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Sample records for 13-cis-retinoic acid ra

  1. Premature physeal closure following 13-cis-retinoic acid and prolonged fenretinide administration in neuroblastoma.

    PubMed

    Steineck, Angela; MacKenzie, John D; Twist, Clare J

    2016-11-01

    Retinoid therapy has contributed to improved outcomes in neuroblastoma. Clinical trials of fenretinide report favorable toxicity and disease stabilization in patients with high risk (HR) neuroblastoma. Skeletal effects have been described with other retinoids, but not with fenretinide to date. Two patients with HR, metastatic, refractory neuroblastoma received protracted courses of oral fenretinide for more than 5 years' duration. Both developed premature long bone physeal closure, causing limb length discrepancies; their neuroblastoma remains in remission. The radiographic and clinical findings reported suggest these skeletal abnormalities may be a consequence of treatment with 13-cis-retinoic acid (13cisRA) followed by prolonged oral fenretinide exposure.

  2. Metabolic characteristics of 13-cis-retinoic acid (isotretinoin) and anti-tumour activity of the 13-cis-retinoic acid metabolite 4-oxo-13-cis-retinoic acid in neuroblastoma

    PubMed Central

    Sonawane, Poonam; Cho, Hwang Eui; Tagde, Ashujit; Verlekar, Dattesh; Yu, Alice L; Reynolds, C Patrick; Kang, Min H

    2014-01-01

    Background and Purpose Isotretinoin (13-cis-retinoic acid; 13-cRA) is a differentiation inducer used to treat minimal residual disease after myeloablative therapy for high-risk neuroblastoma. However, more than 40% of children develop recurrent disease during or after 13-cRA treatment. The plasma concentrations of 13-cRA in earlier studies were considered subtherapeutic while 4-oxo-13-cis-RA (4-oxo-13-cRA), a metabolite of 13-cRA considered by some investigators as inactive, were greater than threefold higher than 13-cRA. We sought to define the metabolic pathways of 13-cRA and investigated the anti-tumour activity of its major metabolite, 4-oxo-13-cRA. Experimental Approach Effects of 13-cRA and 4-oxo-13-cRA on human neuroblastoma cell lines were assessed by DIMSCAN and flow cytometry for cell proliferation, MYCN down-regulation by reverse transcription PCR and immunoblotting, and neurite outgrowth by confocal microscopy. 13-cRA metabolism was determined using tandem MS in human liver microsomes and in patient samples. Key Results Six major metabolites of 13-cRA were identified in patient samples. Of these, 4-oxo-13-cRA was the most abundant, and 4-oxo-13-cRA glucuronide was also detected at a higher level in patients. CYP3A4 was shown to play a major role in catalysing 13-cRA to 4-oxo-13-cRA. In human neuroblastoma cell lines, 4-oxo-13-cRA and 13-cRA were equi-effective at inducing neurite outgrowth, inhibiting proliferation, decreasing MYCN mRNA and protein, and increasing the expression of retinoic acid receptor-β mRNA and protein levels. Conclusions and Implications We showed that 4-oxo-13-cRA is as active as 13-cRA against neuroblastoma cell lines. Plasma levels of both 13-cRA and 4-oxo-13-cRA should be evaluated in pharmacokinetic studies of isotretinoin in neuroblastoma. PMID:25039756

  3. Pharmacokinetics and effects on plasma retinol concentrations of 13-cis-retinoic acid in melanoma patients.

    PubMed Central

    Formelli, F.; Cavadini, E.; Mascheroni, L.; Belli, F.; Cascinelli, N.

    1997-01-01

    The pharmacokinetics of 13-cis-retinoic acid (13cisRA) and its effects on retinol plasma levels were investigated after the first and the last doses in melanoma patients, who participated in a study run to assess tolerance over a long period of a treatment schedule of 13cisRA associated with recombinant interferon alpha2a (rIFN-alpha2a). Melanoma patients with regional node metastases after radical surgery were randomized to be treated for 3 months with rIFN-alpha2a, 3 x 10(6) IU s.c. every other day, associated with oral 13cisRA at doses of 20 mg day(-1) (five patients) or 40 mg every other day (seven patients). Maximum 13cisRA blood concentrations usually occurred 4 h after drug administration, with average values of 406 and 633 ng ml(-1) (i.e. 1.3 and 2.1 microM) after the 20 and 40 mg dose respectively. The average half-life (t(1/2)) was approximately 30 h. The maximum concentration, the t(1/2) and the area under the concentration-time curves from 0 to 48 h (AUC(0-48)) of 13cisRA did not change after multiple dosing, whereas the AUC(0-48) of its major blood metabolite, 4-oxo-13-cis-retinoic acid, increased. Immediately after 13cisRA treatment, retinol plasma levels started to decline and they reached the lowest values (approximately 20% reduction) shortly after the time of maximum 13cisRA concentrations (i.e. 4-12 h after drug intake). Afterwards, values returned to baseline. The amount of retinol reduction in time was correlated with 13cisRA maximum concentrations. PMID:9413958

  4. Oral Accutane (13-cis-retinoic acid) has no effects on spatial learning and memory in male and female Sprague-Dawley rats.

    PubMed

    Ferguson, Sherry A; Berry, Kimberly J

    2007-01-01

    Descriptions of psychiatric effects with Accutane (13-cis-retinoic acid (13-cis-RA)) use prompted a series of studies in a rodent model to ascertain its cognitive effects. Previously, we reported no effects on measures of anhedonia and depression in rats treated with 7.5, 22.5, or 30 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459 [16]; S.A. Ferguson, F.J., Cisneros, J.P. Hanig, K.J. Berry, Chronic oral treatment with Accutane (13-cis-retinoic acid) does not increase measures of anhedonia or depression in male and female Sprague-Dawley rats, (in preparation) [19

  5. The Influence of 13-cis Retinoic Acid on Human Meibomian Gland Epithelial Cells

    PubMed Central

    Ding, Juan; Kam, Wendy R.; Dieckow, Julia; Sullivan, David A.

    2013-01-01

    Purpose. Meibomian gland dysfunction (MGD) is a primary cause of dry eye disease. One of the risk factors for MGD is exposure to 13-cis retinoic acid (13-cis RA), a metabolite of vitamin A. However, the mechanism is not well understood. We hypothesize that 13-cis RA inhibits cell proliferation, promotes cell death, alters gene and protein expressions, and attenuates cell survival pathways in human meibomian gland epithelial cells. Methods. To test our hypotheses, immortalized human meibomian gland epithelial cells were cultured with or without 13-cis RA for varying doses and time. Cell proliferation, cell death, gene expression, and proteins involved in proliferation/survival and inflammation were evaluated. Results. We found that 13-cis RA inhibited cell proliferation, induced cell death, and significantly altered the expression of 6726 genes, including those involved in cell proliferation, cell death, differentiation, keratinization, and inflammation, in human meibomian gland epithelial cells. Further, 13-cis RA also reduced the phosphorylation of Akt and increased the generation of interleukin-1β and matrix metallopeptidase 9. Conclusions. Exposure to 13-cis RA inhibits cell proliferation, increases cell death, alters gene expression, changes signaling pathways, and promotes inflammatory mediator and protease expression in meibomian gland epithelial cells. These effects may be responsible, at least in part, for the 13-cis RA–related induction of MGD. PMID:23722388

  6. [Folliculitis nuchae scleroticans--successful treatment with 13-cis-retinoic acid (isotretinoin)].

    PubMed

    Stieler, W; Senff, H; Jänner, M

    1988-11-01

    Acne keloidalis nuchae is characterized by keloidal papules and plaques. The lesions are located on the occipital scalp and posterior neck. This rare therapy-resistant condition is nearly always seen in men, particularly in negroes. Advanced stages of the disease require surgical excision with split-thickness skin grafts or treatment with a CO2 laser. Oral therapy with 13-cis-retinoic acid (isotretinoin) in a 23-year-old white man resulted in remarkable improvement within a few weeks.

  7. An enzymatic mechanism for generating the precursor of endogenous 13-cis retinoic acid in the brain.

    PubMed

    Takahashi, Yusuke; Moiseyev, Gennadiy; Chen, Ying; Farjo, Krysten; Nikolaeva, Olga; Ma, Jian-Xing

    2011-04-01

    13-cis Retinoic acid (13cRA), a stereoisomeric form of retinoic acid, is naturally generated in the body and is also used clinically to treat acute promyelocytic leukemia, some skin diseases and cancer. Furthermore, it has been suggested that 13cRA modulates brain neurochemical systems because increased 13cRA levels are correlated with depression and increased suicidal tendencies. However, the mechanism for the generation of endogenous 13cRA is not well understood. The present study identified and characterized a novel enzyme in zebrafish brain, 13-cis isomerohydrolase (13cIMH) (EC 5.2.1.7), which exclusively generated 13-cis retinol and can be oxidized to 13cRA. 13cIMH shares 74% amino acid sequence identity with human retinal pigment epithelium specific 65 kDa protein (RPE65), an 11-cis isomerohydrolase in the visual cycle, and retains the key residues essential for the isomerohydrolase activity of RPE65. Similar to RPE65, 13cIMH is a membrane-associated protein, requires all-trans retinyl ester as its intrinsic substrate, and its enzymatic activity is dependent on iron. The purified 13cIMH converted all-trans retinyl ester exclusively to 13-cis retinol with K(m)  = 2.6 μm and k(cat) = 4.4 × 10(-4) ·s(-1) . RT-PCR, western blot analysis and immunohistochemistry detected 13cIMH expression in the brain. These results suggest that 13cIMH may play a key role in the generation of 13cRA, as well as in the modulation of neuronal functions in the brain.

  8. Predicting, Monitoring, and Managing Hypercalcemia Secondary to 13-Cis-Retinoic Acid Therapy in Children With High-risk Neuroblastoma.

