes that contained only two meaningful letters in all codons and encoded 10 to 16 amino acids indicate that such codes are likely to have been nearly optimal with respect to the minimization of translation errors. This near-optimality could be the outcome of extensive early selection during the co-evolution of the code with the primordial, error-prone translation system, or a result of a unique, accidental event. Under this hypothesis, the subsequent expansion of the code resulted in a decrease of the error minimization level that became sustainable owing to the evolution of a high-fidelity translation system

  10. High Temperature Stability of Potassium Beta Alumina

    NASA Technical Reports Server (NTRS)

    Williams, R. M.; Kisor, A.; Ryan, M. A.

    1996-01-01

    None. From Objectives section: Evaluate the stability of potassium beta alumina under potassium AMTEC operating conditions. Evaluate the stability regime in which potassium beta alumina can be fabricated.

  11. Sequential development of intraepithelial gamma delta and alpha beta T lymphocytes expressing CD8 alpha beta in neonatal rat intestine: requirement for the thymus.

    PubMed

    Helgeland, L; Brandtzaeg, P; Rolstad, B; Vaage, J T

    1997-12-01

    Previous studies in congenitally athymic nude rats have suggested that the thymus is important for the development of intestinal T cells. Here we have examined the effect of the nude mutation on intraepithelial lymphocyte (IEL) development from the perinatal period. By immunohistochemistry it was shown that CD3(-)CD8 alpha alpha + putative IEL precursors colonized the epithelium of both normal and athymic neonatal rats. Mature T cells, however, did not develop in athymic neonates. In normal rats, gamma delta T cells were present at birth and alpha beta T cells appeared within 8 days of postnatal life. At this age, the composition and relative number of intraepithelial T cells were similar to that in normal adult rats, with the exception that most neonatal T-cell receptor-gamma delta + and -alpha beta + IEL expressed CD8 beta. By contrast, extrathymic T-cell maturation in the gut of congenitally athymic rats occurred slowly, as CD3+ IEL did not appear until 4-6 months of age. These intraepithelial T cells displayed variable phenotypes and appeared to be induced by environmental antigens as they were not found in isolator-kept old nudes. In conclusion, the present results indicate that the major colonization of the gut epithelium with gamma delta and alpha beta T cells expressing CD8 alpha beta takes place perinatally and requires the presence of the thymus. The developmental relationship between these neonatal T cells and more immature CD3- CD8 alpha alpha +/- IEL remains elusive. PMID:9497485

  12. Identification of cellular target genes of the Epstein-Barr virus transactivator Zta: activation of transforming growth factor beta igh3 (TGF-beta igh3) and TGF-beta 1.

    PubMed Central

    Cayrol, C; Flemington, E K

    1995-01-01

    The lytic switch transactivator Zta initiates the ordered cascade of Epstein-Barr virus gene expression that culminates in virus production. Zta is a sequence-specific DNA-binding protein that transactivates early viral promotes via cis-acting sequences. Activation of some of these genes is mediated through binding to consensus AP-1 promoter elements. This observation suggests that Zta may also regulate the expression of cellular genes. While many targets of Zta have been identified in the Epstein-Barr virus genome, putative host cell targets remain largely unknown. To address this issue, a tetracycline-regulated Zta expression system was generated, and differential hybridization screening was used to isolate Zta-responsive cellular genes. The major target identified by this analysis is a gene encoding a fasciclin-like secreted factor, transforming growth factor beta igh3 (TGF-beta igh3), that was originally identified as a gene that is responsive to the potent immunosuppressor TGF-beta 1. Northern (RNA) blot analysis demonstrated that induction of Zta expression results in a 10-fold increase in TGF-beta igh3 mRNA levels. Zta was also found to increase TGF-beta 1 mRNA levels as well as the amount of active TGF-beta 1 secreted into the medium. Interestingly, alpha 1-collagen IV, which has been shown to potentiate the effects of TGF-beta 1, is also a cellular target of Zta. These results suggest that Zta could play a role in modulating the host cell environment through activating the expression of secreted factors. PMID:7769680

  13. Putative Genes Involved in Saikosaponin Biosynthesis in Bupleurum Species

    PubMed Central

    Lin, Tsai-Yun; Chiou, Chung-Yi; Chiou, Shu-Jiau

    2013-01-01

    Alternative medicinal agents, such as the herb Bupleurum, are increasingly used in modern medicine to supplement synthetic drugs. First, we present a review of the currently known effects of triterpene saponins-saikosaponins of Bupleurum species. The putative biosynthetic pathway of saikosaponins in Bupleurum species is summarized, followed by discussions on identification and characterization of genes involved in the biosynthesis of saikosaponins. The purpose is to provide a brief review of gene extraction, functional characterization of isolated genes and assessment of expression patterns of genes encoding enzymes in the process of saikosaponin production in Bupleurum species, mainly B. kaoi. We focus on the effects of MeJA on saikosaponin production, transcription patterns of genes involved in biosynthesis and on functional depiction. PMID:23783277

  14. Mycobacteriophage putative GTPase-activating protein can potentiate antibiotics.

    PubMed

    Yan, Shuangquan; Xu, Mengmeng; Duan, Xiangke; Yu, Zhaoxiao; Li, Qiming; Xie, Longxiang; Fan, Xiangyu; Xie, Jianping

    2016-09-01

    The soaring incidences of infection by antimicrobial resistant (AR) pathogens and shortage of effective antibiotics with new mechanisms of action have renewed interest in phage therapy. This scenario is exemplified by resistant tuberculosis (TB), caused by resistant Mycobacterium tuberculosis. Mycobacteriophage SWU1 A321_gp67 encodes a putative GTPase-activating protein. Mycobacterium smegmatis with gp67 overexpression showed changed colony formation and biofilm morphology and supports the efficacy of streptomycin and capreomycin against Mycobacterium. gp67 down-regulated the transcription of genes involved in cell wall and biofilm development. To our knowledge, this is the first report to show that phage protein in addition to lysin or recombination components can synergize with existing antibiotics. Phage components might represent a promising new clue for better antibiotic potentiators. PMID:27345061

  15. Design and synthesis of inositolphosphoglycan putative insulin mediators.

    PubMed

    López-Prados, Javier; Cuevas, Félix; Reichardt, Niels-Christian; de Paz, José-Luis; Morales, Ezequiel Q; Martín-Lomas, Manuel

    2005-03-01

    The binding modes of a series of molecules, containing the glucosamine (1-->6) myo-inositol structural motif, into the ATP binding site of the catalytic subunit of cAMP-dependent protein kinase (PKA) have been analysed using molecular docking. These calculations predict that the presence of a phosphate group at the non-reducing end in pseudodisaccharide and pseudotrisaccharide structures properly orientate the molecule into the binding site and that pseudotrisaccharide structures present the best shape complementarity. Therefore, pseudodisaccharides and pseudotrisaccharides have been synthesised from common intermediates using effective synthetic strategies. On the basis of this synthetic chemistry, the feasibility of constructing small pseudotrisaccharide libraries on solid-phase using the same intermediates has been explored. The results from the biological evaluation of these molecules provide additional support to an insulin-mediated signalling system which involves the intermediacy of inositolphosphoglycans as putative insulin mediators. PMID:15731862

  16. Mammalian mitochondrial beta-oxidation.

    PubMed Central

    Eaton, S; Bartlett, K; Pourfarzam, M

    1996-01-01

    The enzymic stages of mammalian mitochondrial beta-oxidation were elucidated some 30-40 years ago. However, the discovery of a membrane-associated multifunctional enzyme of beta-oxidation, a membrane-associated acyl-CoA dehydrogenase and characterization of the carnitine palmitoyl transferase system at the protein and at the genetic level has demonstrated that the enzymes of the system itself are incompletely understood. Deficiencies of many of the enzymes have been recognized as important causes of disease. In addition, the study of these disorders has led to a greater understanding of the molecular mechanism of beta-oxidation and the import, processing and assembly of the beta-oxidation enzymes within the mitochondrion. The tissue-specific regulation, intramitochondrial control and supramolecular organization of the pathway is becoming better understood as sensitive analytical and molecular techniques are applied. This review aims to cover enzymological and organizational aspects of mitochondrial beta-oxidation together with the biochemical aspects of inherited disorders of beta-oxidation and the intrinsic control of beta-oxidation. PMID:8973539

  17. Putative regulatory factors associated with intramuscular fat content.

    PubMed

    Cesar, Aline S M; Regitano, Luciana C A; Koltes, James E; Fritz-Waters, Eric R; Lanna, Dante P D; Gasparin, Gustavo; Mourão, Gerson B; Oliveira, Priscila S N; Reecy, James M; Coutinho, Luiz L

    2015-01-01

    Intramuscular fat (IMF) content is related to insulin resistance, which is an important prediction factor for disorders, such as cardiovascular disease, obesity and type 2 diabetes in human. At the same time, it is an economically important trait, which influences the sensorial and nutritional value of meat. The deposition of IMF is influenced by many factors such as sex, age, nutrition, and genetics. In this study Nellore steers (Bos taurus indicus subspecies) were used to better understand the molecular mechanisms involved in IMF content. This was accomplished by identifying differentially expressed genes (DEG), biological pathways and putative regulatory factors. Animals included in this study had extreme genomic estimated breeding value (GEBV) for IMF. RNA-seq analysis, gene set enrichment analysis (GSEA) and co-expression network methods, such as partial correlation coefficient with information theory (PCIT), regulatory impact factor (RIF) and phenotypic impact factor (PIF) were utilized to better understand intramuscular adipogenesis. A total of 16,101 genes were analyzed in both groups (high (H) and low (L) GEBV) and 77 DEG (FDR 10%) were identified between the two groups. Pathway Studio software identified 13 significantly over-represented pathways, functional classes and small molecule signaling pathways within the DEG list. PCIT analyses identified genes with a difference in the number of gene-gene correlations between H and L group and detected putative regulatory factors involved in IMF content. Candidate genes identified by PCIT include: ANKRD26, HOXC5 and PPAPDC2. RIF and PIF analyses identified several candidate genes: GLI2 and IGF2 (RIF1), MPC1 and UBL5 (RIF2) and a host of small RNAs, including miR-1281 (PIF). These findings contribute to a better understanding of the molecular mechanisms that underlie fat content and energy balance in muscle and provide important information for the production of healthier beef for human consumption. PMID:26042666

  18. Putative Regulatory Factors Associated with Intramuscular Fat Content

    PubMed Central

    Cesar, Aline S. M.; Regitano, Luciana C. A.; Koltes, James E.; Fritz-Waters, Eric R.; Lanna, Dante P. D.; Gasparin, Gustavo; Mourão, Gerson B.; Oliveira, Priscila S. N.; Reecy, James M.; Coutinho, Luiz L.

    2015-01-01

    Intramuscular fat (IMF) content is related to insulin resistance, which is an important prediction factor for disorders, such as cardiovascular disease, obesity and type 2 diabetes in human. At the same time, it is an economically important trait, which influences the sensorial and nutritional value of meat. The deposition of IMF is influenced by many factors such as sex, age, nutrition, and genetics. In this study Nellore steers (Bos taurus indicus subspecies) were used to better understand the molecular mechanisms involved in IMF content. This was accomplished by identifying differentially expressed genes (DEG), biological pathways and putative regulatory factors. Animals included in this study had extreme genomic estimated breeding value (GEBV) for IMF. RNA-seq analysis, gene set enrichment analysis (GSEA) and co-expression network methods, such as partial correlation coefficient with information theory (PCIT), regulatory impact factor (RIF) and phenotypic impact factor (PIF) were utilized to better understand intramuscular adipogenesis. A total of 16,101 genes were analyzed in both groups (high (H) and low (L) GEBV) and 77 DEG (FDR 10%) were identified between the two groups. Pathway Studio software identified 13 significantly over-represented pathways, functional classes and small molecule signaling pathways within the DEG list. PCIT analyses identified genes with a difference in the number of gene-gene correlations between H and L group and detected putative regulatory factors involved in IMF content. Candidate genes identified by PCIT include: ANKRD26, HOXC5 and PPAPDC2. RIF and PIF analyses identified several candidate genes: GLI2 and IGF2 (RIF1), MPC1 and UBL5 (RIF2) and a host of small RNAs, including miR-1281 (PIF). These findings contribute to a better understanding of the molecular mechanisms that underlie fat content and energy balance in muscle and provide important information for the production of healthier beef for human consumption. PMID:26042666

  19. Are Putative Periodontal Pathogens Reliable Diagnostic Markers?▿

    PubMed Central

    Riep, Birgit; Edesi-Neuß, Lilian; Claessen, Friderike; Skarabis, Horst; Ehmke, Benjamin; Flemmig, Thomas F.; Bernimoulin, Jean-Pierre; Göbel, Ulf B.; Moter, Annette

    2009-01-01

    Periodontitis is one of the most common chronic inflammatory diseases. A number of putative bacterial pathogens have been associated with the disease and are used as diagnostic markers. In the present study, we compared the prevalence of oral bacterial species in the subgingival biofilm of generalized aggressive periodontitis (GAP) (n = 44) and chronic periodontitis (CP) (n = 46) patients with that of a periodontitis-resistant control group (PR) (n = 21). The control group consisted of subjects at least 65 years of age with only minimal or no periodontitis and no history of periodontal treatment. A total of 555 samples from 111 subjects were included in this study. The samples were analyzed by PCR of 16S rRNA gene fragments and subsequent dot blot hybridization using oligonucleotide probes specific for Aggregatibacter (Actinobacillus) actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, a Treponema denticola-like phylogroup (Treponema phylogroup II), Treponema lecithinolyticum, Campylobacter rectus, Fusobacterium spp., and Fusobacterium nucleatum, as well as Capnocytophaga ochracea. Our data confirm a high prevalence of the putative periodontal pathogens P. gingivalis, P. intermedia, and T. forsythia in the periodontitis groups. However, these species were also frequently detected in the PR group. For most of the species tested, the prevalence was more associated with increased probing depth than with the subject group. T. lecithinolyticum was the only periodontopathogenic species showing significant differences both between GAP and CP patients and between GAP patients and PR subjects. C. ochracea was associated with the PR subjects, regardless of the probing depth. These results indicate that T. lecithinolyticum may be a diagnostic marker for GAP and C. ochracea for periodontal health. They also suggest that current presumptions of the association of specific bacteria with periodontal health and disease require further

  20. Astrocytes in the optic nerve head express putative mechanosensitive channels

    PubMed Central

    Choi, Hee Joo; Sun, Daniel

    2015-01-01

    Purpose To establish whether optic nerve head astrocytes express candidate molecules to sense tissue stretch. Methods We used conventional PCR, quantitative PCR, and single-cell reverse transcription PCR (RT–PCR) to assess the expression of various members of the transient receptor potential (TRP) channel family and of the recently characterized mechanosensitive channels Piezo1 and 2 in optic nerve head tissue and in single, isolated astrocytes. Results Most TRP subfamilies (TRPC, TRPM, TRPV, TRPA, and TRPP) and Piezo1 and 2 were expressed in the optic nerve head of the mouse. Quantitative real-time PCR analysis showed that TRPC1, TRPM7, TRPV2, TRPP2, and Piezo1 are the dominant isoforms in each subfamily. Single-cell RT–PCR revealed that many TRP isoforms, TRPC1–2, TRPC6, TRPV2, TRPV4, TRPM2, TRPM4, TRPM6–7, TRPP1–2, and Piezo1–2, are expressed in astrocytes of the optic nerve head, and that most astrocytes express TRPC1 and TRPP1–2. Comparisons of the TRPP and Piezo expression levels between different tissue regions showed that Piezo2 expression was higher in the optic nerve head and the optic nerve proper than in the brain and the corpus callosum. TRPP2 also showed higher expression in the optic nerve head. Conclusions Astrocytes in the optic nerve head express multiple putative mechanosensitive channels, in particular the recently identified channels Piezo1 and 2. The expression of putative mechanosensitive channels in these cells may contribute to their responsiveness to traumatic or glaucomatous injury. PMID:26236150

  1. Cryptic Species in Putative Ancient Asexual Darwinulids (Crustacea, Ostracoda)

    PubMed Central

    Schön, Isa; Pinto, Ricardo L.; Halse, Stuart; Smith, Alison J.; Martens, Koen; Birky, C. William

    2012-01-01

    Background Fully asexually reproducing taxa lack outcrossing. Hence, the classic Biological Species Concept cannot be applied. Methodology/Principal Findings We used DNA sequences from the mitochondrial COI gene and the nuclear ITS2 region to check species boundaries according to the evolutionary genetic (EG) species concept in five morphospecies in the putative ancient asexual ostracod genera, Penthesilenula and Darwinula, from different continents. We applied two methods for detecting cryptic species, namely the K/θ method and the General Mixed Yule Coalescent model (GMYC). We could confirm the existence of species in all five darwinulid morphospecies and additional cryptic diversity in three morphospecies, namely in Penthesilenula brasiliensis, Darwinula stevensoni and in P. aotearoa. The number of cryptic species within one morphospecies varied between seven (P. brasiliensis), five to six (D. stevensoni) and two (P. aotearoa), respectively, depending on the method used. Cryptic species mainly followed continental distributions. We also found evidence for coexistence at the local scale for Brazilian cryptic species of P. brasiliensis and P. aotearoa. Our ITS2 data confirmed that species exist in darwinulids but detected far less EG species, namely two to three cryptic species in P. brasiliensis and no cryptic species at all in the other darwinulid morphospecies. Conclusions/Significance Our results clearly demonstrate that both species and cryptic diversity can be recognized in putative ancient asexual ostracods using the EG species concept, and that COI data are more suitable than ITS2 for this purpose. The discovery of up to eight cryptic species within a single morphospecies will significantly increase estimates of biodiversity in this asexual ostracod group. Which factors, other than long-term geographic isolation, are important for speciation processes in these ancient asexuals remains to be investigated. PMID:22802945

  2. Effect of beta blockade and beta stimulation on stage fright.

    PubMed

    Brantigan, C O; Brantigan, T A; Joseph, N

    1982-01-01

    Stage fright, physiologically the "fight or flight" reaction, is a disabling condition to the professional musician. Because it is mediated by the sympathetic nervous system, we have investigated the effects of beta blockade on musical performance with propranolol in a double blind fashion and the effects of beta stimulation using terbutaline. Stage fright symptoms were evaluated in two trials, which included a total of 29 subjects, by questionnaire and by the State Trai Anxiety Inventory. Quality of musical performance was evaluated by experienced music critics. Beta blockade eliminates the physical impediments to performance caused by stage fright and even eliminates the dry mouth so frequently encountered. The quality of musical performance as judged by experienced music critics is significantly improved. This effect is achieved without tranquilization. Beta stimulating drugs increase stage fright problems, and should be used in performing musicians only after consideration of the detrimental effects which they may have on musical performance. PMID:6120650

  3. Variants of beta-glucosidase

    SciTech Connect

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

    2015-07-14

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

  4. Variants of beta-glucosidases

    SciTech Connect

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

    2014-10-07

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

  5. Variants of beta-glucosidases

    DOEpatents

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

    2008-08-19

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

  6. Variants of beta-glucosidase

    DOEpatents

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

    2009-12-29

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

  7. Interferon Beta-1b Injection

    MedlinePlus

    ... course of disease where symptoms flare up from time to time) of multiple sclerosis (MS, a disease in which ... interferon beta-1b injection at around the same time of day each time you inject it. Follow ...

  8. Peginterferon Beta-1a Injection

    MedlinePlus

    ... course of disease where symptoms flare up from time to time) of multiple sclerosis (MS, a disease in which ... peginterferon beta-1a injection at around the same time of day each time you inject it. Follow ...

  9. Genetics Home Reference: beta thalassemia

    MedlinePlus

    ... a blood disorder that reduces the production of hemoglobin . Hemoglobin is the iron-containing protein in red blood ... In people with beta thalassemia , low levels of hemoglobin lead to a lack of oxygen in many ...

  10. Questions Students Ask: Beta Decay.

    ERIC Educational Resources Information Center

    Koss, Jordan; Hartt, Kenneth

    1988-01-01

    Answers a student's question about the emission of a positron from a nucleus. Discusses the problem from the aspects of the uncertainty principle, beta decay, the Fermi Theory, and modern physics. (YP)

  11. Physics with Beta-Beam

    SciTech Connect

    Agarwalla, Sanjib Kumar; Choubey, Sandhya; Raychaudhuri, Amitava

    2008-02-21

    A Beta-beam would be a high intensity source of pure {nu}{sub e} and/or {nu}-bar{sub e} flux with known spectrum, ideal for precision measurements. Myriad of possible set-ups with suitable choices of baselines, detectors and the beta-beam neutrino source with desired energies have been put forth in the literature. In this talk we present a comparitive discussion of the physics reach of a few such experimental set-ups.

  12. Medium Beta Superconducting Accelerating Structures

    SciTech Connect

    Jean Delayen

    2001-09-01

    While, originally, the development of superconducting structures was cleanly divided between low-beta resonators for heavy ions and beta=1 resonators for electrons, recent interest in protons accelerators (high and low current, pulsed and cw) has necessitated the development of structures that bridge the gap between the two. These activities have resulted both in new geometries and in the adaptation of well-known geometries optimized to this intermediate velocity range. Their characteristics and properties are reviewed.

  13. Beta function and anomalous dimensions

    SciTech Connect

    Pica, Claudio; Sannino, Francesco

    2011-06-01

    We demonstrate that it is possible to determine the coefficients of an all-orders beta-function linear in the anomalous dimensions using as data the 2-loop coefficients together with the first one of the anomalous dimensions which are universal. The beta function allows us to determine the anomalous dimension of the fermion masses at the infrared fixed point, and the resulting values compare well with the lattice determinations.

  14. The Controversy, Challenges, and Potential Benefits of Putative Female Germline Stem Cells Research in Mammals

    PubMed Central

    Pan, Zezheng; Sun, Mengli; Liang, Xia; Li, Jia; Zhou, Fangyue; Zhong, Zhisheng; Zheng, Yuehui

    2016-01-01

    The conventional view is that female mammals lose their ability to generate new germ cells after birth. However, in recent years, researchers have successfully isolated and cultured a type of germ cell from postnatal ovaries in a variety of mammalian species that have the abilities of self-proliferation and differentiation into oocytes, and this finding indicates that putative germline stem cells maybe exist in the postnatal mammalian ovaries. Herein, we review the research history and discovery of putative female germline stem cells, the concept that putative germline stem cells exist in the postnatal mammalian ovary, and the research progress, challenge, and application of putative germline stem cells in recent years. PMID:26788065

  15. The Controversy, Challenges, and Potential Benefits of Putative Female Germline Stem Cells Research in Mammals.

    PubMed

    Pan, Zezheng; Sun, Mengli; Liang, Xia; Li, Jia; Zhou, Fangyue; Zhong, Zhisheng; Zheng, Yuehui

    2016-01-01

    The conventional view is that female mammals lose their ability to generate new germ cells after birth. However, in recent years, researchers have successfully isolated and cultured a type of germ cell from postnatal ovaries in a variety of mammalian species that have the abilities of self-proliferation and differentiation into oocytes, and this finding indicates that putative germline stem cells maybe exist in the postnatal mammalian ovaries. Herein, we review the research history and discovery of putative female germline stem cells, the concept that putative germline stem cells exist in the postnatal mammalian ovary, and the research progress, challenge, and application of putative germline stem cells in recent years. PMID:26788065

  16. Apollo applications of beta fiber glass

    NASA Technical Reports Server (NTRS)

    Naimer, J.

    1971-01-01

    The physical characteristics of Beta fiber glass are discussed. The application of Beta fiber glass for fireproofing the interior of spacecraft compartments is described. Tests to determine the flammability of Beta fiber glass are presented. The application of Beta fiber glass for commercial purposes is examined.

  17. [Serum beta 2 microglobulin (beta 2M) following renal transplantation].

    PubMed

    Pacheco-Silva, A; Nishida, S K; Silva, M S; Ramos, O L; Azjen, H; Pereira, A B

    1994-01-01

    Although there was an important improvement in graft and patient survival the last 10 years, graft rejection continues to be a major barrier to the success of renal transplantation. Identification of a laboratory test that could help to diagnose graft rejection would facilitate the management of renal transplanted patients. PURPOSE--To evaluate the utility of monitoring serum beta 2M in recently transplanted patients. METHODS--We daily determined serum beta 2M levels in 20 receptors of renal grafts (10 from living related and 10 from cadaveric donors) and compared them to their clinical and laboratory evolution. RESULTS--Eight patients who presented immediate good renal function following grafting and did not have rejection had a mean serum beta 2M of 3.7 mg/L on the 4th day post transplant. The sensitivity of the test for the diagnosis of acute rejection was 87.5%, but the specificity was only 46%. Patients who presented acute tubular necrosis (ATN) without rejection had a progressive decrease in their serum levels of beta 2M, while their serum creatinine changed as they were dialyzed. In contrast, patients with ATN and concomitance of acute rejection or CSA nephrotoxicity presented elevated beta 2M and creatinine serum levels. CONCLUSION--Daily monitoring of serum beta 2M does not improve the ability to diagnose acute rejection in patients with good renal function. However, serum beta 2M levels seemed to be useful in diagnosing acute rejection or CSA nephrotoxicity in patients with ATN. PMID:7787867

  18. A Putative Multiple-Demand System in the Macaque Brain

    PubMed Central

    Bell, Andrew H.; Buckley, Mark J.; Mitchell, Anna S.; Sallet, Jerome; Duncan, John

    2016-01-01

    In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this “multiple-demand” (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using fMRI connectivity in 35 rhesus macaques. Putative macaque MD regions, mapped from frontoparietal MD regions defined in humans, were found to be functionally connected under anesthesia. To further refine these regions, an iterative process was used to maximize their connectivity cross-validated across animals. Finally, whole-brain connectivity analyses identified voxels that were robustly connected to MD regions, revealing seven clusters across frontoparietal and insular cortex comparable to human MD regions and one unexpected cluster in the lateral fissure. The proposed macaque MD regions can be used to guide future electrophysiological investigation of MD neural coding and in task-based fMRI to test predictions of similar functional properties to human MD cortex. SIGNIFICANCE STATEMENT In humans, a frontoparietal “multiple-demand” (MD) brain network is recruited during a wide range of cognitively demanding tasks. Because this suggests a fundamental function, one might expect a similar

  19. High beta plasmas in the PBX tokamak

    SciTech Connect

    Bol, K.; Buchenauer, D.; Chance, M.; Couture, P.; Fishman, H.; Fonck, R.; Gammel, G.; Grek, B.; Ida, K.; Itami, K.

    1986-04-01

    Bean-shaped configurations favorable for high ..beta.. discharges have been investigated in the Princeton Beta Experiment (PBX) tokamak. Strongly indented bean-shaped plasmas have been successfully formed, and beta values of over 5% have been obtained with 5 MW of injected neutral beam power. These high beta discharges still lie in the first stability regime for ballooning modes, and MHD stability analysis implicates the external kink as responsible for the present ..beta.. limit.

  20. Rapid Discrimination Among Putative Mechanistic Models of Biochemical Systems

    PubMed Central

    Lomnitz, Jason G.; Savageau, Michael A.

    2016-01-01

    An overarching goal in molecular biology is to gain an understanding of the mechanistic basis underlying biochemical systems. Success is critical if we are to predict effectively the outcome of drug treatments and the development of abnormal phenotypes. However, data from most experimental studies is typically noisy and sparse. This allows multiple potential mechanisms to account for experimental observations, and often devising experiments to test each is not feasible. Here, we introduce a novel strategy that discriminates among putative models based on their repertoire of qualitatively distinct phenotypes, without relying on knowledge of specific values for rate constants and binding constants. As an illustration, we apply this strategy to two synthetic gene circuits exhibiting anomalous behaviors. Our results show that the conventional models, based on their well-characterized components, cannot account for the experimental observations. We examine a total of 40 alternative hypotheses and show that only 5 have the potential to reproduce the experimental data, and one can do so with biologically relevant parameter values. PMID:27578053

  1. The inducible CAM plants in putative lunar lander experiments

    NASA Astrophysics Data System (ADS)

    Burlak, Olexii; Zaetz, Iryna; Soldatkin, Olexii; Rogutskyy, Ivan; Danilchenko, Boris; Mikheev, Olexander; de Vera, Jean-Pierre; Vidmachenko, Anatolii; Foing, Bernard H.; Kozyrovska, Natalia

    Precursory lunar lander experiments on growing plants in locker-based chambers will increase our understanding of effect of lunar conditions on plant physiology. The inducible CAM (Cras-sulacean Acid Metabolism)-plants are reasonable model for a study of relationships between environmental challenges and changes in plant/bacteria gene expression. In inducible CAM-plants the enzymatic machinery for the environmentally activated CAM switches on from a C3-to a full-CAM mode of photosynthesis in response to any stresses (Winter et al., 2008). In our study, Kalanchoe spp. are shown to be promising candidates for putative lunar experiments as resistant to irradiation and desiccation, especially after inoculation with a bacterial consortium (Boorlak et al., 2010). Within frames of the experiment we expect to get information about the functional activity of CAM-plants, in particular, its organogenesis, photosystem, the circadian regulation of plant metabolism on the base of data gaining with instrumental indications from expression of the reporter genes fused to any genes involved in vital functions of the plant (Kozyrovska et al., 2009). References 1. Winter K., Garcia M., Holtum J. (2008) J. Exp. Bot. 59(7):1829-1840 2. Bourlak O., Lar O., Rogutskyy I., Mikheev A., Zaets I., Chervatyuk N., de Vera J.-P., Danilchenko A.B. Foing B.H., zyrovska N. (2010) Space Sci. Technol. 3. Kozyrovska N.O., Vidmachenko A.P., Foing B.H. et al. Exploration/call/estec/ESA. 2009.

  2. Flamingo cadherin: a putative host receptor for Streptococcus pneumoniae.

    PubMed

    Blau, Karin; Portnoi, Maxim; Shagan, Marilou; Kaganovich, Antonina; Rom, Slava; Kafka, Daniel; Chalifa Caspi, Vered; Porgador, Angel; Givon-Lavi, Noga; Gershoni, Jonathan M; Dagan, Ron; Mizrachi Nebenzahl, Yaffa

    2007-06-15

    Streptococcus pneumoniae fructose bisphosphate aldolase (FBA) is a cell wall-localized lectin. We demonstrate that recombinant (r) FBA and anti-rFBA antibodies inhibit encapsulated and unencapsulated S. pneumoniae serotype 3 adherence to A549 type II lung carcinoma epithelial cells. A random combinatorial peptide library expressed by filamentous phage was screened with rFBA. Eleven of 30 rFBA-binding phages inhibited 90% of S. pneumoniae adhesion to A549 cells. The insert peptide sequence of 9 of these phages matched the Flamingo cadherin receptor (FCR) when aligned against the human genome. A peptide comprising a putative FBA-binding region of FCR (FCRP) inhibited 2 genetically and capsularly unrelated pairs of encapsulated and unencapsulated S. pneumoniae strains from binding to A549 cells. Moreover, FCRP inhibited S. pneumoniae nasopharyngeal and lung colonization and, possibly, pneumonia development in the mouse intranasal inoculation model system. These data indicate that FBA is an S. pneumoniae adhesin and that FCR is its host receptor. PMID:17492599

  3. Formation of putative chloroplast cytochromes in isolated developing pea chloroplasts

    SciTech Connect

    Thaver, S.S.; Bhava, D.; Castelfranco, P.A.

    1986-04-01

    In addition to chlorophyll-protein complexes, other proteins were labeled when isolated developing pea chloroplasts were incubated with (/sup 14/C)-5-aminolevulinic acid (/sup 14/C)-ALA. The major labeled band (M/sub r/ = 43 kDa by LDS-PAGE) was labeled even in the presence of chloramphenicol. Heme-dependent peroxidase activity (as detected by the tetramethyl benzidine-H/sub 2/O/sub 2/ stain) was not visibly associated with this band. The radioactive band was stable to heat, 5% HCl in acetone, and was absent if the incubation with (/sup 14/C)-5-aminolevulinic acid was carried out in the presence of N-methyl protoporphyrin IX dimethyl ester (a specific inhibitor of ferrochelatase). Organic solvent extraction procedures for the enrichment of cytochrome f from chloroplast membranes also extracted this unknown labeled product. It was concluded that this labeled product was probably a c-type cytochrome. The effect of exogenous iron, iron chelators, gabaculine (an inhibitor of ALA synthesis) and other incubation conditions upon the in vitro formation of putative chloroplast cytochromes will be discussed.

  4. Ameloblastin as a putative marker of specific bone compartments.

    PubMed

    Jacques, Jaime; Hotton, Dominique; Asselin, Audrey; De la Dure-Molla, Muriel; Coudert, Amélie E; Isaac, Juliane; Berdal, Ariane

    2014-08-01

    Ameloblastin (AMBN), a member of the enamel matrix protein family, has been recently identified as integral part of the skeleton beyond the enamel. However, the specific role of endogenous AMBN in bone tissue is not fully elucidated. This study aims at investigating mRNA expression of AMBN in wild-type mice in different bone sites from early embryonic to adult stages. AMBN mRNA expression started at pre-dental stages in mouse embryos (E10.5) in both head and body parts. Using laser capture microdissection on 3-day-old mice, we showed an unambiguous mRNA expression of AMBN in extra-dental tissue (mandible bone). Screening of AMBN mRNA expression in adult mice (15-week-old) revealed that mRNA expression of AMBN varied according to the bone site; a higher mRNA levels in mandibular and frontal bone compartments were observed when compared to tibia and occipital bones. These results strongly suggest that AMBN expression may be regulated in a site-specific manner and identify AMBN as a putative in vivo marker of the site-specific fingerprint of bone organs. PMID:25158194

  5. Hematopoietic activity in putative mouse primordial germ cell populations.

    PubMed

    Scaldaferri, Maria Lucia; Klinger, Francesca Gioia; Farini, Donatella; Di Carlo, Anna; Carsetti, Rita; Giorda, Ezio; De Felici, Massimo

    2015-05-01

    In the present paper, starting from the observation of heterogeneous expression of the GOF-18ΔPE-GFP Pou5f1 (Oct3/4) transgene in putative mouse PGC populations settled in the aorta-gonad-mesonephros (AGM) region, we identified various OCT3/4 positive populations showing distinct expression of PGC markers (BLIMP-1, AP, TG-1, STELLA) and co-expressing several proteins (CD-34, CD-41, FLK-1) and genes (Brachyury, Hox-B4, Scl/Tal-1 and Gata-2) of hematopoietic precursors. Moreover, we found that Oct3/4-GFP(weak) CD-34(weak/high) cells possess robust hematopoietic colony forming activity (CFU) in vitro. These data indicate that the cell population usually considered PGCs moving toward the gonadal ridges encompasses a subset of cells co-expressing several germ cell and hematopoietic markers and possessing hematopoietic activity. These results are discussed within of the current model of germline segregation. PMID:25684074

  6. Putative BRAF activating fusion in a medullary thyroid cancer

    PubMed Central

    Kasaian, Katayoon; Wiseman, Sam M.; Walker, Blair A.; Schein, Jacqueline E.; Hirst, Martin; Moore, Richard A.; Mungall, Andrew J.; Marra, Marco A.; Jones, Steven J.M.

    2016-01-01

    Medullary thyroid cancer (MTC) is a malignancy of the calcitonin-producing parafollicular cells of the thyroid gland. Surgery is the only curative treatment for this cancer. External beam radiation therapy is reserved for adjuvant treatment of MTC with aggressive features. Targeted therapeutics vandetanib and cabozantinib are approved for the treatment of aggressive and metastatic tumors that are not amenable to surgery. The use of these multikinase inhibitors are supported by the observed overactivation of the RET oncoprotein in a large subpopulation of MTCs. However, not all patients carry oncogenic alterations of this kinase. Hence, there is still a need for comprehensive molecular characterization of MTC utilizing whole-genome and transcriptome-sequencing methodologies with the aim of identifying targetable mutations. Here, we describe the genomic profiles of two medullary thyroid cancers and report the presence of a putative oncogenic BRAF fusion in one. Such alterations, previously observed in other malignancies and known targets of available drugs, can benefit patients who currently have no treatment options. PMID:27148585

  7. Inhalation of two putative Gulf War toxins by mice.

    PubMed

    Repine, John E; Wilson, Paul; Elkins, Nancy; Klawitter, Jelena; Christians, Uwe; Peters, Ben; Smith, Dwight M

    2016-06-01

    We employed our inhalation methodology to examine whether biomarkers of inflammation and oxidative stress would be produced in mice following inhalation of aerosols containing carbonaceous particles or the vapor of pesticides prevalent during the first Gulf War. Exposure to two putative Gulf War Illness toxins, fine airborne particles and the pesticide malathion, increased biomarkers of inflammation and oxidative stress in Friend virus B (FVB) female mice. Mice inhaling particles 24 h before had increased lung lavage and plasma Leukotriene B4 (LTB4) (a biomarker of inflammation) and PGF2α (a biomarker of oxidative stress) levels, lung lavage protein and lung lavage lactic dehydrogenase (LDH) levels. These changes were a function of particle density and exposure time. Compared to particle inhalation, mice inhaling malathion 24 h before had small increase in plasma LTB4 and PGF2α levels but no increase in lung lavage LTB4, lung lavage protein, lung lavage LDH, and lung lavage alveolar macrophage (AM) levels compared to unexposed control mice. AM from particle-exposed mice contained phagocytosed particles, while AM from malathion-exposed mice showed no abnormalities. Our results indicate that inhaling particles or malathion can alter inflammatory and oxidative biomarkers in mice and raise the possibility that these toxins may have altered inflammation and oxidative stress biomarkers in Gulf War-exposed individuals. PMID:26950528

  8. Putative BRAF activating fusion in a medullary thyroid cancer.

    PubMed

    Kasaian, Katayoon; Wiseman, Sam M; Walker, Blair A; Schein, Jacqueline E; Hirst, Martin; Moore, Richard A; Mungall, Andrew J; Marra, Marco A; Jones, Steven J M

    2016-03-01

    Medullary thyroid cancer (MTC) is a malignancy of the calcitonin-producing parafollicular cells of the thyroid gland. Surgery is the only curative treatment for this cancer. External beam radiation therapy is reserved for adjuvant treatment of MTC with aggressive features. Targeted therapeutics vandetanib and cabozantinib are approved for the treatment of aggressive and metastatic tumors that are not amenable to surgery. The use of these multikinase inhibitors are supported by the observed overactivation of the RET oncoprotein in a large subpopulation of MTCs. However, not all patients carry oncogenic alterations of this kinase. Hence, there is still a need for comprehensive molecular characterization of MTC utilizing whole-genome and transcriptome-sequencing methodologies with the aim of identifying targetable mutations. Here, we describe the genomic profiles of two medullary thyroid cancers and report the presence of a putative oncogenic BRAF fusion in one. Such alterations, previously observed in other malignancies and known targets of available drugs, can benefit patients who currently have no treatment options. PMID:27148585

  9. Phytophthora infestans specific phosphorylation patterns and new putative control targets.

    PubMed

    Frades, Itziar; Andreasson, Erik

    2016-04-01

    In this study we applied biomathematical searches of gene regulatory mechanisms to learn more about oomycete biology and to identify new putative targets for pesticides or biological control against Phytophthora infestans. First, oomycete phylum-specific phosphorylation motifs were found by discriminative n-gram analysis. We found 11.600 P. infestans specific n-grams, mapping 642 phosphoproteins. The most abundant group among these related to phosphatidylinositol metabolism. Due to the large number of possible targets found and our hypothesis that multi-level control is a sign of usefulness as targets for intervention, we identified overlapping targets with a second screen. This was performed to identify proteins dually regulated by small RNA and phosphorylation. We found 164 proteins to be regulated by both sRNA and phosphorylation and the dominating functions where phosphatidylinositol signalling/metabolism, endocytosis, and autophagy. Furthermore we performed a similar regulatory study and discriminative n-gram analysis of proteins with no clear orthologs in other species and proteins that are known to be unique to P. infestans such as the RxLR effectors, Crinkler (CRN) proteins and elicitins. We identified CRN proteins with specific phospho-motifs present in all life stages. PITG_12626, PITG_14042 and PITG_23175 are CRN proteins that have species-specific phosphorylation motifs and are subject to dual regulation. PMID:27020162

  10. Crystal Structure of a Putative Lysostaphin Peptidase from Vibrio cholerae

    SciTech Connect

    Ragumani, S.; Kumaran, D; Burley, S; Swaminathan, S

    2008-01-01

    Peptidoglycan (PGN) constitutes the cell walls of virtually all bacteria, making it a target of the innate immune system. PGN is a polymer of alternating {Beta} (1{yields}4) linked N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), crossbridged by oligopeptide stems. Lysotaphin type enzymes are believed to cleave the glycl-glycine and glycyl-alanine bonds that occur in glycine-rich cross-bridges. Lysostaphins represent potential anti staphylococcal agents. Specifically, they can eradicate S.aureus nasal colonization in the rat model and are effective in treating methicillin-resistant S. aureus endophthalmitis in rabbits. These enzymes belong to the metalloendopeptidase family and possess a conserved HXH active site motif.

  11. Dissecting Wnt/beta-catenin signaling during gastrulation using RNA interference in mouse embryos.

    PubMed

    Lickert, Heiko; Cox, Brian; Wehrle, Christian; Taketo, Makoto M; Kemler, Rolf; Rossant, Janet

    2005-06-01

    Differential gene regulation integrated in time and space drives developmental programs during embryogenesis. To understand how the program of gastrulation is regulated by Wnt/beta-catenin signaling, we have used genome-wide expression profiling of conditional beta-catenin mutant embryos. Known Wnt/beta-catenin target genes, known components of other signaling pathways, as well as a number of uncharacterized genes were downregulated in these mutants. To further narrow down the set of differentially expressed genes, we used whole-mount in situ screening to associate gene expression with putative domains of Wnt activity. Several potential novel target genes were identified by this means and two, Grsf1 and Fragilis2, were functionally analyzed by RNA interference (RNAi) in completely embryonic stem (ES) cell-derived embryos. We show that the gene encoding the RNA-binding factor Grsf1 is important for axial elongation, mid/hindbrain development and axial mesoderm specification, and that Fragilis2, encoding a transmembrane protein, regulates epithelialization of the somites and paraxial mesoderm formation. Intriguingly, the knock-down phenotypes recapitulate several aspects of Wnt pathway mutants, suggesting that these genes are components of the downstream Wnt response. This functional genomic approach allows the rapid identification of functionally important components of embryonic development from large datasets of putative targets. PMID:15857914

  12. Putative mechanisms mediating tolerance for audiovisual stimulus onset asynchrony.

    PubMed

    Bhat, Jyoti; Miller, Lee M; Pitt, Mark A; Shahin, Antoine J

    2015-03-01

    Audiovisual (AV) speech perception is robust to temporal asynchronies between visual and auditory stimuli. We investigated the neural mechanisms that facilitate tolerance for audiovisual stimulus onset asynchrony (AVOA) with EEG. Individuals were presented with AV words that were asynchronous in onsets of voice and mouth movement and judged whether they were synchronous or not. Behaviorally, individuals tolerated (perceived as synchronous) longer AVOAs when mouth movement preceded the speech (V-A) stimuli than when the speech preceded mouth movement (A-V). Neurophysiologically, the P1-N1-P2 auditory evoked potentials (AEPs), time-locked to sound onsets and known to arise in and surrounding the primary auditory cortex (PAC), were smaller for the in-sync than the out-of-sync percepts. Spectral power of oscillatory activity in the beta band (14-30 Hz) following the AEPs was larger during the in-sync than out-of-sync perception for both A-V and V-A conditions. However, alpha power (8-14 Hz), also following AEPs, was larger for the in-sync than out-of-sync percepts only in the V-A condition. These results demonstrate that AVOA tolerance is enhanced by inhibiting low-level auditory activity (e.g., AEPs representing generators in and surrounding PAC) that code for acoustic onsets. By reducing sensitivity to acoustic onsets, visual-to-auditory onset mapping is weakened, allowing for greater AVOA tolerance. In contrast, beta and alpha results suggest the involvement of higher-level neural processes that may code for language cues (phonetic, lexical), selective attention, and binding of AV percepts, allowing for wider neural windows of temporal integration, i.e., greater AVOA tolerance. PMID:25505102

  13. Putative Risk Factors in Developmental Dyslexia: A Case-Control Study of Italian Children

    ERIC Educational Resources Information Center

    Mascheretti, Sara; Marino, Cecilia; Simone, Daniela; Quadrelli, Ermanno; Riva, Valentina; Cellino, Maria Rosaria; Maziade, Michel; Brombin, Chiara; Battaglia, Marco

    2015-01-01

    Although dyslexia runs in families, several putative risk factors that cannot be immediately identified as genetic predict reading disability. Published studies analyzed one or a few risk factors at a time, with relatively inconsistent results. To assess the contribution of several putative risk factors to the development of dyslexia, we conducted…

  14. Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug.

    PubMed

    Lapin, I

    2001-01-01

    Phenibut (beta-phenyl-gamma-aminobutyric acid HCl) is a neuropsychotropic drug that was discovered and introduced into clinical practice in Russia in the 1960s. It has anxiolytic and nootropic (cognition enhancing) effects. It acts as a GABA-mimetic, primarily at GABA(B) and, to some extent, at GABA(A) receptors. It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA), a putative endogenous anxiogenic. The psychopharmacological activity of phenibut is similar to that of baclofen, a p-Cl-derivative of phenibut. This article reviews the structure-activity relationship of phenibut and its derivatives. Emphasis is placed on the importance of the position of the phenyl ring, the role of the carboxyl group, and the activity of optical isomers. Comparison of phenibut with piracetam and diazepam reveals similarities and differences in their pharmacological and clinical effects. Phenibut is widely used in Russia to relieve tension, anxiety, and fear, to improve sleep in psychosomatic or neurotic patients; as well as a pre- or post-operative medication. It is also used in the therapy of disorders characterized by asthenia and depression, as well as in post-traumatic stress, stuttering and vestibular disorders. PMID:11830761

  15. Structure and mapping of the human thymopoietin (TMPO) gene and relationship of human TMPO {beta} to rat lamin-associated polypeptide 2

    SciTech Connect

    Harris, C.A.; Andryuk, P.J.; Cline, S.W.; Seikierka, J.J.; Goldstein, G.

    1995-07-20

    Thymopoietins (TMPOs, previously abbreviated TPs) {alpha}(75kDa), {beta}(51 kDa), and {gamma}(39 kDa) are related nuclear proteins expressed in many or all tissues. TMPO {alpha} is present diffusely throughout the nucleus, while TMPOs {beta} and {gamma} are localized to the nuclear membrane. Here we report the cloning and analysis of a single TMPO gene encoding TMPOs {alpha}, {beta}, and {gamma}, which are produced by alternative mRNA splicing, as previously inferred from cDNA sequences. The eight exons of the TMPO gene are spread over {approximately}35 kb. Exon 4, which is spliced into TMPS {alpha} mRNA, contains sequences that encode a putative basic nuclear localization motif. Exon 8, which is spliced into TMPO {beta} and {gamma} mRNAs, encodes a hydrophobic putative membrane-spanning domain that is thought to target TMPOs {beta} and {gamma} to the nuclear membrane. TMPO {Beta} appears to be the human homologue of the recently described rat protein LAP2 (lamina-associated polypeptide 2), which is thought to play an important role in the regulation of nuclear architecture by binding lamin B1 and chromosomes in a manner regulated by phosphorylation during mitosis. The human TMPO gene maps to chromosome band 12q22. 28 refs., 6 figs., 1 tab.

  16. Identification of Putative Natriuretic Hormones Isolated from Human Urine

    PubMed Central

    Kramer, Herbert J.