    PubMed

    Chen, Suet Ching; Murphy, Dermot; Sastry, Jairam; Shaikh, Mohamad G

    2015-08-01

    13-cis-retinoic acid is an established component of treatment for children with high-risk neuroblastoma. However, significant hypercalcemia is increasingly recognized as a potentially life-threatening dosage-related side effect. We present 2 patients with significant hypercalcemia secondary to 13-cis-retinoic acid and their management, and identified the predictive factors for susceptibility to hypercalcemia. Assessing glomerular filtration rate and concomitant medication help predict individual susceptibility to hypercalcemia. Calcium levels should be monitored at days 1, 7, and 14 of each course of retinoic acid. An algorithm for the management of hypercalcemia during the affected and subsequent cycles of retinoid therapy is proposed.

  9. Induction of reversible changes in cell-surface glycoconjugates and lung colonization potential by 13-cis retinoic acid.

    PubMed

    Couch, M J; Pauli, B U; Weinstein, R S; Coon, J S

    1988-06-01

    Murine squamous carcinoma cells (KLN205) grown in a medium supplemented with the retinoid, 13-cis retinoic acid (RA), had dose-dependent, selective increases in the expression of certain lectin receptors, which correlated with a dramatic decrease in the ability to form pulmonary colonies (P = .0003) (Couch MJ, Pauli BU, Weinstein RS, Coon JS: JNCI, 78:971-977, 1987). These findings suggest a possible relationship between the RA-induced glycoconjugate alterations and the decreased experimental metastatic behavior. We further define the mechanism of RA's action. The finding that RA treatment (5 X 10(-6) M, 5 X 10(-7) M) did not perturb the cell cycle of KLN205 cells provides further proof that the decreased metastatic behavior is not attributable to any inhibition in the rate of growth or to alterations in the cell cycle. Furthermore, since stable subpopulations with variable lectin binding could not be detected, the mechanism of RA's action does not appear to be due to selection of variant tumor-cell subpopulations. Finally, in a series of experiments designed to determine the reversibility of the RA treatment, the RA-induced decrease in metastatic behavior reverted back to a more metastatic state in the same time frame (3 days) as the reversion of the RA-induced changes in cell-surface glycoconjugate expression. This reversion provides further evidence for a close relationship between the RA-induced modulation of tumor cell-surface glycoconjugate expression and the decreased metastatic behavior; it suggests that transient, reversible modulation of the tumor cell surface may play a role in determining metastatic behavior.

  10. 13-cis-retinoic acid in silicone-fluorosilicone copolymer oil in a rabbit model of proliferative vitreoretinopathy.

    PubMed

    Veloso, A A; Kadrmas, E F; Larrosa, J M; Sandberg, M A; Tolentino, F I; Refojo, M F

    1997-09-01

    The purpose of this study was to evaluate the effect of 13-cis-Retinoic Acid (RA) in Silicone-Fluorosilicone Copolymer Oil (SiFO) in a rabbit model of proliferative vitreoretinopathy (PVR). Rabbits underwent gas-compression vitrectomy. During gas-SiFO exchange, group 1 was injected with 1 ml (10 microg ml-1) 13-cis-RA in SiFO, group 2 with 1.5 ml (9 microg 1.5 ml-1) all-trans-RA in SiFO, group 3 with 1 ml SiFO alone, and group 4 with balanced salt solution (BSS). Groups 1-4 were also injected with 0.1 ml suspension of fibroblasts (75,000 0.1 ml-1) and 0.05 ml platelet rich plasma (70,000 0.1 ml-1), and were observed for 4 weeks. Group 5 was injected with SiFO alone, group 6 with 1 ml (10 microg ml-1) 13-cis-RA in SiFO, group 7 with 1.5 ml (9 microg 1.5 ml-1) all-trans-RA in SiFO, and group 8 with BSS. After 4 weeks, groups 5-7 underwent SiFO-BSS exchange. ERG and histopathology were performed to test for retinal toxicity in groups 5-8. The incidence of traction retinal detachment at 4 weeks was: group 1, 42.9%; group 2, 36.4%; group 3, 87.5%; and group 4, 88.9%. A significant difference in the incidence of PVR was noted between treated eyes (groups 1 and 2) and control eyes (groups 3 and 4) at 2, 3, and 4 weeks (P<0.05). No significant difference in the incidence of PVR was found between groups 1 and 2 during the same observation periods. ERG and histopathological studies showed no differences between the treated and the control fellow eyes (group 5-7) after 4 weeks. 13-cis-RA in SiFO (10 microg ml-1) is as effective as all-trans-RA in SiFO (9 microg 1.5 ml-1) in controlling the incidence of PVR when used for short term retinal tamponade and does not appear to be associated with retinal toxicity.

  11. 13-cis-retinoic acid in silicone-fluorosilicone copolymer oil in a rabbit model of proliferative vitreoretinopathy.

    PubMed

    Veloso, A A; Kadrmas, E F; Larrosa, J M; Sandberg, M A; Tolentino, F I; Refojo, M F

    1997-09-01

    The purpose of this study was to evaluate the effect of 13-cis-Retinoic Acid (RA) in Silicone-Fluorosilicone Copolymer Oil (SiFO) in a rabbit model of proliferative vitreoretinopathy (PVR). Rabbits underwent gas-compression vitrectomy. During gas-SiFO exchange, group 1 was injected with 1 ml (10 microg ml-1) 13-cis-RA in SiFO, group 2 with 1.5 ml (9 microg 1.5 ml-1) all-trans-RA in SiFO, group 3 with 1 ml SiFO alone, and group 4 with balanced salt solution (BSS). Groups 1-4 were also injected with 0.1 ml suspension of fibroblasts (75,000 0.1 ml-1) and 0.05 ml platelet rich plasma (70,000 0.1 ml-1), and were observed for 4 weeks. Group 5 was injected with SiFO alone, group 6 with 1 ml (10 microg ml-1) 13-cis-RA in SiFO, group 7 with 1.5 ml (9 microg 1.5 ml-1) all-trans-RA in SiFO, and group 8 with BSS. After 4 weeks, groups 5-7 underwent SiFO-BSS exchange. ERG and histopathology were performed to test for retinal toxicity in groups 5-8. The incidence of traction retinal detachment at 4 weeks was: group 1, 42.9%; group 2, 36.4%; group 3, 87.5%; and group 4, 88.9%. A significant difference in the incidence of PVR was noted between treated eyes (groups 1 and 2) and control eyes (groups 3 and 4) at 2, 3, and 4 weeks (P<0.05). No significant difference in the incidence of PVR was found between groups 1 and 2 during the same observation periods. ERG and histopathological studies showed no differences between the treated and the control fellow eyes (group 5-7) after 4 weeks. 13-cis-RA in SiFO (10 microg ml-1) is as effective as all-trans-RA in SiFO (9 microg 1.5 ml-1) in controlling the incidence of PVR when used for short term retinal tamponade and does not appear to be associated with retinal toxicity. PMID:9299179

  12. Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats.

    PubMed

    Ferguson, Sherry A; Cisneros, F Javier; Gough, B; Hanig, Joseph P; Berry, Kimberly J

    2005-10-01

    Oral treatment with the anti-acne drug Accutane (isotretinoin, 13-cis-retinoic acid) has been associated with suicide ideation and depression. Here, depression-like behaviors (i.e., behavioral despair and anhedonia) were quantified in adult Sprague-Dawley rats gavaged daily beginning at postnatal day (PND) 82 with 13-cis-RA (7.5 or 22.5 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg ). Tested at PND 130-131 in the Forced Swim Test, 7.5 mg/kg 13-cis-RA marginally decreased immobility and slightly increased climb/struggle durations whereas neither all-trans-retinoic acid group differed from controls. Voluntary saccharin solution (0.03%) intake at PND 102-104 and PND 151-153 was not different from controls in any treated group, although all RA-treated groups had lower intakes. Swim speed in a water maze at PND 180 was similar across groups, indicating no RA-induced differences in physical ability. Open field activity was mildly decreased at PND 91 in 7.5 mg/kg-treated males only, but it was within the control range at PND 119, 147, and 175. Thus, at serum levels similar to those in humans receiving the drug, chronic 13-cis-RA treatment did not severely affect depression-like behaviors in rats. These data do not substantiate the hypothesis of 13-cis-RA-induced depression.

  13. Inhibition of 13-cis retinoic acid-induced gene expression of reactive-resistance genes by thalidomide in glioblastoma tumours in vivo.

    PubMed

    Milanovic, Dusan; Sticht, Carsten; Röhrich, Manuel; Maier, Patrick; Grosu, Anca-L; Herskind, Carsten

    2015-10-01

    The cell differentiation potential of 13-cis retinoic acid (RA) has not succeeded in the clinical treatment of glioblastoma (GBM) so far. However, RA may also induce the expression of resistance genes such as HOXB7 which can be suppressed by Thalidomide (THAL). Therefore, we tested if combined treatment with RA+THAL may inhibit growth of glioblastoma in vivo. Treatment with RA+THAL but not RA or THAL alone significantly inhibited tumour growth. The synergistic effect of RA and THAL was corroborated by the effect on proliferation of glioblastoma cell lines in vitro. HOXB7 was not upregulated but microarray analysis validated by real-time PCR identified four potential resistance genes (IL-8, HILDPA, IGFBPA, and ANGPTL4) whose upregulation by RA was suppressed by THAL. Furthermore, genes coding for small nucleolar RNAs (snoRNA) were identified as a target for RA for the first time, and their upregulation was maintained after combined treatment. Pathway analysis showed upregulation of the Ribosome pathway and downregulation of pathways associated with proliferation and inflammation. In conclusion, combined treatment with RA + THAL delayed growth of GBM xenografts and suppressed putative resistance genes associated with hypoxia and angiogenesis. This encourages further pre-clinical and clinical studies of this drug combination in GBM.

  14. Treatment of recurrent malignant gliomas with 13-cis-retinoic acid naphthalene triazole.

    PubMed

    Jia, Pi-Feng; Gu, Wei-Ting; Zhang, Wei-Feng; Li, Feng

    2015-05-01

    Glioblastoma multiforme and anaplastic astrocytoma are challenges to clinical biologists at present. The patients with glioblastoma have median survival of less than 12 months, despite advances in radiotherapeutical, chemotherapeutical and conventional surgical modalities. Retinoic acids are known to effect in vitro proliferation, differentiation, and apoptosis in colon, prostate, lung, and leukemia cancers. Retinoids are known to have anti-proliferation, anti-migration, and anti-invasive activity against human malignant gliomas, suggesting that retinoids are suitable anticancer agents to inhibit progression of tumors. Recurrent malignant cerebral gliomas have been treated with ATRA and 13-cis RA. However, the side effects associated with the use of high doses of retinoic acid demand for some more potent derivative free from such effects. The present clinical trials are undertaken to investigate the clinical safety and possible efficacy of administering retinoic acid naphthalene triazole (RANT) to patients with recurrent malignant gliomas. The toxicities observed in the patients during RANT treatment were mild. These preliminary results suggest that RANT is more potent compared to RA against recurrent malignant gliomas.

  15. Combination of 13 cis-retinoic acid and tolfenamic acid induces apoptosis and effectively inhibits high-risk neuroblastoma cell proliferation.

    PubMed

    Shelake, Sagar; Eslin, Don; Sutphin, Robert M; Sankpal, Umesh T; Wadwani, Anmol; Kenyon, Laura E; Tabor-Simecka, Leslie; Bowman, W Paul; Vishwanatha, Jamboor K; Basha, Riyaz

    2015-11-01

    Chemotherapeutic regimens used for the treatment of Neuroblastoma (NB) cause long-term side effects in pediatric patients. NB arises in immature sympathetic nerve cells and primarily affects infants and children. A high rate of relapse in high-risk neuroblastoma (HRNB) necessitates the development of alternative strategies for effective treatment. This study investigated the efficacy of a small molecule, tolfenamic acid (TA), for enhancing the anti-proliferative effect of 13 cis-retinoic acid (RA) in HRNB cell lines. LA1-55n and SH-SY5Y cells were treated with TA (30μM) or RA (20μM) or both (optimized doses, derived from dose curves) for 48h and tested the effect on cell viability, apoptosis and selected molecular markers (Sp1, survivin, AKT and ERK1/2). Cell viability and caspase activity were measured using the CellTiter-Glo and Caspase-Glo kits. The apoptotic cell population was determined by flow cytometry with Annexin-V staining. The expression of Sp1, survivin, AKT, ERK1/2 and c-PARP was evaluated by Western blots. The combination therapy of TA and RA resulted in significant inhibition of cell viability (p<0.0001) when compared to individual agents. The anti-proliferative effect is accompanied by a decrease in Sp1 and survivin expression and an increase in apoptotic markers, Annexin-V positive cells, caspase 3/7 activity and c-PARP levels. Notably, TA+RA combination also caused down regulation of AKT and ERK1/2 suggesting a distinct impact on survival and proliferation pathways via signaling cascades. This study demonstrates that the TA mediated inhibition of Sp1 in combination with RA provides a novel therapeutic strategy for the effective treatment of HRNB in children.

  16. Inhibition of the visual cycle in vivo by 13-cis retinoic acid protects from light damage and provides a mechanism for night blindness in isotretinoin therapy.

    PubMed

    Sieving, P A; Chaudhry, P; Kondo, M; Provenzano, M; Wu, D; Carlson, T J; Bush, R A; Thompson, D A

    2001-02-13

    Isotretinoin (13-cis retinoic acid) is frequently prescribed for severe acne [Peck, G. L., Olsen, T. G., Yoder, F. W., Strauss, J. S., Downing, D. T., Pandya, M., Butkus, D. & Arnaud-Battandier, J. (1979) N. Engl. J. Med. 300, 329-333] but can impair night vision [Fraunfelder, F. T., LaBraico, J. M. & Meyer, S. M. (1985) Am. J. Ophthalmol. 100, 534-537] shortly after the beginning of therapy [Shulman, S. R. (1989) Am. J. Public Health 79, 1565-1568]. As rod photoreceptors are responsible for night vision, we administered isotretinoin to rats to learn whether night blindness resulted from rod cell death or from rod functional impairment. High-dose isotretinoin was given daily for 2 months and produced systemic toxicity, but this caused no histological loss of rod photoreceptors, and rod-driven electroretinogram amplitudes were normal after prolonged dark adaptation. Additional studies showed, however, that even a single dose of isotretinoin slowed the recovery of rod signaling after exposure to an intense bleaching light, and that rhodopsin regeneration was markedly slowed. When only a single dose was given, rod function recovered to normal within several days. Rods and cones both showed slow recovery from bleach after isotretinoin in rats and in mice. HPLC analysis of ocular retinoids after isotretinoin and an intense bleach showed decreased levels of rhodopsin chromophore, 11-cis retinal, and the accumulation of the biosynthetic intermediates, 11-cis and all-trans retinyl esters. Isotretinoin was also found to protect rat photoreceptors from light-induced damage, suggesting that strategies of altering retinoid cycling may have therapeutic implications for some forms of retinal and macular degeneration. PMID:11172037

  17. Adaptive dosing approaches to the individualization of 13-cis-retinoic acid (isotretinoin) treatment for children with high-risk neuroblastoma

    PubMed Central

    Veal, Gareth J.; Errington, Julie; Rowbotham, Sophie E.; Illingworth, Nicola A.; Malik, Ghada; Cole, Michael; Daly, Ann K.; Pearson, Andrew D.J.; Boddy, Alan V.

    2012-01-01

    Purpose To investigate the feasibility of adaptive dosing and the impact of pharmacogenetic variation on 13-cisRA disposition in high-risk neuroblastoma patients. Experimental Design 13cisRA (160mg/m2 or 5.33mg/kg/day) was administered to 103 patients ≤21 years and plasma concentrations of 13-cisRA and 4-oxo-13-cisRA quantitated on day 14 of treatment. 71 patients were recruited to a dose adjustment group, targeting a 13-cisRA Cmax of 2μM, with dose increases of 25-50% implemented for patients with Cmax values <2μM. A population pharmacokinetic model was applied and polymorphisms in relevant cytochrome P450 genes analyzed. Results 13-cisRA Cmax values ranged from 0.42–11.2μM, with 34/103 (33%) patients failing to achieve a Cmax >2μM. Dose increases carried out in 20 patients in the dose adjustment study group led to concentrations >2μM in 18 patients (90%). 8/11 (73%) patients <12kg, receiving a dose of 5.33mg/kg, failed to achieve a Cmax ≥2μM. Significantly lower Cmax values were observed for patients treated with 5.33mg/kg versus 160mg/m2 (1.9±1.2 versus 3.1±2.0μM; mean±SD; P=0.023). Cmax was higher in patients who swallowed 13-cisRA capsules as compared to receiving the drug extracted from capsules (4.0±2.2 versus 2.6±1.8μM; P=0.0012). The target Cmax was achieved by 93% (25/27) versus 55% (42/76) of patients in these two groups respectively. No clear relationships were found between genetic variants and 13-cisRA pharmacokinetic parameters. Conclusions Dosing regimen and method of administration have a marked influence on 13-cisRA plasma concentrations. Body weight-based dosing should not be implemented for children <12kg and pharmacological data support higher doses for children unable to swallow 13-cisRA capsules. PMID:23087409

  18. Osteotoxicity after chronic dietary administration of 13-CIS-retinoic acid, retinyl palmitate or selenium in mice exposed to tumor initiation and promotion

    SciTech Connect

    Forsyth, K.S.; Gensler, H.L.; Watson, R.R. )

    1989-01-01

    In view of the clinical trials of retinoids as therapeutic agents for premalignant skin lesions, a radiographic study was undertaken to measure skeletal toxicities after chronic dietary administration of retinoids in mice exposed to tumor initiation and promotion. CD-1 mice were initiated with 0.15 moles of 7,12-dimethylbenz(a)anthracene and promoted twice daily with 8 nmoles of 12-O-tetradecanoylphorbol-13-acetate for 23 weeks. Diets were supplemented with 60 IU, 200 IU, or 700 IU or retinyl palmitate (RP) per g diet. After 5 weeks, the 700 IU of RP/g diet was lowered to 350 IU/g diet. Administration of these diets to mice during the 23 weeks of tumor promotion results in a 0-fold, 2-fold, or 10-fold increase in bone fractures, respectively. Osteoporotic bone lesions identified on radiographs rose 0-fold, 0-fold, and 10-fold at the respective doses, whereas metaphyseal flares increased O-fold, 1.4-fold, and 3.6-fold. Bone deformities was augmented O-fold, 1.8-fold and 2.9-fold at the respective doses. Addition of selenium did not alter the bone toxicity of RP. 13-cis-retionic acid (CRA) was less toxic at 700 IU/g diet than was RP at that dose, as evidence by the death of 12 of 70 mice by the 6th week of dietary RP and no deaths in the 35 mice fed 700 IU CRA/g diet for 23 weeks. CRA at 700 IU/g diet resulted in 3/4 as many osteoporotic bones, 1/3 as many bone fractures, 4/5 as many metaphyseal flares, and a similar number of bone deformities as mice fed 700/350 IU/g diet. At the dose of 200 IU/g food, osterotoxicities were similar in the mice fed diets supplemented with RP and CRA.