    2015-01-01

    This brief review describes some representative methodological approaches to the isolation of putative endogenous inhibitors of epithelial sodium transport – i.e., as ouabain-like factors (OLF) that inhibit the sodium transport enzyme Na-K-ATPase or inhibit the epithelial sodium channel (ENaC). Gel chromatography and reverse-phase (RP)-high performance liquid chromatography (HPLC) of lyophilized and reconstituted 24 h-urine from salt-loaded healthy humans led to two active fractions, a hydrophilic OLF-1 and a lipophilic OLF-2, whose mass (Ms)-spectroscopic data indicate a Mr of 391 (1, 2). Further identification was attempted by Ms-, infrared (IR)-, ultraviolet (UV)-, and 1H-NMR-spectroscopy. OLF-1 and OLF-2 may be closely related if not identical to (di)ascorbic acid or its salts such as vanadium (V)-Vv-diascorbate with Mr 403 (3) and VIV-diascorbate. OLF-1 and Vv-diascorbate are about 10-fold stronger inhibitors of Na-K-ATPase than OLF-2 and VIV-diascorbate, respectively. In conscious rats, i.v. infusion of OLF-1 and OLF-2 resulted in a strong natriuresis. In a similar study, Cain et al. (4) isolated a sodium transport inhibitor from the urine of uremic patients by gel chromatography and RP-HPLC. In uremic rats, a natriuretic response to the injection of the active material was found. Xanthurenic acid 8-O-β-d-glucoside (Mr 368) and xanthurenic acid 8-O-sulfate (Mr 284) were identified as endogenous inhibitors of sodium transport acting, e.g., by ENaC blockade. No definite relation to blood pressure, body fluid volume, or sodium balance has been reported for any of these above factors, and further studies to identify the natriuretic and/or ouabain-like compound(s) or hormone(s) will be needed. PMID:26052310

  17. Credibility Analysis of Putative Disease-Causing Genes Using Bioinformatics

    PubMed Central

    Abel, Olubunmi; Powell, John F.; Andersen, Peter M.; Al-Chalabi, Ammar

    2013-01-01

    Background Genetic studies are challenging in many complex diseases, particularly those with limited diagnostic certainty, low prevalence or of old age. The result is that genes may be reported as disease-causing with varying levels of evidence, and in some cases, the data may be so limited as to be indistinguishable from chance findings. When there are large numbers of such genes, an objective method for ranking the evidence is useful. Using the neurodegenerative and complex disease amyotrophic lateral sclerosis (ALS) as a model, and the disease-specific database ALSoD, the objective is to develop a method using publicly available data to generate a credibility score for putative disease-causing genes. Methods Genes with at least one publication suggesting involvement in adult onset familial ALS were collated following an exhaustive literature search. SQL was used to generate a score by extracting information from the publications and combined with a pathogenicity analysis using bioinformatics tools. The resulting score allowed us to rank genes in order of credibility. To validate the method, we compared the objective ranking with a rank generated by ALS genetics experts. Spearman's Rho was used to compare rankings generated by the different methods. Results The automated method ranked ALS genes in the following order: SOD1, TARDBP, FUS, ANG, SPG11, NEFH, OPTN, ALS2, SETX, FIG4, VAPB, DCTN1, TAF15, VCP, DAO. This compared very well to the ranking of ALS genetics experts, with Spearman's Rho of 0.69 (P = 0.009). Conclusion We have presented an automated method for scoring the level of evidence for a gene being disease-causing. In developing the method we have used the model disease ALS, but it could equally be applied to any disease in which there is genotypic uncertainty. PMID:23755159

  18. NMDA antagonist properties of the putative antiaddictive drug, ibogaine.

    PubMed

    Popik, P; Layer, R T; Fossom, L H; Benveniste, M; Geter-Douglass, B; Witkin, J M; Skolnick, P

    1995-11-01

    Both anecdotal reports in humans and preclinical studies indicate that ibogaine interrupts addiction to a variety of abused substances including alcohol, opiates, nicotine and stimulants. Based on the similarity of these therapeutic claims to recent preclinical studies demonstrating that N-methyl-D-aspartate (NMDA) antagonists attenuate addiction-related phenomena, we examined the NMDA antagonist properties of ibogaine. Pharmacologically relevant concentrations of ibogaine produce a voltage-dependent block of NMDA receptors in hippocampal cultures (Ki, 2.3 microM at -60 mV). Consistent with this observation, ibogaine competitively inhibits [3H]1-[1-(2-thienyl)-cyclohexyl]piperidine binding to rat forebrain homogenates (Ki, 1.5 microM) and blocks glutamate-induced cell death in neuronal cultures (IC50, 4.5 microM). Moreover, at doses previously reported to interfere with drug-seeking behaviors, ibogaine substitutes as a discriminative stimulus (ED50, 64.9 mg/kg) in mice trained to discriminate the prototypic voltage-dependent NMDA antagonist, dizocilpine (0.17 mg/kg), from saline. Consistent with previous reports, ibogaine reduced naloxone-precipitated jumping in morphine-dependent mice (ED50, 72 mg/kg). Although pretreatment with glycine did not affect naloxone-precipitated jumping in morphine-dependent mice, it abolished the ability of ibogaine to block naloxone-precipitated jumping. Taken together, these findings link the NMDA antagonist actions of ibogaine to a putative "antiaddictive" property of this alkaloid, its ability to reduce the expression of morphine dependence. PMID:7473163

  19. Molecular diagnosis of putative Stargardt disease probands by exome sequencing

    PubMed Central

    2012-01-01

    Background The commonest genetic form of juvenile or early adult onset macular degeneration is Stargardt Disease (STGD) caused by recessive mutations in the gene ABCA4. However, high phenotypic and allelic heterogeneity and a small but non-trivial amount of locus heterogeneity currently impede conclusive molecular diagnosis in a significant proportion of cases. Methods We performed whole exome sequencing (WES) of nine putative Stargardt Disease probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Follow-up dideoxy sequencing was performed for confirmation and to screen for mutations in an additional set of affected individuals lacking a definitive molecular diagnosis. Results Whole exome sequencing revealed seven likely disease-causing variants across four genes, providing a confident genetic diagnosis in six previously uncharacterized participants. We identified four previously missed mutations in ABCA4 across three individuals. Likely disease-causing mutations in RDS/PRPH2, ELOVL, and CRB1 were also identified. Conclusions Our findings highlight the enormous potential of whole exome sequencing in Stargardt Disease molecular diagnosis and research. WES adequately assayed all coding sequences and canonical splice sites of ABCA4 in this study. Additionally, WES enables the identification of disease-related alleles in other genes. This work highlights the importance of collecting parental genetic material for WES testing as the current knowledge of human genome variation limits the determination of causality between identified variants and disease. While larger sample sizes are required to establish the precision and accuracy of this type of testing, this study supports WES for inherited early onset macular degeneration disorders as an alternative to standard mutation screening techniques. PMID:22863181

  20. SUT2, a Putative Sucrose Sensor in Sieve Elements

    PubMed Central

    Barker, Laurence; Kühn, Christina; Weise, Andreas; Schulz, Alexander; Gebhardt, Christiane; Hirner, Brigitte; Hellmann, Hanjo; Schulze, Waltraud; Ward, John M.; Frommer, Wolf B.

    2000-01-01

    In leaves, sucrose uptake kinetics involve high- and low-affinity components. A family of low- and high-affinity sucrose transporters (SUT) was identified. SUT1 serves as a high-affinity transporter essential for phloem loading and long-distance transport in solanaceous species. SUT4 is a low-affinity transporter with an expression pattern overlapping that of SUT1. Both SUT1 and SUT4 localize to enucleate sieve elements of tomato. New sucrose transporter–like proteins, named SUT2, from tomato and Arabidopsis contain extended cytoplasmic domains, thus structurally resembling the yeast sugar sensors SNF3 and RGT2. Features common to these sensors are low codon bias, environment of the start codon, low expression, and lack of detectable transport activity. In contrast to LeSUT1, which is induced during the sink-to-source transition of leaves, SUT2 is more highly expressed in sink than in source leaves and is inducible by sucrose. LeSUT2 protein colocalizes with the low- and high-affinity sucrose transporters in sieve elements of tomato petioles, indicating that multiple SUT mRNAs or proteins travel from companion cells to enucleate sieve elements. The SUT2 gene maps on chromosome V of potato and is linked to a major quantitative trait locus for tuber starch content and yield. Thus, the putative sugar sensor identified colocalizes with two other sucrose transporters, differs from them in kinetic properties, and potentially regulates the relative activity of low- and high-affinity sucrose transport into sieve elements. PMID:10899981

  1. Identification of Putative Natriuretic Hormones Isolated from Human Urine.

    PubMed

    Kramer, Herbert J

    2015-01-01

    This brief review describes some representative methodological approaches to the isolation of putative endogenous inhibitors of epithelial sodium transport - i.e., as ouabain-like factors (OLF) that inhibit the sodium transport enzyme Na-K-ATPase or inhibit the epithelial sodium channel (ENaC). Gel chromatography and reverse-phase (RP)-high performance liquid chromatography (HPLC) of lyophilized and reconstituted 24 h-urine from salt-loaded healthy humans led to two active fractions, a hydrophilic OLF-1 and a lipophilic OLF-2, whose mass (Ms)-spectroscopic data indicate a Mr of 391 (1, 2). Further identification was attempted by Ms-, infrared (IR)-, ultraviolet (UV)-, and (1)H-NMR-spectroscopy. OLF-1 and OLF-2 may be closely related if not identical to (di)ascorbic acid or its salts such as vanadium (V)-V(v)-diascorbate with Mr 403 (3) and V(IV)-diascorbate. OLF-1 and V(v)-diascorbate are about 10-fold stronger inhibitors of Na-K-ATPase than OLF-2 and V(IV)-diascorbate, respectively. In conscious rats, i.v. infusion of OLF-1 and OLF-2 resulted in a strong natriuresis. In a similar study, Cain et al. (4) isolated a sodium transport inhibitor from the urine of uremic patients by gel chromatography and RP-HPLC. In uremic rats, a natriuretic response to the injection of the active material was found. Xanthurenic acid 8-O-β-d-glucoside (Mr 368) and xanthurenic acid 8-O-sulfate (Mr 284) were identified as endogenous inhibitors of sodium transport acting, e.g., by ENaC blockade. No definite relation to blood pressure, body fluid volume, or sodium balance has been reported for any of these above factors, and further studies to identify the natriuretic and/or ouabain-like compound(s) or hormone(s) will be needed. PMID:26052310

  2. Localization of p24 putative cargo receptors in the early secretory pathway depends on the biosynthetic activity of the cell.

    PubMed Central

    Kuiper, R P; Bouw, G; Janssen, K P; Rötter, J; van Herp, F; Martens, G J

    2001-01-01

    Members of the p24 family of putative cargo receptors (subdivided into p24-alpha, -beta, -gamma and -delta) are localized in the intermediate-and cis-Golgi compartments of the early secretory pathway, and are thought to play an important role in protein transport. In the present study, we wondered what effect increased biosynthetic cell activity with resulting high levels of protein transport would have on the subcellular localization of p24. We examined p24 localization in Xenopus intermediate pituitary melanotrope cells, which in black- and white-adapted animals are biosynthetically highly active and virtually inactive respectively. In addition, p24 localization was studied in Xenopus anterior pituitary cells whose activity is not changed during background adaptation. Using organelle fractionation, we found that in the inactive melanotropes and moderately active anterior pituitary cells of white-adapted animals, the p24-alpha, -beta, -gamma and -delta proteins are all located in the Golgi compartment. In the highly active melanotropes, but not in the anterior cells of black-adapted animals, the steady-state distribution of all four p24 members changed towards the intermediate compartment and subdomains of the endoplasmic reticulum (ER), most probably the ER exit sites. In the active melanotropes, the major cargo protein pro-opiomelanocortin was mostly localized to ER subdomains and partially co-localized with the p24 proteins. Furthermore, in the active cells, in vitro blocking of protein biosynthesis by cycloheximide or dispersion of the Golgi complex by brefeldin A led to a redistribution of the p24 proteins, indicating their involvement in ER-to-Golgi protein transport and extensive cycling in the early secretory pathway. We conclude that the subcellular localization of p24 proteins is dynamic and depends on the biosynthetic activity of the cell. PMID:11716771

  3. Putative fasciclin-like arabinogalactan-proteins (FLA) in wheat (Triticum aestivum) and rice (Oryza sativa): identification and bioinformatic analyses.

    PubMed

    Faik, Ahmed; Abouzouhair, Jaouad; Sarhan, Fathey

    2006-11-01

    Putative plant adhesion molecules include arabinogalactan-proteins having fasciclin-like domains. In animal, fasciclin proteins participate in cell adhesion and communication. However, the molecular basis of interactions in plants is still unknown and none of these domains have been characterized in cereals. This work reports the characterization of 34 wheat (Triticum aestivum) and 24 rice (Oryza sativa) Fasciclin-Like Arabinogalactan-proteins (FLAs). Bioinformatics analyses show that cereal FLAs share structural characteristics with known Arabidopsis FLAs including arabinogalactan-protein and fasciclin conserved domains. At least 70% of the wheat and rice FLAs are predicted to be glycosylphosphatidylinositol-anchored to the plasma membranes. Expression analyses determined from the relative abundance of ESTs in the publicly available wheat EST databases and from RNA gel blots indicate that most of these genes are weakly expressed and found mainly in seeds and roots. Furthermore, most wheat genes were down regulated by abiotic stresses except for TaFLA9 and 12 where cold treatment induces their expression in roots. Plant fasciclin-like domains were predicted to have 3-D homology with FAS1 domain of the fasciclin I insect neural cell adhesion molecule with an estimated precision above 70%. The structural analysis shows that negatively charged amino acids are concentrated along the beta1-alpha3-alpha4-beta2 edges, while the positively charged amino acids are concentrated on the back side of the folds. This highly charged surface distribution could provide a way of mediating protein-protein interactions via electrostatic forces similar to many other adhesion molecules. The identification of wheat FLAs will facilitate studying their function in plant growth and development and their role in stress response. PMID:16944204

  4. Multilocus analysis using putative fungal effectors to describe a population of Fusarium oxysporum from Sugar Beet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sugar beet (Beta vulgaris L.) Fusarium yellows is caused by Fusarium oxysporum f. sp. betae and leads to significant reductions in root yield, sucrose percentage, juice purity, and storage for sugar beet producers. F. oxysporum f. sp. betae can be highly variable and many F. oxysporum isolated from...

  5. Interleukin-1beta induces hyperpolarization and modulates synaptic inhibition in preoptic and anterior hypothalamic neurons.

    PubMed

    Tabarean, I V; Korn, H; Bartfai, T

    2006-09-15

    Most of the inflammatory effects of the cytokine interleukin 1beta (IL-1beta) are mediated by induction of cyclooxygenase (COX)2 and the subsequent synthesis and release of prostaglandin E2. This transcription-dependent process takes 45-60 min, but IL-1beta, a well-characterized endogenous pyrogen also exerts faster neuronal actions in the preoptic area/anterior hypothalamus. Here, we have studied the fast (1-3 min) signaling by IL-1beta using whole-cell patch clamp recordings in preoptic area/anterior hypothalamus neurons. Exposure to IL-1beta (0.1-1 nM) hyperpolarized a subset ( approximately 20%) of preoptic area/anterior hypothalamus neurons, decreased their input resistance and reduced their firing rate. These effects were associated with an increased frequency of bicuculline-sensitive spontaneous inhibitory postsynaptic currents and putative miniature inhibitory postsynaptic currents, strongly suggesting a presynaptic mechanism of action. These effects require the type 1 interleukin 1 receptor (IL-1R1), and the adapter protein myeloid differentiation primary response protein (MyD88), since they were not observed in cultures obtained from IL-1R1 (-/-) or from MyD88 (-/-) mice. Ceramide, a second messenger of the IL-1R1-dependent fast signaling cascade, is produced by IL-1R1-MyD88-mediated activation of the neutral sphingomyelinase. C2-ceramide, its cell penetrating analog, also increased the frequency of miniature inhibitory postsynaptic currents in a subset of cells. Both IL-1beta and ceramide reduced the delayed rectifier and the A-type K(+) currents in preoptic area/anterior hypothalamus neurons. The latter effect may account in part for the increased spontaneous inhibitory postsynaptic current frequency as suggested by experiments with the A-type K(+) channel blockers 4-aminopyridine. Taken together our data suggest that IL-1beta inhibits the activity of preoptic area/anterior hypothalamus neurons by increasing the presynaptic release of GABA. PMID

  6. Mechanism of inactivation of alanine racemase by beta, beta, beta-trifluoroalanine

    SciTech Connect

    Faraci, W.S.; Walsh, C.T.

    1989-01-24

    The alanine racemases are a group of PLP-dependent bacterial enzymes that catalyze the racemization of alanine, providing D-alanine for cell wall synthesis. Inactivation of the alanine racemases from the Gram-negative organism Salmonella typhimurium and Gram-positive organism Bacillus stearothermophilus with beta, beta, beta-trifluoroalanine has been studied. The inactivation occurs with the same rate constant as that for formation of a broad 460-490-nm chromophore. Loss of two fluoride ions per mole of inactivated enzyme and retention of (1-/sup 14/C)trifluoroalanine label accompany inhibition, suggesting a monofluoro enzyme adduct. Partial denaturation (1 M guanidine) leads to rapid return of the initial 420-nm chromophore, followed by a slower (t1/2 approximately 30 min-1 h) loss of the fluoride ion and /sup 14/CO/sub 2/ release. At this point, reduction by NaB/sub 3/H/sub 4/ and tryptic digestion yield a single radiolabeled peptide. Purification and sequencing of the peptide reveals that lysine-38 is covalently attached to the PLP cofactor. A mechanism for enzyme inactivation by trifluoroalanine is proposed and contrasted with earlier results on monohaloalanines, in which nucleophilic attack of released aminoacrylate on the PLP aldimine leads to enzyme inactivation. For trifluoroalanine inactivation, nucleophilic attack of lysine-38 on the electrophilic beta-difluoro-alpha, beta-unsaturated imine provides an alternative mode of inhibition for these enzymes.

  7. Interplanetary Lyman-beta emissions

    NASA Technical Reports Server (NTRS)

    Paresce, F.

    1973-01-01

    Derivation of the intensity of the diffuse hydrogen Lyman-beta glow at 1025 A which is due to resonance scattering of the solar H I 1025 A line by interstellar and interplanetary hydrogen. Two sources of neutral hydrogen are considered: the local interstellar medium interacting with the solar system, and the dust deionization of the H(+) component of the solar wind. It is shown that if the dust geometrical factor is less than or equal to five quintillionths per cm, observations of backscattered Lyman-beta radiation will provide a unique determination of the density and temperature of the local interstellar medium.

  8. Beta Adrenergic Receptors in Keratinocytes

    PubMed Central

    Sivamani, Raja K.; Lam, Susanne T.; Isseroff, R. Rivkah

    2007-01-01

    Synopsis Beta2 adrenergic receptors were identified in keratinocytes more than 30 years ago, but their function in the epidermis continues to be elucidated. Abnormalities in their expression, signaling pathway, or in the generation of endogenous catecholamine agonists by keratinocytes have been implicated in the pathogenesis of cutaneous diseases such as atopic dermatitis, vitiligo and psoriasis. New studies also indicate that the beta2AR also modulates keratinocyte migration, and thus can function to regulate wound re-epithelialization. This review focuses on the function of these receptors in keratinocytes and their contribution to cutaneous physiology and disease. PMID:17903623

  9. BETA-GAMMA PERSONNEL DOSIMETER

    DOEpatents

    Davis, D.M.; Gupton, E.D.; Hart, J.C.; Hull, A.P.

    1961-01-17

    A personnel dosimeter is offered which is sensitive to both gamma and soft beta radiations from all directions within a hemisphere. The device is in the shape of a small pill box which is worn on a worker-s wrist. The top and sides of the device are provided with 50 per cent void areas to give 50 per cent response to the beta rays and complete response to the gamma rays. The device is so constructed as to have a response which will approximate the dose received by the basal layer of the human epidermis.

  10. Sequence and expression of a halobacterial beta-galactosidase gene.

    PubMed

    Holmes, M L; Dyall-Smith, M L

    2000-04-01

    Studies of gene expression in haloarchaea have been greatly hindered by the lack of a convenient reporter gene. In a previous study, a beta-galactosidase from Haloferax alicantei was purified and several peptide sequences determined. The peptide sequences have now been used to clone the entire beta-galactosidase gene (designated bgaH) along with some flanking chromosomal DNA. The deduced amino acid sequence of BgaH was 665 amino acids (74 kDa) and showed greatest amino acid similarity to members of glycosyl hydrolase family 42 [classification of Henrissat, B., and Bairoch, A. (1993) New families in the classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem J 293: 781-788]. Within this family, BgaH was most similar (42-43% aa identity) to enzymes from extremely thermophilic bacteria such as Thermotoga and Thermus. Family 42 enzymes are only distantly related to the Sulfolobus LacS and Escherichia coli LacZ enzymes (families one and two respectively). Three open reading frames (ORFs) upstream of bgaH were readily identified by database searches as glucose-fructose oxidoreductase, 2-dehydro-3-deoxyphosphogluconate aldolase and 2-keto-3-deoxygluconate kinase, enzymes that are also involved in carbohydrate metabolism. Downstream of bgaH there was an ORF which contained a putative fibronectin III motif. The bgaH gene was engineered into a halobacterial plasmid vector and introduced into Haloferax volcanii, a widely used strain that lacks detectable beta-galactosidase activity. Transformants were shown to express the enzyme; colonies turned blue when sprayed with Xgal and enzyme activity could be easily quantitated using a standard ONPG assay. In an accompanying publication, Patenge et al. (2000) have demonstrated the utility of bgaH as a promoter reporter in Halobacterium salinarum. PMID:10760168

  11. Mind Operational Semantics and Brain Operational Architectonics: A Putative Correspondence

    PubMed Central

    Benedetti, Giulio; Marchetti, Giorgio; Fingelkurts, Alexander A; Fingelkurts, Andrew A

    2010-01-01

    ) of different complexity within OA’s theory: EOMC could correspond to simple OMs, correlators to complex OMs and the correlational network to a set of simple and complex OMs. Finally, a set of experiments is proposed to verify the putative correspondence between OS and OA and prove the existence of an integrated continuum between brain and mind. PMID:21113277

  12. Putative functions of extracellular matrix glycoproteins in secondary palate morphogenesis

    PubMed Central

    d'Amaro, Rocca; Scheidegger, Rolf; Blumer, Susan; Pazera, Pawel; Katsaros, Christos; Graf, Daniel; Chiquet, Matthias

    2012-01-01

    Cleft palate is a common birth defect in humans. Elevation and fusion of paired palatal shelves are coordinated by growth and transcription factors, and mutations in these can cause malformations. Among the effector genes for growth factor signaling are extracellular matrix (ECM) glycoproteins. These provide substrates for cell adhesion (e.g., fibronectin, tenascins), but also regulate growth factor availability (e.g., fibrillins). Cleft palate in Bmp7 null mouse embryos is caused by a delay in palatal shelf elevation. In contrast, palatal shelves of Tgf-β3 knockout mice elevate normally, but a cleft develops due to their failure to fuse. However, nothing is known about a possible functional interaction between specific ECM proteins and Tgf-β/Bmp family members in palatogenesis. To start addressing this question, we studied the mRNA and protein distribution of relevant ECM components during secondary palate development, and compared it to growth factor expression in wildtypewild type and mutant mice. We found that fibrillin-2 (but not fibrillin-1) mRNA appeared in the mesenchyme of elevated palatal shelves adjacent to the midline epithelial cells, which were positive for Tgf-β3 mRNA. Moreover, midline epithelial cells started expressing fibronectin upon contact of the two palatal shelves. These findings support the hypothesis that fibrillin-2 and fibronectin are involved in regulating the activity of Tgf-β3 at the fusing midline. In addition, we observed that tenascin-W (but not tenascin-C) was misexpressed in palatal shelves of Bmp7-deficient mouse embryos. In contrast to tenascin-C, tenascin-W secretion was strongly induced by Bmp7 in embryonic cranial fibroblasts in vitro. These results are consistent with a putative function for tenascin-W as a target of Bmp7 signaling during palate elevation. Our results indicate that distinct ECM proteins are important for morphogenesis of the secondary palate, both as downstream effectors and as regulators of Tgf

  13. Putative cryomagma interaction with aerosols deposit at Titan's surface

    NASA Astrophysics Data System (ADS)

    Coll, Patrice; Navarro-Gonzalez, Rafael; Raulin, Francois; Coscia, David; Ramirez, Sandra I.; Buch, Arnaud; Szopa, Cyril; Poch, Olivier; Cabane, Michel; Brassé, Coralie

    The largest moon of Saturn, Titan, is known for its dense, nitrogen-rich atmosphere. The organic aerosols which are produced in Titan’s atmosphere are of great astrobiological interest, particularly because of their potential evolution when they reach the surface and may interact with putative ammonia-water cryomagma [1]. In this context we have followed the evolution of alkaline pH hydrolysis (25wt% ammonia-water) of Titan aerosol analogues, that have been qualified as representative of Titan’s aerosols [2]. Indeed the first results obtained by the ACP experiment onboard Huygens probe revealed that the main products obtained after thermolysis of Titan’s collected aerosols, were ammonia (NH3) and hydrogen cyanide (HCN). Then performing a direct comparison of the volatiles produced after a thermal treatment done in conditions similar to the ones used by the ACP experiment, we may estimate that the tholins we used are relevant to chemical analogues of Titan’s aerosols, and to note free of oxygen. Taking into account recent studies proposing that the subsurface ocean may contain a lower fraction of ammonia (about 5wt% or less [3]), and assuming the presence of specific gas species [4, 5], in particular CO2 and H2S, trapped in likely internal ocean, we determine a new probable composition of the cryomagma which could potentially interact with deposited Titan’s aerosols. We then carried out different hydrolyses, taking into account this composition, and we established the influence of the hydrolysis temperature on the organic molecules production. References: [1] Mitri et al., 2008. Resurfacing of Titan by ammonia-water cryomagma. Icarus. 196, 216-224. [2] Coll et al. 2013, Can laboratory tholins mimic the chemistry producing Titan's aerosols? A review in light of ACP experimental results, Planetary and Space Science 77, 91-103. [3] Tobie et al. 2012. Titan’s Bulk Composition Constrained by Cassini-Huygens: implication for internal outgassing. The

  14. Putative functions of extracellular matrix glycoproteins in secondary palate morphogenesis.

    PubMed

    d'Amaro, Rocca; Scheidegger, Rolf; Blumer, Susan; Pazera, Pawel; Katsaros, Christos; Graf, Daniel; Chiquet, Matthias

    2012-01-01

    Cleft palate is a common birth defect in humans. Elevation and fusion of paired palatal shelves are coordinated by growth and transcription factors, and mutations in these can cause malformations. Among the effector genes for growth factor signaling are extracellular matrix (ECM) glycoproteins. These provide substrates for cell adhesion (e.g., fibronectin, tenascins), but also regulate growth factor availability (e.g., fibrillins). Cleft palate in Bmp7 null mouse embryos is caused by a delay in palatal shelf elevation. In contrast, palatal shelves of Tgf-β3 knockout mice elevate normally, but a cleft develops due to their failure to fuse. However, nothing is known about a possible functional interaction between specific ECM proteins and Tgf-β/Bmp family members in palatogenesis. To start addressing this question, we studied the mRNA and protein distribution of relevant ECM components during secondary palate development, and compared it to growth factor expression in wildtypewild type and mutant mice. We found that fibrillin-2 (but not fibrillin-1) mRNA appeared in the mesenchyme of elevated palatal shelves adjacent to the midline epithelial cells, which were positive for Tgf-β3 mRNA. Moreover, midline epithelial cells started expressing fibronectin upon contact of the two palatal shelves. These findings support the hypothesis that fibrillin-2 and fibronectin are involved in regulating the activity of Tgf-β3 at the fusing midline. In addition, we observed that tenascin-W (but not tenascin-C) was misexpressed in palatal shelves of Bmp7-deficient mouse embryos. In contrast to tenascin-C, tenascin-W secretion was strongly induced by Bmp7 in embryonic cranial fibroblasts in vitro. These results are consistent with a putative function for tenascin-W as a target of Bmp7 signaling during palate elevation. Our results indicate that distinct ECM proteins are important for morphogenesis of the secondary palate, both as downstream effectors and as regulators of Tgf

  15. X-ray diffraction analysis of scrapie prion: intermediate and folded structures in a peptide containing two putative alpha-helices.

    PubMed

    Inouye, H; Kirschner, D A

    1997-05-01

    Small proteinaceous infectious particles called prions cause certain neurodegenerative diseases in human and animals. Limited proteolysis of infectious scrapie prions PrP(Sc) yields an N-truncated polypeptide termed PrP 27-30, which encompasses residues 90 to 231 of PrP(Sc) and which assembles into 100 to 200 A wide amyloid rods. It has been hypothesized that the infectious prion is converted from its non-infectious cellular form (PrP(C)) by means of an alpha-helical to beta-sheet conformational change. Secondary structure analysis, computer modeling, and structural biophysics methods support this hypothesis. Residues 90 to 145 of PrP, which contain two putative alpha-helical domains H1 and H2, may be of particular relevance to the disease pathogenesis, as C-terminal truncation at residue 145 was found in a patient with an inherited prion disease. Moreover, our recent X-ray diffraction analysis suggests that the peptide consisting of these residues (designated SHa 90-145) closely models the amyloidogenic beta-sheet core of PrP. In the current study, we have analyzed in detail the X-ray diffraction patterns of SHa 90-145. Two samples were examined: one that was dehydrated under ambient conditions whilst in an external magnetic field (to induce fibril orientation), and another that was sealed after partial drying. The dried, magnetically oriented sample showed a cross-beta diffraction pattern in which the fiber axis (rotation axis) was parallel to the H-bonding direction of the beta-sheets. The major wide-angle peaks indicate the presence of approximately 40 A wide beta-crystallites, which constitute the protofilament. Each crystallite is composed of several orthogonal unit cells, normal to the fiber (a-axis) direction, having lattice constants a = 9.69 A, b = 6.54 A, and c = 18.06 A. Electron density maps were calculated by iterative Fourier synthesis using beta-silk as an initial phase model. The distribution of density indicated that there were two types of beta

  16. Caliber Schools. Caliber: Beta Academy

    ERIC Educational Resources Information Center

    EDUCAUSE, 2015

    2015-01-01

    Caliber: Beta Academy is reimagining education as we know it, with the belief that the innovations in its model will allow 100% of its students to graduate ready to attend and succeed in a competitive four-year college and beyond. The academic model of the school features personalized learning plans, blended learning for English and math,…

  17. Spectrometers for Beta Decay Electrons

    NASA Astrophysics Data System (ADS)

    Jiang, Yong; Hirshfield, Jay

    2015-04-01

    Inspired by the neutrino mass direct measurement experiment Project 8, precision spectrometers are proposed to simultaneously measure energy and momentum of beta-decay electrons produced in rare nuclear events with improved energy resolution. For detecting single beta decay electrons near the end-point from a gaseous source such as tritium, one type of spectrometer is proposed to utilize stimulated cyclotron resonance interaction of microwaves with electrons in a waveguide immersed in a magnetic mirror. In the external RF fields, on-resonance electrons will satisfy both the cyclotron resonance condition and waveguide dispersion relationship. By correlating the resonances at two waveguide modes, one can associate the frequencies with both the energy and longitudinal momentum of an on-resonance electron to account for the Doppler shifts. For detecting neutrino-less double-beta decay, another spectrometer is proposed with thin foil of double-beta-allowed material immersed in a magnetic field, and RF antenna array for detection of synchrotron radiation from electrons. It utilizes the correlation between the antenna signals including higher harmonics of radiation to reconstruct the total energy distribution.

  18. Neutron Beta Decay Studies with Nab

    SciTech Connect

    Baessler, S.; Alarcon, R.; Alonzi, L. P.; Balascuta, S.; Barron-Palos, L.; Bowman, James David; Bychkov, M. A.; Byrne, J.; Calarco, J; Chupp, T.; Cianciolo, T. V.; Crawford, C.; Frlez, E.; Gericke, M. T.; Glück, F.; Greene, G. L.; Grzywacz, R. K.; Gudkov, V.; Harrison, D.; Hersman, F. W.; Ito, T.; Makela, M.; Martin, J.; McGaughey, P. L.; McGovern, S.; Page, S.; Penttila, Seppo I; Pocanic, Dinko; Salas-Bacci, A.; Tompkins, Z.; Wagner, D.; Wilburn, W. S.; Young, A. R.

    2013-01-01

    Precision measurements in neutron beta decay serve to determine the coupling constants of beta decay and allow for several stringent tests of the standard model. This paper discusses the design and the expected performance of the Nab spectrometer.

  19. Antibacterial activity of recombinant murine beta interferon.

    PubMed Central

    Fujiki, T; Tanaka, A

    1988-01-01

    Recombinant murine beta interferon was protective and therapeutic for mice against Listeria monocytogenes infection in vivo. The recombinant murine beta interferon caused enhanced H2O2 release by macrophages in vivo, but not in vitro. PMID:3343048

  20. Neoclassical transport in high [beta] tokamaks

    SciTech Connect

    Cowley, S.C.

    1992-12-01

    Neoclassical, transport in high [beta] large aspect ratio tokamaks is calculated. The variational method introduced by Rosenbluth, et al., is used to calculate the full Onsager matrix in the banana regime. These results are part of a continuing study of the high [beta] large aspect ratio equilibria introduced in Cowley, et al. All the neoclassical coefficients are reduced from their nominal low [beta] values by a factor ([var epsilon]/q[sup 2][beta])[sup [1/2

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

    SciTech Connect

    Morant, Marc Dominique

    2014-04-29

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

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

    DOEpatents

    Morant, Marc Dominique

    2014-05-06

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

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

    DOEpatents

    Morant, Marc Dominique

    2014-05-06

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

  4. Genetics Home Reference: beta-ureidopropionase deficiency

    MedlinePlus

    ... eliminate beta-ureidopropionase enzyme activity. Loss of this enzyme function reduces the production of beta-aminoisobutyric acid and ... aminoisobutyric acid and beta-alanine may impair the function of these molecules in the ... in enzyme activity caused by a particular UPB1 gene mutation, ...

  5. Anionic ring-opening polymerization of beta-alkoxymethyl-substituted beta-lactones.

    PubMed

    Adamus, Grazyna; Kowalczuk, Marek

    2008-02-01

    We report on anionic ring-opening polymerization (ROP) of racemic beta-(methoxymethyl)-beta-propiolactone (MOMPL) and beta-(ethoxymethyl)-beta-propiolactone (EOMPL) initiated by supramolecular complex of potassium acetate and tetrabutylammonium acetate (Bu4N+ Ac) as well as by tetrabutylammonium hydroxide, respectively. Structure of the resulting polymers has been established at the molecular level by electrospray ionization multistage mass spectrometry (ESI-MS(n)) and has been confirmed by FT-IR, NMR, and GPC analyses. Similar behavior of MOMPL and EOMPL with respect to already-studied beta-alkyl-substituted beta-lactones, e.g., beta-butyrolactone (MPL), has been observed under the conditions of anionic ROP (including observed side reactions leading to unsaturated end groups) and the already-established mechanisms of anionic polymerization of beta-alkyl-substituted beta-lactones are extended on beta-alkoxymethyl-substituted ones. PMID:18179174

  6. Abundant Intergenic TAACTGA Direct Repeats and Putative Alternate RNA Polymerase β′ Subunits in Marine Beggiatoaceae Genomes: Possible Regulatory Roles and Origins

    PubMed Central

    MacGregor, Barbara J.

    2015-01-01

    The genome sequences of several giant marine sulfur-oxidizing bacteria present evidence of a possible post-transcriptional regulatory network that may have been transmitted to or from two distantly related bacteria lineages. The draft genome of a Cand. “Maribeggiatoa” filament from the Guaymas Basin (Gulf of California, Mexico) seafloor contains 169 sets of TAACTGA direct repeats and one indirect repeat, with two to six copies per set. Related heptamers are rarely or never found as direct repeats. TAACTGA direct repeats are also found in some other Beggiatoaceae, Thiocystis violascens, a range of Cyanobacteria, and five Bacteroidetes. This phylogenetic distribution suggests they may have been transmitted horizontally, but no mechanism is evident. There is no correlation between total TAACTGA occurrences and repeats per genome. In most species the repeat units are relatively short, but longer arrays of up to 43 copies are found in several Bacteroidetes and Cyanobacteria. The majority of TAACTGA repeats in the Cand. “Maribeggiatoa” Orange Guaymas (BOGUAY) genome are within several nucleotides upstream of a putative start codon, suggesting they may be binding sites for a post-transcriptional regulator. Candidates include members of the ribosomal protein S1, Csp (cold shock protein), and Csr (carbon storage regulator) families. No pattern was evident in the predicted functions of the open reading frames (ORFs) downstream of repeats, but some encode presumably essential products such as ribosomal proteins. Among these is an ORF encoding a possible alternate or modified RNA polymerase beta prime subunit, predicted to have the expected subunit interaction domains but lacking most catalytic residues. A similar ORF was found in the Thioploca ingrica draft genome, but in no others. In both species they are immediately upstream of putative sensor kinase genes with nearly identical domain structures. In the marine Beggiatoaceae, a role for the TAACTGA repeats in

  7. Abundant Intergenic TAACTGA Direct Repeats and Putative Alternate RNA Polymerase β' Subunits in Marine Beggiatoaceae Genomes: Possible Regulatory Roles and Origins.

    PubMed

    MacGregor, Barbara J

    2015-01-01

    The genome sequences of several giant marine sulfur-oxidizing bacteria present evidence of a possible post-transcriptional regulatory network that may have been transmitted to or from two distantly related bacteria lineages. The draft genome of a Cand. "Maribeggiatoa" filament from the Guaymas Basin (Gulf of California, Mexico) seafloor contains 169 sets of TAACTGA direct repeats and one indirect repeat, with two to six copies per set. Related heptamers are rarely or never found as direct repeats. TAACTGA direct repeats are also found in some other Beggiatoaceae, Thiocystis violascens, a range of Cyanobacteria, and five Bacteroidetes. This phylogenetic distribution suggests they may have been transmitted horizontally, but no mechanism is evident. There is no correlation between total TAACTGA occurrences and repeats per genome. In most species the repeat units are relatively short, but longer arrays of up to 43 copies are found in several Bacteroidetes and Cyanobacteria. The majority of TAACTGA repeats in the Cand. "Maribeggiatoa" Orange Guaymas (BOGUAY) genome are within several nucleotides upstream of a putative start codon, suggesting they may be binding sites for a post-transcriptional regulator. Candidates include members of the ribosomal protein S1, Csp (cold shock protein), and Csr (carbon storage regulator) families. No pattern was evident in the predicted functions of the open reading frames (ORFs) downstream of repeats, but some encode presumably essential products such as ribosomal proteins. Among these is an ORF encoding a possible alternate or modified RNA polymerase beta prime subunit, predicted to have the expected subunit interaction domains but lacking most catalytic residues. A similar ORF was found in the Thioploca ingrica draft genome, but in no others. In both species they are immediately upstream of putative sensor kinase genes with nearly identical domain structures. In the marine Beggiatoaceae, a role for the TAACTGA repeats in translational

  8. Identification of amino acid residues that form part of the ligand-binding pocket of integrin alpha5 beta1.

    PubMed

    Mould, A P; Burrows, L; Humphries, M J

    1998-10-01

    Arg-Arg-Glu-Thr-Ala-Trp-Ala (RRETAWA) is a novel ligand peptide for integrin alpha5 beta1, which blocks alpha5 beta1-mediated cell adhesion to fibronectin (Koivunen, E., Wang, B., and Ruoslahti, E. (1994) J. Cell Biol. 124, 373-380). Here we have localized the binding site for RRETAWA on alpha5 beta1 using inhibitory monoclonal antibodies (mAbs) and site-directed mutagenesis. A cyclic peptide containing this sequence (*CRRETAWAC*) had little effect on the binding of most anti-alpha5 and anti-beta1 mAbs to alpha5 beta1 but completely blocked binding of the anti-alpha5 mAb 16 in a directly competitive manner. Hence, the binding site of RRETAWA appears to closely overlap with the epitope of mAb 16. *CRRETAWAC* also acted as a direct competitive inhibitor of the binding of Arg-Gly-Asp (RGD)-containing fibronectin fragments to alpha5 beta1, suggesting that the binding site for RRETAWA is also closely overlapping with that for RGD. However, differences between the binding sites of RRETAWA and RGD were apparent in that (i) RGD peptides allosterically inhibited the binding of mAb 16 to alpha5 beta1, and (ii) several mAbs that perturbed binding of alpha5 beta1 to RGD had little effect on binding of alpha5 beta1 to RRETAWA. A double mutation in alpha5 (S156G/W157S) blocked the interaction of both RRETAWA and mAb 16 with alpha5 beta1 but had no effect on fibronectin binding or on the binding of other anti-alpha5 mAbs. Ser156-Trp157 is located near the apex of a putative loop region on the upper surface of a predicted beta-propeller structure formed by the NH2-terminal repeats of alpha5. Our findings suggest that this sequence forms part of the ligand-binding pocket of alpha5 beta1. Furthermore, as Ser156-Trp157 is unique to the alpha5 subunit, it may be responsible for the specific recognition of RRETAWA by alpha5 beta1. PMID:9748233

  9. Molecular cloning, immunochemical localization to the vacuole, and expression in transgenic yeast and tobacco of a putative sugar transporter from sugar beet.

    PubMed Central

    Chiou, T J; Bush, D R

    1996-01-01

    Several plant genes have been cloned that encode members of the sugar transporter subgroup of the major facilitator superfamily of transporters. Here we report the cloning, expression, and membrane localization of one of these porters found in sugar beet (Beta vulgaris L.). This clone, cDNA-1, codes for a protein with 490 amino acids and an estimated molecular mass of 54 kD. The predicted membrane topology and sequence homology suggest that cDNA-1 is a member of the sugar transporter family. RNA gel blot analysis revealed that this putative sugar transporter is expressed in all vegetative tissues and expression increases with development in leaves. DNA gel blot analysis indicated that multiple gene copies exist for this putative sugar transporter in the sugar beet genome. Antibodies directed against small peptides representing the N- and C-terminal domains of the cDNA1 protein identified a 40-kD polypeptide in microsomes isolated from cDNA-1-transformed yeast (Saccharomyces cerevisiae). Moreover, the same protein was identified in sugar beet and transgenic tobacco (Nicotaina tobacum L.) membrane fractions. Detailed analysis of the transporter's distribution across linear sucrose gradients and flotation centrifugations showed that it co-migrates with tonoplast membrane markers. We conclude that this carrier is located on the tonoplast membrane and that it may mediate sugar partitioning between the vacuole and cytoplasmic compartments. PMID:8742332

  10. Detection and characterization of mammalian DNA polymerase beta mutants by functional complementation in Escherichia coli.

    PubMed Central

    Sweasy, J B; Loeb, L A

    1993-01-01

    We have designed and utilized a bacterial complementation system to identify and characterize mammalian DNA polymerase beta mutants. In this complementation system, wild-type rat DNA polymerase beta replaces both the replicative and repair functions of DNA polymerase I in the Escherichia coli recA718 polA12 double mutant; our 263 DNA polymerase beta mutants replace E. coli polymerase I less efficiently or not at all. Of the 10 mutants that have been shown to contain DNA sequence alterations, 2 exhibit a split phenotype with respect to complementation of the growth defect and methylmethanesulfonate sensitivity of the double mutant; one is a null mutant. The mutants possessing a split phenotype contain amino acid residue alterations within a putative nucleotide binding site of DNA polymerase beta. This approach for the isolation and evaluation of mutants of a mammalian DNA polymerase in E. coli may ultimately lead to a better understanding of the mechanism of action of this enzyme and to precisely defining its role in vertebrate cells. Images Fig. 2 PMID:8506308

  11. Human and rodent MaxiK channel beta-subunit genes: cloning and characterization.

    PubMed

    Jiang, Z; Wallner, M; Meera, P; Toro, L

    1999-01-01

    Voltage- and Ca2+-sensitive K+ (MaxiK) channels play key roles in controlling neuronal excitability and vascular tone. We cloned and analyzed human and rodent genes for the modulatory beta subunit, KCNMB1. The human and mouse beta-subunit genes are approximately 11 and approximately 9 kb in length, respectively, and have a four exon-three intron structure. Primer extension assay localized the transcription initiation site at 442 (human) or 440 (mouse) bp upstream of the translation initiation codon, agreeing with the transcript size in Northern blots. Both genes have a TATA-less putative promoter region, with a transcription initiator-like region, and motifs characteristic of regulated promoters, including muscle-specific enhancing factors-1 and -2. Consistent with a tissue-specific expression of KCNMB1, regulated at the transcriptional level, beta-subunit transcripts are abundant in smooth muscle and heart, but scarce in lymphatic tissues, brain, and liver. Expressed rat and mouse beta subunits increase the apparent Ca2+ sensitivity of the human MaxiK channel alpha subunit. PMID:9888999

  12. Sequence analysis of PER-1 extended-spectrum beta-lactamase from Pseudomonas aeruginosa and comparison with class A beta-lactamases.

    PubMed Central

    Nordmann, P; Naas, T

    1994-01-01

    We have determined the nucleotide sequence (EMBL accession number, Z 21957) of the cloned chromosomal PER-1 extended-spectrum beta-lactamase gene from a Pseudomonas aeruginosa RNL-1 clinical isolate, blaPER-1 corresponds to a 924-bp open reading frame which encodes a polypeptide of 308 amino acids. This open reading frame is preceded by a -10 and a -35 region consistent with a putative P. aeruginosa promoter. Primer extension analysis of the PER-1 mRNA start revealed that this promoter was active in P. aeruginosa but not in Escherichia coli, in which PER-1 expression was driven by vector promoter sequences. N-terminal sequencing identified the PER-1 26-amino-acid leader peptide and enabled us to calculate the molecular mass (30.8 kDa) of the PER-1 mature form. Analysis of the percent GC content of blaPER-1 and of its 5' upstream sequences, as well as the codon usage for blaPER-1, indicated that blaPER-1 may have been inserted into P. aeruginosa genomic DNA from a nonpseudomonad bacterium. The PER-1 gene showed very low homology with other beta-lactamase genes at the DNA level. By using computer methods, assessment of the extent of identity between PER-1 and 10 beta-lactamase amino acid sequences indicated that PER-1 is a class A beta-lactamase. PER-1 shares around 27% amino acid identity with the sequenced extended-spectrum beta-lactamases of the TEM-SHV series and MEN-1 from Enterobacteriaceae species. The use of parsimony methods showed that PER-1 is not more closely related to gram-negative than to gram-positive bacterial class A beta-lactamases. Surprisingly, among class A beta-lactamases, PER-1 was most closely related to the recently reported CFXA from Bacteroides vulgatus, with which it shared 40% amino acid identity. This work indicates that non-Enterobacteriaceae species such as P. aeruginosa may possess class A extended-spectrum beta-lactamase genes possibly resulting from intergeneric DNA transfer. Images PMID:8141562

  13. Transcript Abundance of Putative Lipid Phosphate Phosphatases During Development of Trypanosoma brucei in the Tsetse Fly.

    PubMed

    Alves e Silva, Thiago Luiz; Savage, Amy F; Aksoy, Serap

    2016-04-01

    African trypanosomes (Trypanosoma brucei spp.) cause devastating diseases in sub-Saharan Africa. Trypanosomes differentiate repeatedly during development in tsetse flies before gaining mammalian infectivity in fly salivary glands. Lipid phosphate phosphatases (LPPs) are involved in diverse biological processes, such as cell differentiation and cell migration. Gene sequences encoding two putative T. brucei LPP proteins were used to search the T. brucei genome, revealing two additional putative family members. Putative structural features and transcript abundance during parasite development in tsetse fly were characterized. Three of the four LPP proteins are predicted to have six transmembrane domains, while the fourth shows only one. Semiquantitative gene expression revealed differential regulation of LPPs during parasite development. Transcript abundance for three of the four putative LPP genes was elevated in parasites infecting salivary glands, but not mammalian-infective metacyclic cells in fly saliva, indicating a potential role of this family in parasite establishment in tsetse salivary glands. PMID:26856918

  14. Sequence analysis and enzyme kinetics of the L2 serine beta-lactamase from Stenotrophomonas maltophilia.

    PubMed Central

    Walsh, T R; MacGowan, A P; Bennett, P M

    1997-01-01

    The L2 serine active-site beta-lactamase from Stenotrophomonas maltophilia has been classified as a clavulanic acid-sensitive cephalosporinase. The gene encoding this enzyme from S. maltophilia 1275 IID has been cloned on a 3.3-kb fragment into pK18 under the control of a Ptac promoter to generate recombinant plasmid pUB5840; when expressed in Escherichia coli, this gene confers resistance to cephalosporins and penicillins. Sequence analysis has revealed an open reading frame (ORF) of 909 bp with a GC content of 71.6%, comparable to that of the L1 metallo-beta-lactamase gene (68.4%) from the same bacterium. The ORF encodes an unmodified protein of 303 amino acids with a predicted molecular mass of 31.5 kDa, accommodating a putative leader peptide of 27 amino acids. Comparison of the amino acid sequence with those of other beta-lactamases showed it to be most closely related (54% identity) to the BLA-A beta-lactamase from Yersinia enterocolitica. Sequence identity is most obvious near the STXK active-site motif and the SDN loop motif common to all serine active-site penicillinases. Sequences outside the conserved regions display low homology with comparable regions of other class A penicillinases. Kinetics of the enzyme from the cloned gene demonstrated an increase in activity with cefotaxime but markedly less activity with imipenem than previously reported. Hence, the S. maltophilia L2 beta-lactamase is an inducible Ambler class A beta-lactamase which would account for the sensitivity to clavulanic acid. PMID:9210666

  15. Sterile neutrinos in neutrinoless double beta decay

    SciTech Connect

    Benes, P.; Faessler, Amand; Simkovic, F.; Kovalenko, S.