  19. Murine Anti-GD2 Monoclonal Antibody 3F8 Combined With Granulocyte-Macrophage Colony-Stimulating Factor and 13-Cis-Retinoic Acid in High-Risk Patients With Stage 4 Neuroblastoma in First Remission

    PubMed Central

    Cheung, Nai-Kong V.; Cheung, Irene Y.; Kushner, Brian H.; Ostrovnaya, Irina; Chamberlain, Elizabeth; Kramer, Kim; Modak, Shakeel

    2012-01-01

    Purpose Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored. Patients and Methods One hundred sixty-nine children diagnosed with stage 4 NB (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 ± GM-CSF ± 13-cis-retinoic acid (CRA) protocols after achieving first remission (complete remission/very good partial remission). Patients enrolled in regimen A (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT); and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT, whereas 28 of 85 required additional induction therapy and were deemed ultra high risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative reverse transcription polymerase chain reaction. Survival probability was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by multivariate Cox regression model. Results At 5 years from the start of immunotherapy, progression-free survival (PFS) improved from 44% for HR patients receiving regimen A to 56% and 62% for those receiving regimens B and C, respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated sites. Independent adverse prognostic factors included UHR (PFS) and post–cycle two MRD (PFS and OS), whereas the prognostic factors for improved outcome were missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse antibody response (OS), and regimen C (OS). Conclusion Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only

  20. Retinoic acid inhibits migration of cranial neural crest cells in the cultured mouse embryo.

    PubMed

    Pratt, R M; Goulding, E H; Abbott, B D

    1987-01-01

    Clinical observations have demonstrated that isotretinoin (13-cis-retinoic acid; cis-RA) is a human teratogen causing primarily heart and craniofacial malformations. Isotretinoin exposure to the early postimplantation mouse embryo in culture results in specific defects in craniofacial development that may be due to an interference in the early migration of cranial neural crest (CNC) cells [Goulding and Pratt, 1986]. The present study was designed to test this hypothesis by examining the migration of these cells in whole embryo culture. Day 8 CD-1 mouse embryos were cultured for 6-48 hr in the presence or absence of cis-RA at 2 X 10(-6) to 2 X 10(-5) M. Embryos either were fixed for light microscopy using Nichols' method for localization of CNC cells or were processed for scanning and transmission electron microscopy. At the light microscopic level, CNC cells in the mid-brain region of control embryos had migrated to the region of the first and second visceral arches after 6 hr in culture. Cis-RA interfered with this migration; CNC cells in treated embryos either did not leave the neuroepithelium (NE) or were aggregated near the NE. Autoradiographic studies indicated that cis-RA did not affect the overall viability or DNA synthesis of the CNC cells. However, at the TEM level, there was a dramatic increase in the number of cellular blebs in the CNC cells. Our results demonstrate a direct effect of 13-cis-RA on the CNC cells and suggest that this effect is due to alterations in the cell surface.

  1. Rapid determination of retinoic acid and its main isomers in plasma by second-order high-performance liquid chromatography data modeling.

    PubMed

    Teglia, Carla M; Cámara, María S; Goicoechea, Héctor C

    2014-12-01

    This paper reports the development of a method based on high-performance liquid chromatography (HPLC) coupled to second-order data modeling with multivariate curve resolution-alternating least-squares (MCR-ALS) for quantification of retinoic acid and its main isomers in plasma in only 5.5 min. The compounds retinoic acid (RA), 13-cis-retinoic acid, 9-cis-retinoic acid, and 9,13-di-cis-retinoic acid were partially separated by use of a Poroshell 120 EC-C18 (3.0 mm × 30 mm, 2.7 μm particle size) column. Overlapping not only among the target analytes but also with the plasma interferents was resolved by exploiting the second-order advantage of the multi-way calibration. A validation study led to the following results: trueness with recoveries of 98.5-105.9 % for RA, 95.7-110.1 % for 13-cis-RA, 97.1-110.8 % for 9-cis-RA, and 99.5-110.9 % for 9,13-di-cis-RA; repeatability with RSD of 3.5-3.1 % for RA, 3.5-1.5 % for 13-cis-RA, 4.6-2.7 % for 9-cis-RA, and 5.2-2.7 % for 9,13-di-cis-RA (low and high levels); and intermediate precision (inter-day precision) with RSD of 3.8-3.0 % for RA, 2.9-2.4 % for 13-cis-RA, 3.6-3.2 % for 9,13-di-cis-RA, and 3.2-2.9 % for 9-cis-RA (low and high levels). In addition, a robustness study revealed the method was suitable for monitoring patients with dermatological diseases treated with pharmaceutical products containing RA and 13-cis-RA.

  2. The Role of Retinoic Acid (RA) in Spermatogonial Differentiation.

    PubMed

    Busada, Jonathan T; Geyer, Christopher B

    2016-01-01

    Retinoic acid (RA) directs the sequential, but distinct, programs of spermatogonial differentiation and meiotic differentiation that are both essential for the generation of functional spermatozoa. These processes are functionally and temporally decoupled, as they occur in distinct cell types that arise over a week apart, both in the neonatal and adult testis. However, our understanding is limited in terms of what cellular and molecular changes occur downstream of RA exposure that prepare differentiating spermatogonia for meiotic initiation. In this review, we describe the process of spermatogonial differentiation and summarize the current state of knowledge regarding RA signaling in spermatogonia. PMID:26559678

  3. Retinoic acid isomers up-regulate ATP binding cassette A1 and G1 and cholesterol efflux in rat astrocytes: implications for their therapeutic and teratogenic effects.

    PubMed

    Chen, Jing; Costa, Lucio G; Guizzetti, Marina

    2011-09-01

    Recent studies suggest that retinoids may be effective in the treatment of Alzheimer's disease, although exposure to an excess of retinoids during gestation causes teratogenesis. Cholesterol is essential for brain development, but high levels of cholesterol have been associated with Alzheimer's disease. We hypothesized that retinoic acid may affect cholesterol homeostasis in rat astrocytes, which regulate cholesterol distribution in the brain, through the up-regulation of cholesterol transporters ATP binding cassette (Abc)a1 and Abcg1. Tretinoin, 13-cis retinoic acid (13-cis-RA), 9-cis-RA, and the selective retinoid X receptor (RXR) agonist methoprene significantly increased cholesterol efflux induced by cholesterol acceptors and protein levels of Abca1 by 2.3- (± 0.25), 3.6- (± 0.42), 4.1- (± 0.5), and 1.75- (± 0.43) fold, respectively, and Abcg1 by 2.1- (± 0.26), 2.2- (± 0.33), 2.5- (± 0.23), and 2.2- (± 0.21) fold, respectively. 13-cis-RA and 9-cis-RA also significantly increased mRNA levels of Abca1 (maximal induction 7.3 ± 0.42 and 2.7 ± 0.17, respectively) and Abcg1 (maximal induction 2.0 ± 0.18 and 1.8 ± 0.09, respectively), and the levels of membrane-bound Abca1 (2.5 ± 0.3 and 2.5 ± 0.40-fold increase, respectively), whereas they significantly decreased intracellular cholesterol content without affecting cholesterol synthesis. The effect of 9-cis-RA on cholesterol homeostasis in astrocytes can be ascribed to the activation of RXR, whereas the effects of 13-cis-RA and tretinoin were independent of either RXRs or retinoic acid receptors. These findings suggest that retinoids affect cholesterol homeostasis in astrocytes and that this effect may be involved in both their therapeutic and teratogenic actions.

  4. Specificity in the synergism between retinoic acid and EGF on the growth of adult human skin fibroblasts

    SciTech Connect

    Harper, R.A. )

    1988-10-01

    Vitamin A (retinol) and five retinoids were tested for their ability to enhance epidermal growth factor (EGF) stimulation of adult human skin fibroblast growth in vitro. The retinoids utilized in this study were RO-1-5488 (all-trans-retinoic acid), RO-4-3780 (13-cis-retinoic acid), RO-10-9359, RO-10-1670, and RO-21-6583. Retinol and each retinoid were capable of stimulating fibroblast growth alone (0-86%), while 13-cis and all-trans-retinoic acid were the most potent in potentiating the EGF promotion of fibroblast growth. Since retinoic acid might enhance the EGF stimulation of cell growth by increasing either EGF receptor number or binding affinity, the binding of {sup 125}I-labeled EGF was carried out in the presence of retinoic acid and the data were subjected to a Scatchard-type analysis. No change in EGF receptor number or affinity was seen in the presence of retinoic acid. The data indicate a specific interaction between retinoid acid and EGF which results in the potentiation of the EGF-stimulated cell growth. Furthermore, the mechanism of this interaction does not seem to involve the initial binding of EGF to its plasma membrane receptor or the available number of EGF receptors located on the cell surface.

  5. Sulfuric acid vapor in the atmosphere of Venus as observed by the Venus Express Radio Science experiment VeRa

    NASA Astrophysics Data System (ADS)

    Oschlisniok, Janusz; Pätzold, Martin; Häusler, Bernd; Tellmann, Silvia; Bird, Mike; Andert, Tom

    2016-04-01

    The cloud deck within Venus' atmosphere, which covers the entire planet between approx. 50 and 70 km altitude, consists mostly of liquid and gaseous sulfuric acid. The gaseous part increases strongly just below the main clouds and builds an approx. 15 km thick haze layer of H2SO4. This region is responsible for a strong absorption of radio waves as seen in VeRa radio science observations. The amount of the absorption, which is used to derive the abundance of gaseous sulfuric acid, depends on the signal frequency. VeRa probed the atmosphere of Venus between 2006 and 2015 with radio signals at 13 cm (S-band) and 3.6 cm (X-band) wavelengths. We present H2SO4 profiles derived from S-band and X-band absorption during the first occultation season in 2006. The comparison of the H2SO4 profiles derived from both frequency bands provides a reliable picture of the H2SO4 abundance. Distinct differences in the S- and X-band profiles may give a clue to increased SO2 abundances. The derived VeRa results shall be compared with results provided by other experiments onboard Venus Express as well as with previous missions.