    2005-04-01

    We study possible contribution of the Majorana neutrino mass eigenstate {nu}{sub h}, dominated by a sterile neutrino component, to neutrinoless double beta (0{nu}{beta}{beta}) decay. A special emphasis is made on accurate calculation of the corresponding nuclear matrix elements. From the current experimental lower bound on the 0{nu}{beta}{beta}-decay half-life of 76 Ge we derive stringent constraints on the {nu}{sub h}-{nu}{sub e} mixing in a wide region of the values of {nu}{sub h} mass. We discuss cosmological and astrophysical status of {nu}{sub h} in this mass region.

  16. Beta Genus Papillomaviruses and Skin Cancer

    PubMed Central

    Howley, Peter M.; Pfister, Herbert J.

    2015-01-01

    A role for the beta genus HPVs in keratinocyte carcinoma (KC) remains to be established. In this article we examine the potential role of the beta HPVs in cancer revealed by the epidemiology associating these viruses with KC and supported by oncogenic properties of the beta HPV proteins. Unlike the cancer associated alpha genus HPVs, in which transcriptionally active viral genomes are invariably found associated with the cancers, that is not the case for the beta genus HPVs and keratinocyte carcinomas. Thus a role for the beta HPVs in KC would necessarily be in the carcinogenesis initiation and not in the maintenance of the tumor. PMID:25724416

  17. Bioavailability of beta-carotene (betaC) from purple carrots is the same as typical orange carrots while high-betaC carrots increase betaC stores in Mongolian gerbils (Meriones unguiculatus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin A (VA) deficiency is a worldwide public health problem. Biofortifying existing sources of beta-carotene (betaC) and increasing dietary betaC could help combat the issue. Two studies were performed to investigate the relative betaC bioavailability of a betaC supplement to purple, high-betaC o...

  18. Quantitative autoradiography of. beta. /sub 1/- and. beta. /sub 2/-adrenergic receptors in rat brain

    SciTech Connect

    Rainbow, T.C.; Parsons, B.; Wolfe, B.B.

    1984-03-01

    The authors used quantitative autoradiography to localize in rat brain ..beta../sub 1/- and ..beta../sub 2/-adrenergic receptors. These receptors were labeled in vitro with /sup 125/I-labeled pindolol, an antagonist of ..beta..-adrenergic receptors that binds nonselectively to both ..beta../sub 1/ and ..beta../sub 2/ subtypes. The selective inhibition of /sup 125/I-labeled pindolol binding with specific antagonists of ..beta../sub 1/ and ..beta../sub 2/ receptors allowed the visualization of ..beta..-adrenergic receptor subtypes. High levels of ..beta../sub 1/ receptors were observed in the cingulate cortex, layers I and II of the cerebral cortex, the hippocampus, the Islands of Calleja, and the gelatinosus, mediodorsal, and ventral nuclei of the thalamus. High levels of ..beta../sub 2/ receptors were found in the molecular layer of the cerebellum, over pia mater, and in the central, paraventricular, and caudal lateral posterior thalamic nuclei. Approximately equal levels of ..beta../sub 1/ and ..beta../sub 2/ receptors occurred in the substantia nigra, the olfactory tubercle, layer IV of the cerebral cortex, the medial preoptic nucleus, and all nuclei of the medulla. The pronounced differences in the ratio of ..beta../sub 1/ to ..beta../sub 2/ receptors among brain regions suggests that the subtypes of ..beta..-adrenergic receptors may play different roles in neuronal function. 38 references, 3 figures, 1 table.

  19. Active macrophage-associated TGF-beta co-localizes with type I procollagen gene expression in atherosclerotic human pulmonary arteries.

    PubMed Central

    Bahadori, L.; Milder, J.; Gold, L.; Botney, M.

    1995-01-01

    Vascular remodeling in adult atherosclerotic pulmonary arteries is characterized by discrete areas of neointimal smooth muscle cell extracellular matrix gene expression in close proximity to non-foamy macrophages, suggesting regulation by local macrophage-associated factors. The purpose of these studies was to begin addressing the role of putative macrophage-associated factors such as transforming growth factor-beta (TGF-beta), by determining the spatial relationship between TGF-beta and neointimal matrix gene expression in human atherosclerotic pulmonary arteries. For example, the participation of TGF-beta in vascular remodeling could be inferred by its colocalization with non-foamy macrophages in areas of active matrix synthesis. In situ hybridization and immunohistochemistry demonstrated focal neointimal procollagen gene expression in close association with non-foamy but not foamy macrophages. Immunohistochemistry with isoform-specific anti-TGF-beta antibodies demonstrated all three isoforms of TGF-beta associated with non-foamy macrophages, but foamy macrophages were not immunoreactive. Neointimal and medial smooth muscle cells stained lightly. In contrast, intense TGF-beta immunoreactivity was also associated with medial smooth muscle cells in normal nonremodeling vessels. Immunohistochemistry with antibodies specific for latent TGF-beta was similar to immunohistochemistry for mature TGF-beta in both remodeling and nonremodeling vessels. Finally, using an antibody specific for active TGF-beta 1, immunoreactivity was only seen in non-foamy neointimal macrophages but not in foamy macrophages or medial smooth muscle cells from hypertensive or normal vessels. These observations suggest non-foamy macrophages may participate in modulating matrix gene expression in atherosclerotic remodeling via a TGF-beta-dependent mechanism. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7747808

  20. The first armadillo repeat is involved in the recognition and regulation of beta-catenin phosphorylation by protein kinase CK1.

    PubMed

    Bustos, Victor H; Ferrarese, Anna; Venerando, Andrea; Marin, Oriano; Allende, Jorge E; Pinna, Lorenzo A

    2006-12-26

    Multiple phosphorylation of beta-catenin by glycogen synthase kinase 3 (GSK3) in the Wnt pathway is primed by CK1 through phosphorylation of Ser-45, which lacks a typical CK1 canonical sequence. Synthetic peptides encompassing amino acids 38-64 of beta-catenin are phosphorylated by CK1 on Ser-45 with low affinity (K(m) approximately 1 mM), whereas intact beta-catenin is phosphorylated at Ser-45 with very high affinity (K(m) approximately 200 nM). Peptides extended to include a putative CK1 docking motif (FXXXF) at 70-74 positions or a F74AA mutation in full-length beta-catenin had no significant effect on CK1 phosphorylation efficiency. beta-Catenin C-terminal deletion mutants up to residue 181 maintained their high affinity, whereas removal of the 131-181 fragment, corresponding to the first armadillo repeat, was deleterious, resulting in a 50-fold increase in K(m) value. Implication of the first armadillo repeat in beta-catenin targeting by CK1 is supported in that the Y142E mutation, which mimics phosphorylation of Tyr-142 by tyrosine kinases and promotes dissociation of beta-catenin from alpha-catenin, further improves CK1 phosphorylation efficiency, lowering the K(m) value to <50 nM, approximating the physiological concentration of beta-catenin. In contrast, alpha-catenin, which interacts with the N-terminal region of beta-catenin, prevents Ser-45 phosphorylation of CK1 in a dose-dependent manner. Our data show that the integrity of the N-terminal region and the first armadillo repeat are necessary and sufficient for high-affinity phosphorylation by CK1 of Ser-45. They also suggest that beta-catenin association with alpha-catenin and beta-catenin phosphorylation by CK1 at Ser-45 are mutually exclusive. PMID:17172446

  1. Ofloxacin/beta-cyclodextrin complexation.

    PubMed

    Koester, L S; Guterres, S S; Le Roch, M; Eifler-Lima, V L; Zuanazzi, J A; Bassani, V L

    2001-07-01

    Ofloxacin (OFX) is a fluorquinolone characterized by photochemical instability. With the goal to improve its photostability in aqueous solutions, the complexation of ofloxacin with beta-cyclodextrin was investigated. The complexes showed a water solubility enhancement of approximately 2.6 times; nevertheless, the photodegradation of ofloxacin was not reduced. The complexes obtained were characterized by thermal and 1H nuclear magnetic resonance (NMR) analysis, which revealed an interaction between ofloxacin and beta-cyclodextrin. The last analysis indicated that only partial inclusion of the N-methylpiperazinyl moiety occurred, which can explain the fact that photostabilization was not improved. This partial inclusion phenomenon could be explained also by computer-aided molecular modeling. PMID:11548860

  2. Beta-catenin expression in human cancers.

    PubMed Central

    Takayama, T.; Shiozaki, H.; Shibamoto, S.; Oka, H.; Kimura, Y.; Tamura, S.; Inoue, M.; Monden, T.; Ito, F.; Monden, M.

    1996-01-01

    Cell-cell adhesion in tissue is mainly regulated by homotypic interaction of cadherin molecules, which are anchored to the cytoskeleton via cytoplasmic proteins, including alpha- and beta-catenin. Although we previously demonstrated that alpha-catenin is crucial for cadherin function in vivo, little is known about the role of beta-catenin. We examined the expression of beta-catenin in human carcinoma samples along with normal tissue (esophagus, stomach, and colon) by immunostaining using our antibody for beta-catenin. Normal epithelium strongly expressed beta-catenin. However, beta-catenin expression was frequently reduced in primary tumors of the esophagus (10 of 15, 67%), stomach (9 of 19, 47%), and colon (11 of 22, 50%). From an immunoprecipitation study, we found that beta-catenin forms a complex with E-cadherin not only in the normal epithelium but also in cancerous tissues. In coexpression patterns of E-cadherin and beta-catenin, 43 (77%) of the 56 tumors showed a similar expression of both molecules, whereas the other 13 tumors (23%) showed positive staining for E-cadherin and reduced expression of beta-catenin. These findings suggest that beta-catenin forms a complex with E-cadherin in vivo and down-regulation of beta-catenin expression is associated with malignant transformation. Images Figure 1 Figure 2 Figure 3 PMID:8546224

  3. Molecular basis for amyloid-[beta] polymorphism

    SciTech Connect

    Colletier, Jacques-Philippe; Laganowsky, Arthur; Landau, Meytal; Zhao, Minglei; Soriaga, Angela B.; Goldschmidt, Lukasz; Flot, David; Cascio, Duilio; Sawaya, Michael R.; Eisenberga, David

    2011-10-19

    Amyloid-beta (A{beta}) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. A{beta} molecules form {beta}-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of A{beta} has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate A{beta} polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of A{beta}. These structures, all of short, self-complementing pairs of {beta}-sheets termed steric zippers, reveal a variety of modes of self-association of A{beta}. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to A{beta}. These structures and molecular models contribute fundamental information for understanding A{beta} polymorphic nature and pathogenesis.

  4. Structural connectivity patterns associated with the putative visual word form area and children's reading ability.

    PubMed

    Fan, Qiuyun; Anderson, Adam W; Davis, Nicole; Cutting, Laurie E

    2014-10-24

    With the advent of neuroimaging techniques, especially functional MRI (fMRI), studies have mapped brain regions that are associated with good and poor reading, most centrally a region within the left occipito-temporal/fusiform region (L-OT/F) often referred to as the visual word form area (VWFA). Despite an abundance of fMRI studies of the putative VWFA, research about its structural connectivity has just started. Provided that the putative VWFA may be connected to distributed regions in the brain, it remains unclear how this network is engaged in constituting a well-tuned reading circuitry in the brain. Here we used diffusion MRI to study the structural connectivity patterns of the putative VWFA and surrounding areas within the L-OT/F in children with typically developing (TD) reading ability and with word recognition deficits (WRD; sometimes referred to as dyslexia). We found that L-OT/F connectivity varied along a posterior-anterior gradient, with specific structural connectivity patterns related to reading ability in the ROIs centered upon the putative VWFA. Findings suggest that the architecture of the putative VWFA connectivity is fundamentally different between TD and WRD, with TD showing greater connectivity to linguistic regions than WRD, and WRD showing greater connectivity to visual and parahippocampal regions than TD. Findings thus reveal clear structural abnormalities underlying the functional abnormalities in the putative VWFA in WRD. PMID:25152466

  5. [Beta-adrenergic receptor blocker poisoning].

    PubMed

    Reingardiene, Dagmara

    2007-01-01

    Beta-adrenergic receptor blocking drugs are used in the treatment of hypertension, angina, myocardial infarction, cardiac dysrhythmia, cardiomyopathy, migraine headache, thyrotoxicosis, and glaucoma. beta-adrenergic receptor blocking agents are competitive antagonist at beta(1), beta(2), or both types of adrenergic receptors. Overdoses of beta-adrenergic receptor blockers are uncommon, but are associated with significant morbidity and mortality. This review article discusses the properties of beta-adrenergic receptor blockers, presents the doses of these drugs causing toxicity and doses, after ingestion of which, referral to an emergency department is recommended. Clinical presentation of overdose (the cardiovascular, neurologic manifestations, pulmonary and other complications), diagnosis, and treatment (gastrointestinal decontamination; the usage of atropine, phosphodiesterase inhibitors, glucagon, insulin; indications for cardiac pacing, extracorporeal procedures of drug removal, etc.) are analyzed. In addition, this article focuses on clinical course and prognosis of beta-blocker overdose. PMID:17768375

  6. Estimating beta-mixing coefficients

    PubMed Central

    McDonald, Daniel J.; Shalizi, Cosma Rohilla; Schervish, Mark

    2015-01-01

    The literature on statistical learning for time series assumes the asymptotic independence or “mixing” of the data-generating process. These mixing assumptions are never tested, and there are no methods for estimating mixing rates from data. We give an estimator for the beta-mixing rate based on a single stationary sample path and show it is L1-risk consistent. PMID:26279742

  7. [The beta-adrenergic receptor].

    PubMed

    Bicho, M P; Manso, C F

    1992-12-01

    The Authors review the constitution and mechanism of action of the beta adrenergic receptor. It is part of a large family which includes visual pigments, muscarinic, serotonergic, olfactive and substance K receptors. Catecholamines given an electron to the receptor. It goes then successively to the alpha submit of Gs protein ant to adenylyl cyclase. The process of activation consists in a successive transfer of one electron. PMID:1337834

  8. Molecular characterization and differential expression of beta-1,3-glucanase during ripening in banana fruit in response to ethylene, auxin, ABA, wounding, cold and light-dark cycles.

    PubMed

    Roy Choudhury, Swarup; Roy, Sujit; Singh, Sanjay Kumar; Sengupta, Dibyendu N

    2010-08-01

    beta-1,3-Glucanases (E.C. 3.2.1.39) are widely distributed enzyme among bacteria, fungi, and higher plants. Analyses of accumulation levels of beta-1,3-glucanase protein in various tissues in banana have clearly indicated abundance of beta-1,3-glucanase protein accumulation in ripe pulp tissue. After cloning of beta-1,3-glucanase from banana pulp (cultivar Cavendish), we have carried out an in silico analysis to investigate the sequential, structural, and phylogenetic characteristics of the putative banana beta-1,3-glucanase protein. As like other ripening specific genes, beta-1,3-glucanase is regulated in response to a wide variety of factors. Therefore, we have analyzed the transcript accumulation pattern and protein levels of beta-1,3-glucanase in response to ethylene, auxin, ABA, wounding and, low temperature in preclimacteric banana fruit. Expression profile analyses have indicated that whereas exogenous application of ethylene strongly stimulated beta-1,3-glucanase transcript accumulation, ABA partially induced the expression of the gene. On the other hand, wound treatment did not induce beta-1,3-glucanase expression. Conversely, auxin and cold treatment negatively regulated beta-1,3-glucanase gene expression and thus inhibited glucanase activity. In addition, beta-1,3-glucanase transcript level was markedly decreased by constant exposure to white light. Protein level and enzymatic activity of beta-1,3-glucanase were substantially increased with considerable decrease in fruit firmness by ethylene treatment and reduced exposure to white light conditions as compared with other treatments. Together, the overall study of beta-1,3-glucanase expression pattern, glucanase activity, and changes in fruit firmness during ripening in various conditions suggest the possible physiological function of beta-1,3-glucanase in fruit pulp softening. PMID:20467747

  9. Decreased glycogen synthase kinase 3-beta levels and related physiological changes in Bacillus anthracis lethal toxin-treated macrophages.

    PubMed

    Tucker, Amy E; Salles, Isabelle I; Voth, Daniel E; Ortiz-Leduc, William; Wang, Han; Dozmorov, Igor; Centola, Michael; Ballard, Jimmy D

    2003-08-01

    The lethal factor (LF) component of Bacillus anthracis lethal toxin (LeTx) cleaves mitogen activated protein kinase kinases (MAPKKs) in a variety of different cell types, yet only macrophages are rapidly killed by this toxin. The reason for this selective killing is unclear, but suggests other factors may also be involved in LeTx intoxication. In the current study, DNA membrane arrays were used to identify broad changes in macrophage physiology after treatment with LeTx. Expression of genes regulated by MAPKK activity did not change significantly, yet a series of genes under glycogen synthase kinase-3-beta (GSK-3beta) regulation changed expression following LeTx treatment. Correlating with these transcriptional changes GSK-3beta was found to be below detectable levels in toxin-treated cells and an inhibitor of GSK-3beta, LiCl, sensitized resistant IC-21 macrophages to LeTx. In addition, zebrafish embryos treated with LeTx showed signs of delayed pigmentation and cardiac hypertrophy; both processes are subject to regulation by GSK-3beta. A putative compensatory response to loss of GSK-3beta was indicated by differential expression of three motor proteins following toxin treatment and Kif1C, a motor protein involved in sensitivity to LeTx, increased expression in toxin-sensitive cells yet decreased in resistant cells following toxin treatment. Differential expression of microtubule-associating proteins and a decrease in the level of cellular tubulin were detected in LeTx-treated cells, both of which can result from loss of GSK-3beta activity. These data provide new information on LeTx's overall influence on macrophage physiology and suggest loss of GSK-3beta contributes to cytotoxicity. PMID:12864812

  10. TGF-{beta} modulates {beta}-Catenin stability and signaling in mesenchymal proliferations

    SciTech Connect

    Amini Nik, Saeid; Ebrahim, Rasoul Pour; Dam, Kim van; Cassiman, Jean-Jacques; Tejpar, Sabine . E-mail: sabine.tejpar@med.kuleuven.be

    2007-08-01

    Here for the first time we showed, despite the oncogenic mutations in {beta}-Catenin, that TGF-{beta} is a modulator of {beta}-Catenin levels in tumoral fibroblasts as well as non-tumoral fibroblasts. The results show that the TGF-{beta} pathway is active in desmoids cells and in in situ tumors. A dose dependent increase in {beta}-Catenin protein levels was observed after TGF-{beta} treatment in combination with an increased repression of GSK-3{beta} both in normal and tumoral fibroblasts. TGF-{beta} stimulation also led to an altered - up to 5 fold - transcriptional activity of {beta}-Catenin responsive promoters, such as IGFBP6 as well as increase of TOPflash activity. TGF-{beta} stimulation increased cell proliferation and BrdU incorporation 2.5 times. Taken together, we propose that TGF-{beta} is a modulator of {beta}-Catenin levels in tumoral fibroblasts and non-tumoral fibroblasts, despite the oncogenic mutations already present in this gene in tumoral fibroblasts of desmoid tumors. This modulation of {beta}-Catenin levels by TGF-{beta} may be involved in determining the tumoral phenotype of the cells.

  11. Can Genetic Analysis of Putative Blood Alzheimer’s Disease Biomarkers Lead to Identification of Susceptibility Loci?

    PubMed Central

    Huebinger, Ryan M.; Shewale, Shantanu J.; Koenig, Jessica L.; Mitchel, Jeffrey S.; O’Bryant, Sid E.; Waring, Stephen C.; Diaz-Arrastia, Ramon; Chasse, Scott

    2015-01-01

    Although 24 Alzheimer’s disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10-7. Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel

  12. Cloning of cellobiose phosphoenolpyruvate-dependent phosphotransferase genes: Functional expression in recombinant Escherichia coli and identification of a putative binding region for disaccharides

    SciTech Connect

    Lai, Xiaokuang; Davis, F.C.; Ingram, L.O.; Hespell, R.B.

    1997-02-01

    Genomic libraries from nine cellobiose-metabolizing bacteria were screened for cellobiose utilization. Positive clones were recovered from six libraries, all of which encode phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) proteins. Clones from Bacillus subtilis, Butyrivibrio fibrisolvens, and Klebsiella oxytoca allowed the growth of recombinant Escherichia coli in cellobiose-M9 minimal medium. The K. oxytoca clone, pLOI1906, exhibited an unusually broad substrate range (cellobiose, arbutin, salicin, and methylumbelliferyl derivatives of glucose, cellobiose, mannose, and xylose) and was sequenced. The insert in this plasmid encoded the carboxy-terminal region of a putative regulatory protein, cellobiose permease (single polypeptide), and phospho-{beta}-glucosidase, which appear to form an operon (casRAB). Subclones allowed both casA and casB to be expressed independently, as evidenced by in vitro complementation. An analysis of the translated sequences from the EIIC domains of cellobiose, aryl-{beta}-glucoside, and other disaccharide permeases allowed the identification of a 50-amino-acid conserved region. A disaccharide consensus sequence is proposed for the most conserved segment (13 amino acids), which may represent part of the EIIC active site for binding and phosphorylation. 63 refs., 4 figs., 4 tabs.

  13. Smed-Evi/Wntless is required for beta-catenin-dependent and -independent processes during planarian regeneration.

    PubMed

    Adell, Teresa; Salò, Emili; Boutros, Michael; Bartscherer, Kerstin

    2009-03-01

    Planarians can regenerate a whole animal from only a small piece of their body, and have become an important model for stem cell biology. To identify regenerative processes dependent on Wnt growth factors in the planarian Schmidtea mediterranea (Smed), we analyzed RNAi phenotypes of Evi, a transmembrane protein specifically required for the secretion of Wnt ligands. We show that, during regeneration, Smed-evi loss-of-function prevents posterior identity, leading to two-headed planarians that resemble Smed-beta-catenin1 RNAi animals. In addition, we observe regeneration defects of the nervous system that are not found after Smed-beta-catenin1 RNAi. By systematic knockdown of all putative Smed Wnts in regenerating planarians, we identify Smed-WntP-1 and Smed-Wnt11-2 as the putative posterior organizers, and demonstrate that Smed-Wnt5 is a regulator of neuronal organization and growth. Thus, our study provides evidence that planarian Wnts are major regulators of regeneration, and that they signal through beta-catenin-dependent and -independent pathways. PMID:19211673

  14. Modification of Cys-837 identifies an actin-binding site in the beta-propeller protein scruin.

    PubMed Central

    Sun, S; Footer, M; Matsudaira, P

    1997-01-01

    In the acrosomal process of Limulus sperm, the beta-propeller protein scruin cross-links actin into a crystalline bundle. To confirm that scruin has the topology of a beta-propeller protein and to understand how scruin binds actin, we compared the solvent accessibility of cysteine residues in scruin and the acrosomal process by chemical modification with (1,5-IAEDANS). In soluble scruin, the two most reactive cysteines of soluble scruin are C837 and C900, whereas C146, C333, and C683 are moderately reactive. This pattern of reactivity is consistent with the topology of a typical beta-propeller protein; all of the reactive cysteines map to putative loops and turns whereas the unreactive cysteines lie within the predicted interior of the protein. The chemical reactivities of cysteine in the acrosomal process implicate C837 at an actin-binding site. In contrast to soluble scruin, in the acrosomal process, C837 is completely unreactive while the other cysteines become less reactive. Binding studies of chemically modified scruin correlate the extent of modification at C837 with the extent of inhibition of actin binding. Furthermore, peptides corresponding to residues flanking C837 bind actin and narrow a possible actin-binding region to a KQK sequence. On the basis of these studies, our results suggest that an actin-binding site lies in the C-terminal domain of scruin and involves a putative loop defined by C837. Images PMID:9188095

  15. Beta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter covers the use of wild beets in sugar beet improvement, including the basic botany of the species, its distribution; geographical locations of genetic diversity; morphology; cytology and karyotype; genome size; taxonomic position; agricultural status (model plant/weeds/invasive species/...

  16. Transcriptional repression by RING finger protein TIF1 beta that interacts with the KRAB repressor domain of KOX1.

    PubMed Central

    Moosmann, P; Georgiev, O; Le Douarin, B; Bourquin, J P; Schaffner, W

    1996-01-01

    Many of the vertebrate zinc finger factors of the Kruppel type (C2H2 zinc fingers) contain in their N-terminus a conserved sequence referred to as the KRAB (Kruppel-associated box) domain that, when tethered to DNA, efficiently represses transcription. Using the yeast two-hybrid system, we have isolated an 835 amino acid RING finger (C3HC4 zinc finger) protein, TIF1 beta (also named KAP-1), that specifically interacts with the KRAB domain of the human zinc finger factor KOX1/ZNF10. TIF1 beta, TIF1 alpha, PML and efp belong to a characteristic subgroup of RING finger proteins that contain one or two other Cys/His-rich clusters (B boxes) and a putative coiled-coil in addition to the classical C3HC4 RING finger motif (RBCC configuration). Like TIF1 alpha, TIF1 beta also contains an additional Cys/His cluster (PHD finger) and a bromo-related domain. When tethered to DNA, TIF1 beta can repress transcription in transiently transfected mammalian cells both from promoter-proximal and remote (enhancer) positions, similarly to the KRAB domain itself. We propose that TIF1 beta is a mediator of the transcriptional repression exerted by the KRAB domain. PMID:9016654

  17. beta-Galactosidase enzyme fragment complementation for the measurement of Wnt/beta-catenin signaling.

    PubMed

    Verkaar, Folkert; Blankesteijn, W Matthijs; Smits, Jos F M; Zaman, Guido J R

    2010-04-01

    Wnt/beta-catenin signaling is an important regulator of cell polarity, proliferation, and stem cell maintenance during development and adulthood. Wnt proteins induce the nuclear accumulation of beta-catenin, which regulates the expression of Wnt-responsive genes through association with TCF/LEF transcription factors. Aberrant Wnt/beta-catenin signaling has been implicated in a plethora of pathologies and, most notably, underlies initiation and expansion of several cancers. Here, we apply enzyme fragment complementation to measure the nuclear accumulation of beta-catenin. beta-Catenin was tagged with a peptide fragment of beta-galactosidase and transfected into cells expressing a corresponding deletion mutant of the enzyme exclusively in the nucleus. Stimulation of the cells with recombinant Wnt-3a restored beta-galactosidase activity in a dose-dependent manner with nanomolar potency. Using the assay, we confirmed that Wnt-5a represses beta-catenin-driven reporter gene activity downstream of nuclear entry of beta-catenin. In addition, we tested a library of >2000 synthetic chemical compounds for their ability to induce beta-catenin nuclear accumulation. The immunosuppressive protein kinase C inhibitor sotrastaurin (AEB-071) was identified as an activator of Wnt/beta-catenin signaling at micromolar concentrations. It was confirmed that the compound stabilizes endogenous beta-catenin protein and can induce TCF/LEF-dependent gene transcription. Subsequent biochemical profiling of >200 kinases revealed both isoforms of glycogen synthase kinase 3, as previously unappreciated targets of sotrastaurin. We show that the beta-catenin nuclear accumulation assay contributes to our knowledge of molecular interactions within the Wnt/beta-catenin pathway and can be used to find new therapeutics targeting Wnt/beta-catenin signaling.-Verkaar, F., Blankesteijn, W. M., Smits, J. F. M., Zaman, G. J. R. beta-Galactosidase enzyme fragment complementation for the measurement of Wnt/beta

  18. Hyper-beta-alaninemia associated with beta-aminoaciduria and gamma-aminobutyricaciduaia, somnolence and seizures.

    PubMed

    Scriver, C R; Pueschel, S; Davies, E

    1966-03-24

    Hyper-beta-alaninemia was found in a somnolent, convulsing infant. Hyper-beta-aminoaciduria (beta-ala, betaAIB and taurine) was also observed, varying directly with plasma beta-alanine concentration. The beta-aminoaciduria is explained by the interaction between beta-alanine and a specific cellular-transport system with preference for beta-amino compounds. Gamma-aminobutyricaciduria was also observed, its excretion being independent of beta-alanine levels. Dietary modifications, pyridoxine, pantothenic acid and antibiotic therapy were not beneficial. Post-mortem tissues had elevated levels of beta-alanine and carnosine; GABA levels in brain were probably elevated for the age of the patient. A proposed block in beta-alanine-alpha-ketoglutarate transaminase would expand the free beta-alanine pool, thus increasing tissue carnosine. beta-Alanine is a central-nervous-system depressant. Associated inhibition of GABA transaminase and displacement of GABA from central-nervous-system binding sites would produce GABAuria and convulsions. PMID:17926374

  19. Neutrino Factories and Beta Beams

    SciTech Connect

    Zisman, Michael S.

    2006-06-21

    In this paper we briefly review the concepts of Neutrino Factories and Beta Beam facilities, and indicate the main challenges in terms of beam performance and technological developments. We also describe the worldwide organizations that have embarked on defining and carrying out the necessary R&D on component design, beam simulations of facility performance, and benchmarking of key subsystems via actual beam tests. Currently approved subsystem tests include the Muon Ionization Cooling Experiment (MICE), under construction at Rutherford Appleton Laboratory, and the Mercury Intense Target (MERIT) experiment, to be carried out at CERN. These experiments are briefly described, and their schedules are indicated.

  20. A putative function for the arabidopsis Fe-Phytosiderophore transporter homolog AtYSL2 in Fe and Zn homeostasis.

    PubMed

    Schaaf, Gabriel; Schikora, Adam; Häberle, Jennifer; Vert, Grégory; Ludewig, Uwe; Briat, Jean-François; Curie, Catherine; von Wirén, Nicolaus

    2005-05-01

    Although Arabidopsis thaliana does not produce phytosiderophores (PS) under Fe deficiency, it contains eight homologs of the metal-PS/metal-nicotianamine (NA) transporter ZmYS1 from maize. This study aimed to investigate whether one of the closest Arabidopsis homologs to ZmYS1, AtYSL2, is involved in metal-chelate transport. Northern analysis revealed high expression levels of AtYSL2 in Fe-sufficient or Fe-resupplied roots, while under Fe deficiency transcript levels decreased. Quantitative real-time polymerase chain reaction (PCR) and analysis of transgenic plants expressing an AtYSL2 promoter::beta-glucuronidase gene further allowed the detection of down-regulated AtYSL2 gene expression under Zn and Fe deficiency. In contrast to ZmYS1, AtYSL2 did not mediate metal-PS or metal-NA transport in yeast mutants defective in Cu or Fe uptake, nor did AtYSL2 mediate Fe(II)-NA-, Fe(III)-NA- or Ni(II)-NA-inducible currents when assayed by two-electrode voltage clamp in Xenopus oocytes. Moreover, truncation of the N-terminus to remove putative phosphorylation sites that might trigger autoinhibition did not confer functionality to AtYSL2. A direct growth comparison of yeast cells transformed with AtYSL2 in two different yeast expression vectors showed that transformation with empty pFL61 repressed growth even under non-limiting Fe supply. We therefore conclude that the yeast complementation assay previously employed does not allow the identification of AtYSL2 as an Fe-NA transporter. Transgenic plants expressing an AtYSL2 promoter::beta-glucuronidase gene showed expression in root endodermis and pericycle cells facing the meta-xylem tubes. Taken together, our investigations support an involvement of AtYSL2 in Fe and Zn homeostasis, although functionality or substrate specificity are likely to differ between AtYSL2 and ZmYS1. PMID:15753101

  1. Method for preparing Pb-. beta. ''-alumina ceramic

    DOEpatents

    Hellstrom, E.E.

    1984-08-30

    A process is disclosed for preparing impermeable, polycrystalline samples of Pb-..beta..''-alumina ceramic from Na-..beta..''-alumina ceramic by ion exchange. The process comprises two steps. The first step is a high-temperature vapor phase exchange of Na by K, followed by substitution of Pb for K by immersing the sample in a molten Pb salt bath. The result is a polycrystalline Pb-..beta..''-alumina ceramic that is substantially crack-free.

  2. C3 polymorphism in beta-thalassemia.

    PubMed

    Germenis, A; Kalantzi, M; Karamerou, A; Politi, C; Fertakis, A

    1984-01-01

    The distribution of phenotypes and gene frequencies of the third component of complement (C3) were studied in 106 beta-thalassemic patients and in 112 carriers of the beta-thalassemia trait. A statistically significant association was found between the C3F gene and homozygous beta-thalassemia. It can be suggested that this association may be related with the high incidence of infections encountered in these patients. PMID:6419525

  3. Milk Intolerance, Beta-Casein and Lactose

    PubMed Central

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

    2015-01-01

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

  4. Gyrokinetic turbulence simulations at high plasma beta

    SciTech Connect

    Pueschel, M. J.; Kammerer, M.; Jenko, F.

    2008-10-15

    Electromagnetic gyrokinetic turbulence simulations employing Cyclone Base Case parameters are presented for {beta} values up to and beyond the kinetic ballooning threshold. The {beta} scaling of the turbulent transport is found to be linked to a complex interplay of linear and nonlinear effects. Linear investigation of the kinetic ballooning mode is performed in detail, while nonlinearly, it is found to dominate the turbulence only in a fairly narrow range of {beta} values just below the respective ideal limit. The magnetic transport scales like {beta}{sup 2} and is well described by a Rechester-Rosenbluth-type ansatz.

  5. Milk Intolerance, Beta-Casein and Lactose.

    PubMed

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

    2015-09-01

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

  6. Regulation of pancreatic beta-cell mass.

    PubMed

    Bouwens, Luc; Rooman, Ilse

    2005-10-01

    Beta-cell mass regulation represents a critical issue for understanding diabetes, a disease characterized by a near-absolute (type 1) or relative (type 2) deficiency in the number of pancreatic beta cells. The number of islet beta cells present at birth is mainly generated by the proliferation and differentiation of pancreatic progenitor cells, a process called neogenesis. Shortly after birth, beta-cell neogenesis stops and a small proportion of cycling beta cells can still expand the cell number to compensate for increased insulin demands, albeit at a slow rate. The low capacity for self-replication in the adult is too limited to result in a significant regeneration following extensive tissue injury. Likewise, chronically increased metabolic demands can lead to beta-cell failure to compensate. Neogenesis from progenitor cells inside or outside islets represents a more potent mechanism leading to robust expansion of the beta-cell mass, but it may require external stimuli. For therapeutic purposes, advantage could be taken from the surprising differentiation plasticity of adult pancreatic cells and possibly also from stem cells. Recent studies have demonstrated that it is feasible to regenerate and expand the beta-cell mass by the application of hormones and growth factors like glucagon-like peptide-1, gastrin, epidermal growth factor, and others. Treatment with these external stimuli can restore a functional beta-cell mass in diabetic animals, but further studies are required before it can be applied to humans. PMID:16183912

  7. Important Role of a Putative Lytic Transglycosylase Cj0843c in β-Lactam Resistance in Campylobacter jejuni

    PubMed Central

    Zeng, Ximin; Gillespie, Barbara; Lin, Jun

    2015-01-01

    Beta-lactam antibiotics are an important class of antibiotics for treating bacterial infections. Despite prevalent β-lactam resistance in Campylobacter jejuni, the leading bacterial cause of human diarrhea in developed countries, molecular mechanism of β-lactam resistance in C. jejuni is still largely unknown. In this study, C. jejuni 81–176 was used for random transposon mutagenesis. Screening of a 2,800-mutant library identified 22 mutants with increased susceptibility to ampicillin. Of these mutants, two mutants contains mutations in Cj0843c (a putative lytic transglycosylase gene) and in its upstream gene Cj0844c, respectively. Complementation experiment demonstrated that the Cj0843 contributes to β-lactam resistance. The Cj0843c insertional mutation was subsequently introduced to diverse C. jejuni clinical strains for MIC test, showing that Cj0843c contributes to both intrinsic and acquired β-lactam resistance of C. jejuni. Consistent with this finding, inactivation of Cj0843c also dramatically reduced β-lactamase activity. Genomic examination and PCR analysis showed Cj0843c is widely distributed in C. jejuni. High purity recombinant Cj0843c was produced for generation of specific antiserum. The Cj0843 was localized in the periplasm, as demonstrated by immunoblotting using specific antibodies. Turbidimetric assay further demonstrated the capability of the purified Cj0843c to hydrolyze cell walls. Inactivation of Cj0843c also significantly reduced C. jejuni colonization in the intestine. Together, this study identifies a mechanism of β-lactam resistance in C. jejuni and provides insights into the role of cell wall metabolism in regulating β-lactamase activity. PMID:26635760

  8. Laccase activity and putative laccase genes in marine-derived basidiomycetes.

    PubMed

    Bonugli-santos, Rafaella C; Durrant, Lucia R; Sette, Lara D

    2010-10-01

    Studies of laccases from marine-derived fungi are limited. In the present work, putative laccase genes from three marine-derived basidiomycetes and their laccase activities were evaluated. High amounts of laccase were produced by the fungal strains Marasmiellus sp. CBMAI 1062 (971.2UL⁻¹) and Peniophora sp. CBMAI 1063 (709.03UL⁻¹) when grown for 21d at 28°C in MA2ASW medium prepared with artificial seawater. Marine-derived basidiomycetes produced multiple distinct laccase sequences of about 200bp with 73-90% similarity to terrestrial basidiomycete laccases. Marasmiellus sp. CBMAI 1062 and Tinctoporellus sp. CBMAI 1061 showed the greatest laccase gene diversity with three and four distinct putative laccase sequences, respectively. This is the first report of laccase genes from marine-derived fungi, and our results revealed new putative laccases produced by three basidiomycetes. PMID:20943196

  9. Complete genome sequences of a putative new alphapartitivirus detected in Rosa spp.

    PubMed

    Phelan, James; James, Delano

    2016-09-01

    A putative new alphapartitivirus was detected by next-generation sequencing (NGS) in Rosa spp. and identified as rose partitivirus isolate Phyllis Bide (RoPV-PB). The virus is bipartite with a dsRNA1 fragment (1937 bp) encoding a putative RdRp and a dsRNA2 fragment (1811 bp) encoding the putative CP subunit of the virus. dsRNA1 of RoPV-BP is closely related to Vicia faba partitivirus 1, with identities of 67 % and 72 % for the nucleotide (nt) and deduced amino acid (aa) sequences, respectively. In NGS analysis of RoPV-BP, coverage was uneven across both dsRNA fragments, with GC/AT content appearing to be a major determinant of depth of coverage. PMID:27368993

  10. Genotypic Variation for Drought Tolerance in Beta vulgaris

    PubMed Central

    OBER, E. S.; LUTERBACHER, M. C.

    2002-01-01

    Insufficient soil moisture during summer months is now the major cause of sugar beet yield losses in the UK. However, selection for increased drought tolerance has not been a breeding priority until recently. Genetic variation for drought tolerance is an essential prerequisite for the development of more stress‐tolerant varieties, but commercial sugar beet varieties seem to have similar yield responses to drought. The objective of this study was to assess the degree of genotypic variation for drought tolerance within a wide range of sugar beet germplasm and genebank accessions within Beta. Thirty sugar beet genotypes were screened under field drought conditions, and putative drought tolerant and sensitive lines (in terms of yield reduction in polythene‐covered vs. irrigated plots) were identified. Significant genotype × water treatment interactions were found for dry matter yield and relative leaf expansion rate. Genotypic differences for drought susceptibility index were also significant. Differential sensitivity of seedling shoot growth to water deficit was examined by comparing 350 genebank accessions in a simple growth chamber screen. Methods of data management were devised to highlight lines for entry into subsequent field tests. The results of the field and seedling screens indicate that there is variation for tolerance to water deficits within sugar beet and related types, and that there are lines that show greater drought tolerance than selected commercial varieties. Divergent lines showing contrasting behaviour should aid in the identification of key morpho‐physiological traits that confer drought tolerance. PMID:12102517

  11. Noninvasive monitoring of beta-adrenergic tone during isoproterenol infusions.

    PubMed

    Easley, R B; Rodbard, D

    1977-12-01

    Sphygmo-Recording is a simple, noninvasive technique for analysis of pulse wave contour and timing which has been used to evaluate the change in cardiac dynamics during isoproterenol infusion. The QKd interval, i.e., the time interval between the onset of the QRS complex and the onset of the Korotkoff sound at the brachial artery when the sphygomomanometer cuff is at diastolic pressure, is normally 205 +/- 15 msec. Continuous intravenous infusion of isoproterenol at 0.01, 0.02, and 0.03 microgram/kg/min into 12 euthyroid normotensive adult volunteers for 10-min intervals resulted in decreases of 55, 79, and 89 msec in QKd and increases of heart rate of 14, 27, and 43 beats/min, respectively. The corresponding changes in dP/dt, i.e., slope of the pulse wave upstroke at the brachial artery determined noninvasively from the same records, were 0.65, 1.47, and 2.26 mm Hg/msec. These results confirm previous studies which indicate that the chronotropic response of normal subjects to isoproterenol infusion is comparable to that previously reported in patients with the putative "hyperdynamic beta-adrenergic state." PMID:200395

  12. Pin1 promotes production of Alzheimer's amyloid {beta} from {beta}-cleaved amyloid precursor protein

    SciTech Connect

    Akiyama, Hirotada; Shin, Ryong-Woon; Uchida, Chiyoko; Kitamoto, Tetsuyuki; Uchida, Takafumi . E-mail: uchidat@cir.tohoku.ac.jp

    2005-10-21

    Here we show that prolyl isomerase Pin1 is involved in the A{beta} production central to the pathogenesis of Alzheimer's disease. Enzyme immunoassay of brains of the Pin1-deficient mice revealed that production of A{beta}40 and A{beta}42 was lower than that of the wild-type mice, indicating that Pin1 promotes A{beta} production in the brain. GST-Pin1 pull-down and immunoprecipitation assay revealed that Pin1 binds phosphorylated Thr668-Pro of C99. In the Pin1 {sup -/-} MEF transfected with C99, Pin1 co-transfection enhanced the levels of A{beta}40 and A{beta}42 compared to that without Pin1 co-transfection. In COS7 cells transfected with C99, Pin1 co-transfection enhanced the generation of A{beta}40 and A{beta}42, and reduced the expression level of C99, facilitating the C99 turnover. Thus, Pin1 interacts with C99 and promotes its {gamma}-cleavage, generating A{beta}40 and A{beta}42. Further, GSK3 inhibitor lithium blocked Pin1 binding to C99 by decreasing Thr668 phosphorylation and attenuated A{beta} generation, explaining the inhibitory effect of lithium on A{beta} generation.

  13. Antibodies to beta 1 and beta 2 adrenoreceptors in Chagas' disease.

    PubMed Central

    Sterin-Borda, L; Perez Leiros, C; Wald, M; Cremaschi, G; Borda, E

    1988-01-01

    Evidence accumulated over the last decade concerning human and experimental models suggests that an immunopathological mechanism may be involved in the pathogenesis of chronic Chagas' disease. In this paper we demonstrate the existence of two different circulating IgG in chagasic patients which bind with myocardial beta 1 and spleen cell beta 2 adrenoceptors, acting as non-competitive inhibitors. Both chagasic IgG against beta 1 and beta 2 adrenoceptor increased intracellular levels of cAMP that could be blocked by specific beta 1 and beta 2 adrenoceptor antagonists. The specificity for beta 1 and beta 2 adrenoceptors and the independence of other tissue reactive antibodies was demonstrated by IgG absorption with turkey red blood cell (TRBC), human lymphocytes (HL) or guinea pig red blood cells (GPRBC). The F(ab')2 fraction acted similarly. This supports the specificity of beta 1 and beta 2 adrenoceptors to the chagasic IgG and the independence of the other tissue reactive antibodies, such as EVI system. The probable pathogenic role of both beta 1 and beta 2 adrenergic chagasic antibody is discussed. PMID:2853016

  14. Imperfect World of beta beta-decay Nuclear Data Sets

    SciTech Connect

    Pritychenko, B.

    2015-01-03

    The precision of double-beta ββ-decay experimental half lives and their uncertainties is reanalyzed. The method of Benford's distributions has been applied to nuclear reaction, structure and decay data sets. First-digit distribution trend for ββ-decay T2v1/2 is consistent with large nuclear reaction and structure data sets and provides validation of experimental half-lives. A complementary analysis of the decay uncertainties indicates deficiencies due to small size of statistical samples, and incomplete collection of experimental information. Further experimental and theoretical efforts would lead toward more precise values of-decay half-lives and nuclear matrix elements.

  15. The Yersinia adhesin YadA collagen-binding domain structure is a novel left-handed parallel beta-roll.

    PubMed

    Nummelin, Heli; Merckel, Michael C; Leo, Jack C; Lankinen, Hilkka; Skurnik, Mikael; Goldman, Adrian

    2004-02-25

    The crystal structure of the recombinant collagen-binding domain of Yersinia adhesin YadA from Yersinia enterocolitica serotype O:3 was solved at 1.55 A resolution. The trimeric structure is composed of head and neck regions, and the collagen binding head region is a novel nine-coiled left-handed parallel beta-roll. Before the beta-roll, the polypeptide loops from one monomer to the rest, and after the beta-roll the neck region does the same, making the transition from the globular head region to the narrower stalk domain. This creates an intrinsically stable 'lock nut' structure. The trimeric form of YadA is required for collagen binding, and mutagenesis of its surface residues allowed identification of a putative collagen-binding surface. Furthermore, a new structure-sequence motif for YadA beta-roll was used to identify putative YadA-head-like domains in a variety of human and plant pathogens. Such domains may therefore be a common bacterial strategy for avoiding host response. PMID:14765110

  16. [Hemoglobin C -- beta-thalassemia disease and homozygous beta-thalassemia in a black African family (author's transl)].

    PubMed

    Basset, P; Fall, M; Oudart, J L

    1975-01-01

    The study of a Malian family has allowed to prove existence of two types of beta-thalassemia genes: the beta0 gene which suppresses the synthesis of the beta chain into cis position and the beta+ gene which slows down only partially this synthesis. The difference between this two genes has been possible owing to the hemoglobin C found in this family and induced by the betaC mutated gene. The segregation of the four genes betaA, betaC, beta0 thal, and beta+ thal. has allowed to compare all the possible phenotypes deriving from the combinations by two of these allelic genes. PMID:128735

  17. Identification of the catalytic residues of the first family of beta(1-3)glucanosyltransferases identified in fungi.

    PubMed Central

    Mouyna, I; Monod, M; Fontaine, T; Henrissat, B; Léchenne, B; Latgé, J P

    2000-01-01

    A new family of glycosylphosphatidylinositol-anchored beta(1-3)glucanosyltransferases (Gelp), recently identified and characterized in the filamentous fungus Aspergillus fumigatus, showed functional similarity to the Gas/Phr/Epd protein families, which are involved in yeast morphogenesis. Sequence comparisons and hydrophobic cluster analysis (HCA) showed that all the Gas/Phr/Epd/Gel proteins belong to a new family of glycosylhydrolases, family 72. We confirmed by site-directed mutagenesis and biochemical analysis that the two conserved glutamate residues (the putative catalytic residues of this family, as determined by HCA) are involved in the active site of this family of glycosylhydrolases. PMID:10769178

  18. Directed evolution of beta -glucosidase A from Paenibacillus polymyxa to thermal resistance.

    PubMed

    Gonzalez-Blasco, G; Sanz-Aparicio, J; Gonzalez, B; Hermoso, J A; Polaina, J

    2000-05-01

    The beta-glucosidase encoded by the bglA gene from Paenibacillus polymyxa has a half-life time of 15 min at 35 degrees C and no detectable activity at 55 degrees C. We have isolated random mutations that enhance the thermoresistance of the enzyme. Following a directed evolution strategy, we have combined some of the isolated mutations to obtain a beta-glucosidase with a half-life of 12 min at 65 degrees C, in the range of resistance of thermophilic enzymes. No significant alteration of the kinetic parameters of the enzyme was observed. One of the mutants isolated in the screening for thermoresistant beta-glucosidase had the same resistance to denaturation as the wild type. This mutation caused the accumulation of enzyme in E. coli, probably due to its lower turnover. The structural changes responsible for the properties of the mutant enzymes have been analyzed. The putative causes increasing thermoresistance are as follows: the formation of an extra salt bridge, the replacement of an Asn residue exposed to the solvent, stabilization of the hydrophobic core, and stabilization of the quaternary structure of the protein. PMID:10788490

  19. Reversible transition between alpha-helix and beta-sheet conformation of a transmembrane domain.

    PubMed

    Yassine, Wissam; Taib, Nada; Federman, Silvina; Milochau, Alexandra; Castano, Sabine; Sbi, Walid; Manigand, Claude; Laguerre, Michel; Desbat, Bernard; Oda, Reiko; Lang, Jochen

    2009-09-01

    Despite the important functions of protein transmembrane domains, their structure and dynamics are often scarcely known. The SNARE proteins VAMP/synaptobrevin and syntaxin 1 are implicated in membrane fusion. Using different spectroscopic approaches we observed a marked sensitivity of their transmembrane domain structure in regard to the lipid/peptide ratio. In the dilute condition, peptides corresponding to the complete transmembrane domain fold into an alpha-helix inserted at approximately 35 degrees to the normal of the membranes, an observation in line with molecular simulations. Upon an increase in the peptide/lipid ratio, the peptides readily exhibited transition to beta-sheet structure. Moreover, the insertion angle of these beta-sheets increased to 54 degrees and was accompanied by a derangement of lipid acyl chains. For both proteins the transition from alpha-helix to beta-sheet was reversible under certain conditions by increasing the peptide/lipid ratio. This phenomenon was observed in different model systems including multibilayers and small unilamellar vesicles. In addition, differences in peptide structure and transitions were observed when using distinct lipids (DMPC, DPPC or DOPC) thus indicating parameters influencing transmembrane domain structure and conversion from helices to sheets. The putative functional consequences of this unprecedented dynamic behavior of a transmembrane domain are discussed. PMID:19482005

  20. The COBRA Double Beta Decay Search Experiment

    NASA Astrophysics Data System (ADS)

    Stewart, D. Y.