  6. Molecular Pathways: Current Role and Future Directions of the Retinoic Acid Pathway In Cancer Prevention and Treatment

    PubMed Central

    Connolly, Roisin M.; Nguyen, Nguyen K.; Sukumar, Saraswati

    2013-01-01

    Retinoids and their naturally metabolized and synthetic products (e.g. all-trans retinoic acid, 13-cis retinoic acid, bexarotene) induce differentiation in various cell types. Retinoids exert their actions mainly through binding to the nuclear retinoic acid receptors (α, β, γ), which are transcriptional and homeostatic regulators whose functions are often compromised early in neoplastic transformation. The retinoids have been investigated extensively for their utility in cancer prevention and treatment. Success has been achieved with their use in the treatment of subtypes of leukemia harboring chromosomal translocations. Promising results have been observed in the breast cancer prevention setting, where fenretinide prevention trials have provided a strong rationale for further investigation in young women at high-risk for breast cancer. Ongoing phase 3 randomized trials investigating retinoids in combination with chemotherapy in non-small cell lung cancer aim to definitively characterize the role of retinoids in this tumor type. The limited treatment success observed to date in the prevention and treatment of solid tumors may relate to the frequent epigenetic silencing of RARβ. Robust evaluation of RARβ and downstream genes may permit optimized use of retinoids in the solid tumor arena. PMID:23322901

  7. Oral treatment with ACCUTANE does not increase measures of anhedonia or depression in rats.

    PubMed

    Ferguson, Sherry A; Cisneros, F Javier; Hanig, Joseph P; Berry, Kimberly J

    2007-01-01

    Reports of depression and/or suicide with ACCUTANE (13-cis-retinoic acid (13-cis-RA)) use prompted studies in a rodent model to ascertain its potential effects. Previously, there were no effects on measures of anhedonia (intake of a saccharin-flavored solution) and depression (forced swim test (FST) behaviors) in rats treated with 7.5 or 22.5 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459.]. Here, dose and temporal thresholds were investigated by increasing the maximum 13-cis-RA dose to 30 mg/kg, extending treatment duration, and measuring behaviors repeatedly. Beginning on post-natal day 59, male and female Sprague-Dawley rats were gavaged with soybean oil, 7.5 or 30 mg/kg/day of 13-cis-RA for approximately 19 weeks. FST behaviors were measured after 24, 82, and 131 treatment days and saccharin intake (0.03% solution) was measured at baseline and after 14, 35, 56, and 112 treatment days. Body weight and food intake were not altered by treatment. FST durations of swim, climb/struggle, and immobility were unaffected by 13-cis-RA at any time during treatment. More males than females required "rescue" in the FST but there was no treatment effect on number of rats requiring early removal. 13-cis-RA treatment had no effects on saccharin intake at any time. Given that the 7.5 mg/kg dose produces serum levels which parallel those of humans [S.A. Ferguson, P.H. Siitonen, F.J. Cisneros, B. Gough, J.F. Young, Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats, Basic Clin. Pharmacol. Toxicol 98 (2006) 582-587.], these results are quite relevant. Combined with previous results, these results provide further evidence that 13-cis-RA does not produce behavioral alterations indicative of depression

  8. Synthesis and characterization of a new retinoic acid ECPIRM as potential chemotherapeutic agent for human cutaneous squamous carcinoma.

    PubMed

    Zhang, Mengli; Tao, Yue; Ma, Pengcheng; Wang, Dechuan; He, Chundi; Cao, Yuping; Wei, Jun; Li, Lingjun; Tao, Lei

    2015-01-01

    Cutaneous squamous cell carcinoma (CSCC) is one of the most common cancers worldwide, requiring effective therapeutic interventions. Retinoids are important chemopreventive and therapeutic agents for a variety of human cancers including CSCC. In this study we synthesized a novel retinoic derivative N-(4-ethoxycarbonylphenyl) isoretinamide (ECPIRM) and evaluated its biological activities and possible mechanisms in human cutaneous squamous cell lines. ECPIRM had better inhibitory effect on the proliferation of squamous carcinoma cells SCL-1 and colo-16, compared with All-trans retinoic acid and 13-cis retinoic acid. ECPIRM had less toxicity to normal keratinocyte cell line HaCaT. Mechanistically, ECPIRM induced G1 cell cycle arrest in SCL-1 cells, via the downregulation of CDK2, CDK4, cycling D1 and cyclin E expression and upregulation of p21. In addition, these effects were at least partially due to the inhibition of JNK/ ERK-AP-1 signaling pathway by ECPIRM. Importantly, these effects of ECPIRM are independent of the classical retinoid receptor pathway, suggesting that the novel compound will have less side-effects in chemotherapy. These findings demonstrate that ECPIRM is a potential inhibitor of MPAK-AP-1 pathway, and is a potential therapeutic agent against CSCC.

  9. Synthesis and characterization of a new retinoic acid ECPIRM as potential chemotherapeutic agent for human cutaneous squamous carcinoma.

    PubMed

    Zhang, Mengli; Tao, Yue; Ma, Pengcheng; Wang, Dechuan; He, Chundi; Cao, Yuping; Wei, Jun; Li, Lingjun; Tao, Lei

    2015-01-01

    Cutaneous squamous cell carcinoma (CSCC) is one of the most common cancers worldwide, requiring effective therapeutic interventions. Retinoids are important chemopreventive and therapeutic agents for a variety of human cancers including CSCC. In this study we synthesized a novel retinoic derivative N-(4-ethoxycarbonylphenyl) isoretinamide (ECPIRM) and evaluated its biological activities and possible mechanisms in human cutaneous squamous cell lines. ECPIRM had better inhibitory effect on the proliferation of squamous carcinoma cells SCL-1 and colo-16, compared with All-trans retinoic acid and 13-cis retinoic acid. ECPIRM had less toxicity to normal keratinocyte cell line HaCaT. Mechanistically, ECPIRM induced G1 cell cycle arrest in SCL-1 cells, via the downregulation of CDK2, CDK4, cycling D1 and cyclin E expression and upregulation of p21. In addition, these effects were at least partially due to the inhibition of JNK/ ERK-AP-1 signaling pathway by ECPIRM. Importantly, these effects of ECPIRM are independent of the classical retinoid receptor pathway, suggesting that the novel compound will have less side-effects in chemotherapy. These findings demonstrate that ECPIRM is a potential inhibitor of MPAK-AP-1 pathway, and is a potential therapeutic agent against CSCC. PMID:25991427

  10. 40 CFR 721.6120 - Phosphoric acid, 1,2-eth-a-ne-diyl tet-ra-kis(2-chloro-1-meth-yl-ethyl) ester.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphoric acid, 1,2-eth-a-ne-diyl tet-ra-kis(2-chloro-1-meth-yl-ethyl) ester. 721.6120 Section 721.6120 Protection of Environment...-diyl tet-ra-kis(2-chloro-1-meth-yl-ethyl) ester. (a) Chemical substances and significant new...

  11. 40 CFR 721.6120 - Phosphoric acid, 1,2-eth-a-ne-diyl tet-ra-kis(2-chloro-1-meth-yl-ethyl) ester.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphoric acid, 1,2-eth-a-ne-diyl tet-ra-kis(2-chloro-1-meth-yl-ethyl) ester. 721.6120 Section 721.6120 Protection of Environment...-diyl tet-ra-kis(2-chloro-1-meth-yl-ethyl) ester. (a) Chemical substances and significant new...

  12. The Neurobiology of Retinoic Acid in Affective Disorders

    PubMed Central

    Bremner, J Douglas; McCaffery, Peter

    2009-01-01

    Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from Vitamin A that perform a large number of functions, many via the vitamin A product, retinoic acid. This signaling molecule binds to specific retinoic acid receptors in the brain which, like the glucocorticoid and thyroid hormone receptors, are part of the nuclear receptor superfamily and regulate gene transcription. Research in the field of retinoic acid in the CNS has focused on the developing brain, in part stimulated by the observation that isotretinoin (13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne, is highly teratogenic for the CNS. More recent work has suggested that retinoic acid may influence the adult brain; animal studies indicated that the administration of isotretinoin is associated with alterations in behavior as well as inhibition of neurogenesis in the hippocampus. Clinical evidence for an association between retinoids and depression includes case reports in the literature, studies of health care databases, and other sources. A preliminary PET study in human subjects showed that isotretinoin was associated with a decrease in orbitofrontal metabolism. Several studies have shown that the molecular components required for retinoic acid signaling are expressed in the adult brain ; the overlap of brain areas implicated in retinoic acid function and stress and depression suggest that retinoids could play a role in affective disorders. This report reviews the evidence in this area and describes several systems that may be targets of retinoic acid and which contribute

  13. All-trans retinoic acid (RA) stimulates events in organ-cultured human skin that underlie repair. Adult skin from sun-protected and sun-exposed sites responds in an identical manner to RA while neonatal foreskin responds differently.

    PubMed Central

    Varani, J; Perone, P; Griffiths, C E; Inman, D R; Fligiel, S E; Voorhees, J J

    1994-01-01

    Adult human skin from a sun-protected site (hip) and from a sun-exposed site (forearm) was maintained in organ culture for 12 d in the presence of a serum-free, growth factor-free basal medium. Cultures were incubated under conditions optimized for keratinocyte growth (i.e., in 0.15 mM extracellular Ca2+) or for fibroblast growth (i.e., in 1.4 mM extracellular Ca2+). Treatment with all-trans retinoic acid (RA) induced histological changes in the organ-cultured skin under both conditions which were similar to the changes seen in intact skin after topical application. These included expansion of the viable portion of the epidermis and activation of cells in the dermis. In sun-damaged skin samples, which were characterized by destruction of normal connective tissue elements and presence of thick, dark-staining elastotic fibers, a zone of healthy connective tissue could be seen immediately below the dermo-epidermal junction. This zone was more prominent in RA-treated organ cultures than in matched controls. Associated with these histological changes was an increase in overall protein and extracellular matrix synthesis. In concomitant studies, it was found that RA treatment enhanced survival and proliferation of adult keratinocytes and adult dermal fibroblasts under both low- and high-Ca2+ conditions. In all of these assays, responses of sun-protected and sun-exposed skin were identical. In contrast, responses of neonatal foreskin to RA were similar to those of adult skin in the presence of low-Ca2+ culture medium, but under conditions of high extracellular Ca2+ RA provided little or no additional stimulus. Together these studies suggest that the ability of RA to enhance repair of sun-damaged skin (documented in previous studies) may reflect its ability to influence the behavior of skin in a manner that is age dependent but independent of sun-exposure status. Images PMID:7962521

  14. The all-trans retinoic acid (atRA)-regulated gene Calmin (Clmn) regulates cell cycle exit and neurite outgrowth in murine neuroblastoma (Neuro2a) cells

    SciTech Connect

    Marzinke, Mark A.; Clagett-Dame, Margaret

    2012-01-01

    The vitamin A metabolite all-trans retinoic acid (atRA) functions in nervous system development and regulates cell proliferation and differentiation. Neuroblastoma cells (SH-SY5Y and Neuro2a or N2A) exposed to atRA undergo growth inhibition and neuronal differentiation, both of which are preceded by an increase in Clmn mRNA. Treatment of N2A cells with atRA produces a reduction in phosphohistone 3 immunostaining and BrdU incorporation, both indicators of a reduction in cell proliferation. These effects are nearly eliminated in atRA-treated shClmn knockdown cells. Loss of Clmn in the mouse N2A cell line also results in a significant reduction of atRA-mediated neurite outgrowth, a response that can be rescued by reintroduction of the Clmn sequence. In contrast, ectopic overexpression of Clmn produces an increase in the cyclin dependent kinase inhibitor, p21{sup Cip1}, a decrease in cyclin D1 protein and an increase in hypophosphorylated Rb, showing that Clmn participates in G{sub 1}/S arrest. Clmn overexpression alone is sufficient to inhibit N2A cell proliferation, whereas both Clmn and atRA must be present to induce neurite outgrowth. This study shows that the atRA-responsive gene Clmn promotes exit from the cell cycle, a requisite event for neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer Calmin is a retinoic acid-responsive gene. Black-Right-Pointing-Pointer Calmin promotes cell cycle exit in N2A cells. Black-Right-Pointing-Pointer Calmin overexpression increases p21Cip1 and decreases cyclin D1. Black-Right-Pointing-Pointer Calmin is required for RA-induced growth inhibition and neurite outgrowth.

  15. Okadaic acid: An additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter

    SciTech Connect

    Suganuma, Masami; Fujiki, Hirota; Suguri, Hiroko; Yoshizawa, Shigeru; Hirota, Mitsuru; Nakayasu, Michie ); Ojika, Makoto; Wakamatsu, Kazumasa; Yamada, Kiyoyuki ); Sugimura, Takashi )

    1988-03-01

    Okadaic acid is a polyether compound of a C{sub 38} fatty acid, isolated from a black sponge, Halichondria okadai. Previous studies showed that okadaic acid is a skin irritant and induces ornithine decarboxylase in mouse skin 4 hr after its application to the skin. This induction was strongly inhibited by pretreatment of the skin with 13-cis-retinoic acid. A two-stage carcinogenesis experiment in mouse skin initiated by a single application of 100 {mu}g of 7,12-dimethylbenz(a)anthracene (DMBA) and followed by application of 10 {mu}g of okadaic acid twice a week revealed that okadaic acid is a potent additional tumor promoter: tumors developed in 93% of the mice treated with DMBA and okadaic acid by week 16. In contrast, tumors were found in only one mouse each in the groups treated with DMBA alone or okadaic acid alone. An average of 2.6 tumors per mouse was found in week 30 in the group treated with DMBA and okadaic acid. Unlike phorbol 12-tetradecanoate 13-acetate (TPA), teleocidin, and aplysiatoxin, okadaic acid did not inhibit the specific binding of ({sup 3}H)TPA to a mouse skin particulate fraction when added up to 100 {mu}M or activate calcium-activated, phospholipid-dependent protein kinase (protein kinase C) in vitro when added up to 1.2 {mu}M. Therefore, the actions of okadaic acid and phorbol ester may be mediated in different ways. These results show that okadaic acid is a non-TPA-type tumor promoter in mouse skin carcinogenesis.

  16. IL-1ra delivered from poly(lactic-co-glycolic acid) microspheres attenuates IL-1β-mediated degradation of nucleus pulposus in vitro

    PubMed Central

    2012-01-01

    Introduction Inflammation plays a key role in the progression of intervertebral disc degeneration, a condition strongly implicated as a cause of lower back pain. The objective of this study was to investigate the therapeutic potential of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with interleukin-1 receptor antagonist (IL-1ra) for sustained attenuation of interleukin-1 beta (IL-1β) mediated degradative changes in the nucleus pulposus (NP), using an in vitro model. Methods IL-1ra was encapsulated in PLGA microspheres and release kinetics were determined over 35 days. NP agarose constructs were cultured to functional maturity and treated with combinations of IL-1β and media conditioned with IL-1ra released from microspheres at intervals for up to 20 days. Construct mechanical properties, glycosaminoglycan content, nitrite production and mRNA expression of catabolic mediators were compared to properties for untreated constructs using unpaired Student's t-tests. Results IL-1ra release kinetics were characterized by an initial burst release reducing to a linear release over the first 10 days. IL-1ra released from microspheres attenuated the degradative effects of IL-1β as defined by mechanical properties, glycosaminoglycans (GAG) content, nitric oxide production and mRNA expression of inflammatory mediators for 7 days, and continued to limit functional degradation for up to 20 days. Conclusions In this study, we successfully demonstrated that IL-1ra microspheres can attenuate the degradative effects of IL-1β on the NP for extended periods. This therapeutic strategy may be appropriate for treating early-stage, cytokine-mediated disc degeneration. Ongoing studies are focusing on testing IL-1ra microspheres in an in vivo model of disc degeneration, as a prelude to clinical translation. PMID:22863285

  17. Fasting Induces IL-1 Resistance and Free-Fatty Acid-Mediated Up-Regulation of IL-1R2 and IL-1RA

    PubMed Central

    Joesting, Jennifer J.; Moon, Morgan L.; Gainey, Stephen J.; Tisza, Brittany L.; Blevins, Neil A.; Freund, Gregory G.

    2014-01-01

    Objective: Weight-loss is a near societal obsession and many diet programs use significant calorie restriction including fasting/short term starvation to generate rapid effects. Fasting is also a well-recognized cause of immunosuppression especially within the innate immune system. In this study, we sought to determine if the IL-1 arm of the neuroimmune system was down-regulated by a 24 h fast and how fasting might generate this effect. Design: Mice were allowed ad libitum access to food or had food withheld for 24 h. Expression of the endogenous IL-1 antagonists, IL-1 receptor type 2 (IL-1R2), and IL-1 receptor antagonist (IL-1RA) was determined as were sickness behaviors before and after IL-1β administration. Results: Fasting markedly increased gene expression of IL-1R2 (83-fold in adipose tissue, 9.5-fold in liver) and IL-1RA (68-fold in liver). Fasted mice were protected from IL-1β-induced weight-loss, hypoglycemia, loss of locomotor, and social anxiety. These protections were coupled to a large positive interaction of fasting and IL-1β on IL-1R2 gene expression in adipose tissue and liver (2.6- and 1.6-fold, respectively). Fasting not only increased IL-1RA and IL-1R2 protein 2.5- and 3.2-fold, respectively, in liver but also increased IL-1R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4-fold increase in plasma free-fatty acids (FFAs) and a 2.1-fold increase in plasma corticosterone. Inhibition, of glucocorticoid action with mifepristone did not impact fasting-dependent IL-1R2 or IL-1RA gene expression. Administration of the FFA, palmitate, to mice increased liver IL-1R2 and IL-1RA gene expression by 14- and 11-fold, respectively. Conclusion: These findings indicate that fasting augments expression of endogenous IL-1 antagonists inducing IL-1 resistance. Fasting-induced increases in plasma FFAs appears to be a signal that drives immunosuppression during fasting/short term starvation. PMID:25071776

  18. Effect of retinoic acid on HPV titration and colposcopic changes in Korean patients with dysplasia of the uterine cervix.

    PubMed

    Ahn, W S; Lee, J M; Namkoong, S E; Lee, H Y; Kim, S J

    1997-01-01

    Retinoids, a family of molecules capable of profound impact on many biological functions, have antiproliferative, differentiative, and immunomodulatory properties. The present study assessed the effect of 13-cis-retinoic acid (13-CRA) treatment in 13 chronic cervicitis and 52 cervical intraepithelial neoplasia patients. We examined low- and high-risk human papilloma virus titer (using the hybrid capture method) and made a colposcopic and cervicographic examination before and after treatment with 13-CRA at 1 mg/kg for 4 to 12 weeks. Patients were between 27 and 64 years, the average age being 36.6 years. Histology revealed chronic cervicitis in 13 cases, mild dysplasia in 18 cases, moderate dysplasia in 18 cases, and severe dysplasia in 16 cases, totaling 65 cases. The expression rate of high-risk human papilloma virus (HPV 16, 18) was 9 of 13 cases (69%) in chronic cervicitis, 7 of 18 cases (38%) in mild dysplasia, 9 of 18 cases (50%) in moderate dysplasia, and 12 of 16 cases (75%) in severe dysplasia, with the overall expression rate being 37 of 65 cases (57%). Following 13-CRA treatment, decreases in high-risk titer were observed in 6 of 9 cases (66%) of chronic cervicitis, 4 of 11 cases (36%) of mild dysplasia, 7 of 9 cases (77%) of moderate dysplasia, and 8 of 12 cases (75%) of severe dysplasia. Overall, HPV titer decreased in 25 of 41 cases (61%). Minimal changes were found in colposcopic and cervicographic observations during the study. In summary, high-risk HPV titer decreased after treatment with 13-CRA in the majority of patients with cervical intraepithelial neoplasia. This study supports the potential of retinoids to interrupt multi-step carcinogenesis, possibly by down-regulation of gene products (E6,E7) produced by HPV infection.