    2006-11-01

    The COBRA experiment aims to use a large quantity of CdZnTe semiconductor detectors to search for neutrinoless double beta decay. The current status of the experiment is discussed, and new limits on several double beta modes are presented. Future plans for a large scale experiment are also described.

  1. The COBRA double-beta decay experiment

    NASA Astrophysics Data System (ADS)

    Stewart, D. Y.; COBRA Collaboration

    2007-09-01

    The COBRA experiment aims to use a large quantity of Cadmium-Zinc-Telluride (CdZnTe) semiconductor detectors to search for neutrinoless double-beta decay (0 υββ). The current status of the experiment is discussed, and new limits on several double-beta modes are presented. Future plans for a large-scale experiment are also described.

  2. Beta-agonists and animal welfare

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. Resistance to beta-lactams--the permutations.

    PubMed

    Amyes, S G B

    2003-12-01

    The beta-lactam family of antimicrobials, in particular penicillins and cephalosporins, is the mainstay of treatment for community-acquired infections. However, the emergence of resistant isolates to these agents has raised concerns regarding the continued efficacy of existing therapies. Resistance to beta-lactams is most commonly expressed by the microbial production of beta-lactamases that hydrolyze the beta-lactam ring. Three further resistance mechanisms include conformational changes in penicillin-binding proteins (PBPs); permeability changes in the outer membrane; and active efflux of the antimicrobial. In addition to the pre-requisite efficacy and tolerability profiles, new beta-lactams should address these four resistance mechanisms. Overcoming resistance may be a serendipitous event or arrived at by design. A unique synthetic beta-lactam class, which demonstrates promise in terms of its activity against the range of bacteria responsible for community-acquired infections and its inherent stability to hydrolysis by beta-lactamases, is the penems. This discrete class of hybrid molecules combines properties from the penicillin (penam) and cephalosporin (cephem) beta-lactam classes. Faropenem is an example of a penem with a broad spectrum of activity designed to address these resistance issues. PMID:14998075

  4. Interferon Beta-1a Intramuscular Injection

    MedlinePlus

    ... symptoms flare up from time to time) of multiple sclerosis (MS, a disease in which the nerves do not ... known how interferon beta-1a works to treat MS. ... doctor.Interferon beta-1a controls the symptoms of MS but does not cure it. Continue to use ...

  5. Beta maritima: the Origin of Beets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Along the undisturbed shores, especially of the Mediterranean Sea and the European North Atlantic Ocean, is a widespread plant called Beta maritima (Beta vulgaris subspecies maritima) by the botanists, or more commonly sea beet. Nothing for the inexperienced observer's eye distinguishes it from surr...

  6. The COBRA Double Beta Decay Search Experiment

    SciTech Connect

    Stewart, D. Y.

    2006-11-17

    The COBRA experiment aims to use a large quantity of CdZnTe semiconductor detectors to search for neutrinoless double beta decay. The current status of the experiment is discussed, and new limits on several double beta modes are presented. Future plans for a large scale experiment are also described.

  7. PBX: the Princeton beta experiment

    SciTech Connect

    Bol, K.; Chance, M.; Dewar, R.

    1983-09-01

    A rearrangement of the divertor coils in PDX will enable a test in 1984 of the MHD stability properties of deeply indented bean-shaped plasmas. The goal is a beta of 10%. Indentation is expected to counter the deterioration of MHD stability against pressure driven modes that is occasioned by the larger aspect ratios typical of anticipated reactor oriented devices. Indeed, as shown by M. Chance et al., indentation may offer direct access to the second region of stability for ballooning modes, and numerical analyses with PEST show the internal kink to be stabilized completely with even relatively modest indentation. The internal kink is implicated in the loss of beam ions in PDX. In this report the theoretical basis for the forthcoming experiment, and the design considerations underlying the modification from PDX to PBX, are described in detail. Additional theoretical material, including an analysis of particle orbits in an indented tokamak plasma, is appended.

  8. DREAM: Research to Operations Beta

    NASA Astrophysics Data System (ADS)

    Friedel, Reiner; Reeves, Geoffrey; Zaharia, Sorin; Koller, Josef; Chen, Yue; Henderson, Mike; Thomsen, Davis

    The Dynamic Radiation Environment Assimilation Model (DREAM) is a dataassimilative model of the Earth's radiation belts that has, until recently, been used primarily as a re-search tool to understand radiation belt dynamics and to develop Kalman filter techniques for application to magnetospheric modeling. More recently, the emphasis of the DREAM program has shifted toward implementation of an operational prototype for testing and validation at the Air Force Research Laboratory's (AFRL) Space Weather Forecast Laboratory (SWFL) and NASA's Community Coordinated Modeling Center (CCMC). The transition has required significant effort, funding, and shifting of priorities that serve as a recent example of the oppor-tunities and challenges of transitioning a model from research to operations (R2O). DREAM is still in the early stages of transition to operations but we do not see any significant obstacles to success. We present here the BETA version of this model, operating in real-time, using GOES energetic particle data as input.

  9. The chromosphere of Beta Cassiopeiae

    NASA Technical Reports Server (NTRS)

    Teays, Terry J.; Schmidt, Edward G.; Pasinetti Fracassini, Laura E.; Fracassini, Massimo

    1989-01-01

    High-resolution, long-wavelength IUE observations and ground-based photometry of the Delta Scuti star Beta Cas is reported. The ground-based observations were used together with previous results of Antonello et al. (1986) to ensure that the IUE observations were correctly phased relative to the photometric variation. Fluxes for the emission core of the Mg II k 2796-A line were obtained from the UV spectra over several cycles in 1986 and 1987. It is found that there is an increase in the emission during part of the cycle, but it occurs near minimum light in contrast to another Delta Scuti star, Rho Pup, and the classical Cepheids (where it occurs near maximum light). The mean level of chromospheric activity is comparable to other early F dwarfs.

  10. Beta-peptide bundles with fluorous cores.

    PubMed

    Molski, Matthew A; Goodman, Jessica L; Craig, Cody J; Meng, He; Kumar, Krishna; Schepartz, Alanna

    2010-03-24

    We reported recently that certain beta-peptides self-assemble spontaneously into cooperatively folded bundles whose kinetic and thermodynamic metrics mirror those of natural helix bundle proteins. The structures of four such beta-peptide bundles are known in atomic detail. These structures reveal a solvent-sequestered, hydrophobic core stabilized by a unique arrangement of leucine side chains and backbone methylene groups. Here we report that this hydrophobic core can be re-engineered to contain a fluorous subdomain while maintaining the characteristic beta-peptide bundle fold. Like alpha-helical bundles possessing fluorous cores, fluorous beta-peptide bundles are stabilized relative to hydrocarbon analogues and undergo cold denaturation. Beta-peptide bundles with fluorous cores represent the essential first step in the synthesis of orthogonal protein assemblies that can sequester selectively in an interstitial membrane environment. PMID:20196598

  11. Effect of finite. beta. on stellarator transport

    SciTech Connect

    Mynick, H.E.

    1984-04-01

    A theory of the modification of stellarator transport due to the presence of finite plasma pressure is developed, and applied to a range of stellarator configurations. For many configurations of interest, plasma transport can change by more than an order of magnitude in the progression from zero pressure to the equilibrium ..beta.. limit of the device. Thus, a stellarator with transport-optimized vacuum fields can have poor confinement at the desired operating ..beta... Without an external compensating field, increasing ..beta.. tends to degrade confinement, unless the initial field structure is very carefully chosen. The theory permits one to correctly determine this vacuum structure, in terms of the desired structure of the field at a prescribed operating ..beta... With a compensating external field, the deleterious effect of finite ..beta.. on transport can be partially eliminated.

  12. Process for reducing beta activity in uranium

    DOEpatents

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

    1986-10-07

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

  13. beta -Lactamases: which ones are clinically important?

    PubMed

    Rice, Louis B.; Bonomo, Robert A.

    2000-06-01

    The introduction of a large array of beta-lactam antibiotics has spawned the emergence of an even larger variety of beta-lactamases designed to confer resistance to these agents. beta-lactamases are produced by both gram-positive and gram-negative bacteria, but their clinical importance is far greater among the gram-negatives. The virtual explosion in our knowledge about the variety of these enzymes can often create confusion and frustration among those not well versed in the field. In this paper, we attempt to focus the discussion of beta-lactamases on those enzymes that are of the greatest clinical importance, the Ambler Class A and C enzymes. We also discuss the growing importance of the Ambler Class B metallo beta-lactamases, which hydrolyze carbapenems and are increasing in prevalence in areas of significant carbapenem usage. Copyright 2000 Harcourt Publishers Ltd. PMID:11498383

  14. Process for reducing beta activity in uranium

    DOEpatents

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

    1985-04-11

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

  15. Simultaneous beta/gamma digital spectroscopy

    NASA Astrophysics Data System (ADS)

    Farsoni, Abdollah T.

    A state-of-the-art radiation detection system for simultaneous spectroscopy of beta-particles and gamma-rays has been developed. The system utilizes a triple-layer phoswich detector and a customized Digital Pulse Processor (DPP) built in our laboratory. The DPP board was designed to digitally capture the analog signal pulses and, following several digital preprocessing steps, transfer valid pulses to the host computer for further digital processing. A MATLAB algorithm was developed to digitally discriminate beta and gamma events and reconstruct separate beta and gamma-ray energy spectra with minimum crosstalk. The spectrometer proved to be an effective tool for recording separate beta and gamma-ray spectra from mixed radiation fields. The system as a beta-gamma spectrometer will have broad-ranging applications in nuclear non-proliferation, radioactive waste management, worker safety, systems reliability, dose assessment, and risk analysis.

  16. Process for reducing beta activity in uranium

    DOEpatents

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

    1986-01-01

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

  17. Gamma-ray blind beta particle probe

    DOEpatents

    Weisenberger, Andrew G.

    2001-01-01

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

  18. Beta Pictoris planet finally imaged?

    NASA Astrophysics Data System (ADS)

    2008-11-01

    A team of French astronomers using ESO's Very Large Telescope have discovered an object located very close to the star Beta Pictoris, and which apparently lies inside its disc. With a projected distance from the star of only 8 times the Earth-Sun distance, this object is most likely the giant planet suspected from the peculiar shape of the disc and the previously observed infall of comets onto the star. It would then be the first image of a planet that is as close to its host star as Saturn is to the Sun. Sharpening Up Jupiter ESO PR Photo 42a/08 Beta Pictoris as seen in infrared light The hot star Beta Pictoris is one of the best-known examples of stars surrounded by a dusty 'debris' disc. Debris discs are composed of dust resulting from collisions among larger bodies like planetary embryos or asteroids. They are a bigger version of the zodiacal dust in our Solar System. Its disc was the first to be imaged -- as early as 1984 -- and remains the best-studied system. Earlier observations showed a warp of the disc, a secondary inclined disc and infalling comets onto the star. "These are indirect, but tell-tale signs that strongly suggest the presence of a massive planet lying between 5 and 10 times the mean Earth-Sun distance from its host star," says team leader Anne-Marie Lagrange. "However, probing the very inner region of the disc, so close to the glowing star, is a most challenging task." In 2003, the French team used the NAOS-CONICA instrument (or NACO [1]), mounted on one of the 8.2 m Unit Telescopes of ESO's Very Large Telescope (VLT), to benefit from both the high image quality provided by the Adaptive Optics system at infrared wavelengths and the good dynamics offered by the detector, in order to study the immediate surroundings of Beta Pictoris. Recently, a member of the team re-analysed the data in a different way to seek the trace of a companion to the star. Infrared wavelengths are indeed very well suited for such searches. "For this, the real challenge

  19. Genetics Home Reference: mucolipidosis III alpha/beta

    MedlinePlus

    ... Health Conditions mucolipidosis III alpha/beta mucolipidosis III alpha/beta Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Mucolipidosis III alpha/beta is a slowly progressive disorder that affects ...

  20. Genetics Home Reference: mucolipidosis II alpha/beta

    MedlinePlus

    ... Health Conditions mucolipidosis II alpha/beta mucolipidosis II alpha/beta Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Mucolipidosis II alpha/beta (also known as I-cell disease) is ...

  1. Genistein, the Isoflavone in Soybean, Causes Amyloid Beta Peptide Accumulation in Human Neuroblastoma Cell Line: Implications in Alzheimer's Disease.

    PubMed

    Chatterjee, Gargi; Roy, Debashree; Khemka, Vineet Kumar; Chattopadhyay, Mrittika; Chakrabarti, Sasanka

    2015-11-01

    The isoflavone, genistein, present in soybean is being actively investigated for its potential beneficial effect against Alzheimer's disease. Our data, however, show that in SHSY5Y cells genistein causes increased expression (mRNA and protein) of amyloid precursor protein (APP), increased mRNA expression and activity of β-secretase and diminished level of insulin degrading enzyme (IDE) which also degrades amyloid beta peptide. These effects of genistein lead to enhanced accumulation of amyloid beta peptide (Aβ42) in SHSY5Y cells. The results do not support the view that genistein could be a putative drug against AD and instead strengthen the epidemiological study which implies that genistein content of soybean food product (Tofu) leads to cognitive impairment. PMID:26618047

  2. A molecular and biochemical analysis of the structure of the cyanogenic beta-glucosidase (linamarase) from cassava (Manihot esculenta Cranz).

    PubMed

    Hughes, M A; Brown, K; Pancoro, A; Murray, B S; Oxtoby, E; Hughes, J

    1992-06-01

    The cyanogenic beta-glucosidase (linamarase) of cassava is responsible for the first step in the sequential break-down of two related cyanoglucosides. Hydrolysis of these cyanoglucosides occurs following tissue damage and leads to the production of hydrocyanic acid. This mechanism is widely regarded as a defense mechanism against predation. A linamarase cDNA clone (pCAS5) was isolated from a cotyledon cDNA library using a white clover beta-glucosidase heterologous probe. The nucleotide and derived amino acid sequence is reported and five putative N-asparagine glycosylation sites are identified. Concanavalin A affinity chromatography and endoglycosidase H digestion demonstrate that linamarase from cassava is glycosylated, having high-mannose-type N-asparagine-linked oligosaccharides. Consistent with this structure and the extracellular location of the active enzyme is the identification of an N-terminal signal peptide on the deduced amino acid sequence of pCAS5. PMID:1586156

  3. Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin {beta}E subunit

    SciTech Connect

    Hashimoto, Osamu . E-mail: ohashim@vmas.kitasato-u.ac.jp; Ushiro, Yuuki; Sekiyama, Kazunari; Yamaguchi, Osamu; Yoshioka, Kazuki; Mutoh, Ken-Ichiro; Hasegawa, Yoshihisa

    2006-03-10

    Activins, TGF-{beta} superfamily members, have multiple functions in a variety of cells and tissues. Recently, additional activin {beta} subunit genes, {beta}C and {beta}E, have been identified. To explore the role of activin E, we created transgenic mice overexpressing human activin {beta}E subunit. There were pronounced differences in the pancreata of the transgenic animals as compared with their wild-type counterparts. Pancreatic weight, expressed relative to total body weight, was significantly reduced. Histologically, adipose replacement of acini in the exocrine pancreas was observed. There was a significant decrease in the number of PCNA-positive cells in the acinar cells, indicating reduced proliferation in the exocrine pancreas of the transgenic mice. However, quantitative pancreatic morphometry showed that the total number and mass of the islets of the transgenic mice were comparable with those of the nontransgenic control mice. Our findings suggest a role for activin E in regulating the proliferation of pancreatic exocrine cells.

  4. Increased cAMP levels modulate transforming growth factor-beta/Smad-induced expression of extracellular matrix components and other key fibroblast effector functions.

    PubMed

    Schiller, Meinhard; Dennler, Sylviane; Anderegg, Ulf; Kokot, Agatha; Simon, Jan C; Luger, Thomas A; Mauviel, Alain; Böhm, Markus

    2010-01-01

    cAMP is a key messenger of many hormones and neuropeptides, some of which modulate the composition of extracellular matrix. Treatment of human dermal fibroblasts with dibutyryl cyclic AMP and forskolin antagonized the inductive effects of transforming growth factor-beta (TGF-beta) on the expression of collagen, connective tissue growth factor, tissue inhibitor of matrix metalloproteinase-1, and plasminogen activator inhibitor type I, four prototypical TGF-beta-responsive genes. Increased intracellular cAMP prevented TGF-beta-induced Smad-specific gene transactivation, although TGF-beta-mediated Smad phosphorylation and nuclear translocation remained unaffected. However, increased cAMP levels abolished TGF-beta-induced interaction of Smad3 with its transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP)/p300. Overexpression of the transcriptional co-activator CBP/p300 rescued Smad-specific gene transcription in the presence of cAMP suggesting that sequestration of limited amounts of CBP/p300 by the activated cAMP/CREB pathway is the molecular basis of this inhibitory effect. These findings were extended by two functional assays. Increased intracellular cAMP levels suppressed the inductive activity of TGF-beta to contract mechanically unloaded collagen lattices and resulted in an attenuation of fibroblast migration of mechanically induced cell layer wounds. Of note, cAMP and TGF-beta synergistically induced hyaluronan synthase 2 (HAS2) expression and hyaluronan secretion, presumably via putative CREB-binding sites adjacent to Smad-binding sites within the HAS2 promoter. Our findings identify the cAMP pathway as a potent but differential and promoter-specific regulator of TGF-beta-mediated effects involved in extracellular matrix homeostasis. PMID:19858184

  5. An update on newer beta-lactamases.

    PubMed

    Gupta, Varsha

    2007-11-01

    The resistance to beta-lactam antibiotics is an increasing problem worldwide and beta lactamases production is the most common mechanism of drug resistance. Both global and Indian figures showed a marked increase in the number of beta-lactamases producing organisms. These enzymes extended spectrum beta-lactamases (ESBLs) are numerous and continuous mutation has led to the development of enzymes having expanded substrate profile. To date, there are more than 130 TEM type and more than 50 sulphydryl variable (SHV) type beta-lactamases found in Gram negative bacilli. ESBL producing Enterobacteriaceae are, as a rule, resistant to all cephalosporins and extended spectrum penicillins including the monobactam, aztreonam, while resistance to trimethoprim - sulphamethaxazole and aminoglycosides is frequently co-transferred on the same plasmid. Many ESBL producing organisms also express Amp C beta-lactamases. Amp C- beta-lactamases are clinically significant, as these confer resistance to cephalosporins in the oxyimino group, 7 alpha-methoxy cephalosporins, and are poorly inhibited by clavulanic acid. Carbepenems are the drugs of choice for the treatment of infections caused by ESBL producing organisms but carbapenemases (MBLs) have emerged and have spread from Pseudomonas aeruginosa to Enterobacteriaceae. The routine clinical microbiology laboratories should employ simple methods to recognize these enzymes using various substrates and inhibitors. These organisms may lead to therapeutic dead ends. Presently, the therapy relies on beta-lactam/ beta-lactamases inhibitor combinations, carbepenems and piperacillin - tazobactam plus aminoglycoside combination. Proper infection control practices and barrier precautions are essential to contain the organisms producing beta-lactamases. PMID:18160745

  6. Beta-dosimetry studies at LLNL

    SciTech Connect

    Hankins, D.E.

    1983-01-01

    This paper summarizes three beta-dosimetry studies made recently at the Lawrence Livermore National Laboratory. The first study was to determine the beta-gamma exposure rates at the Los Alamos Godiva IV Critical Assembly. The beta spectra from the assembly were evaluated using absorption curves and the beta-gamma dose-rate ratios were determined at various distances from the assembly. A comparison was made of the doses determined using two types of TLD personnel dosimeters and a film badge. The readings of an Eberline RO-7 instrument and the dose rates determined by TLDs were compared. Shielding provided by various metals, gloves, and clothing were measured. The second study was to determine the beta energy response of the Eberline RO-7 instrument based on measurements made with the PTB beta sources. This study required additional calibration points for the PTB sources which were made using extrapolation chamber measurements. The third study resulted in two techniques to determine the beta energy (E/sub max/) from the readings of this-window portable survey instruments. Both techniques are based on the readings obtained using aluminium filters. One technique is for field application, requires one filter, and provides a quick estimate of the beta energy in three energy groups: < 0.5 MeV, 0.5 MeV to 1.5 MeV and > 1.5 MeV. The second technique is more complex requiring measurements with two or three filters, but gives the beta energy and the approximate shape of the beta spectrum. 9 references, 6 figures.

  7. First Human Case of Fungal Keratitis Caused by a Putatively Novel Species of Lophotrichus.

    PubMed

    Eghrari, Allen O; Gibas, Connie; Watkins, Tonya; Vahedi, Sina; Lee, Rick; Houle, Elizabeth; Suarez, Maria Jose; Eberhart, Charles; Sutton, Deanna A; Wiederhold, Nathan P; Sikder, Shameema; Zhang, Sean X

    2015-09-01

    We report an aggressive fungal keratitis caused by a putatively novel species of Lophotrichus in a patient with traumatic injury to the cornea from a dog paw. The organism was isolated from the patient's necrotic cornea, which perforated despite coverage with hourly fortified broad-spectrum topical antibiotic therapy. This report represents the first case of human infection caused by this species. PMID:26109445

  8. First Human Case of Fungal Keratitis Caused by a Putatively Novel Species of Lophotrichus

    PubMed Central

    Eghrari, Allen O.; Gibas, Connie; Watkins, Tonya; Vahedi, Sina; Lee, Rick; Houle, Elizabeth; Suarez, Maria Jose; Eberhart, Charles; Sutton, Deanna A.; Wiederhold, Nathan P.

    2015-01-01

    We report an aggressive fungal keratitis caused by a putatively novel species of Lophotrichus in a patient with traumatic injury to the cornea from a dog paw. The organism was isolated from the patient's necrotic cornea, which perforated despite coverage with hourly fortified broad-spectrum topical antibiotic therapy. This report represents the first case of human infection caused by this species. PMID:26109445

  9. Diet Does Not Affect Putative Mammary Epithelial Stem Cells in Pre-weaned Holstein Heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Overfeeding prepubertal heifers can impair mammary epithelial growth and development, processes that depend on stem cells. In this study we evaluated effects of diet composition on putative bovine mammary epithelial stem cell populations using a 5-bromo-2-deoxyrudine (BrdU; a thymidine analog) label...

  10. A rapid approach to evaluate putative nursery sites for penaeid prawns

    NASA Astrophysics Data System (ADS)

    Taylor, Matthew D.; Smith, James A.; Boys, Craig A.; Whitney, Hannah

    2016-08-01

    Identifying nursery habitats for an aquatic species generally requires tracing adult individuals back through time and space to the area or habitat in which they developed as juveniles. We develop and trial a study design and analytical approach to evaluate the suitability of using stable isotopes to trace emigrating prawns to putative nursery sites, and evaluate assumptions inherent in the application of the approach using two penaeid species with Type-II life cycles: Penaeus (Melicertus) plebejus and Metapenaeus macleayi. Prawns were collected in putative nursery sites within the Hunter River, Australia, and analysed as composite samples of 6 individuals to provide habitat-specific isotopic signatures. Prawns emigrating from the mouth of the river were used as a proxy for individuals recruiting to the adult population, and assigned to putative nursery sites using a probabilistic mixing model and a simple, distance-based approach. Bivariate (δ15N and δ13C) isotopic data was sufficient to distinguish prawns from different putative nursery sites, and isotopic composition correlated closely with salinity. Approximately 90% of emigrating prawns collected could be assigned to these sites using bivariate isotopic data, and both analytical approaches gave similar results. The design developed here is broadly applicable to a suite of penaeid species, but its application will be most powerful when sampling is also aimed at understanding nursery function by simultaneous monitoring of size structure/growth, density, and trophic relationships within nursery habitats.

  11. Crystal structure and putative substrate identification for the Entamoeba histolytica low molecular weight tyrosine phosphatase.

    PubMed

    Linford, Alicia S; Jiang, Nona M; Edwards, Thomas E; Sherman, Nicholas E; Van Voorhis, Wesley C; Stewart, Lance J; Myler, Peter J; Staker, Bart L; Petri, William A

    2014-01-01

    Entamoeba histolytica is a eukaryotic intestinal parasite of humans, and is endemic in developing countries. We have characterized the E. histolytica putative low molecular weight protein tyrosine phosphatase (LMW-PTP). The structure for this amebic tyrosine phosphatase was solved, showing the ligand-induced conformational changes necessary for binding of substrate. In amebae, it was expressed at low but detectable levels as detected by immunoprecipitation followed by immunoblotting. A mutant LMW-PTP protein in which the catalytic cysteine in the active site was replaced with a serine lacked phosphatase activity, and was used to identify a number of trapped putative substrate proteins via mass spectrometry analysis. Seven of these putative substrate protein genes were cloned with an epitope tag and overexpressed in amebae. Five of these seven putative substrate proteins were demonstrated to interact specifically with the mutant LMW-PTP. This is the first biochemical study of a small tyrosine phosphatase in Entamoeba, and sets the stage for understanding its role in amebic biology and pathogenesis. PMID:24548880

  12. Crystal structure and putative substrate identification for the Entamoeba histolytica low molecular weight tyrosine phosphatase

    PubMed Central

    Linford, Alicia S.; Jiang, Nona M.; Edwards, Thomas E.; Sherman, Nicholas E.; Van Voorhis, Wesley C.; Stewart, Lance J.; Myler, Peter J.; Staker, Bart L.; Petri, William A.

    2014-01-01

    Entamoeba histolytica is a eukaryotic intestinal parasite of humans, and is endemic in developing countries. We have characterized the E. histolytica putative low molecular weight protein tyrosine phosphatase (LMW-PTP). The structure for this amebic tyrosine phosphatase was solved, showing the ligand-induced conformational changes necessary for binding of substrate. In amebae, it was expressed at low but detectable levels as detected by immunoprecipitation followed by immunoblotting. A mutant LMW-PTP protein in which the catalytic cysteine in the active site was replaced with a serine lacked phosphatase activity, and was used to identify a number of trapped putative substrate proteins via mass spectrometry analysis. Seven of these putative substrate protein genes were cloned with an epitope tag and overexpressed in amebae. Five of these seven putative substrate proteins were demonstrated to interact specifically with the mutant LMW-PTP. This is the first biochemical study of a small tyrosine phosphatase in Entamoeba, and sets the stage for understanding its role in amebic biology and pathogenesis. PMID:24548880

  13. Complete Genome Sequence of a Putative Densovirus of the Asian Citrus Psyllid, Diaphorina citri

    PubMed Central

    Nigg, Jared C.; Nouri, Shahideh

    2016-01-01

    Here, we report the complete genome sequence of a putative densovirus of the Asian citrus psyllid, Diaphorina citri. Diaphorina citri densovirus (DcDNV) was originally identified through metagenomics, and here, we obtained the complete nucleotide sequence using PCR-based approaches. Phylogenetic analysis places DcDNV between viruses of the Ambidensovirus and Iteradensovirus genera. PMID:27469948

  14. Diversity of putative archaeal RNA viruses in metagenomic datasets of a yellowstone acidic hot spring.

    PubMed

    Wang, Hongming; Yu, Yongxin; Liu, Taigang; Pan, Yingjie; Yan, Shuling; Wang, Yongjie

    2015-01-01

    Two genomic fragments (5,662 and 1,269 nt in size, GenBank accession no. JQ756122 and JQ756123, respectively) of novel, positive-strand RNA viruses that infect archaea were first discovered in an acidic hot spring in Yellowstone National Park (Bolduc et al., 2012). To investigate the diversity of these newly identified putative archaeal RNA viruses, global metagenomic datasets were searched for sequences that were significantly similar to those of the viruses. A total of 3,757 associated reads were retrieved solely from the Yellowstone datasets and were used to assemble the genomes of the putative archaeal RNA viruses. Nine contigs with lengths ranging from 417 to 5,866 nt were obtained, 4 of which were longer than 2,200 nt; one contig was 204 nt longer than JQ756122, representing the longest genomic sequence of the putative archaeal RNA viruses. These contigs revealed more than 50% sequence similarity to JQ756122 or JQ756123 and may be partial or nearly complete genomes of novel genogroups or genotypes of the putative archaeal RNA viruses. Sequence and phylogenetic analyses indicated that the archaeal RNA viruses are genetically diverse, with at least 3 related viral lineages in the Yellowstone acidic hot spring environment. PMID:25918685

  15. Identification, recombinant expression, and biochemical analysis of putative secondary product glucosyltransferases from Citrus paradisi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavonoid and limonoid glycosides influence taste properties as well as marketability of citrus fruit and products, particularly in grapefruit. In this work, nine grapefruit putative natural product glucosyltransferases (PGTs) were resolved by either using degenerate primers against the semi-conser...

  16. Blueberry mosaic associated virus – A putative, new member of Ophioviridae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blueberry mosaic initially was reported more than 50 years ago and is now known from different parts of the world. A new virus, closely associated with the disease has been identified recently. The virus tentatively named as Blueberry mosaic associated virus (BlMaV), is a putative member of the gen...

  17. Purification and characterization pecan (Carya Illinoinensis) vicilin, a putative food allergen (abstract)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pecan seed storage protein vicilin, a putative food allergen, was recombinantly expressed for and purified by a combination of metal affinity and gel filtration chromatography. The protein was crystallized and studied by crystallography. The obtained crystals belonged to space group P212121 with...

  18. An in-house multiplex pcr method to detect of putative virulence factors in aeromonas species

    PubMed Central

    Aguilera-Arreola, Ma. Guadalupe; Martínez, Alma Aidee Carmona; Castro-Escarpulli, Graciela

    2011-01-01

    A pentaplex PCR was developed and optimised to detect the genes that encode the five most important putative virulence factors in Aeromonas isolates. It seems to be more efficient than previously reported techniques and promises to be a powerful tool for more accurate risk assessments and for monitoring pathogenic strains. PMID:24031758

  19. Complete Coding Genome Sequence of Putative Novel Bluetongue Virus Serotype 27

    PubMed Central

    Jenckel, Maria; Bréard, Emmanuel; Schulz, Claudia; Sailleau, Corinne; Viarouge, Cyril; Hoffmann, Bernd; Beer, Martin; Zientara, Stéphan

    2015-01-01

    We announce the complete coding genome sequence of a novel bluetongue virus (BTV) serotype (BTV-n = putative BTV-27) detected in goats in Corsica, France, in 2014. Sequence analysis confirmed the closest relationship between sequences of the novel BTV serotype and BTV-25 and BTV-26, recently discovered in Switzerland and Kuwait, respectively. PMID:25767218

  20. Complete Genome Sequence of a Putative Densovirus of the Asian Citrus Psyllid, Diaphorina citri.

    PubMed

    Nigg, Jared C; Nouri, Shahideh; Falk, Bryce W

    2016-01-01

    Here, we report the complete genome sequence of a putative densovirus of the Asian citrus psyllid, Diaphorina citri Diaphorina citri densovirus (DcDNV) was originally identified through metagenomics, and here, we obtained the complete nucleotide sequence using PCR-based approaches. Phylogenetic analysis places DcDNV between viruses of the Ambidensovirus and Iteradensovirus genera. PMID:27469948

  1. Isolation and characterization of 17 different genes encoding putative endopolygalacturonase genes from Rhizopus oryzae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polygalacturonase enzymes are a valuable aid in the retting of flax for production of linens and, more recently, production of biofuels from citrus wastes. In a search of the recently sequenced Rhizopus oryzae strain 99-880 genome database, 18 putative endopolygalacturonase genes were identified, w...

  2. Beta-aminopeptidase-catalyzed biotransformations of beta(2)-dipeptides: kinetic resolution and enzymatic coupling.

    PubMed

    Heck, Tobias; Reimer, Artur; Seebach, Dieter; Gardiner, James; Deniau, Gildas; Lukaszuk, Aneta; Kohler, Hans-Peter E; Geueke, Birgit

    2010-05-17

    We have previously shown that the beta-aminopeptidases BapA from Sphingosinicella xenopeptidilytica and DmpA from Ochrobactrum anthropi can catalyze reactions with non-natural beta(3)-peptides and beta(3)-amino acid amides. Here we report that these exceptional enzymes are also able to utilize synthetic dipeptides with N-terminal beta(2)-amino acid residues as substrates under aqueous conditions. The suitability of a beta(2)-peptide as a substrate for BapA or DmpA was strongly dependent on the size of the C(alpha) substituent of the N-terminal beta(2)-amino acid. BapA was shown to convert a diastereomeric mixture of the beta(2)-peptide H-beta(2)hPhe-beta(2)hAla-OH, but did not act on diastereomerically pure beta(2),beta(3)-dipeptides containing an N-terminal beta(2)-homoalanine. In contrast, DmpA was only active with the latter dipeptides as substrates. BapA-catalyzed transformation of the diastereomeric mixture of H-beta(2)hPhe-beta(2)hAla-OH proceeded along two highly S-enantioselective reaction routes, one leading to substrate hydrolysis and the other to the synthesis of coupling products. The synthetic route predominated even at neutral pH. A rise in pH of three log units shifted the synthesis-to-hydrolysis ratio (v(S)/v(H)) further towards peptide formation. Because the equilibrium of the reaction lies on the side of hydrolysis, prolonged incubation resulted in the cleavage of all peptides that carried an N-terminal beta-amino acid of S configuration. After completion of the enzymatic reaction, only the S enantiomer of beta(2)-homophenylalanine was detected (ee>99 % for H-(S)-beta(2)-hPhe-OH, E>500); this confirmed the high enantioselectivity of the reaction. Our findings suggest interesting new applications of the enzymes BapA and DmpA for the production of enantiopure beta(2)-amino acids and the enantioselective coupling of N-terminal beta(2)-amino acids to peptides. PMID:20340152

  3. The crystal structure of porcine reproductive and respiratory syndrome virus nonstructural protein Nsp1beta reveals a novel metal-dependent nuclease.

    PubMed

    Xue, Fei; Sun, Yuna; Yan, Liming; Zhao, Cong; Chen, Ji; Bartlam, Mark; Li, Xuemei; Lou, Zhiyong; Rao, Zihe

    2010-07-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the Arteriviridae family of Nidovirales, is the causative agent of porcine reproductive and respiratory syndrome, which results in enormous economic losses in the swine industry. As the second protein encoded by the PRRSV genome, nsp1beta cleaves itself from the downstream nsp2 protein via a C-terminal papain-like cysteine protease (PCP) domain. Although nsp1beta is known to be involved in virulence, its precise role in the process of viral infection remains unclear. In this work, we describe the homodimeric crystal structure of PRRSV nsp1beta in its natural, self-processed form. We show that the architecture of its N-terminal domain (NTD) adopts a fold closely resembling that of several known nucleases and has intrinsic nuclease activity that is strongly activated by manganese ions in vitro. Key features, however, distinguish nsp1beta from characterized nucleases, including the C-terminal PCP domain (which is responsible for the self-release of nsp1beta from nsp2), a linker domain (LKD) that connects the NTD and the PCP domain, and a C-terminal extension (CTE) that binds to and is stabilized by the putative substrate binding site of the PCPbeta domain. Combined with the reported nuclear localization of this protein, these results shed light on the self-processing mode and precise biological function of nsp1beta and thus offer a multitarget template for future drug discovery. PMID:20410261

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

    PubMed Central

    Wade, Cian; Brown, Peter

    2016-01-01

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

  5. Putative pore-loops of TMEM16/anoctamin channels affect channel density in cell membranes.

    PubMed

    Adomaviciene, Aiste; Smith, Keith J; Garnett, Hannah; Tammaro, Paolo

    2013-07-15

    The recently identified TMEM16/anoctamin protein family includes Ca(2+)-activated anion channels (TMEM16A, TMEM16B), a cation channel (TMEM16F) and proteins with unclear function. TMEM16 channels consist of eight putative transmembrane domains (TMs) with TM5-TM6 flanking a re-entrant loop thought to form the pore. In TMEM16A this region has also been suggested to contain residues involved in Ca(2+) binding. The role of the putative pore-loop of TMEM16 channels was investigated using a chimeric approach. Heterologous expression of either TMEM16A or TMEM16B resulted in whole-cell anion currents with very similar conduction properties but distinct kinetics and degrees of sensitivity to Ca(2+). Furthermore, whole-cell currents mediated by TMEM16A channels were ∼six times larger than TMEM16B-mediated currents. Replacement of the putative pore-loop of TMEM16A with that of TMEM16B (TMEM16A-B channels) reduced the currents by ∼six-fold, while the opposite modification (TMEM16B-A channels) produced a ∼six-fold increase in the currents. Unexpectedly, these changes were not secondary to variations in channel gating by Ca(2+) or voltage, nor were they due to changes in single-channel conductance. Instead, they depended on the number of functional channels present on the plasma membrane. Generation of additional, smaller chimeras within the putative pore-loop of TMEM16A and TMEM16B led to the identification of a region containing a non-canonical trafficking motif. Chimeras composed of the putative pore-loop of TMEM16F transplanted into the TMEM16A protein scaffold did not conduct anions or cations. These data suggest that the putative pore-loop does not form a complete, transferable pore domain. Furthermore, our data reveal an unexpected role for the putative pore-loop of TMEM16A and TMEM16B channels in the control of the whole-cell Ca(2+)-activated Cl(-) conductance. PMID:23613533

  6. Triiodothyronine receptor beta-2 messenger ribonucleic acid expression by somatotropes and thyrotropes: effect of propylthiouracil-induced hypothyroidism in rats.

    PubMed

    Childs, G V; Taub, K; Jones, K E; Chin, W W

    1991-11-01

    mRNA for a thyroid hormone receptor isoform that is unique to the pituitary gland (TR beta-2) is down-regulated by T3. Increases in the expression of this mRNA are seen in rats rendered hypothyroid by treatment with propylthiouracil (PTU). This study used dual labeling to determine which pituitary cells expressed TR beta-2 mRNA in normal and PTU-treated rats. In situ hybridization protocols localized the mRNA (with biotinylated complementary oligonucleotide probes detected by avidin-biotin-peroxidase), and immunoperoxidase protocols identified the pituitary hormone proteins. In dispersed pituitary cells, 20 +/- 2% (average +/- SD) of cells from normal rats and 30 +/- 3% of cells from PTU-treated rats were labeled for TR beta-2 mRNA. PTU caused increases in the area of the labeled cells (from 114 +/- 11 to 225 +/- 7 microns 2), the area of the label per cell (from 27 +/- 3 to 71 +/- 11 microns 2), and label density. PTU produced increases in the percentage of TSH cells from 8 +/- 1% to 19 +/- 2%, decreases in the percentage of GH cells from 27 +/- 3% to 11 +/- 2%, and no change in other cell types. After dual labeling, 73% of cells that expressed TR beta-2 mRNA stored either TSH (35 +/- 8) or GH (38 +/- 6). Less than 10% stored other hormones. When each cell type was analyzed, 56 +/- 3% of TSH cells and 43 +/- 4% of GH cells expressed TR beta-2 mRNA. When these percentages were multiplied by the percentages of each cell type in the overall population, TSH and GH cells with TR beta-2 mRNA represented 6.8 +/- 1% and 11.6 +/- 1% of the pituitary cells, respectively. Less than 1% of all pituitary cells expressed TR beta-2 and ACTH (0.9 +/- 0.06), LH (0.8 +/- 0.1), FSH (0.8 +/- 0.1), and PRL (0.9 +/- 0.04). PTU treatment increased the percentage of TSH cells with TR beta-2 mRNA to 72 +/- 4% and decreased the percentage of GH cells with TR beta-2 mRNA to 30 +/- 3%. However, some enlarged putative TSH cells could not be identified by immunolabel because the storage levels

  7. Synthesis of novel heterobranched beta-cyclodextrins having beta-D-N-acetylglucosaminyl-maltotriose on the side chain.

    PubMed

    Tanimoto, Toshiko; Omatsu, Mizue; Ikuta, Akiko; Nishi, Yuki; Murakami, Hiromi; Nakano, Hirofumi; Kitahata, Sumio

    2005-04-01

    From a mixture of N-acetylglucosaminyl-beta-cyclodextrin (GlcNAc-betaCD) and lactose, beta-D-galactosyl-GlcNAc-betaCD (Gal-GlcNAc-betaCD) was synthesized by the transfer action of beta-galactosidase. GlcNAc-maltotriose (Glc3) and Gal-GlcNAc-Glc3 were produced with hydrolysis of GlcNAc-betaCD by cyclodextrin glycosyltransferase, and Gal-GlcNAc-betaCD by bacterial saccharifying alpha-amylase respectively. Finally, GlcNAc-Glc3-betaCD and Gal-GlcNAc-Glc3-betaCD were synthesized in 5.2% and 3.5% yield when Klebsiella pneumoniae pullulanase was incubated with the mixture of GlcNAc-Glc(3) and betaCD, or Gal-GlcNAc-Glc3 and betaCD respectively. The structures of GlcNAc-Glc3-betaCD and Gal-GlcNAc-Glc3-betaCD were analyzed by FAB-MS and NMR spectroscopy and identified as 6-O-alpha-(6(3)-O-beta-D-N-acetylglucosaminyl-maltotriosyl)-betaCD, and 6-O-alpha-(4-O-beta-D-galactopyranosyl-6(3)-O-beta-D-N-acetylglucosaminyl-maltotriosyl)-betaCD respectively. PMID:15849411

  8. Dissection of upstream regulatory components of the Rho1p effector, 1,3-beta-glucan synthase, in Saccharomyces cerevisiae.

    PubMed Central

    Sekiya-Kawasaki, Mariko; Abe, Mitsuhiro; Saka, Ayaka; Watanabe, Daisuke; Kono, Keiko; Minemura-Asakawa, Masayo; Ishihara, Satoru; Watanabe, Takahide; Ohya, Yoshikazu

    2002-01-01

    In the budding yeast Saccharomyces cerevisiae, one of the main structural components of the cell wall is 1,3-beta-glucan produced by 1,3-beta-glucan synthase (GS). Yeast GS is composed of a putative catalytic subunit encoded by FKS1 and FKS2 and a regulatory subunit encoded by RHO1. A combination of amino acid alterations in the putative catalytic domain of Fks1p was found to result in a loss of the catalytic activity. To identify upstream regulators of 1,3-beta-glucan synthesis, we isolated multicopy suppressors of the GS mutation. We demonstrate that all of the multicopy suppressors obtained (WSC1, WSC3, MTL1, ROM2, LRE1, ZDS1, and MSB1) and the constitutively active RHO1 mutations tested restore 1,3-beta-glucan synthesis in the GS mutant. A deletion of either ROM2 or WSC1 leads to a significant defect of 1,3-beta-glucan synthesis. Analyses of the degree of Mpk1p phosphorylation revealed that among the multicopy suppressors, WSC1, ROM2, LRE1, MSB1, and MTL1 act positively on the Pkc1p-MAPK pathway, another signaling pathway regulated by Rho1p, while WSC3 and ZDS1 do not. We have also found that MID2 acts positively on Pkc1p without affecting 1,3-beta-glucan synthesis. These results suggest that distinct networks regulate the two effector proteins of Rho1p, Fks1p and Pkc1p. PMID:12399379

  9. Identification and functional characterization of a putative IDE, C28F5.4 (ceIDE-1), in Caenorhabditis elegans: Implications for Alzheimer's disease.

    PubMed

    Haque, Rizwanul; Nazir, Aamir

    2016-11-01

    Insulin-degrading enzyme (IDE) is a zinc metalloprotease, known to degrade insulin peptide and amyloid-beta (Aβ); the key protein involved in Alzheimer's disease (AD). Considering the important role played by IDE in disease progression of AD and type 2 diabetes mellitus (T2DM), we endeavored to identify the Caenorhabditis elegans (C. elegans) IDE orthologous genes and test them for their role in AD related outcomes. We employed bioinformatics, reverse genetics and molecular biology approaches towards identification and functional characterization of putative IDE candidates in C. elegans. Using in-silico analysis we have identified seven C. elegans genes that possess HXXEH motif, an identifying marker of IDE. We further carried out functional analysis of the identified genes in Aβ expressing C. elegans strain CL4176 [myo-3/Aβ1-42 long 3'-UTR] via studying effect on Aβ induced toxicity, cholinergic neuroanatomy, content of acetylcholine/acetylcholine-esterase, extent of reactive oxygen species and expression of FOXO transcription factor DAF-16. Our findings reveal that amongst the identified putative IDE orthologs, a functionally uncharacterized gene C28F5.4 had a profound effect on the tested endpoints. Knocking down C28F5.4 modulated the AD associated conditions by decreasing Aβ induced toxicity, severely compromising cholinergic neuroanatomy, reducing expression of acetylcholine-transporter, decreasing acetylcholine content, elevating ROS, with no effect on DAF-16 stress-response protein. These studies provide crucial insight into the structural/functional orthology of IDEs across human and nematode species and further our understanding of the involvement of these proteins and insulin pathway in AD. Further studies could aid in identifying novel drug-targets and in understanding the common modulating factors between AD and T2DM. PMID:27443962

  10. The crystal structure of M. leprae ML2640c defines a large family of putative S-adenosylmethionine-dependent methyltransferases in mycobacteria.