  19. Synergistic activation of retinoic acid (RA)-responsive genes and induction of embryonal carcinoma cell differentiation by an RA receptor {alpha} (RAR{alpha})-, RAR{beta}-, or RAR{gamma}-selective ligand in combination with retinoid Z receptor-specific ligand

    SciTech Connect

    Roy, B.; Taneja, R.; Chambon, P.

    1995-12-01

    This research indicates thatn retinoic acid receptor (RAR)-retinoid X receptor (RXR) heterodimers activate transcription of RA-responsive genes and induce cell differentiation of P19 and F9 cells in a ligand-dependent manner. 43 refs., 4 figs., 2 tabs.

  20. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines.

    PubMed

    Carrier, Marilyn; Joint, Mathilde; Lutzing, Régis; Page, Adeline; Rochette-Egly, Cécile

    2016-01-01

    Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome". Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα), which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression.

  1. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines

    PubMed Central

    Carrier, Marilyn; Joint, Mathilde; Lutzing, Régis; Page, Adeline; Rochette-Egly, Cécile

    2016-01-01

    Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the “kinome”. Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα), which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression. PMID:27362937

  2. Preparation of (228)Ra standard solution.

    PubMed

    Havelka, Miroslav

    2016-03-01

    For the preparation of a standard solution of (228)Ra, (228)Ra was isolated from (232)Th salt. Two simple methods were developed for Th-Ra separation. Both are based on a very good solubility of thorium nitrate in organic solvents. The first one used Ra co-precipitation with Pb in the form of Pb(NO3)2 from acetic acid solution. The second method was based on solvent extraction, remaining Th in the organic phase, while Ra was concentrated in the aqueous phase. The activity of (228)Ra (up to 20kBq) in the standard solution was related to the (232)Th standard by means of gamma ray spectrometry measurement. The obtained uncertainty was less than 0.7% (k=1). The standard solution was free of (232)Th and contained the carrier in the usual concentration (1gL(-1) BaCl2, 10gL(-1) HCl). PMID:26651171

  3. Distribution of sulphuric acid aerosols in the clouds and upper haze of Venus using Venus Express VAST and VeRa temperature profiles

    NASA Astrophysics Data System (ADS)

    Parkinson, Christopher D.; Gao, Peter; Schulte, Rick; Bougher, Stephen W.; Yung, Yuk L.; Bardeen, Charles G.; Wilquet, Valérie; Vandaele, Ann Carine; Mahieux, Arnaud; Tellmann, Silvia; Pätzold, Martin

    2015-08-01

    Observations from Pioneer Venus and from SPICAV/SOIR aboard Venus Express (VEx) have shown the upper haze (UH) of Venus to be highly spatially and temporally variable, and populated by multiple particle size modes. Previous models of this system (e.g., Gao et al., 2014. Icarus 231, 83-98), using a typical temperature profile representative of the atmosphere (viz., equatorial VIRA profile), did not investigate the effect of temperature on the UH particle distributions. We show that the inclusion of latitude-dependent temperature profiles for both the morning and evening terminators of Venus helps to explain how the atmospheric aerosol distributions vary spatially. In this work we use temperature profiles obtained by two instruments onboard VEx, VeRa and SPICAV/SOIR, to represent the latitudinal temperature dependence. We find that there are no significant differences between results for the morning and evening terminators at any latitude and that the cloud base moves downwards as the latitude increases due to decreasing temperatures. The UH is not affected much by varying the temperature profiles; however, the haze does show some periodic differences, and is slightly thicker at the poles than at the equator. We also find that the sulphuric acid "rain" seen in previous models may be restricted to the equatorial regions of Venus, such that the particle size distribution is relatively stable at higher latitudes and at the poles.

  4. Biological activity of all-trans retinol requires metabolic conversion to all-trans retinoic acid and is mediated through activation of nuclear retinoid receptors in human keratinocytes.

    PubMed

    Kurlandsky, S B; Xiao, J H; Duell, E A; Voorhees, J J; Fisher, G J

    1994-12-30

    The biological activity of all-trans retinol, in human keratinocytes, was investigated through metabolic and functional analyses that assessed the capacity for retinol uptake and metabolism and the mechanism of retinol-induced activation of gene transcription. Human keratinocytes converted all-trans retinol predominantly to retinyl esters, which accounted for 60 and 90% of cell-associated radiolabel after a 90-min pulse and a 48-h chase, respectively. Human keratinocytes also metabolized all-trans retinol to low levels of all-trans retinoic acid (11.47-131.3 ng/mg of protein) in a dose-dependent manner, between 0.3 and 10 microM added retinol. Small amounts of 13-cis retinoic acid (5.47-8.62 ng/mg of protein) were detected, but 9-cis retinoic acid was detected only when keratinocytes were incubated with radiolabeled retinol. There was no accumulation of the oxidized catabolic metabolites 4-hydroxy- or 4-oxoretinoic acid; however, 5,6-epoxy retinoic acid was detected at pharmacological levels (10 and 30 microM) of added retinol. Biological activity of retinol was assessed through analysis of two known retinoic acid-mediated responses: 1) reduction of type I epidermal transglutaminase and 2) activation of a retinoic acid receptor-dependent reporter gene, beta RARE3-tk-CAT. Both all-trans retinol and all-trans retinoic acid reduced type I epidermal transglutaminase in a dose-dependent manner; however, the ED50 for all-trans retinol (10 nM) was 10 times greater than for all-trans retinoic acid (1 nM). All-trans retinol also stimulated beta RARE3-tk-CAT reporter gene activity in a dose-dependent manner. Half-maximal induction was observed at 30 nM retinol, which was again 10-fold greater than observed with all-trans retinoic acid. Cotransfection of human keratinocytes with expression vectors for dominant negative mutant retinoic acid and retinoid X receptors reduced retinol-induced beta RARE3-tk-CAT reporter gene activation by 80%. Inhibition of conversion of all

  5. Martin RA-30 Baltimore

    NASA Technical Reports Server (NTRS)

    1943-01-01

    Martin RA-30 Baltimore: The Martin RA-30 Baltimore was a light bomber ordered by the Royal Air Force. Some examples were retained in the United States as part of a 'Reverse Lend-Lease.' This example was flown by the NACA from June 1943 until March 1944.

  6. Measuring the radium quartet (228Ra, 226Ra, 224Ra, 223Ra) in seawater samples using gamma spectrometry.

    PubMed

    van Beek, P; Souhaut, M; Reyss, J-L

    2010-07-01

    Radium isotopes are widely used in marine studies (eg. to trace water masses, to quantify mixing processes or to study submarine groundwater discharge). While 228Ra and 226Ra are usually measured using gamma spectrometry, short-lived Ra isotopes (224Ra and 223Ra) are usually measured using a Radium Delayed Coincidence Counter (RaDeCC). Here we show that the four radium isotopes can be analyzed using gamma spectrometry. We report 226Ra, 228Ra, 224Ra, 223Ra activities measured using low-background gamma spectrometry in standard samples, in water samples collected in the vicinity of our laboratory (La Palme and Vaccarès lagoons, France) but also in seawater samples collected in the plume of the Amazon river, off French Guyana (AMANDES project). The 223Ra and 224Ra activities determined in these samples using gamma spectrometry were compared to the activities determined using RaDeCC. Activities determined using the two techniques are in good agreement. Uncertainties associated with the 224Ra activities are similar for the two techniques. RaDeCC is more sensitive for the detection of low 223Ra activities. Gamma spectrometry thus constitutes an alternate method for the determination of short-lived Ra isotopes.

  7. An RA Big Think

    ERIC Educational Resources Information Center

    Wyatt, Neal

    2007-01-01

    Readers' advisory (RA) librarians use appeal to translate between readers and books, to make connections between readers and myriad other title possibilities based on the effects of the story. Appeal addresses the elements of books that readers respond to, the features that "draw a reader into a book" and help shape a particular reading…

  8. Determination of 226Ra, 224Ra, 223Ra and 228Ra in mineral water samples of the Slovak Republic

    NASA Astrophysics Data System (ADS)

    Durecová, A.; Durec, F.; Bursová, D.

    2006-01-01

    The Slovak Republic is very rich in mineral water sources. In recent years, it has been discovered that a number of mineral waters in the Slovak Republic contain high levels of 226Ra and 228Ra. Moreover, there is a lack of information on 224Ra and 223Ra concentrations in mineral waters as well. The currently approved techniques for alpha emitting radium isotopes are based on radon emanation methods. Due to the long ingrowth periods required by these techniques, any 224Ra and 223Ra in the sample decay away and go undetected. For this reason, we have used an alpha spectrometric method for the simultaneous determination of 226Ra, 223Ra and 224Ra. Radium was concentrated by a lead sulphate co-precipitation. The precipitate was dissolved in EDTA and the radium isotopes were separated from possible interfering radionuclides using barium sulphate micro precipitation. The radium-barium precipitate was filtered and counted by alpha spectrometry. 133Ba was used to quantify the yield by gamma spectrometry. In our laboratory, gamma spectrometry was also used for the determination of 228Ra in mineral water samples. Radium was concentrated by a lead-barium sulphate co-precipitation. 133Ba was used to quantify the yield, found to be 97% on the average, by gamma spectrometry. Furthermore, the committed effective doses for 226Ra, 224Ra, 223Ra, 228Ra intake via ingestion of mineral waters for the members of public were calculated.