    PubMed

    Graña, Martin; Haouz, Ahmed; Buschiazzo, Alejandro; Miras, Isabelle; Wehenkel, Annemarie; Bondet, Vincent; Shepard, William; Schaeffer, Francis; Cole, Stewart T; Alzari, Pedro M

    2007-09-01

    Mycobacterium leprae protein ML2640c belongs to a large family of conserved hypothetical proteins predominantly found in mycobacteria, some of them predicted as putative S-adenosylmethionine (AdoMet)-dependent methyltransferases (MTase). As part of a Structural Genomics initiative on conserved hypothetical proteins in pathogenic mycobacteria, we have determined the structure of ML2640c in two distinct crystal forms. As expected, ML2640c has a typical MTase core domain and binds the methyl donor substrate AdoMet in a manner consistent with other known members of this structural family. The putative acceptor substrate-binding site of ML2640c is a large internal cavity, mostly lined by aromatic and aliphatic side-chain residues, suggesting that a lipid-like molecule might be targeted for catalysis. A flap segment (residues 222-256), which isolates the binding site from the bulk solvent and is highly mobile in the crystal structures, could serve as a gateway to allow substrate entry and product release. The multiple sequence alignment of ML2640c-like proteins revealed that the central alpha/beta core and the AdoMet-binding site are very well conserved within the family. However, the amino acid positions defining the binding site for the acceptor substrate display a higher variability, suggestive of distinct acceptor substrate specificities. The ML2640c crystal structures offer the first structural glimpses at this important family of mycobacterial proteins and lend strong support to their functional assignment as AdoMet-dependent methyltransferases. PMID:17660248

  11. AraPerox. A Database of Putative Arabidopsis Proteins from Plant Peroxisomes1[w

    PubMed Central

    Reumann, Sigrun; Ma, Changle; Lemke, Steffen; Babujee, Lavanya

    2004-01-01

    To identify unknown proteins from plant peroxisomes, the Arabidopsis genome was screened for proteins with putative major or minor peroxisome targeting signals type 1 or 2 (PTS1 or PTS2), as defined previously (Reumann S [2004] Plant Physiol 135: 783–800). About 220 and 60 proteins were identified that carry a putative PTS1 or PTS2, respectively. To further support postulated targeting to peroxisomes, several prediction programs were applied and the putative targeting domains analyzed for properties conserved in peroxisomal proteins and for PTS conservation in homologous plant expressed sequence tags. The majority of proteins with a major PTS and medium to high overall probability of peroxisomal targeting represent novel nonhypothetical proteins and include several enzymes involved in β-oxidation of unsaturated fatty acids and branched amino acids, and 2-hydroxy acid oxidases with a predicted function in fatty acid α-oxidation, as well as NADP-dependent dehydrogenases and reductases. In addition, large protein families with many putative peroxisomal isoforms were recognized, including acyl-activating enzymes, GDSL lipases, and small thioesterases. Several proteins are homologous to prokaryotic enzymes of a novel aerobic hybrid degradation pathway for aromatic compounds and proposed to be involved in peroxisomal biosynthesis of plant hormones like jasmonic acid, auxin, and salicylic acid. Putative regulatory proteins of plant peroxisomes include protein kinases, small heat shock proteins, and proteases. The information on subcellular targeting prediction, homology, and in silico expression analysis for these Arabidopsis proteins has been compiled in the public database AraPerox to accelerate discovery and experimental investigation of novel metabolic and regulatory pathways of plant peroxisomes. PMID:15333753

  12. TGF-beta inhibitors for the treatment of cancer.

    PubMed

    Lahn, Michael; Kloeker, Susanne; Berry, Brandi S

    2005-06-01

    Advances in understanding the role of transforming growth factor (TGF)-beta in tumorigenesis have led to the development of TGF-beta inhibitors for cancer treatment. Three platforms of TGF-beta inhibitors have evolved: antisense oligonucleotides, monoclonal antibodies and small molecules. In this review, the current stage of development of each known TGF-beta inhibitor will be discussed. As part of the risk/benefit assessment of TGF-beta inhibitors, the known effects of TGF-beta deficiency in mice, non-clinical toxicology studies with TGF-beta inhibitors in rats, and the clinical studies with monoclonal antibodies against TGF-beta will be summarised. PMID:16004592

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

    PubMed Central

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

    1996-01-01

    Escherichia coli RNA polymerase (RNAP) alpha subunit serves as the initiator for RNAP assembly, which proceeds according to the pathway 2 alpha-->alpha 2-->alpha 2 beta-->alpha 2 beta beta'-->alpha 2 beta beta' sigma. In this work, we have used hydroxyl-radical protein footprinting to define determinants of alpha for interaction with beta, beta', and sigma. Our results indicate that amino acids 30-75 of alpha are protected from hydroxyl-radical-mediated proteolysis upon interaction with beta (i.e., in alpha 2 beta, alpha 2 beta beta', and alpha 2 beta beta' sigma), and amino acids 175-210 of alpha are protected from hydroxyl-radical-mediated proteolysis upon interaction with beta' (i.e., in alpha 2 beta beta' and alpha 2 beta beta' sigma). The protected regions are conserved in the alpha homologs of prokaryotic, eukaryotic, archaeal, and chloroplast RNAPs and contain sites of substitutions that affect RNAP assembly. We conclude that the protected regions define determinants of alpha for direct functional interaction with beta and beta'. The observed maximal magnitude of protection upon interaction with beta and the observed maximal magnitude of protection upon interaction with beta' both correspond to the expected value for complete protection of one of the two alpha protomers of RNAP (i.e., 50% protection). We propose that only one of the two alpha protomers of RNAP interacts with beta and that only one of the two alpha protomers of RNAP interacts with beta'. Images Fig. 1 Fig. 4 PMID:8816769

  14. Latent TGF-[beta] structure and activation

    SciTech Connect

    Shi, Minlong; Zhu, Jianghai; Wang, Rui; Chen, Xing; Mi, Lizhi; Walz, Thomas; Springer, Timothy A.

    2011-09-16

    Transforming growth factor (TGF)-{beta} is stored in the extracellular matrix as a latent complex with its prodomain. Activation of TGF-{beta}1 requires the binding of {alpha}v integrin to an RGD sequence in the prodomain and exertion of force on this domain, which is held in the extracellular matrix by latent TGF-{beta} binding proteins. Crystals of dimeric porcine proTGF-{beta}1 reveal a ring-shaped complex, a novel fold for the prodomain, and show how the prodomain shields the growth factor from recognition by receptors and alters its conformation. Complex formation between {alpha}v{beta}6 integrin and the prodomain is insufficient for TGF-{beta}1 release. Force-dependent activation requires unfastening of a 'straitjacket' that encircles each growth-factor monomer at a position that can be locked by a disulphide bond. Sequences of all 33 TGF-{beta} family members indicate a similar prodomain fold. The structure provides insights into the regulation of a family of growth and differentiation factors of fundamental importance in morphogenesis and homeostasis.

  15. Study of high-beta ballooning modes

    SciTech Connect

    Price, H.D.; Benjamin, N.M.P.; Kang, B.K.; Lichtenberg, A.J.; Lieberman, M.A.

    1985-01-01

    Ballooning instabilities are studied in the Berkeley multiple mirror experiment. Counterstreaming theta pinch and Marshall gun source hydrogen plasmas are used to achieve a high beta ( ..beta..>25%), where ..beta.. is the ratio of plasma to magnetic pressure at temperatures T/sub e/ = T/sub i/roughly-equal15 eV. Four magnetic field configurations are investigated, each at varying mirror ratios, to explore a range of drive and connection length parameters. In two of these the magnetic field is pulsed from a stable to a locally unstable configuration for initiation of ballooning activity. The other two (static) configurations are a weakly unstable local field region, and the standard linked quadrupole multiple-mirror configuration. Depending on the configuration, critical ..beta..'s are found for the onset of ballooning that vary from 5% for the most unstable configuration to greater than 25% for the standard multiple-mirror configuration. The m = 1 azimuthal mode is predominant, with some admixture of m = 2. The experimental results are compared with predictions from a magnetohydrodynamic theory. In the model the pressure is taken to be isotropic and constant along the axis, except in the diverging field regions at the device ends where the pressure falls to maintain beta constant, consistent with experimental observations. The theoretical results generally predict somewhat higher critical betas for the m = 1 mode than those observed. Estimates of the effect of finite Larmor radii, nearby conducting walls, axially nonuniform pressure profiles and resistivity, are also given.

  16. beta-Endorphin enhances lymphocyte proliferative responses.

    PubMed Central

    Gilman, S C; Schwartz, J M; Milner, R J; Bloom, F E; Feldman, J D

    1982-01-01

    The opioid peptides alpha- and beta-endorphin and [D-Ala2, Met5]enkephalin were investigated for their effect on the proliferation of resting and activated rat splenic lymphocytes in vitro. beta-Endorphin enhanced the proliferative response of spleen cells to the T cell mitogens concanavalin A and phytohemagglutinin. The effect of beta-endorphin was dose dependent and occurred at peptide concentrations similar to those found in rat plasma. alpha-Endorphin and [D-Ala2, Met5]enkephalin did not affect the proliferative responses to any mitogen tested. Furthermore, the potentiating effect of beta-endorphin was not reversed by treatment with 10 microM naloxone. None of the peptides had any effect on resting, unstimulated spleen cells or on the response to a mixture of lipopolysaccharide and dextran sulfate, which is specifically mitogenic for B lymphocytes. The pharmacological properties of the beta-endorphin potentiation indicate that the effect may be mediated by a nonopiate but beta-endorphin-specific mechanism. These results suggest a possible role for peripheral beta-endorphin and may provide a link between stress and disease susceptibility. PMID:6287475

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

    SciTech Connect

    Feng, Ying; Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min; Sun, Gui-yuan; Liu, Rui-tian

    2009-12-25

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

  18. Evidence for Novel [beta]-Sheet Structures in Iowa Mutant [beta]-Amyloid Fibrils

    SciTech Connect

    Tycko, Robert; Sciarretta, Kimberly L.; Orgel, Joseph P.R.O.; Meredith, Stephen C.

    2009-07-24

    Asp23-to-Asn mutation within the coding sequence of {beta}-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-A{beta}40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-A{beta}40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10{sup -3} min{sup -1} and 1.07 x 10{sup -4} min{sup -1} for D23N-A{beta}40 and the wild-type peptide WT-A{beta}40, respectively) and without a lag phase. Electron microscopy shows that D23N-A{beta}40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-{beta} pattern, with a sharp reflection at 4.7 {angstrom} and a broad reflection at 9.4 {angstrom}, which is notably smaller than the value for WT-A{beta}40 fibrils (10.4 {angstrom}). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-A{beta}40 fibrils containing the in-register, parallel {beta}-sheet structure commonly found in WT-A{beta}40 fibrils and most other amyloid fibrils. Antiparallel {beta}-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through 13C-13C and 15N-13C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-A{beta}40 fibrils and the unusual vasculotropic clinical picture in these patients.

  19. Sphingomonas paucimobilis beta-glucosidase Bgl1: a member of a new bacterial subfamily in glycoside hydrolase family 1.

    PubMed Central

    Marques, Ana Rita; Coutinho, Pedro M; Videira, Paula; Fialho, Arsénio M; Sá-Correia, Isabel

    2003-01-01

    The Sphingomonas paucimobilis beta-glucosidase Bgl1 is encoded by the bgl1 gene, associated with an 1308 bp open reading frame. The deduced protein has a potential signal peptide of 24 amino acids in the N-terminal region, and experimental evidence is consistent with the processing and export of the Bgl1 protein through the inner membrane to the periplasmic space. A His(6)-tagged 44.3 kDa protein was over-produced in the cytosol of Escherichia coli from a recombinant plasmid, which contained the S. paucimobilis bgl1 gene lacking the region encoding the putative signal peptide. Mature beta-glucosidase Bgl1 is specific for aryl-beta-glucosides and has no apparent activity with oligosaccharides derived from cellulose hydrolysis and other saccharides. A structure-based alignment established structural relations between S. paucimobilis Bgl1 and other members of the glycoside hydrolase (GH) family 1 enzymes. At subsite -1, the conserved residues required for catalysis by GH1 enzymes are present in Bgl1 with only minor differences. Major differences are found at subsite +1, the aglycone binding site. This alignment seeded a sequence-based phylogenetic analysis of GH1 enzymes, revealing an absence of horizontal transfer between phyla. Bootstrap analysis supported the definition of subfamilies and revealed that Bgl1, the first characterized beta-glucosidase from the genus Sphingomonas, represents a very divergent bacterial subfamily, closer to archaeal subfamilies than to others of bacterial origin. PMID:12444924

  20. Structure of a Putative Lipoate Protein Ligase from Thermoplasma acidophilum and the Mechanism of Target Selection for Post-Translational Modification

    SciTech Connect

    McManus,E.; Luisi, B.; Perham, R.

    2006-01-01

    Lipoyl-lysine swinging arms are crucial to the reactions catalysed by the 2-oxo acid dehydrogenase multienzyme complexes. A gene encoding a putative lipoate protein ligase (LplA) of Thermoplasma acidophilum was cloned and expressed in Escherichia coli. The recombinant protein, a monomer of molecular mass 29 kDa, was catalytically inactive. Crystal structures in the absence and presence of bound lipoic acid were solved at 2.1 Angstroms resolution. The protein was found to fall into the a/{beta} class and to be structurally homologous to the catalytic domains of class II aminoacyl-tRNA synthases and biotin protein ligase, BirA. Lipoic acid in LplA was bound in the same position as biotin in BirA. The structure of the T. acidophilum LplA and limited proteolysis of E. coli LplA together highlighted some key features of the post-translational modification. A loop comprising residues 71-79 in the T. acidophilumligase is proposed as interacting with the dithiolane ring of lipoic acid and discriminating against the entry of biotin. A second loop comprising residues 179-193 was disordered in the T. acidophilum structure; tryptic cleavage of the corresponding loop in the E. coli LplA under non-denaturing conditions rendered the enzyme catalytically inactive, emphasizing its importance. The putative LplA of T. acidophilum lacks a C-terminal domain found in its counterparts in E. coli (Gram-negative) or Streptococcus pneumoniae (Gram-positive). A gene encoding a protein that appears to have structural homology to the additional domain in the E. coli and S. pneumoniae enzymes was detected alongside the structural gene encoding the putative LplA in the T. acidophilum genome. It is likely that this protein is required to confer activity on the LplA as currently purified, one protein perhaps catalysing the formation of the obligatory lipoyl-AMP intermediate, and the other transferring the lipoyl group from it to the specific lysine residue in the target protein.

  1. Fabrication of thin layer beta alumina

    NASA Technical Reports Server (NTRS)

    Tennenhouse, G. J.

    1977-01-01

    Beta alumina tubes having walls 700 microns, 300 microns, and 140 microns were processed by extrusion and sintering utilizing Ford proprietary binder and fabrication systems. Tubes prepared by this method have properties similar to tubes prepared by isostatic pressing and sintering, i.e. density greater than 98% of theoretical and a helium leak rate less than 3 x 10 to the -9th power cc/sq cm/sec. Ford ultrasonic bonding techniques were used for bonding beta alumina end caps to open ended beta -alumina tubes prior to sintering. After sintering, the bond was hermetic, and the integrity of the bonded area was comparable to the body of the tube.

  2. Transport properties of finite-beta microturbulence

    SciTech Connect

    Pueschel, M. J.; Jenko, F.

    2010-06-15

    Via nonlinear gyrokinetic simulations, microturbulent transport is investigated for electromagnetic trapped electron mode (TEM) and ion temperature gradient (ITG) tokamak core turbulence with beta up to and beyond the kinetic ballooning mode threshold. Deviations from linear expectations are explained by zonal flow activity in the TEM case. For the ITG scenario, beta-induced changes are observed in the nonlinear critical gradient upshift--from a certain beta, a strong increase is observed in the Dimits shift. Additionally, a Rechester-Rosenbluth-type model for magnetic transport is applied, and the amplitudes of magnetic field fluctuations are quantified for different types of turbulence.

  3. Syntheses of stable isotope-labeled 6 beta-hydroxycortisol, 6 beta-hydroxycortisone, and 6 beta-hydroxytestosterone.

    PubMed

    Furuta, Takashi; Suzuki, Atsushi; Matsuzawa, Mitsuhiro; Shibasaki, Hiromi; Kasuya, Yasuji

    2003-09-01

    A method is described for the preparation of two types of multi-labeled 6 beta-hydroxycortisol containing either five deuterium atoms at C-19 methyl and C-1 methylene or four 13C atoms at C-1, C-2, C-4, and C-19 in addition to the five deuterium atoms for use as analytical internal standards for gas chromatography-mass spectrometry (GC-MS). BMD derivatives of [1,1,19,19,19-2H(5)]cortisone and [1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisone (cortisone-2H(5)-BMD and cortisone-13C(4),2H(5)-BMD) were first synthesized via indan synthon method starting from optical active 11-oxoindanylpropionic acid and labeled isopropenyl anion ([1,1,3,3,3-2H(5)]- or [1,3-13C(2),1,1,3,3,3-2H(5)]isopropenyl anion). The labeled isopropenyl anion was prepared from commercially available [1,1,1,3,3,3-2H(6)]- or [1,3-13C(2),1,1,1,3,3,3-2H(6)]acetone. Ultraviolet (UV) irradiated autoxidation at C-6 position of 3-ethyl-3,5-dienol ether derivatives of the labeled cortisone-BMDs gave 6 beta-hydroxy-[1,1,19,19,19-2H(5)]cortisone-BMD and 6 beta-hydroxy-[1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisone-BMD, respectively, as a mixture of 6 beta- and 6 alpha-epimers in a ratio of 4:1. Separation of 6 beta- and 6 alpha-epimers by thin-layer chromatography (TLC) and subsequent hydrolysis of the BMD group at C-17 gave pure labeled 6 beta-hydroxycortisone. After protecting the keto group at C-3 of the labeled 6 beta-hydroxycortisone-BMD as semicarbazone, reduction of 11-keto group with NaBH(4) and subsequent removal of the C-3 and C-17 protecting groups gave 6beta-hydroxy-[1,1,19,19,19-2H(5)]cortisol (6 beta-hydroxycortisol-2H(5)) and 6 beta-hydroxy-[1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisol (6 beta-hydroxycortisol-13C(4),2H(5)), respectively, as a mixture of 6 beta- and 6 alpha-epimers (6 beta:6 alpha=4.4:1). The isotopic compositions of 6 beta-hydroxycortisol-2H(5) and 6 beta-hydroxycortisol-13C(4),2H(5) were 90.9 and 92.1 at.%, respectively. Furthermore, 6 beta-hydroxy-[1 alpha,16,16,17 alpha-2H(4

  4. Putative and unique gene sequence utilization for the design of species specific probes as modeled by Lactobacillus plantarum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concept of utilizing putative and unique gene sequences for the design of species specific probes was tested. The abundance profile of assigned functions within the Lactobacillus plantarum genome was used for the identification of the putative and unique gene sequence, csh. The targeted gene (cs...

  5. The role played by endocytosis in albumin-induced secretion of TGF-beta1 by proximal tubular epithelial cells.

    PubMed

    Diwakar, Ramaswamy; Pearson, Alex L; Colville-Nash, Paul; Brunskill, Nigel J; Dockrell, Mark E C

    2007-05-01

    Proteinuria predicts the decline of renal function in chronic kidney disease. Reducing albuminuria has been shown to be associated with a reduction in this rate of decline. Proximal tubular epithelial cells (PTECs), when exposed to albumin produce matrix proteins, proinflammatory and profibrotic cytokines like TGF-beta(1). Some of these effects are dependent on endocytosis of albumin by PTECs. However, conditions like diabetic nephropathy, believed to be associated with reduced albumin endocytosis, are associated with interstitial fibrosis. Moreover, megalin, the putative albumin binding receptor in PTECs, has potential signaling motifs in its cytoplasmic domain, suggesting its ability to signal in response to ligand binding from the apical surface of PTECs. Hence, we looked to see whether albumin-induced secretion of TGF-beta(1) by PTECs is dependent on albumin endocytosis or whether it could occur in the absence of albumin endocytosis. We studied the production of TGF-beta(1) in two accepted models of PTECs, opossum kidney cells and human kidney cell clone-8 cells, with widely varying degrees of endocytosis. We then studied the effect of inhibiting albumin endocytosis with various inhibitors on albumin-induced TGF-beta(1) secretion. Our results indicate that albumin-induced TGF-beta(1) secretion by PTECs does not require albumin endocytosis and therefore the mechanism for the induction of some profibrotic responses by albumin may differ from those required for some of the inflammatory responses. Moreover, we found that albumin-induced TGF-beta(1) secretion by PTECs is not dependent on its interaction with megalin. PMID:17213467

  6. A rapid real-time qRT-PCR assay for ovine beta-actin mRNA.

    PubMed

    Bjarnadottir, Helga; Jonsson, Jon J

    2005-05-01

    Beta-Actin mRNA is often used for normalization in gene expression experiments. We describe a sensitive, rapid and specific quantitative assay for the cytoplasmic ovine beta-actin mRNA. The assay was based on the polymerase chain reaction (PCR) with real-time fluorescence resonance energy transfer (FRET) measurements to amplify cDNA products reverse transcribed from mRNA. A part of the ovine beta-actin sequence was amplified from cDNA from fetal ovine synovial (FOS) cells with mRNA-specific primers and cloned into a plasmid clone. The assay standard curve was constructed with dilutions of this plasmid. The assay was linear over five orders of magnitude and detected down to 600 copies per reaction of target DNA. Intraassay coefficient of variation was 12%. Detection of the beta-actin gene was eliminated by designing FRET probes at splice junctions and detection of putative processed pseudogenes was minimized by using FRET assay design with four oligonucleotides. We measured 0.2 copies per cell in RNA preparations without reverse transcription and DNase digestion. This might represent processed pseudogenes. In constrast, we measured 1400 beta-actin mRNA copies per cell in RNA preparations after the RT and DNase steps. The assay should, therefore, be sensitive enough to measure beta-actin from a single individual cell. Dilution of target DNA in murine RNA or ovine cDNA preparations did not effect efficiency of PCR or linearity of the assay. The quantitative assay described in this work can be used to correct for variations in various real-time qRT-PCR experiments in ovine cells with diverse goals, including gene expression studies, quantitation of viral load in infected cells and in various gene therapy experiments measuring vector load and expression in transduced cells. PMID:15823406

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

    SciTech Connect

    Caselli, E.; Powers, R.A.; Blaszczak, L.C.; Wu, C.Y.E.; Prati, F.; Shoichet, B.K.

    2010-03-05

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

  8. Dopamine beta-hydroxylase deficiency

    PubMed Central

    Senard, Jean-Michel; Rouet, Philippe

    2006-01-01

    Dopamine beta-hydroxylase (DβH) deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS). Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance. PMID:16722595

  9. Cardioprotection by Thymosin Beta 4.

    PubMed

    Pipes, G T; Yang, J

    2016-01-01

    Treatment with thymosin beta 4 (Tβ4) reduces infarct volume and preserves cardiac function in preclinical models of cardiac ischemic injury. These effects stem in part from decreased infarct size, but additional benefits are likely due to specific antifibrotic and proangiogenic activities. Injected or transgenic Tβ4 increase blood vessel growth in large and small animal models, consistent with Tβ4 converting hibernating myocardium to an actively contractile state following ischemia. Tβ4 and its degradation products have antifibrotic effects in in vitro assays and in animal models of fibrosis not related to cardiac injury. This large number of pleiotropic effects results from Tβ4's many interactions with cellular signaling pathways, particularly indirect regulation of cellular motility and movement via the SRF-MRTF-G-actin transcriptional pathway. Variation in effects and effect sizes in animal models may potentially be due to variable distribution of Tβ4. Preclinical studies of PK/PD relationships and a reliable pharmacodynamic biomarker would facilitate clinical development of Tβ4. PMID:27450736

  10. IL-13 improves beta-cell survival and protects against IL-1beta-induced beta-cell death

    PubMed Central

    Rütti, Sabine; Howald, Cédric; Arous, Caroline; Dermitzakis, Emmanouil; Halban, Philippe A.; Bouzakri, Karim

    2015-01-01

    Objectives IL-13 is a cytokine classically produced by anti-inflammatory T-helper-2 lymphocytes; it is decreased in the circulation of type 2 diabetic patients and impacts positively on liver and skeletal muscle. Although IL-13 can exert positive effects on beta-cell lines, its impact and mode of action on primary beta-cell function and survival remain largely unexplored. Methods Beta-cells were cultured for 48 h in the presence of IL-13 alone or in combination with IL-1β or cytokine cocktail (IL-1β, IFNγ, TNFα). Results IL-13 protected human and rat beta-cells against cytokine induced death. However, IL-13 was unable to protect from IL-1β impaired glucose stimulated insulin secretion and did not influence NFκB nuclear relocalization induced by IL-1β. IL-13 induced phosphorylation of Akt, increased IRS2 protein expression and counteracted the IL-1β induced regulation of several beta-cell stress response genes. Conclusions The prosurvival effects of IL-13 thus appear to be mediated through IRS2/Akt signaling with NFκB independent regulation of gene expression. In addition to previously documented beneficial effects on insulin target tissues, these data suggest that IL-13 may be useful for treatment of type 2 diabetes by preserving beta-cell mass or slowing its rate of decline. PMID:26909320

  11. A synopsis of factors regulating beta cell development and beta cell mass.

    PubMed

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

    2016-10-01

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

  12. A comparison of enzymatic phosphorylation and phosphatidylation of beta-L- and beta-D-nucleosides.

    PubMed

    Birichevskaya, Larisa L; Kvach, Sergei V; Sivets, Grigorii G; Kalinichenko, Elena N; Zinchenko, Anatoly I; Mikhailopulo, Igor A

    2007-04-01

    Enzymatic 5'-monophosphorylation and 5'-phosphatidylation of a number of beta-L- and beta-D-nucleosides was investigated. The first reaction, catalyzed by nucleoside phosphotransferase (NPT) from Erwinia herbicola, consisted of the transfer of the phosphate residue from p-nitrophenylphosphate (p-NPP) to the 5'-hydroxyl group of nucleoside; the second was the phospholipase D (PLD)-catalyzed transphosphatidylation of L-alpha-lecithin with a series of beta-L- and beta-D-nucleosides as the phosphatidyl acceptor resulted in the formation of the respective phospholipid-nucleoside conjugates. Some beta-L-nucleosides displayed similar or even higher substrate activity compared to the beta-D-enantiomers. PMID:17206374

  13. Enzyme-catalyzed formation of beta-peptides: beta-peptidyl aminopeptidases BapA and DmpA acting as beta-peptide-synthesizing enzymes.

    PubMed

    Heck, Tobias; Kohler, Hans-Peter E; Limbach, Michael; Flögel, Oliver; Seebach, Dieter; Geueke, Birgit

    2007-09-01

    In recent studies, we discovered that the three beta-peptidyl aminopeptidases, BapA from Sphingosinicella xenopeptidilytica 3-2W4, BapA from S. microcystinivorans Y2, and DmpA from Ochrobactrum anthropi LMG7991, possess the unique feature of cleaving N-terminal beta-amino acid residues from beta- and alpha/beta-peptides. Herein, we investigated the use of the same three enzymes for the reverse reaction catalyzing the oligomerization of beta-amino acids and the synthesis of mixed peptides with N-terminal beta-amino acid residues. As substrates, we employed the beta-homoamino acid derivatives H-beta hGly-pNA, H-beta3 hAla-pNA, H-(R)-beta3 hAla-pNA, H-beta3 hPhe-pNA, H-(R)-beta3 hPhe-pNA, and H-beta3 hLeu-pNA. All three enzymes were capable of coupling the six beta-amino acids to oligomers with chain lengths of up to eight amino acid residues. With the enzyme DmpA as the catalyst, we observed very high conversion rates, which correspond to dimer yields of up to 76%. The beta-dipeptide H-beta3 hAla-beta3 hLeu-OH and the beta/alpha-dipeptide H-beta hGly-His-OH (carnosine) were formed with almost 50% conversion, when a five-fold excess of beta3-homoleucine or histidine was incubated with H-beta3 hAla-pNA and H-beta hGly-pNA, respectively, in the presence of the enzyme BapA from S. microcystinivorans Y2. BapA from S. xenopeptidilytica 3-2W4 turned out to be a versatile catalyst capable of coupling various beta-amino acid residues to the free N-termini of beta- and alpha-amino acids and even to an alpha-tripeptide. Thus, these aminopeptidases might be useful to introduce a beta-amino acid residue as an N-terminal protecting group into a 'natural' alpha-peptide, thereby stabilizing the peptide against degradation by other proteolytic enzymes. PMID:17886858

  14. Beta scaling of transport in microturbulence simulations

    SciTech Connect

    Candy, J.

    2005-07-15

    A systematic study of the beta ({beta}) scaling and spatial structure of thermal and particle transport in gyrokinetic turbulence simulations is presented. Here, {beta} is the ratio of the plasma kinetic pressure to the magnetic pressure. Results show that the nonlinear self-consistent temperature profiles exhibit a (statistically) time-stationary flattening in the vicinity of rational surfaces with a concomitant drop in the electrostatic components of the thermal diffusivity. Simultaneously, the increased magnetic fluctuation amplitude at these surfaces enhances the steady-state electromagnetic (flutter) component of the electron thermal diffusivity. The electromagnetic components of the ion transport coefficients remain close to zero, as expected on theoretical grounds. Only a weak dependence of ion energy transport on {beta} is observed, consistent with recent tokamak experiments [C. C. Petty et al., Phys. Plasmas 11, 2514 (2004)].

  15. Interferon Beta-1a Intramuscular Injection

    MedlinePlus

    ... course of disease where symptoms flare up from time to time) of multiple sclerosis (MS, a disease in which ... interferon beta-1a intramuscular at around the same time of day on your injection days. Follow the ...

  16. Review of modern double beta decay experiments

    NASA Astrophysics Data System (ADS)

    Barabash, A. S.

    2015-10-01

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T1/2(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino ( < 0.46 eV) and a coupling constant of Majoron to neutrino ( < 1.3 . 10-5) are obtained. Prospects of search for neutrinoless double beta decay in new experiments with sensitivity to at the level of ˜ 0.01-0.1 eV are discussed.

  17. Observations of high-beta toroidal plasmas

    NASA Astrophysics Data System (ADS)

    Halle, J. H.; Kellman, A. G.; Post, R. S.; Prager, S. C.; Strait, E. J.; Zarnstorff, M. C.

    1981-05-01

    A range of MHD stable high-beta plasmas is attained both in the kinetic regime with beta equal to 33% (nine times the fluid ballooning limit) and near the single-fluid regime with beta equal to 8% (twice the theoretical limit). It is found that MHD theory is inadequate and that kinetic effects are apparently more powerful than is generally assumed. It is pointed out that since a reactor (with trapped particles, large-gyroradii ions from neutral beams) may be no more fluid-like than the octupole experiments, their designs should perhaps not necessarily be constrained by the MHD ballooning instability beta limit. Diamagnetic current measurements are found to agree roughly with single-fluid results in the fluid-like case but to depart sharply in the kinetic regime.

  18. Genetics Home Reference: beta-mannosidosis

    MedlinePlus

    ... of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins). Beta-mannosidase is involved in the last step ... Inherited Metabolic Diseases ISMRD: The International Advocate for Glycoprotein Storage Diseases The MPS Society (UK) Genetic Testing ...

  19. Review of modern double beta decay experiments

    SciTech Connect

    Barabash, A. S.

    2015-10-28

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T{sub 1/2}(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino (〈m{sub ν}〉 < 0.46 eV) and a coupling constant of Majoron to neutrino (〈g{sub ee}〉 < 1.3 · 10{sup −5}) are obtained. Prospects of search for neutrinoless double beta decay in new experiments with sensitivity to 〈m{sub ν}〉 at the level of ∼ 0.01-0.1 eV are discussed.

  20. PECAM-1 affects GSK-3beta-mediated beta-catenin phosphorylation and degradation.

    PubMed

    Biswas, Purba; Canosa, Sandra; Schoenfeld, David; Schoenfeld, Jonathan; Li, Puyau; Cheas, Lydia C; Zhang, Jin; Cordova, Alfredo; Sumpio, Bauer; Madri, Joseph A

    2006-07-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) regulates a variety of endothelial and immune cell biological responses. PECAM-1-null mice exhibit prolonged and increased permeability after inflammatory insults. We observed that in PECAM-1-null endothelial cells (ECs), beta-catenin remained tyrosine phosphorylated, coinciding with a sustained increase in permeability. Src homology 2 domain containing phosphatase 2 (SHP-2) association with beta-catenin was diminished in PECAM-1-null ECs, suggesting that lack of PECAM-1 inhibits the ability of this adherens junction component to become dephosphorylated, promoting a sustained increase in permeability. beta-Catenin/Glycogen synthase kinase 3 (GSK-3beta) association and beta-catenin serine phosphorylation levels were increased and beta-catenin expression levels were reduced in PECAM-1-null ECs. Glycogen synthase kinase 3 (GSK-3beta) serine phosphorylation (inactivation) was blunted in PECAM-1-null ECs after histamine treatment or shear stress. Our data suggest that PECAM-1 serves as a critical dynamic regulator of endothelial barrier permeability. On stimulation by a vasoactive substance or shear stress, PECAM-1 became tyrosine phosphorylated, enabling recruitment of SHP-2 and tyrosine-phosphorylated beta-catenin to its cytoplasmic domain, facilitating dephosphorylation of beta-catenin, and allowing reconstitution of adherens junctions. In addition, PECAM-1 modulated the levels of beta-catenin by regulating the activity of GSK-3beta, which in turn affected the serine phosphorylation of beta-catenin and its proteosomal degradation, affecting the ability of the cell to reform adherens junctions in a timely fashion. PMID:16816383

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

    ERIC Educational Resources Information Center

    Hanukoglu, Israel

    2015-01-01

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

  2. Solid-state NMR analysis of the {beta}-strand orientation of the protofibrils of amyloid {beta}-protein

    SciTech Connect

    Doi, Takashi; Masuda, Yuichi; Irie, Kazuhiro; Akagi, Ken-ichi; Monobe, Youko; Imazawa, Takayoshi; Takegoshi, K.

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer The supramolecular structure of A{beta}42 protofibrils was analyzed by solid-state NMR. Black-Right-Pointing-Pointer The Ala-21 residue in the A{beta}42 protofibrils is included in a slightly disordered {beta}-strand. Black-Right-Pointing-Pointer The A{beta}42 protofibrils do not form intermolecular in-register parallel {beta}-sheets. -- Abstract: Alzheimer's disease (AD) is caused by abnormal deposition (fibrillation) of a 42-residue amyloid {beta}-protein (A{beta}42) in the brain. During the process of fibrillation, the A{beta}42 takes the form of protofibrils with strong neurotoxicity, and is thus believed to play a crucial role in the pathogenesis of AD. To elucidate the supramolecular structure of the A{beta}42 protofibrils, the intermolecular proximity of the Ala-21 residues in the A{beta}42 protofibrils was analyzed by {sup 13}C-{sup 13}C rotational resonance experiments in the solid state. Unlike the A{beta}42 fibrils, an intermolecular {sup 13}C-{sup 13}C correlation was not found in the A{beta}42 protofibrils. This result suggests that the {beta}-strands of the A{beta}42 protofibrils are not in an in-register parallel orientation. A{beta}42 monomers would assemble to form protofibrils with the {beta}-strand conformation, then transform into fibrils by forming intermolecular parallel {beta}-sheets.

  3. Analysis of structure and expression of the Xenopus thyroid hormone receptor-beta gene to explain its autoinduction.

    PubMed

    Machuca, I; Esslemont, G; Fairclough, L; Tata, J R

    1995-01-01

    Transcription of both Xenopus thyroid hormone receptor (TR) genes, xTR alpha and -beta, is strongly up-regulated by their own ligand T3 during natural or T3-induced metamorphosis of tadpoles and in some Xenopus cell lines. To explain this autoinduction, we analyzed the sequence of 1.6 kilobases of xTR beta promoter for putative T3-responsive elements. Two direct repeat +4 AGGTCA hexamer motifs (DR+4), an imperfect distal (-793/-778) and a perfect proximal (-5/11) site, a DR+1 site, and some possible half-sites were located in the 1.6-kilobase promoter. Transfection of Xenopus XTC-2 cells (which express xTR alpha and -beta) and XL-2 cells (which predominantly express TR alpha) with chloramphenicol acetyltransferase reporter constructs of deletion mutants and promoter fragments showed that the distal and proximal DR+4 sites responded to T3, although other flanking sequences may also play a role. The thyroid hormone-responsive element half-site present as DR+1 in the up-stream sequence at -1260/-950, when cloned in front of a heterologous promoter, functions independently. T3 enhanced transcription from the two DR+4-containing fragments when present together by only 2- to 3-fold due to a high basal activity. Overexpression of unliganded xTR alpha and xTR beta in XTC-2 cells repressed basal activity, which was then enhanced 7- to 4-fold by T3, respectively; with XL-2 cells cotransfected with xTR beta, T3 inducibility increased to 16-fold. Electrophoretic mobility shift assays with recombinant Xenopus TR alpha, TR beta, retinoid-X receptor-alpha (RXR alpha) and RXR gamma proteins showed that TR-RXR heterodimers, but not TR or RXR monomers or homodimers, strongly bound the natural and synthetic distal and proximal DR+4 elements in a ligand-independent manner. TR/RXR heterodimers exhibited the highest binding affinity for a 28-mer oligonucleotide probe for the -5/11 proximal DR+4 site, with only slight binding to DR+1 (retinoid-X-responsive element-like) site. The x

  4. Characterization of a large deletion in the {beta}-globin gene cluster in a newborn with hemoglobin FE

    SciTech Connect

    Louie, E.; Dietz, L.; Shafer, F.

    1994-09-01

    A sample on a newborn with hemoglobin FE screen results was obtained to investigate whether E/E or B/{beta}{degrees} thalassemia was present using polymerase chain reaction (PCR) methodology. The newborn appeared homozygous for the hemoglobin E mutation in our initial study, but the parents` genotypes did not support this diagnosis. The father is homozygous for the absence of the hemoglobin E mutation (non E/non E) and the mother is heterozygous (E/non E) for this mutation. The limitation of PCR analysis is an assumption that the amplification of the two {beta}-globin alleles is equivalent. A large deletion on one {beta}-globin gene, which would produce E/{beta}{degrees} thalassemia, would be missed if it included part or the entire region subjected to amplification. The family results were consistent with either non-paternity, sample mix-up or such a deletion of the {beta}-globin gene in the father and child. To rule out the possibility of non-paternity, two polymorphic loci (HLA on chromosome 6 and a VNTR system of chromosome 17) that are outside of the {beta}-globin gene were analyzed and show that inheritance is consistent and the likelihood of a sample mix-up is then reduced. We therefore believe there is a gene deletion in this family. At the present time, analyses of the RFLPs that are 5{prime} of the {beta}-globin gene cluster show that the polymorphisms most distal from the 5{prime} {beta}-globin gene are not being inherited as expected. These results support our interpretation that a deletion exists in the father and was inherited by the child. The father`s clinical picture of possible HPFH (the father has 12% hemoglobin F) also supports the interpretation of a deletion in this family. Deletions of the {beta}-globin gene within this ethnic group are rare. Currently, Southern blots on the family are being probed to determine the extent of the putative deletion.

  5. Characterization of the putative chloride channel xClC-5 expressed in Xenopus laevis oocytes and comparison with endogenous chloride currents.

    PubMed

    Schmieder, S; Lindenthal, S; Banderali, U; Ehrenfeld, J

    1998-09-01

    1. We recently cloned a putative chloride channel (xClC-5) from the renal cell line A6, which induced the appearance of a Cl- conductance not found in control oocytes after homologous expression in Xenopus oocytes. With the aim of increasing the Xenopus oocyte xClC-5 expression, we constructed a new plasmid in which the native 5' and 3' non-coding regions of xClC-5 were replaced by the non-coding regions of the Xenopus beta-globin sequence and in which a Kozak consensus site was introduced before the initiator ATG. 2. We then compared the induced currents Inative (induced by injection of cRNA presenting the native non-coding regions of xClC-5) and Ibeta-globin (induced by injection of cRNA presenting the non-coding regions of the Xenopus beta-globin sequence) investigating anion selectivity and anion blocker sensitivity. Several differences were found: (1) expression yield and oocyte surviving rate were largely increased by injecting (beta) xClC-5 cRNA, (2) the Ibeta-globin outward rectification score was 2.6 times that of Inative, (3) the anion conductivity sequence was nitrate > bromide > chloride > iodide > gluconate for Ibeta-globin and iodide > bromide > nitrate > chloride > gluconate for Inative, (4) 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), anthracene-9-carboxylic acid (9-AC), DIDS, lanthanum ions, cAMP and ionomycin-induced [Ca2+]i increase inhibited Inative but had no effect on Ibeta-globin, and (5) Inative showed considerable similarity to the previously reported endogenous current appearing after ClC-6 or pICln cRNA injection. 3. Comparison of Inative with the endogenous chloride current ICl,swell which develops under hyposmotic conditions demonstrated several similarities in their electrophysiological and pharmacological characteristics but were nevertheless distinguishable. 4. In vitro translation assays demonstrated that protein synthesis was much greater using the (beta) xClC-5 construct than that of xClC-5. Furthermore, immunoreactivity

  6. Beta/alpha continuous air monitor

    DOEpatents

    Becker, Gregory K.; Martz, Dowell E.

    1989-01-01

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

  7. Giant impacts in the Beta Pic system

    NASA Astrophysics Data System (ADS)

    Jackson, A.

    2014-09-01

    One scenario that can potentially explain the brightness asymmetry in the Beta Pictoris debris disk in the mid-infrared and millimetre is that of a comparatively recent (< 1 Myr ago) impact between planetary scale bodies at an orbital distance of ˜85 AU, as discussed by Dent et al 2014. I will discuss the details of this model, how it applies to Beta Pictoris, and how it may be applied elsewhere.

  8. Searches for neutrinoless double beta decay

    NASA Astrophysics Data System (ADS)

    Schwingenheuer, Bernhard

    2012-07-01

    Neutrinoless double beta decay is a lepton number violating process whose observation would also establish that neutrinos are their own anti-particles. There are many experimental efforts with a variety of techniques. Some (EXO, Kamland-Zen, GERDA phase I and CANDLES) started take data in 2011 and EXO has reported the first measurement of the half life for the double beta decay with two neutrinos of 136Xe. The sensitivities of the different proposals are reviewed.

  9. Topical beta-blocker treatment for migraine.

    PubMed

    Chiam, Patrick J T

    2012-02-01

    Beta-blockers are a well-known prophylactic treatment for migraine; however, treatment by the ocular route has not been widely considered. This case illustrates the resolution of a visual field defect associated with migraine and improvement of symptoms possibly due to administration of a topical beta-blocker. This novel method of treatment especially when visual field defects are present may have a place in the management of migraine. PMID:22278763

  10. N=1 supersymmetric {beta}-functions

    SciTech Connect

    Jones, D. R. T.

    1997-06-15

    Recent results on three-loop, four-loop and large-N{sub f}{beta}-functions in supersymmetric gauge theories are summarised. It is argued that the O(1/N{sub f})-corrected form of {beta}{sub g} in SQCD is consistent with the existence of the conformal window 3N{sub c}/2

  11. Optmization of the beta-beam baseline

    NASA Astrophysics Data System (ADS)

    Benedikt, M.; Fabich, A.; Hancock, S.; Lindroos, M.; Beta-Beam Task Within Eurisol Ds

    2006-05-01

    The beta-beam concept for the production of intense electron (anti-)neutrino beams is now well established. A baseline design has recently been published for a beta-beam facility at CERN. It has the virtue to respect the known limitations of the PS and SPS synchrotrons at CERN but it falls short of delivering the requested annual rate of anti-neutrinos. We here report on a first analysis on how to increase the rate.

  12. TGF-beta: problems and prospects.

    PubMed Central

    Sporn, M B; Roberts, A B

    1990-01-01

    TGF-beta research is proceeding at an exponential pace. Studies in this area have become increasingly relevant to many areas of cell regulation, continually providing new surprises and findings. One may confidently predict that TGF-beta will be one of the key molecules in future attempts to establish an integrated view of the processes whereby cells coordinate their own and mutual functions. We have seen only the beginning, and this minireview is only a glimpse. PMID:2100192

  13. Method for treating beta-spodumene ceramics

    DOEpatents

    Day, J. Paul; Hickman, David L.

    1994-09-27

    A vapor-phase method for treating a beta-spodumene ceramic article to achieve a substitution of exchangeable hydrogen ions for the lithium present in the beta-spodumene crystals, wherein a barrier between the ceramic article and the source of exchangeable hydrogen ions is maintained in order to prevent lithium contamination of the hydrogen ion source and to generate highly recoverable lithium salts, is provided.

  14. Exact relativistic {beta} decay endpoint spectrum

    SciTech Connect

    Masood, S. S.; Nasri, S.; Schechter, J.; Tortola, M. A.; Valle, J. W. F.

    2007-10-15

    The exact relativistic form for the {beta} decay endpoint spectrum is derived and presented in a simple factorized form. We show that our exact formula can be well approximated to yield the endpoint form used in the fit method of the KATRIN Collaboration. We also discuss the three-neutrino case and how information from neutrino oscillation experiments may be useful in analyzing future {beta} decay endpoint experiments.

  15. Beta/alpha continuous air monitor

    DOEpatents

    Becker, G.K.; Martz, D.E.

    1988-06-27

    A single deep layer silicon detector in combination with a microcomputer, recording both alpha and beta activity and the energy of each pulse, distinquishing energy peaks using a novel curve fitting technique to reduce the natural alpha counts in the energy region where plutonium and other transuranic alpha emitters are present, and using a novel algorithm to strip out radon daughter contribution to actual beta counts. 7 figs.

  16. Enhanced antidepressant efficacy of sigma1 receptor agonists in rats after chronic intracerebroventricular infusion of beta-amyloid-(1-40) protein.

    PubMed

    Urani, Alexandre; Romieu, Pascal; Roman, François J; Yamada, Kiyofumi; Noda, Yukihiro; Kamei, Hiroyuki; Manh Tran, Hung; Nagai, Taku; Nabeshima, Toshitaka; Maurice, Tangui

    2004-02-20

    Treatment of depressive symptoms in patients suffering from neurodegenerative disorders remains a challenging issue, since few available antidepressants present an adequate efficacy during pathological aging. Previous reports suggested that selective sigma(1) receptor agonists might constitute putative candidates. We here examined the pharmacological efficacy of igmesine and (+)-SKF-10,047 and the sigma(1) receptor-related neuroactive steroid dehydroepiandrosterone sulfate, in rats infused intracerebroventricularly during 14 days with the beta-amyloid-(1-40) protein and then submitted to the conditioned fear stress test. Igmesine and (+)-SKF-10,047 significantly reduced the stress-induced motor suppression at 30 and 6 mg/kg, respectively, in beta-amyloid-(40-1)-treated control rats. Active doses were decreased, to 10 and 3 mg/kg, respectively, in beta-amyloid-(1-40)-treated animals. The dehydroepiandrosterone sulfate effect was also facilitated, both in dose (10 vs. 30 mg/kg) and intensity, in beta-amyloid-(1-40)-treated rats. Neurosteroid levels were measured in several brain structures after beta-amyloid infusion, in basal and stress conditions. Progesterone levels, both under basal and stress-induced conditions, were decreased in the hippocampus and cortex of beta-amyloid-(1-40)-treated rats. The levels in pregnenolone, dehydroepiandrosterone and their sulfate esters appeared less affected by the beta-amyloid infusion. The sigma(1) receptor agonist efficacy is known to be inversely correlated to brain progesterone levels, synthesized mainly by neurons that are mainly affected by the beta-amyloid toxicity. The present study suggests that sigma(1) receptor agonists, due to their enhanced efficacy in a nontransgenic animal model, may alleviate Alzheimer's disease-associated depressive symptoms. PMID:14975704

  17. Structural and sequence patterns in the loops of beta alpha beta units.

    PubMed

    Edwards, M S; Sternberg, J E; Thornton, J M

    1987-06-01

    The conformation and sequences of the 129 loops of 70 beta alpha beta units from 17 alpha/beta proteins were analysed for patterns. Many different conformations of the loop regions were observed, but 18 of the loops could be classified into one of four loop families with distinctive conformation and sequence patterns. (i) Adjacent alpha beta loops with one residue between the alpha-helix and beta-strand. The residue is a glycine with conformationally restricted phi/psi angles; (ii) adjacent alpha beta loops of three residues with a conformationally restricted glycine as the first of the loop followed by an analine or histidine residue and a third residue with helical phi/psi angles; (iii) adjacent beta alpha loops of 3/4 residues previously reported to bind nucleotides and which have three glycine residues in the loop region; (iv) non-adjacent beta alpha loops of 0 residues with a serine or threonine as the last residue of the beta-strand. The analysis provides information for the model building of loops and prediction of secondary structure from amino acid sequences. PMID:3507703

  18. Transcriptional induction of Streptomyces cacaoi beta-lactamase by a beta-lactam compound.

    PubMed

    Forsman, M; Lindgren, L; Häggström, B; Jaurin, B

    1989-10-01

    The soil bacterium Streptomyces cacaoi produces an extracellular beta-lactamase. The beta-lactamase expression could be induced by the beta-lactam compound 6-amino penicillinoic acid (6-APA). In liquid cultures, a 50-fold increase in beta-lactamase expression was observed within the first three hours after addition of 6-APA. Using the cloned beta-lactamase gene as a probe, it was shown that this increase was mediated at the level of transcriptional initiation. The start point of the induced beta-lactamase transcript was determined, and the nucleotide sequence of the promoter region was analysed. No noticeable homology was found to control regions of inducible beta-lactamase genes of other bacteria. A striking feature was the presence of six direct repeats (ten base pairs each) upstream of the promoter region. Thus, an example of an inducible regulatory gene system in this Gram-positive microorganism is presented. Also, the primary structure of the beta-lactamase was deduced, showing a high degree of homology with class A beta-lactamases. PMID:2559297

  19. Molecular characterization of a novel putative ampelovirus tentatively named grapevine leafroll-associated virus 13.

    PubMed

    Ito, Takao; Nakaune, Ryoji

    2016-09-01

    A novel putative ampelovirus was detected in grapevines that showed typical leafroll symptoms and was tentatively named grapevine leafroll-associated virus (GLRaV)-13 following the series of numbering of other GLRaVs. The complete genome of GLRaV-13 comprised 17,608 nt and contained eleven putative open reading frames, showing genetic features similar to those of viruses belonging to subgroup I of genus Ampelovirus. Phylogenetic trees based on the RNA-dependent RNA polymerase, heat shock protein 70 homolog, and coat protein showed that GLRaV-13 had the closest, but still distant, relationship to GLRaV-1 in the subgroup I cluster. PMID:27289224

  20. Structural characterization of the putative ABC–type 2 transporter from Thermotoga maritima MSB8

    PubMed Central

    Filippova, Ekaterina V.; Tkaczuk, Karolina L.; Chruszcz, Maksymilian; Xu, Xiaohui; Savchenko, Alexei; Edwards, Aled; Minor, Wladek

    2014-01-01

    This study describes the structure of the putative ABC-type 2 transporter TM0543 from Thermotoga maritima MSB8 determined at a resolution of 2.3 Å. In comparative sequence-clustering analysis, TM0543 displays similarity to NatAB-like proteins, which are components of the ABC-type Na+ efflux pump permease. However, the overall structure fold of the predicted nucleotide-binding domain reveals that it is different from any known structure of ABC-type efflux transporters solved to date. The structure of the putative TM0543 domain also exhibits different dimer architecture and topology of its presumed ATP binding pocket, which may indicate that it does not bind nucleotide at all. Structural analysis of calcium ion binding sites found at the interface between TM0543 dimer subunits suggests that protein may be involved in ion-transporting activity. A detailed analysis of the protein sequence and structure is presented and discussed. PMID:25306867

  1. The effect of physical therapy on beta-endorphin levels.

    PubMed

    Bender, Tamás; Nagy, György; Barna, István; Tefner, Ildikó; Kádas, Eva; Géher, Pál

    2007-07-01

    Beta-endorphin (betaE) is an important reliever of pain. Various stressors and certain modalities of physiotherapy are potent inducers of the release of endogenous betaE to the blood stream. Most forms of exercise also increase blood betaE level, especially when exercise intensity involves reaching the anaerobic threshold and is associated with the elevation of serum lactate level. Age, gender, and mental activity during exercise also may influence betaE levels. Publications on the potential stimulating effect of manual therapy and massage on betaE release are controversial. Sauna, mud bath, and thermal water increase betaE levels through conveying heat to the tissues. The majority of the techniques for electrical stimulation have a similar effect, which is exerted both centrally and--to a lesser extent--peripherally. However, the parameters of electrotherapy have not yet been standardised. The efficacy of analgesia and the improvement of general well-being do not necessarily correlate with betaE level. Although in addition to blood, increased brain and cerebrospinal fluid betaE levels are also associated with pain, the majority of studies have concerned blood betaE levels. In general, various modalities of physical therapy might influence endorphin levels in the serum or in the cerebrospinal fluid--this is usually manifested by elevation with potential mitigation of pain. However, a causal relationship between the elevation of blood, cerebrospinal fluid or brain betaE levels and the onset of the analgesic action cannot be demonstrated with certainty. PMID:17483960

  2. Neoclassical transport in high {beta} tokamaks

    SciTech Connect

    Cowley, S.C.

    1992-12-01

    Neoclassical, transport in high {beta} large aspect ratio tokamaks is calculated. The variational method introduced by Rosenbluth, et al., is used to calculate the full Onsager matrix in the banana regime. These results are part of a continuing study of the high {beta} large aspect ratio equilibria introduced in Cowley, et al. All the neoclassical coefficients are reduced from their nominal low {beta} values by a factor ({var_epsilon}/q{sup 2}{beta}){sup {1/2}} II. This factor is the ratio of plasma volume in the boundary layer to the volume in the core. The fraction of trapped particles on a given flux surface (f{sub t}) is also reduced by this factor so that {approximately} {sub ({var_epsilon}}/q{sup 2}{beta}){sup {1/2}}. Special attention is given to the current equation, since this is thought to be relevant at low 3 and therefore may also be relevant at high {beta}. The bootstrap current term is found to exceed the actual current by a factor of the square root of the aspect ratio.

  3. Peptidase activity of beta-lactamases.

    PubMed Central

    Rhazi, N; Galleni, M; Page, M I; Frère, J M

    1999-01-01

    Although beta-lactamases have generally been considered as being devoid of peptidase activity, a low but significant hydrolysis of various N-acylated dipeptides was observed with representatives of each class of beta-lactamases. The kcat/Km values were below 0.1 M(-1). s(-1), but the enzyme rate enhancement factors were in the range 5000-20000 for the best substrates. Not unexpectedly, the best 'peptidase' was the class C beta-lactamase of Enterobacter cloacae P99, but, more surprisingly, the activity was always higher with the phenylacetyl- and benzoyl-d-Ala-d-Ala dipeptides than with the diacetyl- and alpha-acetyl-l-Lys-d-Ala-d-Ala tripeptides, which are the preferred substrates of the low-molecular-mass, soluble dd-peptidases. A comparison between the beta-lactamases and dd-peptidases showed that it might be as difficult for a dd-peptidase to open the beta-lactam ring as it is for the beta-lactamases to hydrolyse the peptides, an observation which can be explained by geometric and stereoelectronic considerations. PMID:10393100

  4. Toward beta cell replacement for diabetes

    PubMed Central

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

    2015-01-01

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

  5. Cardiovascular drug class specificity: beta-blockers.

    PubMed

    Reiter, Michael J

    2004-01-01

    Beta-adrenergic blockers are one of the most frequently prescribed cardiovascular drugs. Numerous beta-blockers are available for clinical use. Although these agents differ substantially, it is not clear whether (and which) differences are clinically relevant. Most of the important differences among agents reflect the relative specificity for beta1-, beta2-, and alpha-adrenergic receptors. Selection of a particular agent and target dose is probably best guided by available trial data, even though data are limited. Nonselective agents (with or without alpha-blocking properties) devoid of intrinsic sympathetic activity (ISA) are most appropriate postinfarction. Evidence exists demonstrating a mortality benefit postinfarction for propranolol, timolol, metoprolol, and, in the presence of left ventricular dysfunction, carvedilol. In the setting of heart failure, the selective agents metoprolol and bisoprolol as well as the nonselective agent carvedilol (which possesses alpha-blocking properties) have a demonstrated mortality benefit. Not all tolerated beta-blockers are associated with a survival benefit and it is probably not advisable to extrapolate benefits to all drugs with similar (although probably not identical) properties. Carvedilol may possess advantages over other beta-blockers and a possible survival advantage, suggested by the recent Carvedilol or Metoprolol European Trial (COMET), although these findings are not universally accepted. Ultimately, selection of a specific agent avoids obvious contraindications and uses trial data to guide selection and dose as long as side effects are absent or tolerable. PMID:15517513

  6. On the origin of the beta cell.

    PubMed

    Oliver-Krasinski, Jennifer M; Stoffers, Doris A

    2008-08-01

    The major forms of diabetes are characterized by pancreatic islet beta-cell dysfunction and decreased beta-cell numbers, raising hope for cell replacement therapy. Although human islet transplantation is a cell-based therapy under clinical investigation for the treatment of type 1 diabetes, the limited availability of human cadaveric islets for transplantation will preclude its widespread therapeutic application. The result has been an intense focus on the development of alternate sources of beta cells, such as through the guided differentiation of stem or precursor cell populations or the transdifferentiation of more plentiful mature cell populations. Realizing the potential for cell-based therapies, however, requires a thorough understanding of pancreas development and beta-cell formation. Pancreas development is coordinated by a complex interplay of signaling pathways and transcription factors that determine early pancreatic specification as well as the later differentiation of exocrine and endocrine lineages. This review describes the current knowledge of these factors as they relate specifically to the emergence of endocrine beta cells from pancreatic endoderm. Current therapeutic efforts to generate insulin-producing beta-like cells from embryonic stem cells have already capitalized on recent advances in our understanding of the embryonic signals and transcription factors that dictate lineage specification and will most certainly be further enhanced by a continuing emphasis on the identification of novel factors and regulatory relationships. PMID:18676806

  7. Polyfluorinated. cap alpha. ,. beta. -unsaturated ketons

    SciTech Connect

    Latypov, R.R.; Belogai, V.D.; Pashkevich, K.I.

    1986-07-10

    The ..cap alpha..,..beta..-unsaturated ketones (..cap alpha..,..beta..-UK), particularly those groups containing fluoroalkyl groups, are of interest as highly reactive compounds having two nonequivalent electrophilic centers. In the present investigation, by boiling polyfluorinated aldehydes with methylketones in glacial acetic acid, they have obtained for the first time the polyfluorinated ..beta..-hydroxy-ketones, the dehydration of which has been used to synthesize the corresponding polyfluorinated ..cap alpha..,..beta..-UK, and their structure and reactions with the nucleophiles NH/sub 3/, PhNH/sub 2/, MeOH have been studied. In the PMR spectra of the ..cap alpha..,..beta..-UK (X)-(XVI) two doublets of triplets are observed at 6.9 and 7.9 ppm, caused by the spin-spin coupling of the olefin protons with the CF/sub 2/ group of the substituent. For ..cap alpha..,..beta..-UK, apart from the cis-trans isomerism relative to the C=C bond, a rotational isomerism is possible, caused by rotation around the C-C single bond. The presence in the IR spectra of absorption bands from nonplanar torsion-deformation vibrations of C-H for a double bond (nu = 975-980 cm/sup -1/) and the high value of the spin-spin coupling constant of the olefin protons (J/sub HH/ = 15 Hz) indicate unambiguously the transconfiguration of the olefin protons.

  8. Toward beta cell replacement for diabetes.

    PubMed

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

    2015-04-01

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

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

    SciTech Connect

    Morant, Marc Dominique

    2014-10-14

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

  10. Complete Genome Sequence of an Avian Paramyxovirus Representative of Putative New Serotype 13

    PubMed Central

    Goraichuk, Iryna; Sharma, Poonam; Stegniy, Borys; Muzyka, Denys; Pantin-Jackwood, Mary J.; Gerilovych, Anton; Solodiankin, Olexii; Bolotin, Vitaliy; Miller, Patti J.; Dimitrov, Kiril M.

    2016-01-01

    Here, we report the complete genome sequence of a virus of a putative new serotype of avian paramyxovirus (APMV). The virus was isolated from a white-fronted goose in Ukraine in 2011 and designated white-fronted goose/Ukraine/Askania-Nova/48-15-02/2011. The genomic characterization of the isolate suggests that it represents the novel avian paramyxovirus group APMV 13. PMID:27469958

  11. Precambrian animal diversity: putative phosphatized embryos from the Doushantuo Formation of China

    NASA Technical Reports Server (NTRS)

    Chen, J. Y.; Oliveri, P.; Li, C. W.; Zhou, G. Q.; Gao, F.; Hagadorn, J. W.; Peterson, K. J.; Davidson, E. H.

    2000-01-01

    Putative fossil embryos and larvae from the Precambrian phosphorite rocks of the Doushantuo Formation in Southwest China have been examined in thin section by bright field and polarized light microscopy. Although we cannot completely exclude a nonbiological or nonmetazoan origin, we identified what appear to be modern cnidarian developmental stages, including both anthozoan planula larvae and hydrozoan embryos. Most importantly, the sections contain a variety of small (

  12. Identification of a putative nuclear export signal motif in human NANOG homeobox domain

    SciTech Connect

    Park, Sung-Won; Do, Hyun-Jin; Huh, Sun-Hyung; Sung, Boreum; Uhm, Sang-Jun; Song, Hyuk; Kim, Nam-Hyung; Kim, Jae-Hwan

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer We found the putative nuclear export signal motif within human NANOG homeodomain. Black-Right-Pointing-Pointer Leucine-rich residues are important for human NANOG homeodomain nuclear export. Black-Right-Pointing-Pointer CRM1-specific inhibitor LMB blocked the potent human NANOG NES-mediated nuclear export. -- Abstract: NANOG is a homeobox-containing transcription factor that plays an important role in pluripotent stem cells and tumorigenic cells. To understand how nuclear localization of human NANOG is regulated, the NANOG sequence was examined and a leucine-rich nuclear export signal (NES) motif ({sup 125}MQELSNILNL{sup 134}) was found in the homeodomain (HD). To functionally validate the putative NES motif, deletion and site-directed mutants were fused to an EGFP expression vector and transfected into COS-7 cells, and the localization of the proteins was examined. While hNANOG HD exclusively localized to the nucleus, a mutant with both NLSs deleted and only the putative NES motif contained (hNANOG HD-{Delta}NLSs) was predominantly cytoplasmic, as observed by nucleo/cytoplasmic fractionation and Western blot analysis as well as confocal microscopy. Furthermore, site-directed mutagenesis of the putative NES motif in a partial hNANOG HD only containing either one of the two NLS motifs led to localization in the nucleus, suggesting that the NES motif may play a functional role in nuclear export. Furthermore, CRM1-specific nuclear export inhibitor LMB blocked the hNANOG potent NES-mediated export, suggesting that the leucine-rich motif may function in CRM1-mediated nuclear export of hNANOG. Collectively, a NES motif is present in the hNANOG HD and may be functionally involved in CRM1-mediated nuclear export pathway.

  13. Obesity attenuates D2 autoreceptor‐mediated inhibition of putative ventral tegmental area dopaminergic neurons

    PubMed Central

    Koyama, Susumu; Mori, Masayoshi; Kanamaru, Syohei; Sazawa, Takuya; Miyazaki, Ayano; Terai, Hiroki; Hirose, Shinichi

    2014-01-01

    Abstract The ventral tegmental area (VTA) in the midbrain is important for food reward. High‐fat containing palatable foods have reinforcing effects and accelerate obesity. We have previously reported that diet‐induced obesity selectively decreased the spontaneous activity of VTA GABA neurons, but not dopamine neurons. The spontaneous activity of VTA dopamine neurons is regulated by D2 autoreceptors. In this study, we hypothesized that obesity would affect the excitability of VTA dopamine neurons via D2 autoreceptors. To examine this hypothesis, we compared D2 receptor‐mediated responses of VTA dopamine neurons between lean and obese mice. Mice fed on a high‐fat (45%) diet and mice fed on a standard diet were used as obese and lean models, respectively. Brain slice preparations were made from these two groups. Spontaneous activity of VTA neurons was recorded by extracellular recording. Putative VTA dopamine neurons were identified by firing inhibition with a D2 receptor agonist quinpirole, and electrophysiological criteria (firing frequency <5 Hz and action potential current duration >1.2 msec). Single‐dose application of quinpirole (3−100 nmol/L) exhibited similar firing inhibition of putative VTA dopamine neurons between lean and obese mice. In stepwise application by increasing quinpirole concentrations of 3, 10, 30, and 100 nmol/L subsequently, quinpirole‐induced inhibition of firing decreased in putative VTA dopamine neurons of obese mice compared with those of lean mice. In conclusion, high‐fat diet‐induced obesity attenuated D2 receptor‐mediated inhibition of putative VTA dopamine neurons due to the acceleration of D2 receptor desensitization. PMID:24793981

  14. Complete Genome Sequence of an Avian Paramyxovirus Representative of Putative New Serotype 13.

    PubMed

    Goraichuk, Iryna; Sharma, Poonam; Stegniy, Borys; Muzyka, Denys; Pantin-Jackwood, Mary J; Gerilovych, Anton; Solodiankin, Olexii; Bolotin, Vitaliy; Miller, Patti J; Dimitrov, Kiril M; Afonso, Claudio L

    2016-01-01

    Here, we report the complete genome sequence of a virus of a putative new serotype of avian paramyxovirus (APMV). The virus was isolated from a white-fronted goose in Ukraine in 2011 and designated white-fronted goose/Ukraine/Askania-Nova/48-15-02/2011. The genomic characterization of the isolate suggests that it represents the novel avian paramyxovirus group APMV 13. PMID:27469958

  15. Differential expression of the Wnt putative receptors Frizzled during mouse somitogenesis.

    PubMed

    Borello, U; Buffa, V; Sonnino, C; Melchionna, R; Vivarelli, E; Cossu, G

    1999-12-01

    The expression of eight murine Frizzled (1,3-9) genes was studied during mouse somitogenesis, in order to correlate the Wnt-dependent activation of myogenesis with the expression of specific Frizzled putative receptors. Frizzled 1, 3, 6, 7, 8, and 9 have specific expression in the forming and differentiating somites. The genes analyzed have a complex and partly overlapping pattern of expression in other regions of the embryo. PMID:10559494

  16. Purification and characterization of a thermostable beta-galactosidase from kidney beans (Phaseolus vulgaris L.) cv. PDR14.

    PubMed

    Biswas, Shyamasri; Kayastha, Arvind M; Seckler, Robert

    2003-04-01

    Using five different steps, beta-Galactosidase has been purified from kidney beans to apparent electrophoretic homogeneity with approximately 90-fold purification with a specific activity of 281 units mg-1 protein. A single band was observed in native PAGE. Activity staining of the native gel with 5-bromo 4-chloro 3-indoxyl beta-D-galactopyranoside (X-Gal) at pH 4.0 also produced a single band. Analytical gel filtration in Superdex G-75 revealed the molecular mass of the native protein to be approximately 75 kD. 10% SDS-PAGE under reducing conditions showed two subunits of molecular masses, 45 and 30 kD, respectively. Hence, beta-galactosidase from kidney beans is a heterodimer. A typical protein profile with lambda max at 280 nm was observed and A280/A260 ratio was 1.52. The N-terminal sequence of the 45 kD band showed 86% sequence homology with an Arabidopsis thaliana and 85% with Lycopersicon esculentum putative beta-galactosidase sequences. The Electrospray Mass Spectrometric analysis of this band also revealed a peptide fragment that had 90% sequence homology with an Arabidopsis thaliana putative beta-galactosidase sequence. The N-terminal sequencing of the 30 kD band as well as mass spectrometric analysis both by MALDI-TOF and ES MS revealed certain sequences that matched with phytohemagglutinin of kidney beans. The optimum pH of the enzyme was 4.0 and it hydrolysed o- and p-nitrophenyl beta-D galactopyranoside with a Km value of 0.63 mmol/L and 0.74 mmol/L, respectively. The energy of activation calculated from the Arrhenius equation was 14.8 kcal/mol enzyme site. The enzyme was found to be comparatively thermostable showing maximum activity at 67 degrees C. Thermal denaturation of the enzyme at 65 degrees C obeys single exponential decay with first order-rate constant 0.105 min-1. Galactose, a hydrolytic product of this enzyme was a competitive inhibitor with a Ki of 2.7 mmol/L. PMID:12756912

  17. Biomineralization by a Newly-Isolated Stalk-Forming Fe-oxidizing Bacterium: Towards Interpretation of Putative Fe Microfossils

    NASA Astrophysics Data System (ADS)

    Krepski, S. T.; Chan, C. S.

    2010-12-01

    Diverse aerobic, lithotrophic Fe-oxidizing bacteria (FeOB) produce distinctive extracellular Fe-rich filaments, which resemble putative Fe microfossils dating from recent to 1.7 Ga (Slack et al., 2007, EPSL: 243). The filament morphology, texture, and composition are promising biosignatures for these FeOB; however, somewhat similar morphologies have been shown to result from chemical precipitates. In order to accurately identify and interpret such biosignatures, morphology must described in detail and be linked to physiological function and growth conditions in extant organisms. Towards this goal, we aimed to isolate a novel, stalk-forming microaerophilic FeOB, since there exist few isolates. We successfully obtained a pure strain (named R-1) from a circumneutral, freshwater Fe seep in Christiana Creek, Newark, DE. This strain produces a twisted stalk, similar to Gallionella and Mariprofundus in morphology and in mineralogy. Our work shows that R-1 is a neutrophilic obligate FeOB, unable to oxidize other organic or inorganic substrates. It is a Beta-Proteobacterium in the Gallionellaceae family but is phylogenetically distinct from previously isolated Gallionella sp. and Sideroxydans sp. The closest cultured relative is S. lithotrophicus (97% similar) and the closest environmental clone is 98% similar. We have begun growing R-1 and the marine stalk-forming FeOB Mariprofundus ferrooxydans in microslide cultures, which allow direct microscope observation without disturbing growth. We are monitoring oxygen concentration gradients and FeOB response to oxygen levels. In order to link morphology to biological function and growth conditions, we will observe stalk formation under various conditions and document various morphological and textural parameter (e.g. branching and orientation) to establish criteria for biogenicity. No organisms are known to make stalks under anaerobic conditions, so if these structures are detected in the rock record, they could be used as

  18. Targets of TGF-beta signaling in Caenorhabditis elegans dauer formation.

    PubMed

    Inoue, T; Thomas, J H

    2000-01-01

    Caenorhabditis elegans dauer formation is controlled by multiple environmental factors. The chemosensory neuron ASI regulates dauer formation by secretion of DAF-7/TGF-beta, but the molecular targets of the DAF-7 ligand are incompletely defined and the cellular targets are unknown. We genetically characterized and cloned a putative transducer of DAF-7 signaling called daf-14 and found that it encodes a Smad protein. DAF-14 Smad has a highly unusual structure completely lacking the N-terminal domain found in all other Smad proteins known to date. daf-14 genetically interacts with daf-8, which encodes another Smad, and the interaction suggests partial functional redundancy between these two Smad proteins. We also studied the cellular targets of DAF-7 signaling by studying the sites of action of daf-14 and daf-4, the putative receptor for DAF-7. daf-14::gfp is expressed in multiple tissues that are remodeled during dauer formation. However, analysis of mosaics generated by free duplication loss and tissue-specific expression constructs indicate cell-nonautonomous function of daf-4, arguing against direct DAF-7 signaling to tissues throughout the animal. Instead, these experiments suggest the nervous system as a target of DAF-7 signaling and that the nervous system in turn regulates dauer formation by other tissues. PMID:10625546

  19. Genetic characterization of Amazonian bovine papillomavirus reveals the existence of four new putative types.

    PubMed

    da Silva, Flavio R C; Daudt, Cíntia; Streck, André F; Weber, Matheus N; Filho, Ronaldo V Leite; Driemeier, David; Canal, Cláudio W

    2015-08-01

    Papillomaviruses are small and complex viruses that belong to the Papillomaviridae family, which comprises 39 genera. The bovine papillomavirus (BPV) causes an infectious disease that is characterized by chronic and proliferative benign tumors that affect cattle worldwide. Different genotypes of BPVs can cause distinct skin and mucosal lesions and the immunity they raise has low cross-protection. This report aimed to genotype BPVs in cattle from Northern Brazil based on nucleotide partial sequences of the L1 ORF. Skin wart samples from 39 bovines clinically and histopathologically diagnosed as cutaneous papillomatosis from Acre and Rondônia States were analyzed. The results revealed four already reported BPV types (BPVs 1, 2, 11, and 13), nine putative new BPV subtypes and four putative new BPV types as well as two putative new BPV types that were already reported. To our knowledge, this is the first record of BPVs from the Brazilian Amazon region that identified new possible BPV types and subtypes circulating in this population. These findings point to the great genetic diversity of BPVs that are present in this region and highlight the importance of this knowledge before further studies about vaccination are attempted. PMID:26116287

  20. Identification of Putative Coffee Rust Mycoparasites via Single-Molecule DNA Sequencing of Infected Pustules

    PubMed Central

    Marino, John A.; Perfecto, Ivette; Vandermeer, John

    2015-01-01

    The interaction of crop pests with their natural enemies is a fundament to their control. Natural enemies of fungal pathogens of crops are poorly known relative to those of insect pests, despite the diversity of fungal pathogens and their economic importance. Currently, many regions across Latin America are experiencing unprecedented epidemics of coffee rust (Hemileia vastatrix). Identification of natural enemies of coffee rust could aid in developing management strategies or in pinpointing species that could be used for biocontrol. In the present study, we characterized fungal communities associated with coffee rust lesions by single-molecule DNA sequencing of fungal rRNA gene bar codes from leaf discs (≈28 mm2) containing rust lesions and control discs with no rust lesions. The leaf disc communities were hyperdiverse in terms of fungi, with up to 69 operational taxonomic units (putative species) per control disc, and the diversity was only slightly reduced in rust-infected discs, with up to 63 putative species. However, geography had a greater influence on the fungal community than whether the disc was infected by coffee rust. Through comparisons between control and rust-infected leaf discs, as well as taxonomic criteria, we identified 15 putative mycoparasitic fungi. These fungi are concentrated in the fungal family Cordycipitaceae and the order Tremellales. These data emphasize the complexity of diverse fungi of unknown ecological function within a leaf that might influence plant disease epidemics or lead to the development of species for biocontrol of fungal disease. PMID:26567299

  1. CopA:GFP localizes to putative Golgi equivalents in Aspergillus nidulans.

    PubMed

    Breakspear, Andrew; Langford, Kelly J; Momany, Michelle; Assinder, Susan J

    2007-12-01

    The Golgi complex is a main component of the eukaryotic secretory system and functions to modify nascent proteins sent from the endoplasmic reticulum. Ultrastructural studies of filamentous fungi have shown Golgi to be individual smooth membrane cisternae that are referred to as Golgi equivalents or dictyosomes. The Aspergillus nidulans copA gene encodes a homolog of mammalian coat protein (alpha-COP), a constituent of the Golgi-localized COPI vesicle coat. Here, the localization of A. nidulansalpha-COP was examined in live cells using the reporter green fluorescent protein (GFP). CopA:GFP localized to putative Golgi equivalents that were concentrated at hyphal tips. The localization was disrupted by the fungal metabolite brefeldin A. To investigate the significance of the microtubule cytoskeleton in the localization of putative Golgi equivalents, the copA:gfp fusion was expressed in a temperature-sensitive dynein mutant. In addition, a wild-type strain expressing copA:gfp was treated with the microtubule-disrupting drug nocodazole. The results suggest that the microtubule cytoskeleton is not the primary mechanism of localizing putative Golgi equivalents in A. nidulans. PMID:17986089

  2. Putative periodontopathic bacteria and herpesviruses in pregnant women: a case-control study

    PubMed Central

    Lu, Haixia; Zhu, Ce; Li, Fei; Xu, Wei; Tao, Danying; Feng, Xiping

    2016-01-01

    Little is known about herpesvirus and putative periodontopathic bacteria in maternal chronic periodontitis. The present case-control study aimed to explore the potential relationship between putative periodontopathic bacteria and herpesviruses in maternal chronic periodontitis.Saliva samples were collected from 36 pregnant women with chronic periodontitis (cases) and 36 pregnant women with healthy periodontal status (controls). Six putative periodontopathic bacteria (Porphyromonas gingivalis [Pg], Aggregatibacer actinomycetemcomitans [Aa], Fusobacterium nucleatum [Fn], Prevotella intermedia [Pi], Tannerella forsythia [Tf], and Treponema denticola [Td]) and three herpesviruses (Epstein-Barr virus [EBV], human cytomegalovirus [HCMV], and herpes simplex virus [HSV]) were detected. Socio-demographic data and oral health related behaviors, and salivary estradiol and progesterone levels were also collected. The results showed no significant differences in socio-demographic background, oral health related behaviors, and salivary estradiol and progesterone levels between the two groups (all P > 0.05). The detection rates of included periodontopathic microorganisms were not significantly different between the two groups (all P > 0.05), but the coinfection rate of EBV and Pg was significantly higher in the case group than in the control group (P = 0.028). EBV and Pg coinfection may promote the development of chronic periodontitis among pregnant women. PMID:27301874

  3. GIP2, a Putative Transcription Factor That Regulates the Aurofusarin Biosynthetic Gene Cluster in Gibberella zeae

    PubMed Central

    Kim, Jung-Eun; Jin, Jianming; Kim, Hun; Kim, Jin-Cheol; Yun, Sung-Hwan; Lee, Yin-Won

    2006-01-01

    Gibberella zeae (anamorph: Fusarium graminearum) is an important pathogen of maize, wheat, and rice. Colonies of G. zeae produce yellow-to-tan mycelia with the white-to-carmine red margins. In this study, we focused on nine putative open reading frames (ORFs) closely linked to PKS12 and GIP1, which are required for aurofusarin biosynthesis in G. zeae. Among them is an ORF designated GIP2 (for Gibberella zeae pigment gene 2), which encodes a putative protein of 398 amino acids that carries a Zn(II)2Cys6 binuclear cluster DNA-binding domain commonly found in transcription factors of yeasts and filamentous fungi. Targeted gene deletion and complementation analyses confirmed that GIP2 is required for aurofusarin biosynthesis. Expression of GIP2 in carrot medium correlated with aurofusarin production by G. zeae and was restricted to vegetative mycelia. Inactivation of the 10 contiguous genes in the ΔGIP2 strain delineates an aurofusarin biosynthetic gene cluster. Overexpression of GIP2 in both the ΔGIP2 and the wild-type strains increases aurofusarin production and reduces mycelial growth. Thus, GIP2 is a putative positive regulator of the aurofusarin biosynthetic gene cluster, and aurofusarin production is negatively correlated with vegetative growth by G. zeae. PMID:16461721

  4. Cloning and molecular characterization of a putative voltage-gated sodium channel gene in the crayfish.

    PubMed

    Coskun, Cagil; Purali, Nuhan

    2016-06-01

    Voltage-gated sodium channel genes and associated proteins have been cloned and studied in many mammalian and invertebrate species. However, there is no data available about the sodium channel gene(s) in the crayfish, although the animal has frequently been used as a model to investigate various aspects of neural cellular and circuit function. In the present work, by using RNA extracts from crayfish abdominal ganglia samples, the complete open reading frame of a putative sodium channel gene has firstly been cloned and molecular properties of the associated peptide have been analyzed. The open reading frame of the gene has a length of 5793 bp that encodes for the synthesis of a peptide, with 1930 amino acids, that is 82% similar to the α-peptide of a sodium channel in a neighboring species, Cancer borealis. The transmembrane topology analysis of the crayfish peptide indicated a pattern of four folding domains with several transmembrane segments, as observed in other known voltage-gated sodium channels. Upon analysis of the obtained sequence, functional regions of the putative sodium channel responsible for the selectivity filter, inactivation gate, voltage sensor, and phosphorylation have been predicted. The expression level of the putative sodium channel gene, as defined by a qPCR method, was measured and found to be the highest in nervous tissue. PMID:27032955

  5. A multistep bioinformatic approach detects putative regulatory elements in gene promoters

    PubMed Central

    Bortoluzzi, Stefania; Coppe, Alessandro; Bisognin, Andrea; Pizzi, Cinzia; Danieli, Gian Antonio

    2005-01-01

    Background Searching for approximate patterns in large promoter sequences frequently produces an exceedingly high numbers of results. Our aim was to exploit biological knowledge for definition of a sheltered search space and of appropriate search parameters, in order to develop a method for identification of a tractable number of sequence motifs. Results Novel software (COOP) was developed for extraction of sequence motifs, based on clustering of exact or approximate patterns according to the frequency of their overlapping occurrences. Genomic sequences of 1 Kb upstream of 91 genes differentially expressed and/or encoding proteins with relevant function in adult human retina were analyzed. Methodology and results were tested by analysing 1,000 groups of putatively unrelated sequences, randomly selected among 17,156 human gene promoters. When applied to a sample of human promoters, the method identified 279 putative motifs frequently occurring in retina promoters sequences. Most of them are localized in the proximal portion of promoters, less variable in central region than in lateral regions and similar to known regulatory sequences. COOP software and reference manual are freely available upon request to the Authors. Conclusion The approach described in this paper seems effective for identifying a tractable number of sequence motifs with putative regulatory role. PMID:15904489

  6. Putative periodontopathic bacteria and herpesviruses in pregnant women: a case-control study.

    PubMed

    Lu, Haixia; Zhu, Ce; Li, Fei; Xu, Wei; Tao, Danying; Feng, Xiping

    2016-01-01

    Little is known about herpesvirus and putative periodontopathic bacteria in maternal chronic periodontitis. The present case-control study aimed to explore the potential relationship between putative periodontopathic bacteria and herpesviruses in maternal chronic periodontitis.Saliva samples were collected from 36 pregnant women with chronic periodontitis (cases) and 36 pregnant women with healthy periodontal status (controls). Six putative periodontopathic bacteria (Porphyromonas gingivalis [Pg], Aggregatibacer actinomycetemcomitans [Aa], Fusobacterium nucleatum [Fn], Prevotella intermedia [Pi], Tannerella forsythia [Tf], and Treponema denticola [Td]) and three herpesviruses (Epstein-Barr virus [EBV], human cytomegalovirus [HCMV], and herpes simplex virus [HSV]) were detected. Socio-demographic data and oral health related behaviors, and salivary estradiol and progesterone levels were also collected. The results showed no significant differences in socio-demographic background, oral health related behaviors, and salivary estradiol and progesterone levels between the two groups (all P > 0.05). The detection rates of included periodontopathic microorganisms were not significantly different between the two groups (all P > 0.05), but the coinfection rate of EBV and Pg was significantly higher in the case group than in the control group (P = 0.028). EBV and Pg coinfection may promote the development of chronic periodontitis among pregnant women. PMID:27301874

  7. Emissions of putative isoprene oxidation products from mango branches under abiotic stress

    PubMed Central

    Jardine, Kolby J.; Meyers, Kimberly; Abrell, Leif; Alves, Eliane G.; Yanez Serrano, Ana Maria; Kesselmeier, Jürgen; Karl, Thomas; Guenther, Alex; Vickers, Claudia; Chambers, Jeffrey Q.

    2013-01-01

    Although several per cent of net carbon assimilation can be re-released as isoprene emissions to the atmosphere by many tropical plants, much uncertainty remains regarding its biological significance. In a previous study, we detected emissions of isoprene and its oxidation products methyl vinyl ketone (MVK) and methacrolein (MACR) from tropical plants under high temperature/light stress, suggesting that isoprene is oxidized not only in the atmosphere but also within plants. However, a comprehensive analysis of the suite of isoprene oxidation products in plants has not been performed and production relationships with environmental stress have not been described. In this study, putative isoprene oxidation products from mango (Mangifera indica) branches under abiotic stress were first identified. High temperature/light and freeze–thaw treatments verified direct emissions of the isoprene oxidation products MVK and MACR together with the first observations of 3-methyl furan (3-MF) and 2-methyl-3-buten-2-ol (MBO) as putative novel isoprene oxidation products. Mechanical wounding also stimulated emissions of MVK and MACR. Photosynthesis under 13CO2 resulted in rapid (<30min) labelling of up to five carbon atoms of isoprene, with a similar labelling pattern observed in the putative oxidation products. These observations highlight the need to investigate further the mechanisms of isoprene oxidation within plants under stress and its biological and atmospheric significance.

  8. The relationship of obsessive-compulsive disorder to putative spectrum disorders: results from an Indian study.

    PubMed

    Jaisoorya, T S; Reddy, Y C Janardhan; Srinath, S

    2003-01-01

    The relationship between obsessive-compulsive disorder (OCD) and putative obsessive-compulsive (OC) spectrum disorders is unclear. This study investigates the prevalence of putative OC spectrum disorders in OCD subjects in a controlled clinical design. The putative OC spectrum disorders studied included somatoform disorders (body dysmorphic disorder [BDD] and hypochondriasis), eating disorders, tic disorders (e.g., Tourette's syndrome [TS]), and impulse control disorders (e.g., trichotillomania). Only those disorders that are commonly noted to be possibly related to OCD are studied. Included in this study were 231 subjects with a diagnosis of OCD according to DSM-IV criteria and 200 controls who were not screened for psychiatric morbidity. The subjects and controls were assessed in detail by extensive clinical and semistructured interviews by expert clinical psychiatrists. The lifetime diagnoses were made by consensus of two psychiatrists. Prevalence of tic disorders, hypochondriasis, BDD, and trichotillomania was significantly greater in OCD subjects compared to controls. However, the prevalence of sexual compulsions, pathological gambling, eating disorders, and depersonalization disorder was not greater in the OCD subjects compared to controls. The findings of this comorbidity study suggest that tic disorders, hypochondriasis, BDD, and trichotillomania are perhaps part of the OC spectrum disorders. There is a need to evaluate evidence from other sources such as epidemiological, neurobiological, and family studies to further our understanding of the concept of OC spectrum disorders. PMID:12923710

  9. Putative fossil life in a hydrothermal system of the Dellen impact structure, Sweden

    NASA Astrophysics Data System (ADS)

    Lindgren, Paula; Ivarsson, Magnus; Neubeck, Anna; Broman, Curt; Henkel, Herbert; Holm, Nils G.

    2010-07-01

    Impact-generated hydrothermal systems are commonly proposed as good candidates for hosting primitive life on early Earth and Mars. However, evidence of fossil microbial colonization in impact-generated hydrothermal systems is rarely reported in the literature. Here we present the occurrence of putative fossil microorganisms in a hydrothermal system of the 89 Ma Dellen impact structure, Sweden. We found the putative fossilized microorganisms hosted in a fine-grained matrix of hydrothermal alteration minerals set in interlinked fractures of an impact breccia. The putative fossils appear as semi-straight to twirled filaments, with a thickness of 1-2 μm, and a length between 10 and 100 μm. They have an internal structure with segmentation, and branching of filaments occurs frequently. Their composition varies between an outer and an inner layer of a filament, where the inner layer is more iron rich. Our results indicate that hydrothermal systems in impact craters could potentially be capable of supporting microbial life. This could have played an important role for the evolution of life on early Earth and Mars.

  10. A Pipeline for Classifying Relationships Using Dense SNP/SNV Data and Putative Pedigree Information.

    PubMed

    Zeng, Zhen; Weeks, Daniel E; Chen, Wei; Mukhopadhyay, Nandita; Feingold, Eleanor

    2016-02-01

    When genome-wide association studies (GWAS) or sequencing studies are performed on family-based datasets, the genotype data can be used to check the structure of putative pedigrees. Even in datasets of putatively unrelated people, close relationships can often be detected using dense single-nucleotide polymorphism/variant (SNP/SNV) data. A number of methods for finding relationships using dense genetic data exist, but they all have certain limitations, including that they typically use average genetic sharing, which is only a subset of the available information. Here, we present a set of approaches for classifying relationships in GWAS datasets or large-scale sequencing datasets. We first propose an empirical method for detecting identity by descent segments in close relative pairs using un-phased dense SNP data and demonstrate how that information can assist in building a relationship classifier. We then develop a strategy to take advantage of putative pedigree information to enhance classification accuracy. Our methods are tested and illustrated with two datasets from two distinct populations. Finally, we propose classification pipelines for checking and identifying relationships in datasets containing a large number of small pedigrees. PMID:26709242

  11. Prevalence and putative risk markers of challenging behavior in students with intellectual disabilities.

    PubMed

    Dworschak, Wolfgang; Ratz, Christoph; Wagner, Michael

    2016-11-01

    Numerous studies have reported a high prevalence of challenging behavior among students with intellectual disabilities (ID). They discuss different putative risk markers as well as their influence on the occurrence of challenging behavior. The study investigates the prevalence of challenging behavior and evaluates in terms of a replication study well-known putative risk markers among a representative sample of students with ID (N=1629) in Bavaria, one of the largest regions in Germany. The research is based on a modified version of the Developmental Behavior Checklist (DBC). Findings indicate a prevalence rate of 52% for challenging behavior. The following putative risk markers are associated with challenging behavior: intense need for care, male gender, lack of communication skills, and residential setting. These risk markers explain 8.4% of the variance concerning challenging behavior. These results reveal that challenging behavior either is to a large extent determined by situations and interactions between individuals and environment and cannot be explained by the measured individual and social risk markers alone, or it is determined by further risk markers that were not measured. PMID:27608371

  12. Phylogeny of Algal Sequences Encoding Carbohydrate Sulfotransferases, Formylglycine-Dependent Sulfatases, and Putative Sulfatase Modifying Factors

    PubMed Central

    Ho, Chai-Ling

    2015-01-01

    Many algae are rich sources of sulfated polysaccharides with biological activities. The physicochemical/rheological properties and biological activities of sulfated polysaccharides are affected by the pattern and number of sulfate moieties. Sulfation of carbohydrates is catalyzed by carbohydrate sulfotransferases (CHSTs) while modification of sulfate moieties on sulfated polysaccharides was presumably catalyzed by sulfatases including formylglycine-dependent sulfatases (FGly-SULFs). Post-translationally modification of Cys to FGly in FGly-SULFs by sulfatase modifiying factors (SUMFs) is necessary for the activity of this enzyme. The aims of this study are to mine for sequences encoding algal CHSTs, FGly-SULFs and putative SUMFs from the fully sequenced algal genomes and to infer their phylogenetic relationships to their well characterized counterparts from other organisms. Algal sequences encoding CHSTs, FGly-SULFs, SUMFs, and SUMF-like proteins were successfully identified from green and brown algae. However, red algal FGly-SULFs and SUMFs were not identified. In addition, a group of SUMF-like sequences with different gene structure and possibly different functions were identified for green, brown and red algae. The phylogeny of these putative genes contributes to the corpus of knowledge of an unexplored area. The analyses of these putative genes contribute toward future production of existing and new sulfated carbohydrate polymers through enzymatic synthesis and metabolic engineering. PMID:26635861

  13. The efficacy and tolerability of mirabegron, a β3 adrenoceptor agonist, in patients with symptoms of overactive bladder

    PubMed Central

    Thiagamoorthy, Ganesh; Kotes, Stephanie; Zacchè, Martino; Cardozo, Linda

    2016-01-01

    Mirabegron, is the only β-3 adrenoreceptor (AR) agonist available for the treatment of overactive bladder (OAB). To assess the efficacy and tolerability of this novel drug therapy, two phase II and six phase III Astellas-sponsored trials have been conducted with over 10,500 adults with OAB recruited. Of these, seven were randomized, double blind, 12-week placebo controlled studies and the other was for 12 months and not placebo controlled. The evidence described would suggest that mirabegron is as efficacious as most antimuscarinics, including tolterodine extended release (ER) 4 mg, compared with placebo with regard to objective measures such as reduction in number of voids per 24 hours, mean volume per void, mean number of episodes of general urinary incontinence, urgency urinary incontinence and urgency per 24 hours; and subjective measures such as severity of urgency, patient perception of bladder condition and validated continence quality of life questionnaires. Regarding tolerability, these data would suggest that patients taking mirabegron suffer a similar rate of adverse effects as those taking placebo alone, whereas the rate in those taking antimuscarinics is greater. Thus mirabegron presents a safe and effective alternative treatment to antimuscarinics for patients with OAB symptoms. Patients who may particularly benefit from mirabegron include those who are unsuitable for antimuscarinics or who have previously struggled with antimuscarinic side effects. PMID:26834839

  14. Oral toxicity of beta-N-acetyl hexosaminidase to insects.

    PubMed

    Dowd, Patrick F; Johnson, Eric T; Pinkerton, T Scott

    2007-05-01

    Insect chitin is a potential target for resistance plant proteins, but plant-derived chitin-degrading enzymes active against insects are virtually unknown. Commercial beta-N-acetylhexosaminidase (NAHA), a chitin-degrading enzyme from jack bean Canavalia ensiformis, caused significant mortality of fall armyworm Spodoptera frugiperda larvae at 75 microg/gm, but no significant mortality was noted with Aspergillus niger NAHA. Maize Zea mays callus transformed to express an Arabidopsis thaliana clone that putatively codes for NAHA caused significantly higher mortality of cigarette beetle Lasioderma serricorne larvae and significantly reduced growth rates (as reflected by survivor weights) of S. frugiperda as compared to callus that expressed control cDNAs. Tassels from model line Hi-II maize (Z. mays) plants transformed with the NAHA gene fed to S. frugiperda caused significantly higher mortality than tassels transformed to express glucuronidase; mortality was significantly correlated with NAHA expression levels detected histochemically. Leaf disks from inbred Oh43 maize plants transformed with the NAHA gene on average had significantly less feeding by caterpillars than null transformants. Leaf disks of Oh43 transformants caused significant mortality of both S. frugiperda and corn earworm Helicoverpa zea larvae, which was associated with higher expression levels of NAHA detected by isoelectric focusing, histochemically, or with antibody. Overall, these results suggest that plant NAHA has a role in insect resistance. Introduction of NAHA genes or enhancement of activity through breeding or genetic engineering has the potential to significantly reduce insect damage and thereby indirectly reduce mycotoxins that are harmful to animals and people. PMID:17417870

  15. Sense and sensitivity of double beta decay experiments

    NASA Astrophysics Data System (ADS)

    Gómez-Cadenas, J. J.; Martín-Albo, J.; Sorel, M.; Ferrario, P.; Monrabal, F.; Muñoz, J.; Novella, P.; Poves, A.

    2011-06-01

    The search for neutrinoless double beta decay is a very active field in which the number of proposals for next-generation experiments has proliferated. In this paper we attempt to address both the sense and the sensitivity of such proposals. Sensitivity comes first, by means of proposing a simple and unambiguous statistical recipe to derive the sensitivity to a putative Majorana neutrino mass, mββ. In order to make sense of how the different experimental approaches compare, we apply this recipe to a selection of proposals, comparing the resulting sensitivities. We also propose a ``physics-motivated range'' (PMR) of the nuclear matrix elements as a unifying criterium between the different nuclear models. The expected performance of the proposals is parametrized in terms of only four numbers: energy resolution, background rate (per unit time, isotope mass and energy), detection efficiency, and ββ isotope mass. For each proposal, both a reference and an optimistic scenario for the experimental performance are studied. In the reference scenario we find that all the proposals will be able to partially explore the degenerate spectrum, without fully covering it, although four of them (KamLAND-Zen, CUORE, NEXT and EXO) will approach the 50 meV boundary. In the optimistic scenario, we find that CUORE and the xenon-based proposals (KamLAND-Zen, EXO and NEXT) will explore a significant fraction of the inverse hierarchy, with NEXT covering it almost fully. For the long term future, we argue that 136Xe-based experiments may provide the best case for a 1-ton scale experiment, given the potentially very low backgrounds achievable and the expected scalability to large isotope masses.

  16. Sense and sensitivity of double beta decay experiments

    SciTech Connect

    Gómez-Cadenas, J.J.; Martín-Albo, J.; Sorel, M.; Ferrario, P.; Monrabal, F.; Muñoz, J.; Novella, P.; Poves, A. E-mail: justo.martin-albo@ific.uv.es E-mail: paola.ferrario@ific.uv.es E-mail: jmunoz@ific.uv.es E-mail: alfredo.poves@uam.es

    2011-06-01

    The search for neutrinoless double beta decay is a very active field in which the number of proposals for next-generation experiments has proliferated. In this paper we attempt to address both the sense and the sensitivity of such proposals. Sensitivity comes first, by means of proposing a simple and unambiguous statistical recipe to derive the sensitivity to a putative Majorana neutrino mass, m{sub ββ}. In order to make sense of how the different experimental approaches compare, we apply this recipe to a selection of proposals, comparing the resulting sensitivities. We also propose a ''physics-motivated range'' (PMR) of the nuclear matrix elements as a unifying criterium between the different nuclear models. The expected performance of the proposals is parametrized in terms of only four numbers: energy resolution, background rate (per unit time, isotope mass and energy), detection efficiency, and ββ isotope mass. For each proposal, both a reference and an optimistic scenario for the experimental performance are studied. In the reference scenario we find that all the proposals will be able to partially explore the degenerate spectrum, without fully covering it, although four of them (KamLAND-Zen, CUORE, NEXT and EXO) will approach the 50 meV boundary. In the optimistic scenario, we find that CUORE and the xenon-based proposals (KamLAND-Zen, EXO and NEXT) will explore a significant fraction of the inverse hierarchy, with NEXT covering it almost fully. For the long term future, we argue that {sup 136}Xe-based experiments may provide the best case for a 1-ton scale experiment, given the potentially very low backgrounds achievable and the expected scalability to large isotope masses.

  17. Apolipoprotein E and beta-amyloid (1-42) regulation of glycogen synthase kinase-3beta.

    PubMed

    Cedazo-Mínguez, A; Popescu, B O; Blanco-Millán, J M; Akterin, S; Pei, J-J; Winblad, B; Cowburn, R F

    2003-12-01

    Glycogen synthase kinase-3beta (GSK-3beta) is implicated in regulating apoptosis and tau protein hyperphosphorylation in Alzheimer's disease (AD). We investigated the effects of two key AD molecules, namely apoE (E3 and E4 isoforms) and beta-amyloid (Abeta) 1-42 on GSK-3beta and its major upstream regulators, intracellular calcium and protein kinases C and B (PKC and PKB) in human SH-SY5Y neuroblastoma cells. ApoE3 induced a mild, transient, Ca2+-independent and early activation of GSK-3beta. ApoE4 effects were biphasic, with an early strong GSK-3beta activation that was partially dependent on extracellular Ca2+, followed by a GSK-3beta inactivation. ApoE4 also activated PKC-alpha and PKB possibly giving the subsequent GSK-3beta inhibition. Abeta(1-42) effects were also biphasic with a strong activation dependent partially on extracellular Ca2+ followed by an inactivation. Abeta(1-42) induced an early and potent activation of PKC-alpha and a late decrease of PKB activity. ApoE4 and Abeta(1-42) were more toxic than apoE3 as shown by MTT reduction assays and generation of activated caspase-3. ApoE4 and Abeta(1-42)-induced early activation of GSK-3beta could lead to apoptosis and tau hyperphosphorylation. A late inhibition of GSK-3beta through activation of upstream kinases likely compensates the effects of apoE4 and Abeta(1-42) on GSK-3beta, the unbalanced regulation of which may contribute to AD pathology. PMID:14622095

  18. Oligomerization and toxicity of A{beta} fusion proteins

    SciTech Connect

    Caine, Joanne M.; Bharadwaj, Prashant R.; Sankovich, Sonia E.; Ciccotosto, Giuseppe D.; Streltsov, Victor A.; Varghese, Jose

    2011-06-10

    Highlights: {yields} We expressed amyloid-{beta} (A{beta}) peptide as a soluble maltose binding protein fusion (MBP-A{beta}42 and MBP-A{beta}16). {yields} The full length A{beta} peptide fusion, MBP-A{beta}42, forms oligomeric species as determined by SDS-PAGE gels, gel filtration and DLS. {yields} The MBP-A{beta}42, but not MBP-A{beta}16 or MBP alone, is toxic to both yeast and mammalian cells as determined by toxicity assays. -- Abstract: This study has found that the Maltose binding protein A{beta}42 fusion protein (MBP-A{beta}42) forms soluble oligomers while the shorter MBP-A{beta}16 fusion and control MBP did not. MBP-A{beta}42, but neither MBP-A{beta}16 nor control MBP, was toxic in a dose-dependent manner in both yeast and primary cortical neuronal cells. This study demonstrates the potential utility of MBP-A{beta}42 as a reagent for drug screening assays in yeast and neuronal cell cultures and as a candidate for further A{beta}42 characterization.

  19. Structural studies of dopamine. beta. -hydroxylase

    SciTech Connect

    Papadopoulos, N.J.

    1985-01-01

    Dopamine ..beta..-hydroxylase catalyzes the conversion of dopamine to norepinephrine, a ..beta..-hydroxylation reaction, utilizing ascorbic acid as reducing agent and molecular oxygen as cosubstrate. Modifications of the previously published purification procedure for D..beta..H have produced findings which show that (1) enzyme is inactivated by ascorbate autooxidation during the isolation procedure, (2) active as well as inactive D..beta..H co-purify throughout the entire purification procedure and (3) beef liver catalase totally protects against this time dependent inactivation. The stoichiometry of copper binding to the active sites of D..beta..H has been investigated using /sup 19/F-NMR and radioactive binding experiments. The data unequivocally show that homogeneous D..beta..H (isolated in the presence of catalase) specifically binds up to approx.8 copper atoms per enzyme tetramer. Distance determinations done using NMR relaxation rate theory show that anion activators of the catalytic reaction are bound at a fairly far distance from the Cu/sup 2 +/ centers. Spin-echo electron paramagnetic resonance spectroscopy indicates that at least one, possibly two, histidines are bound as equatorial ligands to each Cu/sup 2 +/ ion. The combined data indicate that highly purified dopamine ..beta..-hydroxylase contains a 2 copper atom active site, composed of magnetically non-interacting metal centers. Active site components are distant from the Cu/sup 2 +/ centers, suggesting a possible movement of active site residues or components after reduction of enzyme bound copper in order to achieve the insertion of 1 atom of oxygen into the benzylic C-H bond of dopamine.

  20. Infrared Observations of beta Pictoris Analogs

    NASA Astrophysics Data System (ADS)

    Fajardo-Acosta, S. B.; Knacke, R. F.; Telesco, C. M.

    1993-12-01

    We searched for 10 microns silicate emission from circumstellar dust in 13 main-sequence stars that possibly exemplify the beta Pictoris phenomenon. We have previously detected the silicate feature in 51 Oph (Fajardo-Acosta, Telesco, & Knacke 1993, ApJ, in press) through mid-IR narrowband spectrophotometry (FWHM ~ 1 microns) with the MSFC Big Mac camera and the 2--30 microns Facility bolometer at the IRTF. We are using the same instrumentation in our survey of other Vega-type disks. These observations were motivated by the detection of the silicate feature in beta Pic (Telesco & Knacke 1991, ApJ, 372, L29). We followed the detections in beta Pic and 51 Oph with 2.9--13.5 microns intermediate-resolution (lambda /Delta lambda ~ 50) spectroscopy with the Aerospace Corp. Infrared Spectrograph. The higher resolution data confirmed the analogy of the silicate features in beta Pic (Knacke et al. 1993, ApJ, in press) and 51 Oph (Russell et al. 1993, in prep.) to similar features in Solar System cometary spectra. Among the Vega-type stars we recently observed, beta UMa, zeta Lep, sigma Her, and gamma Oph exhibit significant dust emission at 10 microns (>= 0.15 Jy). We expect to resolve whether silicate emission is present with the higher spectral resolution available with the Aerospace Spectrograph. We have compared the spectrum of beta Pic with those in the data compilation of the IRAS Low Resolution Spectrograph. Of the 5425 sources, 88 exhibit 10 microns silicate emission features that match beta Pic's reasonably well. Many of these sources do not have known associations; those that do are typically low-mass giant branch Miras or massive supergiants. We are investigating at least 5 possible associations with early-type main-sequence stars. This research was sponsored by the NASA Origins of Solar Systems Research Program under grant NAGW-2334.

  1. Expression of transforming growth factor beta-like molecules in normal and regenerating arms of the crinoid Antedon mediterranea: immunocytochemical and biochemical evidence.

    PubMed Central

    Patruno, M; Smertenko, A; Candia Carnevali, M D; Bonasoro, F; Beesley, P W; Thorndyke, M C

    2002-01-01

    The phylum Echinodermata is well known for its extensive regenerative capabilities. Although there are substantial data now available that describe the histological and cellular bases of this phenomenon, little is known about the regulatory molecules involved. Here, we use an immunochemical approach to explore the potential role played by putative members of the transforming growth factor-beta (TGF-beta) family of secreted proteins in the arm regeneration process of the crinoid Antedon mediterranea. We show that a TGF-beta-like molecule is present in normal and regenerating arms both in a propeptide form and in a mature form. During regeneration, the expression of the mature form is increased and appears to be accompanied by the appearance of an additional isoform. Immunocytochemistry indicates that TGF-beta-like molecules are normally present in the nervous tissue and are specifically localized in both neural elements and non-neural migratory cells, mainly at the level of the brachial nerve. This pattern increases during regeneration, when the blastemal cells show a particularly striking expression of this molecule. Our data indicate that a TGF-beta-like molecule (or molecules) is normally present in the adult nervous tissues of A. mediterranea and is upregulated significantly during regeneration. We suggest that it can play an important part in the regenerative process. PMID:12350260

  2. Advances in the theory of 0{nu}{beta}{beta} decay

    SciTech Connect

    Iachello, F.; Kotila, J.; Barea, J.

    2011-12-16

    Recent advances in the theory of 0{nu}{beta}{beta} decay are briefly discussed. A complete list of nuclear matrix elements within the framework of the Interacting Boson Model (IBM-2) is given. Results of a novel calculation of phase space factors with exact Dirac wave functions and electron screening are also presented.

  3. Observation of a fast beta collapse during high poloidal-beta discharges in JT-60

    SciTech Connect

    Ishida, S.; Koide, Y.; Ozeki, T.; Kikuchi, M.; Tsuji, S.; Shirai, H.; Naito, O.; Azumi, M. )

    1992-03-09

    A nondisruptive {beta}-limiting phenomenon in a large tokamak under a large bootstrap current fraction, up to {similar to}80% of the plasma current, is described; {beta}=(plasma pressure)/(magnetic pressure). During long-pulse neutral-beam-heated discharges in the JT-60 tokamak, it occurs at {beta}{sub {ital p}}{similar to}3, leading to a limit of the normalized {beta} lower than the Troyon limit. The MHD feature is characterized by a large-amplitude partial relaxation with a fast growth time. A hollow current profile evolution in the high-{beta}{sub {ital p}} regime plays an essential role in the MHD stability, analysis of which shows that the ideal {ital n}=1 kink-ballooning modes can be unstable just before the collapse.

  4. The studies on substrate, product and inhibitor binding to a wild-type and neuronopathic form of human acid-beta-glucosidase.

    PubMed

    Zubrzycki, Igor Z; Borcz, Agnieszka; Wiacek, Magdalena; Hagner, Wojciech

    2007-11-01

    Gaucher disease is a lysosomal storage disorder caused by deficiency of human acid beta-glucosidase. Recent x-ray structural elucidation of the enzyme alone and in the presence of its inhibitor was done, which provided an excellent template for further studies on the binding of substrate, product and inhibitor. To draw correlations between the clinical manifestation of the disease driven by point mutations, L444P and L444R, and the placement and function of putative S-binding sites, the presented theoretical studies were undertaken, which comprised of molecular dynamics and molecular docking methods. The obtained results indicate the D443 and D445 residues as extremely important for physiological functionality of an enzyme. They also show, although indirectly, that binding of the substrate is influenced by an interplay of E235 and E334 residues, constituting putative substrate binding site, and the region flanked by D435 and D445 residues. PMID:17713797

  5. Transforming growth factors-beta 1, -beta 2, and -beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis.

    PubMed Central

    Coker, R. K.; Laurent, G. J.; Shahzeidi, S.; Lympany, P. A.; du Bois, R. M.; Jeffery, P. K.; McAnulty, R. J.

    1997-01-01

    Transforming growth factor (TGF)-beta 1 may potentiate wound healing and fibrosis by stimulating fibroblast collagen deposition. TGF-beta 1 is implicated in the pathogenesis of pulmonary fibrosis, but the role of TGF-beta 2 and TGF-beta 3 remains unclear. We examined their effects on lung fibroblast procollagen metabolism in vitro and localized their gene expression during bleomycin-induced lung fibrosis using in situ hybridization with digoxigenin-labeled riboprobes. All three isoforms stimulated fibroblast procollagen production. TGF-beta 3 was the most potent and also reduced procollagen degradation. In normal mouse lung, TGF-beta 1 and TGF-beta 3 mRNA transcripts were abundant in bronchiolar epithelium. After bleomycin, TGF-beta 1 gene expression was maximally enhanced at 10 days, with the signal being predominant in macrophages. Signal was also enhanced in mesenchymal, pulmonary endothelial, and mesothelial cells. After 35 days, the pattern of TGF-beta 1 gene expression returned to that of control lung. TGF-beta 3 gene expression remained unchanged throughout compared with controls. TGF-beta 2 mRNA was not detected with the antisense probe, but signal obtained with the sense probe suggests the presence of a naturally occurring antisense. This study demonstrates that TGF-beta 1, -beta 2, and -beta 3 all exert profibrotic effects in vitro. However, TGF-beta isoform gene expression is differentially controlled during experimental pulmonary fibrosis with TGF-beta 1 the predominant isoform expressed during pathogenesis. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:9060836

  6. Proliferating pancreatic beta-cells upregulate ALDH.

    PubMed

    Liu, Yinglan; Jiang, Xiaoxin; Zeng, Yong; Zhou, Hui; Yang, Jing; Cao, Renxian

    2014-12-01

    High levels of aldehyde dehydrogenase (ALDH) activity have been regarded as a specific feature of progenitor cells and stem cells. Hence, as an indicator of ALDH activity, aldefluor fluorescence has been widely used for the identification and isolation of stem and progenitor cells. ALDH activity was recently detected in embryonic mouse pancreas, and specifically and exclusively in adult centroacinar and terminal duct cells, suggesting that these duct cells may harbor cells of endocrine and exocrine differentiation potential in the adult pancreas. Here, we report the presence of aldefluor+ beta-cells in a beta-cell proliferation model, partial pancreatectomy. The aldefluor+ beta-cells are essentially all positive for Ki-67 and expressed high levels of cell-cycle activators such as CyclinD1, CyclinD2, and CDK4, suggesting that they are mitotic cells. Our data thus reveal a potential change in ALDH activity of proliferating beta-cells, which provides a novel method for the isolation and analysis of proliferating beta-cells. Moreover, our data also suggest that aldefluor lineage-tracing is not a proper method for analyzing progenitor or stem activity in the adult pancreas. PMID:25028343

  7. Modulation of TGF-beta type 1 receptor: flow cytometric detection with biotinylated TGF-beta.

    PubMed

    Newman, W; Beall, L D; Bertolini, D R; Cone, J L

    1989-10-01

    Transforming growth factor beta type 1 (TGF-beta 1) was reacted with NHS-biotin to yield a derivative of TGF-beta 1 which was biotinylated on lysine residues. The biotinylated form of TGF-beta 1 was separated from the unreacted material by reverse phase chromatography. In three separate bioassays, the derivatized peptide was as active as the starting material. The use of FITC-avidin in conjunction with flow cytometry demonstrated that the binding of biotinylated TGF-beta 1 to its receptor is saturable, competable, and specific. A 100-fold molar excess of underivatized TGF-beta 1 gave 85% inhibition of binding of the biotinylated peptide to the mink lung cell line CCL-64, while TGF-beta 2 showed no inhibition of binding, nor did insulin, calcitonin, or TGF-alpha. Both CCL-64 cells and human umbilical vein endothelial cells showed a density-dependent down-regulation of receptor expression in culture. Several factors were examined that might mediate this effect. The down-regulation was shown not to be due to the secretion of an active form of TGF-beta 1. The extracellular matrix from high-density cells did not decrease expression of the receptor. Fibronectin, collagen, and gelatin were also unable to signal changes in receptor expression, even though in other systems such matrix components can regulate the responsiveness of cells to TGF-beta 1. Lastly, staining simultaneously for DNA content and TGF-beta 1 receptor expression showed that there was no correlation between cell cycle and receptor levels. PMID:2550480

  8. The crystal structure of the Rv0301-Rv0300 VapBC-3 toxin-antitoxin complex from M. tuberculosis reveals a Mg2+ ion in the active site and a putative RNA-binding site

    SciTech Connect

    Min, Andrew B; Miallau, Linda; Sawaya, Michael R; Habel, Jeff; Cascio, Duilio; Eisenberg, David

    2013-01-10

    VapBC pairs account for 45 out of 88 identified toxin-antitoxin (TA) pairs in the Mycobacterium tuberculosis (Mtb) H37Rv genome. A working model suggests that under times of stress, antitoxin molecules are degraded, releasing the toxins to slow the metabolism of the cell, which in the case of VapC toxins is via their RNase activity. Otherwise the TA pairs remain bound to their promoters, autoinhibiting transcription. The crystal structure of Rv0301-Rv0300, an Mtb VapBC TA complex determined at 1.49 Å resolution, suggests a mechanism for these three functions: RNase activity, its inhibition by antitoxin, and its ability to bind promoter DNA. The Rv0301 toxin consists of a core of five parallel beta strands flanked by alpha helices. Three proximal aspartates coordinate a Mg2+ ion forming the putative RNase active site. The Rv0300 antitoxin monomer is extended in structure, consisting of an N-terminal beta strand followed by four helices. The last two helices wrap around the toxin and terminate near the putative RNase active site, but with different conformations. In one conformation, the C-terminal arginine interferes with Mg2+ ion coordination, suggesting a mechanism by which the antitoxin can inhibit toxin activity. At the N-terminus of the antitoxin, two pairs of Ribbon-Helix-Helix (RHH) motifs are related by crystallographic twofold symmetry. The resulting hetero-octameric complex is similar to the FitAB system, but the two RHH motifs are about 30 Å closer together in the Rv0301-Rv0300 complex, suggesting either a different span of the DNA recognition sequence or a conformational change.

  9. Development of an improved fingertip dosimeter for beta radiation

    SciTech Connect

    Couch, N.W.

    1986-01-01

    The dosimeter employs a multi-element, multi-filter concept by stacking four 0.13 mm LiF-teflon TLD's to form the beta detector element. The entire dosimeter is approximately 1 mm thick, flexible, and rugged enough for field use without interference with the manual dexterity of the user. The fingertip dosimeter provides data for determining the beta energy of each exposure. The beta energy can be used to determine the TLD response factor for correcting the TLD output to beta dose in mrad. The data can be used to reconstruct the beta depth dose curve due to single beta or mixed beta exposures. For mixed beta/gamma exposures, the addition of a gamma measuring element would provide data for separating the gamma component for the beta component. The depth dose curve can be used to calculate the beta doses in tissue at 7 mg/cm/sup 2/, for legal reporting purposes, or at any other desired depth within the range of the beta radiation. The fingertip dosimeter was used to monitor extremity beta doses for research lab personnel. The results showed higher fingertip beta doses than had previously been expected. The average monthly beta dose was shown to be approximately 0.5 rad/mo.

  10. Beta-cryptoxanthin as a source of vitamin A.

    PubMed

    Burri, Betty J

    2015-07-01

    Beta-cryptoxanthin is a common carotenoid that is found in fruit, and in human blood and tissues. Foods that are rich in beta-cryptoxanthin include tangerines, persimmons and oranges. Beta-cryptoxanthin has several functions that are important for human health, including roles in antioxidant defense and cell-to-cell communication. Most importantly, beta-cryptoxanthin is a precursor of vitamin A, which is an essential nutrient needed for eyesight, growth, development and immune response. We evaluate the evidence for beta-cryptoxanthin as a vitamin A-forming carotenoid in this paper. Observational, in vitro, animal model and human studies suggest that beta-cryptoxanthin has greater bioavailability from its common food sources than do alpha- and beta-carotene from theirs. Although beta-cryptoxanthin appears to be a poorer substrate for beta-carotene 15,15' oxygenase than is beta-carotene, animal model and human studies suggest that the comparatively high bioavailability of beta-cryptoxanthin from foods makes beta-cryptoxanthin-rich foods equivalent to beta-carotene-rich foods as sources of vitamin A. These results mean that beta-cryptoxanthin-rich foods are probably better sources of vitamin A, and more important for human health in general, than previously assumed. PMID:25270992

  11. A Hypothesis for the Abiotic and Non-Martian Origins of Putative Signs of Ancient Martian Life in ALH84001

    NASA Technical Reports Server (NTRS)

    Treiman, Allan H.

    2001-01-01

    Putative evidence of martian life in ALH84001 can be explained by abiotic and non-martian processes consistent with the meteorite's geological history. Additional information is contained in the original extended abstract.

  12. Beta spectrometry with metallic magnetic calorimeters.

    PubMed

    Loidl, M; Rodrigues, M; Le-Bret, C; Mougeot, X

    2014-05-01

    Metallic magnetic calorimeters are a specific type of cryogenic detectors that have been shown to enable precise measurement of the shape of low energy beta spectra. The aim of their use at LNHB is the determination of the shape factors of beta spectra. The beta source is enclosed in the detector absorber, allowing for very high detection efficiency. It has turned out that the type of source is of crucial importance for the correctness of the measured spectrum. Spectra of (63)Ni measured with several sources prepared by drying a NiCl2 solution differ from one another and from theory, whereas spectra measured with electroplated sources are reproducible and agree with theory. With these latter measurements we could confirm the atomic exchange effect down to very low energy (200 eV). PMID:24368065

  13. Beta-Diversity in Tropical Forest Trees

    NASA Astrophysics Data System (ADS)

    Condit, Richard; Pitman, Nigel; Leigh, Egbert G.; Chave, Jérôme; Terborgh, John; Foster, Robin B.; Núñez V., Percy; Aguilar, Salomón; Valencia, Renato; Villa, Gorky; Muller-Landau, Helene C.; Losos, Elizabeth; Hubbell, Stephen P.

    2002-01-01

    The high alpha-diversity of tropical forests has been amply documented, but beta-diversity-how species composition changes with distance-has seldom been studied. We present quantitative estimates of beta-diversity for tropical trees by comparing species composition of plots in lowland terra firme forest in Panama, Ecuador, and Peru. We compare observations with predictions derived from a neutral model in which habitat is uniform and only dispersal and speciation influence species turnover. We find that beta-diversity is higher in Panama than in western Amazonia and that patterns in both areas are inconsistent with the neutral model. In Panama, habitat variation appears to increase species turnover relative to Amazonia, where unexpectedly low turnover over great distances suggests that population densities of some species are bounded by as yet unidentified processes. At intermediate scales in both regions, observations can be matched by theory, suggesting that dispersal limitation, with speciation, influences species turnover.

  14. Experimental Status of the CKM Angle {beta}

    SciTech Connect

    Hirschauer, James F.

    2009-12-17

    We summarize measurements of the CKM angle {beta} at the B-factories emphasizing a comparison of {beta} measured in the B{sup 0}{yields}cc-barK{sup (*)0} decay channels and {beta}{sub eff} measured in b{yields}qq-bars decay channels, such as B{sup 0}{yields}{omega}K{sub S}{sup 0}, B{sup 0}{yields}{eta}'K{sup 0}, B{sup 0}{yields}{pi}{sup 0}K{sub S}{sup 0}, and B{sup 0}{yields}{sub S}{sup 0}K{sub S}{sup 0}K{sub S}{sup 0}.

  15. High beta and confinement studies of TFTR

    SciTech Connect

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

    1993-01-01

    The project discussed in this report are: Enhanced High Poloidal Beta Operation in TFTR with Deuterium Pellet Injection; Approaching High Q by Utilizing High [beta][sub p] Operation in TFTR; Advanced Tokamak Regime Experiment, and Second Regime Studies at large Major Radius High [beta][sub p] Plasmas. Analysis of the data taken during these experiments as well as continuing analysis of earlier data led to a number important results described in publications in the past year including two invited presentations at the 1992 American Physical Society Division of Plasma Physics Meeting in Seattle an oral presentation at the 1992 IAEA Meeting in Wuertzburg, Germany, and a Physical Review Letter. These results included extending the high 11/2 regime to 1.2 MA current and neutron production rates to more than 3 [times] 10[sup 16] sec[sup [minus

  16. Immunomodulatory activity of interferon-beta

    PubMed Central

    Kasper, Lloyd H; Reder, Anthony T

    2014-01-01

    Multiple sclerosis (MS) is a complex disorder of the central nervous system that appears to be driven by a shift in immune functioning toward excess inflammation that results in demyelination and axonal loss. Beta interferons were the first class of disease-modifying therapies to be approved for patients with MS after treatment with this type I interferon improved the course of MS on both clinical and radiological measures in clinical trials. The mechanism of action of interferon-beta appears to be driven by influencing the immune system at many levels, including antigen-presenting cells, T cells, and B cells. One effect of these interactions is to shift cytokine networks in favor of an anti-inflammatory effect. The pleiotropic mechanism of action may be a critical factor in determining the efficacy of interferon-beta in MS. This review will focus on select immunological mechanisms that are influenced by this type I cytokine. PMID:25356432

  17. Tumor necrosis factor-beta in human pregnancy and labor.

    PubMed

    Laham, N; Van Dunné, F; Abraham, L J; Farrugia, W; Bendtzen, K; Brennecke, S P; Rice, G E

    1997-04-01

    The aims of this study were to determine tumor necrosis factor-beta (TNF-beta) concentration profiles in peripheral venous plasma and amniotic fluid during pregnancy and at the time of labor and to characterise TNF-beta mRNA expression and TNF-beta release from human gestational tissues. In addition, we investigated the expression of TNF-beta binding protein, lymphotoxin-beta (LT-beta), in human gestational tissues. The mean (+/-S.E.M.) TNF-beta concentrations in maternal plasma (TIL, 78 +/- 12 pg/ml, n = 7 vs. TNIL, 304 +/- 88 pg/ml, n = 7) and amniotic fluid (TIL, 8 +/- 5 pg/ml, n = 6 vs. TNIL, 73 +/- 20 pg/ml, n = 20) were significantly (P < 0.05) decreased in association with term labor-onset (TIL) compared to term not-in-labor (TNIL). TNF-beta concentration in maternal plasma and amniotic fluid did not change significantly either with preterm labor (PIL), or during pregnancy. Group-matched comparison of maternal plasma and amniotic fluid TNF-beta concentrations demonstrated that amniotic fluid TNF-beta concentrations were 6-8 fold lower than maternal plasma TNF-beta concentrations. Furthermore, no detectable TNF-beta was secreted from cultured human amniotic, choriodecidual and placental explants. Although, TNF-beta mRNA was detected in amnion, choriodecidual and placenta, LT-beta was similarly expressed in these tissues, suggesting that TNF-beta may be cell membrane bound. These data demonstrate that TNF-beta is present at low levels within the intrauterine environment and may suggest that TNF-beta is specifically inhibited at the maternal-fetal interface. PMID:9185077

  18. Discovering putative prion sequences in complete proteomes using probabilistic representations of Q/N-rich domains

    PubMed Central

    2013-01-01

    Background Prion proteins conform a special class among amyloids due to their ability to transmit aggregative folds. Prions are known to act as infectious agents in neurodegenerative diseases in animals, or as key elements in transcription and translation processes in yeast. It has been suggested that prions contain specific sequential domains with distinctive amino acid composition and physicochemical properties that allow them to control the switch between soluble and β-sheet aggregated states. Those prion-forming domains are low complexity segments enriched in glutamine/asparagine and depleted in charged residues and prolines. Different predictive methods have been developed to discover novel prions by either assessing the compositional bias of these stretches or estimating the propensity of protein sequences to form amyloid aggregates. However, the available algorithms hitherto lack a thorough statistical calibration against large sequence databases, which makes them unable to accurately predict prions without retrieving a large number of false positives. Results Here we present a computational strategy to predict putative prion-forming proteins in complete proteomes using probabilistic representations of prionogenic glutamine/asparagine rich regions. After benchmarking our predictive model against large sets of non-prionic sequences, we were able to filter out known prions with high precision and accuracy, generating prediction sets with few false positives. The algorithm was used to scan all the proteomes annotated in public databases for the presence of putative prion proteins. We analyzed the presence of putative prion proteins in all taxa, from viruses and archaea to plants and higher eukaryotes, and found that most organisms encode evolutionarily unrelated proteins with susceptibility to behave as prions. Conclusions To our knowledge, this is the first wide-ranging study aiming to predict prion domains in complete proteomes. Approaches of this kind could

  19. Two putative-aquaporin genes are differentially expressed during arbuscular mycorrhizal symbiosis in Lotus japonicus

    PubMed Central

    2012-01-01

    Background Arbuscular mycorrhizas (AM) are widespread symbioses that provide great advantages to the plant, improving its nutritional status and allowing the fungus to complete its life cycle. Nevertheless, molecular mechanisms that lead to the development of AM symbiosis are not yet fully deciphered. Here, we have focused on two putative aquaporin genes, LjNIP1 and LjXIP1, which resulted to be upregulated in a transcriptomic analysis performed on mycorrhizal roots of Lotus japonicus. Results A phylogenetic analysis has shown that the two putative aquaporins belong to different functional families: NIPs and XIPs. Transcriptomic experiments have shown the independence of their expression from their nutritional status but also a close correlation with mycorrhizal and rhizobial interaction. Further transcript quantification has revealed a good correlation between the expression of one of them, LjNIP1, and LjPT4, the phosphate transporter which is considered a marker gene for mycorrhizal functionality. By using laser microdissection, we have demonstrated that one of the two genes, LjNIP1, is expressed exclusively in arbuscule-containing cells. LjNIP1, in agreement with its putative role as an aquaporin, is capable of transferring water when expressed in yeast protoplasts. Confocal analysis have demonstrated that eGFP-LjNIP1, under its endogenous promoter, accumulates in the inner membrane system of arbusculated cells. Conclusions Overall, the results have shown different functionality and expression specificity of two mycorrhiza-inducible aquaporins in L. japonicus. One of them, LjNIP1 can be considered a novel molecular marker of mycorrhizal status at different developmental stages of the arbuscule. At the same time, LjXIP1 results to be the first XIP family aquaporin to be transcriptionally regulated during symbiosis. PMID:23046713

  20. Identification of putative rhamnogalacturonan-II specific glycosyltransferases in Arabidopsis using a combination of bioinformatics approaches.

    PubMed

    Voxeur, Aline; André, Aurélie; Breton, Christelle; Lerouge, Patrice

    2012-01-01

    Rhamnogalacturonan-II (RG-II) is a complex plant cell wall polysaccharide that is composed of an α(1,4)-linked homogalacturonan backbone substituted with four side chains. It exists in the cell wall in the form of a dimer that is cross-linked by a borate di-ester. Despite its highly complex structure, RG-II is evolutionarily conserved in the plant kingdom suggesting that this polymer has fundamental functions in the primary wall organisation. In this study, we have set up a bioinformatics strategy aimed at identifying putative glycosyltransferases (GTs) involved in RG-II biosynthesis. This strategy is based on the selection of candidate genes encoding type II membrane proteins that are tightly coexpressed in both rice and Arabidopsis with previously characterised genes encoding enzymes involved in the synthesis of RG-II and exhibiting an up-regulation upon isoxaben treatment. This study results in the final selection of 26 putative Arabidopsis GTs, including 10 sequences already classified in the CAZy database. Among these CAZy sequences, the screening protocol allowed the selection of α-galacturonosyltransferases involved in the synthesis of α4-GalA oligogalacturonides present in both homogalacturonans and RG-II, and two sialyltransferase-like sequences previously proposed to be involved in the transfer of Kdo and/or Dha on the pectic backbone of RG-II. In addition, 16 non-CAZy GT sequences were retrieved in the present study. Four of them exhibited a GT-A fold. The remaining sequences harbored a GT-B like fold and a fucosyltransferase signature. Based on homologies with glycosyltransferases of known functions, putative roles in the RG-II biosynthesis are proposed for some GT candidates. PMID:23272088

  1. Further insight into reproductive incompatibility between putative cryptic species of the Bemisia tabaci whitefly complex.

    PubMed

    Qin, Li; Pan, Li-Long; Liu, Shu-Sheng

    2016-04-01

    The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), with its global distribution and extensive genetic diversity, is now known to be a complex of over 35 cryptic species. However, a satisfactory resolution of the systematics of this species complex is yet to be achieved. Here, we designed experiments to examine reproductive compatibility among species with different levels of mitochondrial cytochrome oxidase I (mtCOI) divergence. The data show that putative species with mtCOI divergence of >8% between them consistently exhibited complete reproductive isolation. However, two of the putative species, Asia II 9 and Asia II 3, with mtCOI divergence of 4.47% between them, exhibited near complete reproductive compatibility in one direction of their cross, and partial reproductive compatibility in the other direction. Together with some recent reports on this topic from the literature, our data indicates that, while divergence in the mtCOI sequences provides a valid molecular marker for species delimitation in most clades, more genetic markers and more sophisticated molecular phylogeny will be required to achieve adequate delimitation of all species in this whitefly complex. While many attempts have been made to examine the reproductive compatibility among genetic groups of the B. tabaci complex, our study represents the first effort to conduct crossing experiments with putative species that were chosen with considerations of their genetic divergence. In light of the new data, we discuss the best strategy and protocols to conduct further molecular phylogenetic analysis and crossing trials, in order to reveal the overall pattern of reproductive incompatibility among species of this whitefly complex. PMID:27001484

  2. A Proteomics Approach to Identify New Putative Cardiac Intercalated Disk Proteins

    PubMed Central

    Soni, Siddarth; Raaijmakers, Antonia J. A.; Raaijmakers, Linsey M.; Damen, J. Mirjam A.; van Stuijvenberg, Leonie; Vos, Marc A.; Heck, Albert J. R.

    2016-01-01

    Aims Synchronous beating of the heart is dependent on the efficient functioning of the cardiac intercalated disk (ID). The ID is composed of a complex protein network enabling electrical continuity and chemical communication between individual cardiomyocytes. Recently, several different studies have shed light on increasingly prevalent cardiac diseases involving the ID. Insufficient knowledge of its composition makes it difficult to study these disease mechanisms in more detail and therefore here we aim expand the ID proteome. Here, using a combination of general membrane enrichment, in-depth quantitative proteomics and an intracellular location driven bioinformatics approach, we aim to discover new putative ID proteins in rat ventricular tissue. Methods and Results General membrane isolation, enriched amongst others also with ID proteins as based on presence of the established markers connexin-43 and n-cadherin, was performed using centrifugation. By mass spectrometry, we quantitatively evaluated the level of 3455 proteins in the enriched membrane fraction (EMF) and its counterpart, the soluble cytoplasmic fraction. These data were stringently filtered to generate a final set of 97 enriched, putative ID proteins. These included Cx43 and n-cadherin, but also many interesting novel candidates. We selected 4 candidates (Flotillin-2 (FLOT2), Nexilin (NEXN), Popeye-domain-containg-protein 2 (POPDC2) and thioredoxin-related-transmembrane-protein 2 (TMX2)) and confirmed their co-localization with n-cadherin in the ID of human and rat heart cryo-sections, and isolated dog cardiomyocytes. Conclusion The presented proteomics dataset of putative new ID proteins is a valuable resource for future research into this important molecular intersection of the heart. PMID:27148881

  3. Temporal Dynamics and Decay of Putatively Allochthonous and Autochthonous Viral Genotypes in Contrasting Freshwater Lakes

    PubMed Central

    Barbosa, Jorge G.; Brown, Julia M.; Donelan, Ryan P.; Eaglesham, James B.; Eggleston, Erin M.; LaBarre, Brenna A.

    2012-01-01

    Aquatic viruses play important roles in the biogeochemistry and ecology of lacustrine ecosystems; however, their composition, dynamics, and interactions with viruses of terrestrial origin are less extensively studied. We used a viral shotgun metagenomic approach to elucidate candidate autochthonous (i.e., produced within the lake) and allochthonous (i.e., washed in from other habitats) viral genotypes for a comparative study of their dynamics in lake waters. Based on shotgun metagenomes prepared from catchment soil and freshwater samples from two contrasting lakes (Cayuga Lake and Fayetteville Green Lake), we selected two putatively autochthonous viral genotypes (phycodnaviruses likely infecting algae and cyanomyoviruses likely infecting picocyanobacteria) and two putatively allochthonous viral genotypes (geminiviruses likely infecting terrestrial plants and circoviruses infecting unknown hosts but common in soil libraries) for analysis by genotype-specific quantitative PCR (TaqMan) applied to DNAs from viruses in the viral size fraction of lake plankton, i.e., 0.2 μm > virus > 0.02 μm. The abundance of autochthonous genotypes largely reflected expected host abundance, while the abundance of allochthonous genotypes corresponded with rainfall and storm events in the respective catchments, suggesting that viruses with these genotypes may have been transported to the lake in runoff. The decay rates of allochthonous and autochthonous genotypes, assessed in incubations where all potential hosts were killed, were generally lower (0.13 to 1.50% h−1) than those reported for marine virioplankton but similar to those for freshwater virioplankton. Both allochthonous and autochthonous viral genotypes were detected at higher concentrations in subsurface sediments than at the water-sediment interface. Our data indicate that putatively allochthonous viruses are present in lake plankton and sediments, where their temporal dynamics reflect active transport to the lake during

  4. TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.

    PubMed

    Marchesan, J; Jiao, Y Z; Schaff, R A; Hao, J; Morelli, T; Kinney, J S; Gerow, E; Sheridan, R; Rodrigues, V; Paster, B J; Inohara, N; Giannobile, W V

    2016-06-01

    Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. Although the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, six being classical pathogens and four putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone-marrow-derived macrophages (BMDM) from wild-type (WT) and Toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. Campylobacter concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2 stimulatory activity. These studies allowed us to provide important evidence on newly identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). PMID:26177212

  5. Crystal Structure of a Putative HTH-Type Transcriptional Regulator yxaF from Bacillus subtilis

    SciTech Connect

    Seetharaman,J.; Kumaran, D.; Bonanno, J.; Burley, S.; Swaminathan, S.

    2006-01-01

    The New York Structural GenomiX Research Consortium (NYSGXRC) has selected the protein coded by yxaF gene from Bacillus subtilis as a target for structure determination. The yxaF protein has 191 residues with a molecular mass of 21 kDa and had no sequence homology to any structure in the Protein Data Bank (PDB) at the time of target selection. We aimed to elucidate the three-dimensional structure for the putative protein yxaF to better understand the relationship between protein sequence, structure, and function. This protein is annotated as a putative helix-turn-helix (HTH) type transcriptional regulator. Many transcriptional regulators like TetR and QacR use a structurally well-defined DNA-binding HTH motif to recognize the target DNA sequences. DNA-HTH motif interactions have been extensively studied. As the HTH motif is structurally conserved in many regulatory proteins, these DNA-protein complexes show some similarity in DNA recognition patterns. Many such regulatory proteins have a ligand-binding domain in addition to the DNA-binding domain. Structural studies on ligand-binding regulatory proteins provide a wealth of information on ligand-, and possibly drug-, binding mechanisms. Understanding the ligand-binding mechanism may help overcome problems with drug resistance, which represent increasing challenges in medicine. The protein encoded by yxaF, hereafter called T1414, shows fold similar to QacR repressor and TetR/CamR repressor and possesses putative DNA and ligand-binding domains. Here, we report the crystal structure of T1414 and compare it with structurally similar drug and DNA-binding proteins.

  6. beta2-Agonists at the Olympic Games.

    PubMed

    Fitch, Kenneth D

    2006-01-01

    The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists. PMID:17085798

  7. The renal action of spirorenone and other 6 beta,7 beta; 15 beta,16 beta-dimethylene-17-spirolactones, a new type of steroidal aldosterone antagonists.

    PubMed

    Casals-Stenzel, J; Buse, M; Wambach, G; Losert, W

    1984-01-01

    The aldosterone antagonistic activity in vivo and the affinity for mineralocorticoid receptors (MCR) in vitro of 3-(17 beta-hydroxy-6 beta,7 beta; 15 beta,16 beta-dimethylene-3-oxo-1, 4-androstadiene-17 alpha-yl) propionic acid gamma-lactone (spirorenone), a new aldosterone antagonist, and four of its derivatives were studied in comparison with spironolactone in rats. Spirorenone was 8.6 times as potent as spironolactone, but showed a lower affinity for the MCR than the standard. The C1/C2 saturated derivative (compound I) had 7.6 times the antialdosterone potency and 2 times the binding activity of spironolactone. The 17-spiroether derivative of spirorenone (compound II) showed a lower aldosterone antagonistic activity (1.7 the potency of spironolactone) as well as a lower affinity for the MCR (0.5 the affinity of spironolactone). The analogue with a 17 beta-hydroxyl group and a 17 alpha-hydroxypropyl side chain (compound III) possessed a very low binding capacity for MCR (1/10 of that of spironolactone) but still a 1.3 times higher antialdosterone activity than spironolactone. This result is probably due to a transformation of compound III to an active metabolite in vivo. Finally, the derivative with a reversed configuration of the 17-spirolactone ring (compound IV) had no biological activity in vivo and no affinity for the MCR. These results show that spirorenone or one of its active derivatives might lead to a new series of potent aldosterone antagonists. PMID:6329237

  8. A putative, novel coli surface antigen 8B (CS8B) of enterotoxigenic Escherichia coli.

    PubMed

    Njoroge, Samuel M; Boinett, Christine J; Madé, Laure F; Ouko, Tom T; Fèvre, Eric M; Thomson, Nicholas R; Kariuki, Samuel

    2015-10-01

    Enterotoxigenic Escherichia coli (ETEC) strains harbor multiple fimbriae and pili to mediate host colonization, including the type IVb pilus, colonization factor antigen III (CFA/III). Not all colonization factors are well characterized or known in toxin positive ETEC isolates, which may have an impact identifying ETEC isolates based on molecular screening of these biomarkers. We describe a novel coli surface antigen (CS) 8 subtype B (CS8B), a family of CFA/III pilus, in a toxin producing ETEC isolate from a Kenyan collection. In highlighting the existence of this putative CS, we provide the sequence and specific primers, which can be used alongside other ETEC primers previously described. PMID:26187892

  9. A specimen of Rhamphorhynchus with soft tissue preservation, stomach contents and a putative coprolite

    PubMed Central

    Henderson, Donald M.; Therrien, François; Habib, Michael B.

    2015-01-01

    Despite being known for nearly two centuries, new specimens of the derived non-pterodactyloid pterosaur Rhamphorhynchus continue to be discovered and reveal new information about their anatomy and palaeobiology. Here we describe a specimen held in the collections of the Royal Tyrrell Museum of Palaeontology, Alberta, Canada that shows both preservation and impressions of soft tissues, and also preserves material interpreted as stomach contents of vertebrate remains and, uniquely, a putative coprolite. The specimen also preserves additional evidence for fibers in the uropatagium. PMID:26312182

  10. The Progress and Prospects of Putative Biomarkers for Liver Cancer Stem Cells in Hepatocellular Carcinoma.

    PubMed

    Xiang, Yan; Yang, Ting; Pang, Bing-Yao; Zhu, Ying; Liu, Yong-Ning

    2016-01-01

    Accumulating evidence suggests that hepatocellular carcinoma (HCC) is organized by liver cancer stem cells (LCSCs), which are a subset of cells with "stem-like" characteristics. Identification of the LCSCs is a fundamental and important problem in HCC research. LCSCs have been investigated by various stem cell biomarkers. There is still lack of consensus regarding the existence of a "global" marker for LCSCs in HCC. In this review article, we summarize the progress and prospects of putative biomarkers for LCSCs in the past decades, which is essential to develop future therapies targeting CSCs and to predict prognosis and curative effect of these therapies. PMID:27610139

  11. The Progress and Prospects of Putative Biomarkers for Liver Cancer Stem Cells in Hepatocellular Carcinoma

    PubMed Central

    Yang, Ting

    2016-01-01

    Accumulating evidence suggests that hepatocellular carcinoma (HCC) is organized by liver cancer stem cells (LCSCs), which are a subset of cells with “stem-like” characteristics. Identification of the LCSCs is a fundamental and important problem in HCC research. LCSCs have been investigated by various stem cell biomarkers. There is still lack of consensus regarding the existence of a “global” marker for LCSCs in HCC. In this review article, we summarize the progress and prospects of putative biomarkers for LCSCs in the past decades, which is essential to develop future therapies targeting CSCs and to predict prognosis and curative effect of these therapies. PMID:27610139

  12. A putative, novel coli surface antigen 8B (CS8B) of enterotoxigenic Escherichia coli

    PubMed Central

    Njoroge, Samuel M.; Boinett, Christine J.; Madé, Laure F.; Ouko, Tom T.; Fèvre, Eric M.; Thomson, Nicholas R.; Kariuki, Samuel

    2015-01-01

    Enterotoxigenic Escherichia coli (ETEC) strains harbor multiple fimbriae and pili to mediate host colonization, including the type IVb pilus, colonization factor antigen III (CFA/III). Not all colonization factors are well characterized or known in toxin positive ETEC isolates, which may have an impact identifying ETEC isolates based on molecular screening of these biomarkers. We describe a novel coli surface antigen (CS) 8 subtype B (CS8B), a family of CFA/III pilus, in a toxin producing ETEC isolate from a Kenyan collection. In highlighting the existence of this putative CS, we provide the sequence and specific primers, which can be used alongside other ETEC primers previously described. PMID:26187892

  13. Bacillus anthracis pXO1 plasmid encodes a putative membrane-bound bacteriocin

    PubMed Central

    Perlińska, Agata

    2014-01-01

    Evolutionary advantages over cousin cells in bacterial pathogens may decide about the success of a specific cell in its environment. Bacteria use a plethora of methods to defend against other cells and many devices to attack their opponents when competing for resources. Bacteriocins are antibacterial proteins that are used to eliminate competition. We report the discovery of a putative membrane-bound bacteriocin encoded by the Bacillus anthracis pathogenic pXO1 plasmid. We analyze the genomic structure of the bacteriocin operon. The proposed mechanisms of action predestine this operon as a potent competitive advantage over cohabitants of the same niche. PMID:25426338

  14. Cloning, expression, purification and crystallization of Schizosaccharomyces pombe Set7, a putative histone methyltransferase.

    PubMed

    Mevius, Damiaan E H F; Shen, Yunpeng; Morishita, Masayo; di Luccio, Eric

    2016-04-01

    Dysfunction of histone-modifying enzymes affects chromatin regulation and is involved in carcinogenesis, tumour progression and other diseases. Histone methyltransferases are a family of key histone-modifying enzymes, but their structures, functions and mechanisms are incompletely understood, thus constraining drug-design efforts. Here, preliminary steps towards structure-function studies of Schizosaccharomyces pombe Set7, a putative histone methyltransferase and the first yeast full-length SET-domain-containing protein to be studied using X-ray crystallography, are reported. The methods from cloning to X-ray diffraction and phasing are discussed and the results will aid in prospective studies of histone-modifying enzymes. PMID:27050258

  15. On the Origin of Dolabriferol: Total Synthesis via Its Putative Contiguous Precursor.

    PubMed

    Karagiannis, Athanasios; Diddi, Naveen; Ward, Dale E

    2016-08-01

    The putative contiguous polypropionate precursor of dolabriferol was synthesized using as the key step a rationally designed enantiomer-selective aldol coupling (i.e., with kinetic resolution) of a racemic C1-C8 ketone fragment with an enantiopure C9-C15 aldehyde fragment. When exposed to alumina, the precursor was cleanly transformed into dolabriferol via a regioselective retro-Claisen fragmentation, providing the first experimental evidence for the proposed origin of dolabriferol and demonstrating that it is a plausible isolation artifact. PMID:27410168

  16. Colonic and colorectal cancer stem cells: progress in the search for putative biomarkers

    PubMed Central

    Willis, Naomi D; Przyborski, Stefan A; Hutchison, Christopher J; Wilson, Robert G

    2008-01-01

    The maintenance of healthy colonic crypts is dependent on the integrity of the adult epithelial stem cells located within them. Perturbations in stem cell dynamics are generally believed to represent the first step towards colorectal tumorigenesis. Experimental manipulation of intestinal stem cells has greatly increased our understanding of them, but further progress has been slowed due to the absence of a reliable stem cell biomarker. In this review we discuss the candidate colonic stem cell biomarkers which have been proposed. Furthermore, we investigate the putative biomarkers for so-called colorectal cancer stem cells, a highly aggressive subpopulation of cells considered to drive tumour development. PMID:18638071

  17. Structure of PA4019, a putative aromatic acid decarboxylase from Pseudomonas aeruginosa

    PubMed Central

    Kopec, Jolanta; Schnell, Robert; Schneider, Gunter

    2011-01-01

    The ubiX gene (PA4019) of Pseudomonas aeruginosa has been annotated as encoding a putative 3-octaprenyl-4-hydroxybenzoate decarboxylase from the ubiquinone-biosynthesis pathway. Based on a transposon mutagenesis screen, this gene was also implicated as being essential for the survival of this organism. The crystal structure of recombinant UbiX determined to 1.5 Å resolution showed that the protein belongs to the superfamily of homo-oligomeric flavine-containing cysteine decarboxylases. The enzyme assembles into a dodecamer with 23 point symmetry. The subunit displays a typical Rossmann fold and contains one FMN molecule bound at the interface between two subunits. PMID:22102023

  18. Colonic and colorectal cancer stem cells: progress in the search for putative biomarkers.

    PubMed

    Willis, Naomi D; Przyborski, Stefan A; Hutchison, Christopher J; Wilson, Robert G

    2008-07-01

    The maintenance of healthy colonic crypts is dependent on the integrity of the adult epithelial stem cells located within them. Perturbations in stem cell dynamics are generally believed to represent the first step towards colorectal tumorigenesis. Experimental manipulation of intestinal stem cells has greatly increased our understanding of them, but further progress has been slowed due to the absence of a reliable stem cell biomarker. In this review we discuss the candidate colonic stem cell biomarkers which have been proposed. Furthermore, we investigate the putative biomarkers for so-called colorectal cancer stem cells, a highly aggressive subpopulation of cells considered to drive tumour development. PMID:18638071

  19. Status of the double beta experiment COBRA

    NASA Astrophysics Data System (ADS)

    Zuber, K.

    2006-07-01

    The COBRA experiment is going to use a large number of CdZnTe semiconductor detectors to perform a search for various double beta decay modes. The current status of the experiment is presented, as well as first results. A half-life measurement of the fourfold forbidden non-unique beta-decay of 113Cd has been performed. Improved half-life limits for the ground state transitions of 64Zn for 0νβ+/EC and 0νEC/EC have been obtained. A short outlook on future activities is given.

  20. Aggregation of beta-amyloid fragments.

    PubMed

    Meinke, Jan H; Hansmann, Ulrich H E

    2007-01-01

    The authors study the folding and aggregation of six chains of the beta-amyloid fragment 16-22 using Monte Carlo simulations. While the isolated fragment prefers a helical form at room temperature, in the system of six interacting fragments one observes both parallel and antiparallel beta sheets below a crossover temperature T(x) approximately equal to 420 K. The antiparallel sheets have lower energy and are therefore more stable. Above the nucleation temperature the aggregate quickly dissolves into widely separated, weakly interacting chains. PMID:17212510

  1. Double-Beta Decay at TUNL

    NASA Astrophysics Data System (ADS)

    Kidd, Mary

    2007-10-01

    Studying double-beta decay at Triangle Universities Nuclear Laboratory (TUNL) is perhaps one of the most promising ways to pinpoint the neutrino mass. What they do not mention is that to study double-beta decay, you probably have to become a certified miner, and if you have a fear of goats, you should stay away. In this talk, I will tell you some of my experiences as a TUNL graduate student, and how I am now nearly qualified for a job in the mining industry.

  2. Beta titanium: a new orthodontic alloy.

    PubMed

    Burstone, C J; Goldberg, A J

    1980-02-01

    Historically, few alloys have been used in the fabrication of orthodontic appliances. This article reviews the gold-based, stainless steel, chrome-cobalt-nickel, and nitinol alloys, as well as beta titanium, a new material for orthodontics. Mechanical properties and manipulative characteristics are summarized to develop a basis for the selection of the proper alloy for a given clinical situation. The beta titanium wire has a unique balance of low stiffness, high springback, formability, and weldability which indicates its use in a wide range of clinical applications. A number of such applications are described. PMID:6928342

  3. Insider Alert 1.0 Beta Version

    SciTech Connect

    Abbott, Robert

    2004-02-01

    Insider Alert 1.0 Beta Version supports interactive selection and graphical display of data generated by the Sandia Cognitive Framework, which simulates the examination of security data by experts of various specialties. Insider Alert also encompasses the configuration and data files input to the Cognitive Framework for this application. Insider Alert 1.0 Beta Version is a computer program for analyzing data indicative of possible espionage or improper handling of data by employees at Sandia National Laboratories (or other facilities with comparable policies and procedures for managing sensitive information) It prioritizes and displays information for review by security analysts.

  4. Insider Alert 1.0 Beta Version

    Energy Science and Technology Software Center (ESTSC)

    2004-02-01

    Insider Alert 1.0 Beta Version supports interactive selection and graphical display of data generated by the Sandia Cognitive Framework, which simulates the examination of security data by experts of various specialties. Insider Alert also encompasses the configuration and data files input to the Cognitive Framework for this application. Insider Alert 1.0 Beta Version is a computer program for analyzing data indicative of possible espionage or improper handling of data by employees at Sandia National Laboratoriesmore » (or other facilities with comparable policies and procedures for managing sensitive information) It prioritizes and displays information for review by security analysts.« less

  5. Introduction of a single isomer beta agonist.

    PubMed

    Rau, J L

    2000-08-01

    The release of levalbuterol offers the first approved single-isomer beta agonist for oral inhalation. Data from in vitro studies support the concept that S albuterol is not inactive and may have properties antagonistic to bronchodilation. There is some variability in the results of clinical studies with the separate isomers of albuterol, which suggests the need for further study. The introduction of levalbuterol into general clinical use in managing asthma and chronic obstructive disease should begin to offer additional information on the effects of a single isomer beta agonist in comparison to previous racemic mixtures. PMID:10963321

  6. Method of producing .beta.-spodumene bodies

    DOEpatents

    Chyung, Kenneth; Day, J. Paul; Holleran, Louis M.; Olszewski, Anthony R.

    1999-01-01

    Beta-spodumene bodies and method of preparing the bodies that involves providing a uniform plastic batch of inorganic raw materials, organic binder, and vehicle, wherein the inorganic raw materials are composed of, in percent by weight, about 75% to 95% minerals, and about 5% to 25% glass. The batch is formed into a green body that is fired to produce a body composed substantially of beta-spodumene, and having a thermal expansion coefficient of <10.times.10.sup.-7 /.degree.C.(0-800.degree. C.), and a strength of .gtoreq.4 Ksi.

  7. Hevea Linamarase-A Nonspecific beta-Glycosidase.

    PubMed

    Selmar, D; Lieberei, R; Biehl, B; Voigt, J

    1987-03-01

    In the leaf tissue of the cyanogenic plant Hevea brasiliensis, which contains large amounts of linamarin, there is no specific linamarase. In Hevea leaves only one beta-glucosidase is detectable. It is responsible for the cleavage of all beta-glucosides and beta-galactosides occurring in Hevea leaf tissue, including the cyanogenic glucoside linamarin. Therefore, the enzyme is referred to as a beta-glycosidase instead of the term beta-glucosidase. This beta-glycosidase has a broad substrate spectrum and occurs in multiple forms. These homo-oligomeric forms are interconvertible by dissociation-association processes. The monomer is a single protein of 64 kilodaltons. PMID:16665288

  8. 4-Pentafluoroethylumbelliferyl-beta-D-glucoside as a new fluorogenic substrate for acid beta-D-glucosidase.

    PubMed

    Tsvetkova, I V; Karpova, E A; Dudukina, T V; Voznyi, Y V

    1996-04-30

    4-Pentafluoroethylumbelliferyl-beta-D-glucoside is proposed as an efficient substrate for human leukocyte acid beta-glucosidase. Its synthesis is described. This substrate was compared directly with 4-trifluoromethylumbelliferyl-beta-D-glucoside synthesized by us earlier and with 4-methylumbelliferyl-beta-D-glucoside which is commonly used for acid beta-glucosidase activity assay. The specific activity of acid beta-glucosidase with 4-pentafluoroethylumbelliferyl-beta-D-glucoside was 3- and 8-fold higher than it was with the substrates mentioned above. The kinetic parameters KM and VMAX for human leukocyte acid beta-glucosidase with the three substrates was determined. One possible application of the newly synthesized substrate is its use in the diagnosis of acid beta-glucosidase hereditary deficiency (Gaucher's disease). PMID:8740577

  9. Human Fucci Pancreatic Beta Cell Lines: New Tools to Study Beta Cell Cycle and Terminal Differentiation

    PubMed Central

    Carlier, Géraldine; Maugein, Alicia; Cordier, Corinne; Pechberty, Séverine; Garfa-Traoré, Meriem; Martin, Patrick; Scharfmann, Raphaël; Albagli, Olivier

    2014-01-01

    Regulation of cell cycle in beta cells is poorly understood, especially in humans. We exploited here the recently described human pancreatic beta cell line EndoC-βH2 to set up experimental systems for cell cycle studies. We derived 2 populations from EndoC-βH2 cells that stably harbor the 2 genes encoding the Fucci fluorescent indicators of cell cycle, either from two vectors, or from a unique bicistronic vector. In proliferating non-synchronized cells, the 2 Fucci indicators revealed cells in the expected phases of cell cycle, with orange and green cells being in G1 and S/G2/M cells, respectively, and allowed the sorting of cells in different substeps of G1. The Fucci indicators also faithfully red out alterations in human beta cell proliferative activity since a mitogen-rich medium decreased the proportion of orange cells and inflated the green population, while reciprocal changes were observed when cells were induced to cease proliferation and increased expression of some beta cell genes. In the last situation, acquisition of a more differentiated beta cell phenotype correlates with an increased intensity in orange fluorescence. Hence Fucci beta cell lines provide new tools to address important questions regarding human beta cell cycle and differentiation. PMID:25259951

  10. Human liver alcohol dehydrogenase. 1. The primary structure of the beta 1 beta 1 isoenzyme.

    PubMed

    Hempel, J; Bühler, R; Kaiser, R; Holmquist, B; de Zalenski, C; von Wartburg, J P; Vallee, B; Jörnvall, H

    1984-12-17

    Determination of the amino acid sequence of the beta 1 subunit from the class I (pyrazole-sensitive) human liver alcohol dehydrogenase isoenzyme beta 1 beta 1 revealed a 373-residue structure differing at 48 positions (including a gap) from that of the subunit of the well studied horse liver alcohol dehydrogenase EE isoenzyme. The structure deduced is compatible with known differences in composition, ultraviolet absorbance, electrophoretic mobility and catalytic properties between the horse and human enzymes. All zinc-liganding residues of the horse E subunit are strictly conserved in the human beta 1 subunit, despite an earlier report of a mutation involving Cys-46. This residue therefore remains conserved in all known alcohol dehydrogenase structures. However, the total cysteine content of the beta 1 structure is raised from 14 in the subunit of the horse enzyme to 15 by a Tyr----Cys exchange. Most exchanges are on the surface of the molecule and of a well conserved nature. Substitutions close to the catalytic centre are of interest to explain the altered substrate specificity and different catalytic activity of the beta 1 homodimer. Functionally, a Ser----Thr exchange at position 48 appears to be of special importance, since Thr-48 in beta 1 instead of Ser-48 in the horse enzyme can restrict available space. Four other substitutions also line the active-site pocket, and appear to constitute partly compensated exchanges. PMID:6391920

  11. Transforming growth factor-beta and transforming growth factor beta-receptor expression in human meningioma cells.

    PubMed Central

    Johnson, M. D.; Federspiel, C. F.; Gold, L. I.; Moses, H. L.

    1992-01-01

    The transforming growth factor-beta (TGF beta) family in mammals includes three closely related peptides that influence proliferation and numerous physiologic processes in most mesenchymal cells. In this study, Northern blots, immunohistochemistry, TGF beta radioreceptor assays, TGF beta receptor affinity labeling and [3H] thymidine incorporation were used to evaluate whether primary cell cultures of human meningiomas synthesize the three TGF beta isoforms, bear TGF beta receptors, and respond to TGF beta. Transcripts for TGF beta 1 and 2 were detected in the three cases analyzed. Transforming growth factor-beta 1 immunoreactivity was detected in three of six cases, and TGF beta 2 and 3 immunoreactivity were detected in each case analyzed. Media conditioned by cells cultured from six meningiomas also contained latent TGF beta-like activity. Transforming growth factor-beta receptor cross-linking studies identified TGF beta binding sites corresponding to the type 1, type 2, and type 3 receptors on meningioma cells. Treatment with active TGF beta 1 produced a statistically significant reduction in [3H] thymidine incorporation after stimulation with 10% fetal calf serum and epidermal growth factor in all six cases studied. Images Figure 1 Figure 2 Figure 4 PMID:1325741

  12. Comparative functional analysis of rat TGF-beta1 and Xenopus laevis TGF-beta5 promoters suggest differential regulations.

    PubMed

    Goswami, Moloy T; Desai, Kartiki V; Kondaiah, Paturu

    2003-07-01

    We have carried out a comparative functional analysis of the rat TGF-beta1 and Xenopus laevis TGF-beta5 promoters across several mammalian and amphibian cell lines. Progressive deletion constructs of both the promoters have been made using a PCR based approach and the basal promoter activities studied in Xenopus tadpole cell line (XTC), Xenopus adult kidney fibroblast cell line (A6), human hepatoma cell line (HepG2), normal rat kidney cell line (NRK), and Chinese hamster ovary cell line (CHO). Data suggests that the basal promoter activity of TGF-beta1 is low as compared to TGF-beta5 promoter in XTC cells but comparable in A6 cells, while TGF-beta5 promoter shows nearly negligible activity as compared to TGF-beta5 promoter in all the tested mammalian cell lines. Moreover, TGF-beta5 promoter is found to be repressed in XTC cells on treatment with TGF-beta5 protein. Thus, the regulation of TGF-beta1 and TGF-beta5 promoters is distinct in amphibian and mammalian species. We therefore suggest that contrary to the suggested functional equivalence of TGF-beta1 and TGF-beta5 proteins, TGF-beta1 and TGF-beta5 genes have distinct functions in their respective species. PMID:12962305

  13. Induction of beta-lactamase by various beta-lactam antibiotics in Enterobacter cloacae.

    PubMed Central

    Minami, S; Yotsuji, A; Inoue, M; Mitsuhashi, S

    1980-01-01

    The induction of beta-lactamase in Enterobacter cloacae GN5797 was studied by using 23 beta-lactam antiobiotics, including newly introduced drugs, as inducers. the beta-lactam antibiotics can be classified into three groups on the basis of their inducer activity. Among the tested cephalosporins, cephamycin derivatives such as cefoxitin, cefmetazole, and YM09330 had high inducer activity even at low drug concentrations. On the other hand, cefoperazone, cefsulodin, piperacillin, and apalcillin showed low inducer activity when compared with the other cephalosporins. PMID:6968541

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

    NASA Astrophysics Data System (ADS)

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

    1996-11-01

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

  15. Effects of plasma {beta} on the plasmoid instability

    SciTech Connect

    Ni Lei; Ziegler, Udo; Huang Yimin; Lin Jun; Mei Zhixing

    2012-07-15

    The effects of the initial upstream plasma {beta} on the plasmoid instability are studied via two-dimensional resistive magnetohydrodynamic simulations. For cases with nonuniform {beta} dependent initial plasma mass density and uniform temperature, our numerical results indicate that the critical Lundquist number for onset of the plasmoid instability depends on the initial plasma {beta}. The critical Lundquist number is approximately 2000-3000 for {beta}=50 and is 8000-10 000 for {beta}=0.2. The higher the {beta}, the smaller the critical Lundquist number is. Similar to previous studies of high-{beta} systems, the average reconnection rate in low {beta} systems is found to become weakly dependent on the Lundquist number in the plasmoid-unstable regime. However, the average reconnection rate, normalized to the asymptotic value of upstream BV{sub A}, is lower in a low {beta} system than that in a high {beta} system. The magnetic energy spectral index, which characterizes fragmentation of the reconnection layer, is approximately two and is insensitive to {beta} in the high-Lunquist number regime. It is also found that the magnetic reconnection rate becomes similar for different {beta} cases, if the initial force-balance is provided by temperature gradient instead of density gradient. Therefore, it is concluded that the {beta}-dependence mentioned above may be largely attributed to the density variation.

  16. Same. beta. -globin gene mutation is present on nine different. beta. -thalassemia chromosomes in a Sardinian population

    SciTech Connect

    Pirastu, M.; Galanello, R.; Doherty, M.A.; Tuveri, T.; Cao, A.; Kan, Y.W.

    1987-05-01

    The predominant ..beta..-thalassemia in Sardinia is the ..beta../sup 0/ type in which no ..beta..-globin chains are synthesized in the homozygous state. The authors determined the ..beta..-thalassemia mutations in this population by the oligonucleotide-probe method and defined the chromosome haplotypes on which the mutation resides. The same ..beta../sup 39(CAG..-->..TAG)/ nonsense mutation was found on nine different chromosome haplotypes. Although this mutation may have arisen more than once, the multiple haplotypes could also be generated by crossing over and gene conversion events. These findings underscore the frequency of mutational events in the ..beta..-globin gene region.

  17. ON THE ORIGIN OF THE SUPERGIANT H I SHELL AND PUTATIVE COMPANION IN NGC 6822

    SciTech Connect

    Cannon, John M.; O'Leary, Erin M.; Weisz, Daniel R.; Skillman, Evan D.; Dolphin, Andrew E.; Bigiel, Frank; Cole, Andrew A.; Walter, Fabian; De Blok, W.J.G. E-mail: eoleary@macalester.edu E-mail: skillman@astro.umn.edu E-mail: bigiel@uni-heidelberg.de E-mail: edeblok@ast.uct.ac.za

    2012-03-10

    We present new Hubble Space Telescope Advanced Camera for Surveys imaging of six positions spanning 5.8 kpc of the H I major axis of the Local Group dIrr NGC 6822, including both the putative companion galaxy and the large H I hole. The resulting deep color-magnitude diagrams show that NGC 6822 has formed >50% of its stars in the last {approx}5 Gyr. The star formation histories of all six positions are similar over the most recent 500 Myr, including low-level star formation throughout this interval and a weak increase in star formation rate during the most recent 50 Myr. Stellar feedback can create the giant H I hole, assuming that the lifetime of the structure is longer than 500 Myr; such long-lived structures have now been observed in multiple systems and may be the norm in galaxies with solid-body rotation. The old stellar populations (red giants and red clump stars) of the putative companion are consistent with those of the extended halo of NGC 6822; this argues against the interpretation of this structure as a bona fide interacting companion galaxy and against its being linked to the formation of the H I hole via an interaction. Since there is no evidence in the stellar population of a companion galaxy, the most likely explanation of the extended H I structure in NGC 6822 is a warped disk inclined to the line of sight.

  18. Uncovering the Putative B-Star Binary Companion of the SN 1993J Progenitor

    NASA Technical Reports Server (NTRS)

    Fox, Ori D.; Bostroem, K. Azalee; Van Dyk, Schuyler D.; Filippenko, Alexei V.; Fransson, Claes; Matheson, Thomas; Cenko, S. Bradley; Chandra, Poonam; Dwarkadas, Vikram; Li, Weidong; Parker, Alex H.; Smith, Nathan

    2014-01-01

    The Type IIb supernova (SN) 1993J is one of only a few stripped-envelope SNe with a progenitor star identified in pre-explosion images. SN IIb models typically invoke H envelope stripping by mass transfer in a binary system. For the case of SN 1993J, the models suggest that the companion grew to 22 solar mass and became a source of ultraviolet (UV) excess. Located in M81, at a distance of only 3.6 Mpc, SN 1993J offers one of the best opportunities to detect the putative companion and test the progenitor model. Previously published near-UV spectra in 2004 showed evidence for absorption lines consistent with a hot (B2 Ia) star, but the field was crowded and dominated by flux from the SN. Here we present Hubble Space Telescope Cosmic Origins Spectrograph and Wide-Field Camera 3 observations of SN 1993J from 2012, at which point the flux from the SN had faded sufficiently to potentially measure the UV continuum properties from the putative companion. The resulting UV spectrum is consistent with contributions from both a hot B star and the SN, although we cannot rule out line-of-sight coincidences.

  19. Evidence for a role for the putative Drosophila hGRX1 orthologue in copper homeostasis.

    PubMed

    Mercer, Stephen W; Burke, Richard

    2016-08-01

    Glutaredoxins are a family of small molecular weight proteins that have a central role in cellular redox regulation. Human GRX1 (hGRX1) has also been shown to play an integral role in copper homeostasis by regulating the redox activity of the metalated sites of copper chaperones such as ATOX1 and SOD1, and the copper efflux proteins ATP7A and ATP7B. To further elucidate the role of hGRX1 in copper homeostasis, we examined the impact of RNA interference-mediated knockdown of CG6852, a putative Drosophila orthologue of hGRX1. CG6852 shares ~41 % amino acid identity with hGRX1 and key functional domains including the metal-binding CXXC motif are conserved between the two proteins. Knockdown of CG6852 in the adult midline caused a thoracic cleft and reduced scutellum, phenotypes that were exacerbated by additional knockdown of copper uptake transporters Ctr1A and Ctr1B. Knockdown of CG6852 in the adult eye enhanced a copper-deficiency phenotype caused by Ctr1A knockdown while ubiquitous knockdown of CG6852 resulted a mild systemic copper deficiency. Therefore we conclude that CG6852 is a putative orthologue of hGRX1 and may play an important role in Drosophila copper homeostasis. PMID:27379771

  20. Biochemical Characterization of Putative Adenylate Dimethylallyltransferase and Cytokinin Dehydrogenase from Nostoc sp. PCC 7120.

    PubMed

    Frébortová, Jitka; Greplová, Marta; Seidl, Michael F; Heyl, Alexander; Frébort, Ivo

    2015-01-01

    Cytokinins, a class of phytohormones, are adenine derivatives common to many different organisms. In plants, these play a crucial role as regulators of plant development and the reaction to abiotic and biotic stress. Key enzymes in the cytokinin synthesis and degradation in modern land plants are the isopentyl transferases and the cytokinin dehydrogenases, respectively. Their encoding genes have been probably introduced into the plant lineage during the primary endosymbiosis. To shed light on the evolution of these proteins, the genes homologous to plant adenylate isopentenyl transferase and cytokinin dehydrogenase were amplified from the genomic DNA of cyanobacterium Nostoc sp. PCC 7120 and expressed in Escherichia coli. The putative isopentenyl transferase was shown to be functional in a biochemical assay. In contrast, no enzymatic activity was detected for the putative cytokinin dehydrogenase, even though the principal domains necessary for its function are present. Several mutant variants, in which conserved amino acids in land plant cytokinin dehydrogenases had been restored, were inactive. A combination of experimental data with phylogenetic analysis indicates that adenylate-type isopentenyl transferases might have evolved several times independently. While the Nostoc genome contains a gene coding for protein with characteristics of cytokinin dehydrogenase, the organism is not able to break down cytokinins in the way shown for land plants. PMID:26376297

  1. Duplications and losses in gene families of rust pathogens highlight putative effectors

    PubMed Central

    Pendleton, Amanda L.; Smith, Katherine E.; Feau, Nicolas; Martin, Francis M.; Grigoriev, Igor V.; Hamelin, Richard; Nelson, C. Dana; Burleigh, J. Gordon; Davis, John M.

    2014-01-01

    Rust fungi are a group of fungal pathogens that cause some of the world's most destructive diseases of trees and crops. A shared characteristic among rust fungi is obligate biotrophy, the inability to complete a lifecycle without a host. This dependence on a host species likely affects patterns of gene expansion, contraction, and innovation within rust pathogen genomes. The establishment of disease by biotrophic pathogens is reliant upon effector proteins that are encoded in the fungal genome and secreted from the pathogen into the host's cell apoplast or within the cells. This study uses a comparative genomic approach to elucidate putative effectors and determine their evolutionary histories. We used OrthoMCL to identify nearly 20,000 gene families in proteomes of 16 diverse fungal species, which include 15 basidiomycetes and one ascomycete. We inferred patterns of duplication and loss for each gene family and identified families with distinctive patterns of expansion/contraction associated with the evolution of rust fungal genomes. To recognize potential contributors for the unique features of rust pathogens, we identified families harboring secreted proteins that: (i) arose or expanded in rust pathogens relative to other fungi, or (ii) contracted or were lost in rust fungal genomes. While the origin of rust fungi appears to be associated with considerable gene loss, there are many gene duplications associated with each sampled rust fungal genome. We also highlight two putative effector gene families that have expanded in Cqf that we hypothesize have roles in pathogenicity. PMID:25018762

  2. Functional analysis of putative genes encoding the PIP2 water channel subfamily in Populus trichocarpa.

    PubMed

    Secchi, Francesca; MacIver, Bryce; Zeidel, Mark L; Zwieniecki, Maciej A

    2009-11-01

    We located fully sequenced putative genes of the plasma membrane intrinsic proteins (PIPs) family in the Populus trichocarpa (Torr. Gray), genome. Of 23 gene candidates, we assigned eight genes to the PIP2 subfamily. All eight putative genes were expressed in vegetative tissues (roots, leaves, bark and wood), and all of them showed water channel activity after being expressed in Xenopus oocytes. Six of eight proteins were affected by mercury ions. No proteins were affected by the presence of nickel or tungsten ions, or by lowering the pH of bathing external solution from 7.4 to 6.5. The presence of copper ions caused seven of eight PIP2 proteins to increase their water transport capacity by as much as 50%. This systematic study of the PIP2 subfamily of proteins in P. trichocarpa provides a basic overview of their activity as water channels and will be a useful reference for future physiological studies of plant water relations that use P. trichocarpa as a model system. PMID:19808706

  3. A putative precursor for the small ribosomal RNA from mitochondria of Saccharomyces cerevisiae.

    PubMed Central

    Osinga, K A; Evers, R F; Van der Laan, J C; Tabak, H F

    1981-01-01

    We have characterized a putative precursor RNA (15.5S) for the 15S ribosomal RNA in mitochondria of Saccharomyces cerevisiae. Hybrids were formed with mitochondrial RNA and mtDNA fragments terminally labelled at restriction sites located within the gene coding for 15S ribosomal RNA and treated with S1 nuclease (Berk, A.J. and Sharp, J.A. (1977) 12, 721-732). Sites of resistant hybrids were measured by agarose gel electrophoresis and end points of RNAs determined. The 15.5S RNA is approximately 80 nucleotides longer than the 15S ribosomal RNA, with the extra sequences being located at the 5'-end. Both 15S ribosomal RNA and 15.5S RNA are fully localised within a 2000 base pair HapII fragment. This putative precursor and the mature 15S ribosomal RNA are also found in petite mutants which retain the 15S ribosomal RNA gene. The petite mutant with the smallest genetic complexity has its end point of deletion (junction) just outside the HapII site located in the 5' flank of the 15S ribosomal RNA genes as determined by S1 nuclease analysis. This leaves a DNA stretch approximately 300 base pairs long where an initiation signal for mitochondrial transcription may be present. Images PMID:6262728

  4. Biochemical Characterization of Putative Adenylate Dimethylallyltransferase and Cytokinin Dehydrogenase from Nostoc sp. PCC 7120

    PubMed Central

    Frébortová, Jitka; Greplová, Marta; Seidl, Michael F.; Heyl, Alexander; Frébort, Ivo

    2015-01-01

    Cytokinins, a class of phytohormones, are adenine derivatives common to many different organisms. In plants, these play a crucial role as regulators of plant development and the reaction to abiotic and biotic stress. Key enzymes in the cytokinin synthesis and degradation in modern land plants are the isopentyl transferases and the cytokinin dehydrogenases, respectively. Their encoding genes have been probably introduced into the plant lineage during the primary endosymbiosis. To shed light on the evolution of these proteins, the genes homologous to plant adenylate isopentenyl transferase and cytokinin dehydrogenase were amplified from the genomic DNA of cyanobacterium Nostoc sp. PCC 7120 and expressed in Escherichia coli. The putative isopentenyl transferase was shown to be functional in a biochemical assay. In contrast, no enzymatic activity was detected for the putative cytokinin dehydrogenase, even though the principal domains necessary for its function are present. Several mutant variants, in which conserved amino acids in land plant cytokinin dehydrogenases had been restored, were inactive. A combination of experimental data with phylogenetic analysis indicates that adenylate-type isopentenyl transferases might have evolved several times independently. While the Nostoc genome contains a gene coding for protein with characteristics of cytokinin dehydrogenase, the organism is not able to break down cytokinins in the way shown for land plants. PMID:26376297

  5. Diversity, Function and Evolution of Genes Coding for Putative Ni-Containing Superoxide Dismutases

    SciTech Connect

    Dupont,C.; Neupane, K.; Shearer, J.; Palenik, B.

    2008-01-01

    We examined the phylogenetic distribution, functionality and evolution of the sodN gene family, which has been shown to code for a unique Ni-containing isoform of superoxide dismutase (Ni-SOD) in Streptomyces. Many of the putative sodN sequences retrieved from public domain genomic and metagenomic databases are quite divergent from structurally and functionally characterized Ni-SOD. Structural bioinformatics studies verified that the divergent members of the sodN protein family code for similar three-dimensional structures and identified evolutionarily conserved amino acid residues. Structural and biochemical studies of the N-terminus 'Ni-hook' motif coded for by the putative sodN sequences confirmed both Ni (II) ligating and superoxide dismutase activity. Both environmental and organismal genomes expanded the previously noted phylogenetic distribution of sodN, and the sequences form four well-separated clusters, with multiple subclusters. The phylogenetic distribution of sodN suggests that the gene has been acquired via horizontal gene transfer by numerous organisms of diverse phylogenetic background, including both Eukaryotes and Prokaryotes. The presence of sodN correlates with the genomic absence of the gene coding for Fe-SOD, a structurally and evolutionarily distinct isoform of SOD. Given the low levels of Fe found in the marine environment from where many sequences were attained, we suggest that the replacement of Fe-SOD with Ni-SOD may be an evolutionary adaptation to reduce iron requirements.

  6. Localization and behavior of putative blastopore determinants in the uncleaved Xenopus egg.

    PubMed

    Shinagawa, A; Kobayashi, S

    2000-12-01

    The present study examines putative blastopore determinants in uncleaved Xenopus eggs. Deletion of marginal and lower portions of Xenopus eggs when between 30 and 50% of the first cell cycle has been completed (0.3-0.5 normalized time (NT)) results in the complete absence of the blastopore, while deletion of the vegetal hemisphere during the same period leads to the formation of a smaller blastopore. Extrusion of only yolk and deep cytoplasm of the vegetal hemisphere during 0.3-0.5 NT does not affect the formation or size of the blastopore. Consistently, transplantation of cortical and subcortical cytoplasm from marginal, but not other, sites of eggs at 0.3-0.5 NT to an animal blastomere from 16-cell stage embryos induces an ectopic blastopore and bottle cell-like cells. This does not occur in the same transplantation from eggs at 0.2 NT. These results suggest that the blastopore determinants become localized to the marginal cortical and/or subcortical cytoplasm during 0.2-0.3 NT. Other results suggest the involvement of a hexyleneglycol-sensitive system in the process of localization of the blastopore determinants to the marginal region during 0.2-0.3 NT. The properties and behavior of the putative blastopore determinants are discussed in relation to those of VegT, which previously has been shown to induce ectopic blastopores. PMID:11142680

  7. A Putative Cro-Like Repressor Contributes to Arylomycin Resistance in Staphylococcus aureus

    PubMed Central

    Craney, Arryn

    2015-01-01

    Antibiotic-resistant bacteria are a significant public health concern and motivate efforts to develop new classes of antibiotics. One such class of antibiotics is the arylomycins, which target type I signal peptidase (SPase), the enzyme responsible for the release of secreted proteins from their N-terminal leader sequences. Despite the essentiality, conservation, and relative accessibility of SPase, the activity of the arylomycins is limited against some bacteria, including the important human pathogen Staphylococcus aureus. To understand the origins of the limited activity against S. aureus, we characterized the susceptibility of a panel of strains to two arylomycin derivatives, arylomycin A-C16 and its more potent analog arylomycin M131. We observed a wide range of susceptibilities to the two arylomycins and found that resistant strains were sensitized by cotreatment with tunicamycin, which inhibits the first step of wall teichoic acid synthesis. To further understand how S. aureus responds to the arylomycins, we profiled the transcriptional response of S. aureus NCTC 8325 to growth-inhibitory concentrations of arylomycin M131 and found that it upregulates the cell wall stress stimulon (CWSS) and an operon consisting of a putative transcriptional regulator and three hypothetical proteins. Interestingly, we found that mutations in the putative transcriptional regulator are correlated with resistance, and selection for resistance ex vivo demonstrated that mutations in this gene are sufficient for resistance. The results begin to elucidate how S. aureus copes with secretion stress and how it evolves resistance to the inhibition of SPase. PMID:25753642

  8. Photochemical generation and kinetic studies of a putative porphyrin-ruthenium(V)-oxo species

    PubMed Central

    Zhang, Rui; Vanover, Eric; Luo, Weilong; Newcomb, Martin

    2014-01-01

    Photo-disproportionation of a bis-porphyrin-diruthenium(IV) μ-oxo dimer gave a porphyrin-ruthenium(III) species and a putative poprhyrin-ruthenium(V)-oxo species that can be detected and studied in real time via laser flash photolysis methods. As determined by its spectral and kinetic behavior, the same oxo transient was also formed by photolysis of a porphyrin-ruthenium(III) N-oxide adduct. Second-order rate constants for reactions with several substrates at 22 °C were determined; representative values of rate constants were kox = 6.6 × 103 M−1 s−1 for diphenylmethanol, kox = 2.5 × 103 M−1 s−1 for styrene, and kox = 1.8 × 103 M−1 s−1 for cyclohexene. The putative porphyrin-ruthenium(V)-oxo transient reacted 5–6 orders of magnitude faster than the corresponding trans-dioxoruthenium(VI)-oxo porphyrins, and the rate constants obtained in this work were similar to those of corrole-iron(V)-oxo derivative. The high reactivity for the photochemically generated ruthenium-oxo species in comparison to other poprhyrin-metal-oxo intermediates suggests it is a true ruthenium(V)-oxo species. PMID:24770388

  9. Characterization of Putative cis-Regulatory Elements in Genes Preferentially Expressed in Arabidopsis Male Meiocytes

    PubMed Central

    Li, Mingjun

    2014-01-01

    Meiosis is essential for plant reproduction because it is the process during which homologous chromosome pairing, synapsis, and meiotic recombination occur. The meiotic transcriptome is difficult to investigate because of the size of meiocytes and the confines of anther lobes. The recent development of isolation techniques has enabled the characterization of transcriptional profiles in male meiocytes of Arabidopsis. Gene expression in male meiocytes shows unique features. The direct interaction of transcription factors (TFs) with DNA regulatory sequences forms the basis for the specificity of transcriptional regulation. Here, we identified putative cis-regulatory elements (CREs) associated with male meiocyte-expressed genes using in silico tools. The upstream regions (1 kb) of the top 50 genes preferentially expressed in Arabidopsis meiocytes possessed conserved motifs. These motifs are putative binding sites of TFs, some of which share common functions, such as roles in cell division. In combination with cell-type-specific analysis, our findings could be a substantial aid for the identification and experimental verification of the protein-DNA interactions for the specific TFs that drive gene expression in meiocytes. PMID:25250331

  10. Effect of putative pheromones on the electrical activity of the human vomeronasal organ and olfactory epithelium.

    PubMed

    Monti-Bloch, L; Grosser, B I

    1991-10-01

    The summated receptor potential was recorded from the vomeronasal organ (VNO) and olfactory epithelium (OE) of 49 human subjects of both sexes (18 to 55 years old) using surface non-polarizable silver-silver chloride electrodes. 15-25 pg of human putative pheromones, clove oil and a diluent were administered to the VNO or the OE in 0.3-1 s pulses from a 0.05 mm dia cannula connected to a multichannel delivery system. Local stimulation of the VNO produces negative potentials of 1.8-11.6 mV showing adaptation. Responses are not obtained when the recording electrode is placed in the nasal respiratory mucosa. Pheromone ER-830 significantly stimulates the male VNO (P less than 0.01; n = 20), while ER-670 produces a significant effect on female subjects (P less than 0.001; n = 20). The other pheromones tested do not show significantly different effects in both male and female (P greater than 0.1). Similar quantities of odorant or diluent produce an insignificant effect on the VNO. Stimulation of the OE with clove oil produces depolarization of 12.3 +/- 3.9 mV, while pheromones do not show a significant effect. Our results show that the VNO is a functional organ in adult humans having receptor sites for human putative pheromones. PMID:1892788

  11. Identification of putative circadian clock genes in the American horseshoe crab, Limulus polyphemus.

    PubMed

    Chesmore, Kevin N; Watson, Winsor H; Chabot, Christopher C

    2016-09-01

    While the American horseshoe crab, Limulus polyphemus, has robust circadian and circatidal rhythms, virtually nothing is known about the molecular basis of these rhythms in this species or any other chelicerate. In this study, next generation sequencing was used to assemble transcriptomic reads and then putative homologs of known core and accessory circadian genes were identified in these databases. Homologous transcripts were discovered for one circadian clock input gene, five core genes, 22 accessory genes, and two possible output pathways. Alignments and functional domain analyses showed generally high conservation between the putative L. polyphemus clock genes and homologs from Drosophila melanogaster and Daphnia pulex. The presence of both cry1 and cry2 in the L. polyphemus transcriptome would classify its system as an "ancestral", type 2 clock system. In addition, a novel duplication of CYCLE, and a novel triplication of PERIOD were found. Investigations are currently underway to determine if any of these "circadian" genes also participate in the molecular processes that drive the Limulus circatidal clock. PMID:27341138

  12. Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA

    PubMed Central

    Turner, Tychele N.; Hormozdiari, Fereydoun; Duyzend, Michael H.; McClymont, Sarah A.; Hook, Paul W.; Iossifov, Ivan; Raja, Archana; Baker, Carl; Hoekzema, Kendra; Stessman, Holly A.; Zody, Michael C.; Nelson, Bradley J.; Huddleston, John; Sandstrom, Richard; Smith, Joshua D.; Hanna, David; Swanson, James M.; Faustman, Elaine M.; Bamshad, Michael J.; Stamatoyannopoulos, John; Nickerson, Deborah A.; McCallion, Andrew S.; Darnell, Robert; Eichler, Evan E.

    2016-01-01

    We performed whole-genome sequencing (WGS) of 208 genomes from 53 families affected by simplex autism. For the majority of these families, no copy-number variant (CNV) or candidate de novo gene-disruptive single-nucleotide variant (SNV) had been detected by microarray or whole-exome sequencing (WES). We integrated multiple CNV and SNV analyses and extensive experimental validation to identify additional candidate mutations in eight families. We report that compared to control individuals, probands showed a significant (p = 0.03) enrichment of de novo and private disruptive mutations within fetal CNS DNase I hypersensitive sites (i.e., putative regulatory regions). This effect was only observed within 50 kb of genes that have been previously associated with autism risk, including genes where dosage sensitivity has already been established by recurrent disruptive de novo protein-coding mutations (ARID1B, SCN2A, NR3C2, PRKCA, and DSCAM). In addition, we provide evidence of gene-disruptive CNVs (in DISC1, WNT7A, RBFOX1, and MBD5), as well as smaller de novo CNVs and exon-specific SNVs missed by exome sequencing in neurodevelopmental genes (e.g., CANX, SAE1, and PIK3CA). Our results suggest that the detection of smaller, often multiple CNVs affecting putative regulatory elements might help explain additional risk of simplex autism. PMID:26749308

  13. Functional analysis of conserved residues in the putative "finger" domain of telomerase reverse transcriptase.

    PubMed

    Bosoy, D; Lue, N F

    2001-12-01

    Telomerase is a ribonucleoprotein reverse transcriptase (RT) responsible for the maintenance of one strand of telomere terminal repeats. The catalytic protein subunit of telomerase, known generically as telomerase reverse transcriptase (TERT), exhibits significant homology to RTs encoded by retroviruses and retroelements. The polymerization mechanisms of telomerase may therefore be similar to those of the "conventional" RTs. In this study, we explored the extent of mechanistic conservation by analyzing mutations of conserved residues within the putative "finger" domain of TERT. Previous analysis has implicated this domain of retroviral RTs in nucleotide and RNA binding and in processivity control. Our results demonstrate that residues conserved between TERT and human immunodeficiency virus-1 RT are more likely than TERT-specific residues to be required for enzyme activity. In addition, residues presumed to make direct contact with either the RNA or nucleotide substrate appear to be functionally more important. Furthermore, distinct biochemical defects can be observed for alterations in the putative RNA- and nucleotide-binding TERT residues in a manner that can be rationalized by their postulated mechanisms of action. This study thus supports a high degree of mechanistic conservation between telomerase and retroviral RTs and underscores the roles of distinct aspects of telomerase biochemistry in telomere length maintenance. PMID:11581271

  14. Sensitivity analysis of the relationship between disease occurrence and distance from a putative source of pollution.

    PubMed

    Dreassi, Emanuela; Lagazio, Corrado; Maule, Milena M; Magnani, Corrado; Biggeri, Annibale

    2008-05-01

    The relation between disease risk and a point source of pollution is usually investigated using distance from the source as a proxy of exposure. The analysis may be based on case-control data or on aggregated data. The definition of the function relating risk of disease and distance is critical, both in a classical and in a Bayesian framework, because the likelihood is usually very flat, even with large amounts of data. In this paper we investigate how the specification of the function relating risk of disease with distance from the source and of the prior distributions on the parameters of the function affects the results when case-control data and Bayesian methods are used. We consider different popular parametric models for the risk distance function in a Bayesian approach, comparing estimates with those derived by maximum likelihood. As an example we have analyzed the relationship between a putative source of environmental pollution (an asbestos cement plant) and the occurrence of pleural malignant mesothelioma in the area of Casale Monferrato (Italy) in 1987-1993. Risk of pleural malignant mesothelioma turns out to be strongly related to distance from the asbestos cement plant. However, as the models appeared to be sensitive to modeling choices, we suggest that any analysis of disease risk around a putative source should be integrated with a careful sensitivity analysis and possibly with prior knowledge. The choice of prior distribution is extremely important and should be based on epidemiological considerations. PMID:18686274

  15. Putative identification of expressed genes associated with attachment of the zebra mussel (Dreissena polymorpha).

    PubMed

    Xu, Wei; Faisal, Mohamed

    2008-01-01

    Because of its aggressive growth and firm attachment to substrata, the zebra mussel (Dreissena polymorpha) has caused severe economic and ecological problems since its invasion into North America. The nature and details of attachment of this nuisance mollusc remains largely unexplored. Byssus, a special glandular apparatus located at the root of the foot of the mussel produces threads and plates through which firm attachment of the mollusc to underwater objects takes place. In an attempt to better understand the adhesion mechanism of the zebra mussel, the suppression subtractive hybridization (SSH) assay was employed to produce a cDNA library with genes unique to the foot of the mussel. Analysis of the SSH cDNA library revealed the presence of 750 new expressed sequence tags (ESTs) including 304 contigs and 446 singlets. Using BLAST search, 365 zebra mussel ESTs showed homology to other gene sequences with putative functions. The putative functions of the homologues included proteins involved in byssal thread formation in zebra and blue mussels, exocrine gland secretion, host defence, and house keeping. The generated data provide, for the first time, some useful insights into the foot structure of the zebra mussel and its underwater adhesion. PMID:18330781

  16. Hyla chrysoscelis (Cope’s gray treefrog) x Hyla cinerea (green treefrog): putative natural hybrid

    USGS Publications Warehouse

    Glorioso, Brad M.; Waddle, J. Hardin; Jenkins, Jill A.; Olivier, Heather M.; Layton, Rebekah R.

    2015-01-01

    Naturally–occurring hybrid treefrogs have been occasionally found in the eastern United States. However, these hybrids are almost always between members of the same species group. On 10 Jun 2014, at 2145 h, we located an individual making an unusual advertisement call along Bayou Manual Road in Sherburne Wildlife Management Area in the Atchafalaya Basin of south-central Louisiana, USA, and brought it back to the laboratory for further study. Physically, the treefrog appeared intermediate between a Green Treefrog and a Cope’s Gray Treefrog, which are members of different species groups. Call analysis also showed the individual to be intermediate between the two putative parental species. Flow cytometry was used to estimate the total genome size from nuclei of whole blood cells, and also determined the individual to be intermediate of the putative parental species. Despite vocalizing for mates, the hybrid did not appear to have viable spermatozoa, and was likely the result of an anomalous mis-mating event between a male Cope’s Gray Treefrog and a female Green Treefrog. To our knowledge, natural hybrids between a Cope’s Gray Treefrog and a Green Treefrog have not been previously reported.

  17. Uncovering the putative B-star binary companion of the SN 1993J progenitor

    SciTech Connect

    Fox, Ori D.; Filippenko, Alexei V.; Bradley Cenko, S.; Li, Weidong; Parker, Alex H.; Azalee Bostroem, K.; Van Dyk, Schuyler D.; Fransson, Claes; Matheson, Thomas; Chandra, Poonam; Dwarkadas, Vikram; Smith, Nathan

    2014-07-20

    The Type IIb supernova (SN) 1993J is one of only a few stripped-envelope SNe with a progenitor star identified in pre-explosion images. SN IIb models typically invoke H envelope stripping by mass transfer in a binary system. For the case of SN 1993J, the models suggest that the companion grew to 22 M{sub ☉} and became a source of ultraviolet (UV) excess. Located in M81, at a distance of only 3.6 Mpc, SN 1993J offers one of the best opportunities to detect the putative companion and test the progenitor model. Previously published near-UV spectra in 2004 showed evidence for absorption lines consistent with a hot (B2 Ia) star, but the field was crowded and dominated by flux from the SN. Here we present Hubble Space Telescope Cosmic Origins Spectrograph and Wide-Field Camera 3 observations of SN 1993J from 2012, at which point the flux from the SN had faded sufficiently to potentially measure the UV continuum properties from the putative companion. The resulting UV spectrum is consistent with contributions from both a hot B star and the SN, although we cannot rule out line-of-sight coincidences.

  18. First detection of circovirus-like sequences in amphibians and novel putative circoviruses in fishes.

    PubMed

    Tarján, Zoltán László; Pénzes, Judit J; Tóth, Róza P; Benkő, Mária

    2014-03-01

    The negative samples of a collection, established originally for seeking new adeno- and herpesviruses in lower vertebrates, were screened for the pres-ence of circoviruses by a consensus nested PCR targeting the gene coding for the replication-associated protein. Six fish samples representing five species, namely asp (Aspius aspius), roach (Rutilus rutilus), common bream (Abramis brama), round goby (Neogobius melanostomus) and monkey goby (Neogobius fluviatilis), as well as three frog samples were found positive for circoviral DNA. Sequence analysis of the amplicons indicated the presence of three novel putative circo-like viruses and a circovirus in Hungarian fishes and one novel circovirus in a common toad (Bufo bufo), and another one in a dead and an alive specimen of green tree frog (Litoria caerulea), respectively. In phylogeny reconstruction, the putative bream circovirus clustered together with circoviruses discovered in other cyprinid fishes recently. Three other piscine circoviral sequences appeared closest to sequences derived from different environmental samples. Surprisingly, the nucleotide sequence derived from two fish samples (a bream and a monkey goby) proved to be from porcine circovirus 2 (PCV2), almost identical to a sequence detected in Sweden previously. This is the first report on the detection of PCV2 in fish and circoviral DNA in amphibian hosts. PMID:24334078

  19. Molecular cloning and functional characterization of a putative sulfite oxidase (SO) ortholog from Nicotiana benthamiana.

    PubMed

    Xia, Zongliang; Su, Xinhong; Wu, Jianyu; Wu, Ke; Zhang, Hua

    2012-03-01

    Sulfite oxidase (SO) catalyzes the oxidation of sulfite to sulfate and thus has important roles in diverse metabolic processes. However, systematic molecular and functional investigations on the putative SO from tobacco (Nicotiana benthamiana) have hitherto not been reported. In this work, a full-length cDNA encoding putative sulfite oxidase from N. benthamiana (NbSO) was isolated. The deduced NbSO protein shares high homology and typical structural features with other species SOs. Phylogenetic analysis indicates that NbSO cDNA clone encodes a tobacco SO isoform. Southern blot analysis suggests that NbSO is a single-copy gene in the N. benthamiana genome. The NbSO transcript levels were higher in aerial tissues and were up-regulated in N. benthamiana during sulfite stress. Reducing the SO expression levels through virus-induced gene silencing caused a substantial accumulation in sulfite content and less sulfate accumulation in N. benthamiana leaves when exposed to sulfite stress, and thus resulted in decreased tolerance to sulfite stress. Taken together, this study improves our understanding on the molecular and functional properties of plant SO and provides genetic evidence on the involvement of SO in sulfite detoxification in a sulfite-oxidizing manner in N. benthamiana plants. PMID:21667106

  20. A putative ATPase mediates RNA transcription and capping in a dsRNA virus

    PubMed Central

    Yu, Xuekui; Jiang, Jiansen; Sun, Jingchen; Zhou, Z Hong

    2015-01-01

    mRNA transcription in dsRNA viruses is a highly regulated process but the mechanism of this regulation is not known. Here, by nucleoside triphosphatase (NTPase) assay and comparisons of six high-resolution (2.9–3.1 Å) cryo-electron microscopy structures of cytoplasmic polyhedrosis virus with bound ligands, we show that the large sub-domain of the guanylyltransferase (GTase) domain of the turret protein (TP) also has an ATP-binding site and is likely an ATPase. S-adenosyl-L-methionine (SAM) acts as a signal and binds the methylase-2 domain of TP to induce conformational change of the viral capsid, which in turn activates the putative ATPase. ATP binding/hydrolysis leads to an enlarged capsid for efficient mRNA synthesis, an open GTase domain for His217-mediated guanylyl transfer, and an open methylase-1 domain for SAM binding and methyl transfer. Taken together, our data support a role of the putative ATPase in mediating the activation of mRNA transcription and capping within the confines of the virus. DOI: http://dx.doi.org/10.7554/eLife.07901.001 PMID:26240998