  9. 40 CFR 721.6120 - Phosphoric acid, 1,2-eth-a-ne-diyl tet-ra-kis(2-chloro-1-meth-yl-ethyl) ester.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphoric acid, 1,2-eth-a-ne-diyl tet... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6120 Phosphoric acid, 1,2-eth-a-ne... subject to reporting. (1) The chemical substance identified as phosphoric acid, 1,2-ethanediyl...

  10. 40 CFR 721.6120 - Phosphoric acid, 1,2-eth-a-ne-diyl tet-ra-kis(2-chloro-1-meth-yl-ethyl) ester.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Phosphoric acid, 1,2-eth-a-ne-diyl tet... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6120 Phosphoric acid, 1,2-eth-a-ne... subject to reporting. (1) The chemical substance identified as phosphoric acid, 1,2-ethanediyl...

  11. 40 CFR 721.6120 - Phosphoric acid, 1,2-eth-a-ne-diyl tet-ra-kis(2-chloro-1-meth-yl-ethyl) ester.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phosphoric acid, 1,2-eth-a-ne-diyl tet... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6120 Phosphoric acid, 1,2-eth-a-ne... subject to reporting. (1) The chemical substance identified as phosphoric acid, 1,2-ethanediyl...

  12. Rapid Method for Ra-226 and Ra-228 in Water Samples

    SciTech Connect

    Maxwell, Sherrod, L. III

    2006-02-10

    The measurement of radium isotopes in natural waters is important for oceanographic studies and for public health reasons. Ra-226 (1620 year half-life) is one of the most toxic of the long-lived alpha emitters present in the environment due to its long life and its tendency to concentrate in bones, which increases the internal radiation dose of individuals. The analysis of radium-226 and radium-228 in natural waters can be tedious and time-consuming. Different sample preparation methods are often required to prepare Ra-226 and Ra-228 for separate analyses. A rapid method has been developed at the Savannah River Environmental Laboratory that effectively separates both Ra-226 and Ra-228 (via Ac-228) for assay. This method uses MnO{sub 2} Resin from Eichrom Technologies (Darien, IL, USA) to preconcentrate Ra-226 and Ra-228 rapidly from water samples, along with Ba-133 tracer. DGA Resin{reg_sign} (Eichrom) and Ln-Resin{reg_sign} (Eichrom) are employed in tandem to prepare Ra-226 for assay by alpha spectrometry and to determine Ra-228 via the measurement of Ac-228 by gas proportional counting. After preconcentration, the manganese dioxide is dissolved from the resin and passed through stacked Ln-Resin-DGA Resin cartridges that remove uranium and thorium interferences and retain Ac-228 on DGA Resin. The eluate that passed through this column is evaporated, redissolved in a lower acidity and passed through Ln-Resin again to further remove interferences before performing a barium sulfate microprecipitation. The Ac-228 is stripped from the resin, collected using cerium fluoride microprecipitation and counted by gas proportional counting. By using vacuum box cartridge technology with rapid flow rates, sample preparation time is minimized.

  13. Leaching of 226Ra from components of uranium mill tailings

    USGS Publications Warehouse

    Landa, E.R.

    1991-01-01

    A sequential extraction procedure was used to characterize the geochemical forms of 226Ra retained by mixtures of quartz sand and a variety of fine-grained rock and mineral species. These mixtures had previously been exposed to the sulfuric acid milling liquor of a simulated acid-leach uranium milling circuit. For most test cases, the major fraction of the 226Ra was extracted with 1 mol/1 NH4Cl and was deemed to be exchangeable. However, 226Ra retained by the barite-containing mixture was resistant to both 1 mol/1 NH4Cl and 1 mol/HCHCl extraction. ?? 1991.

  14. Ra-228, Ra-226 and Ra-228/Ra-226 Activity Ratio in the Northern South China Sea

    NASA Astrophysics Data System (ADS)

    Yu-Chia, C.

    2004-05-01

    We report for the first time the surface water distributions of Ra-228 and Ra-226 in the northern South China Sea (SCS) and vertical profiles in the central deep basin of the SCS. Being a marginal sea, the SCS displays activities of both nuclides much higher than the open oceans. The surface water Ra-228 varies between 22 and 33 dpm/100L with higher values at stations adjacent to the landmass. The surface water Ra-226 varies from 10 to 15 dpm/100L with a distribution pattern similar to that of Ra-228. The Ra-228/Ra-226 activity ratio is fairly constant at about 2 or slightly higher. Ra-228 decreases rapidly from a surface maximum of about 22 dpm/100L to about 12 dpm/100L at and below 300m depth in the deep central basin. The deep water values are much higher than those of the open oceans. Ra-226, on the other hand, shows a surface activity of 14 dpm/100L, decreases to 10 dpm/100L at 200m, and then increases monotonically with depth to about 35 dpm/100L at and below 3000m. This distribution pattern is similar to that observed in the western North Pacific but the activity is higher by about 5 dpm/100L for the entire water column. The resulting Ra-228/Ra-226 is greater than one above 250m and becomes less than one below this depth with the ratio decreasing to about 0.35 in the deep water below 3000m. This ratio remains much greater than that in the open oceans, implying a strong Ra-228 input relative to Ra-226 into the SCS deep water.

  15. Occurrence of 224Ra, 226Ra, 228Ra, gross alpha, and uranium in California groundwater.

    PubMed

    Ruberu, Shiyamalie R; Liu, Yun-Gang; Perera, S Kusum

    2005-12-01

    One hundred and twelve groundwater wells sampled from all the major aquifers in California were analyzed for 224Ra, 226Ra, 228Ra, gross alpha, and uranium. The results showed that radium is found in relatively low concentration, 1.56 x 10(-2)-1.23 Bq L(-1) (0.42-33 pCi L(-1)) for 224Ra, 2.2 x 10(-3)-0.81 Bq L(-1) (0.06-22 pCi L(-1)) for 226Ra, and 8.5 x 10(-3)-1.31 Bq L(-1) (0.23-35 pCi L(-1)) for 228Ra in California groundwater. Uranium was found at the highest concentration on both mass and activity basis and was correlated with the gross alpha measurement. Short-lived radioisotopes showed no significant contribution to gross alpha measurements. There was a strong correlation between 224Ra and 228Ra activities, suggesting the latter to be an indicator for the occurrence of the former. Comparison of 226Ra to 238U, 224Ra to 226Ra, and 226Ra to 228Ra showed scattered data indicating no correlation between each of these isotope pairs. Approximately 4% of the wells were found to exceed the U.S. Environmental Protection Agency (EPA) established maximum contaminant level for total radium of 0.185 Bq L(-1) (5 pCi L(-1)). Analysis of 228Ra by gamma-ray spectroscopy was in good agreement with the U.S. EPA-approved procedure.

  16. 226Ra and 228Ra in Iowa drinking water.

    PubMed

    Kriege, L B; Hahne, R M

    1982-10-01

    The University Hygienic Laboratory has been performing radiochemical analyses on drinking water in the state of Iowa for over 20 yr. Approximately one half of the 1250 community water supplies that exist in Iowa have been sampled roughly once every 3 yr for the past decade. Originally, raw and finished waters that showed a gross alpha activity of greater than or equal to 3.0 pCi/L were analyzed for 226Ra, but starting in July 1976, finished waters were analyzed for both 226Ra and 228Ra if the gross alpha activity was greater than or equal to 2.0 pCi/L. As of 10 June 1981, 604 community water supplies had submitted composited samples that have been analyzed for gross alpha, 226Ra, and 228Ra concentrations in compliance with the federal Safe Drinking Water Act (Public Law 93-523). Approximately 10% of these supplies were found to exceed the EPA-established maximum contaminant level (MCL) for 226Ra plus 228Ra of 5 pCi/L. The results revealed, consistent with several other investigators (Mc81; Mi80; Mic80), that some supplies had higher concentrations of 228Ra than of 226Ra. It was also concluded, in agreement with McCurdy and Mellor (Mc81), that some ground water samples cannot be accurately measured for gross alpha activity due to their high dissolved solids content. PMID:7152914

  17. Radium isotope ((223)Ra, (224)Ra, (226)Ra and (228)Ra) distribution near Brazil's largest port, Paranaguá Bay, Brazil.

    PubMed

    Dias, Thais H; de Oliveira, Joselene; Sanders, Christian J; Carvalho, Franciane; Sanders, Luciana M; Machado, Eunice C; Sá, Fabian

    2016-10-15

    This work investigates the (223)Ra, (224)Ra, (226)Ra and (228)Ra isotope distribution in river, estuarine waters and sediments of the Paranaguá Estuarine Complex (PEC). The stratification of the Ra isotopes along water columns indicate differing natural sources. In sediments, the radium isotope activities was inversely proportional to the particle size. The highest concentrations of (223)Ra, (224)Ra, (226)Ra and (228)Ra in the water column were found in the bottom more saline waters and towards the inner of the estuary. These relatively high concentrations towards the bottom of the estuary may be attributed to the influence of tidally driven groundwater source and desorption from particles at the maximum turbidity zone. The apparent river water ages from the radium isotope ratios, (223)Ra/(224)Ra and (223)Ra/(228)Ra, indicate that the principal rivers that flow into the estuary have residence times from between 6 and 11days.

  18. Radium isotope ((223)Ra, (224)Ra, (226)Ra and (228)Ra) distribution near Brazil's largest port, Paranaguá Bay, Brazil.

    PubMed

    Dias, Thais H; de Oliveira, Joselene; Sanders, Christian J; Carvalho, Franciane; Sanders, Luciana M; Machado, Eunice C; Sá, Fabian

    2016-10-15

    This work investigates the (223)Ra, (224)Ra, (226)Ra and (228)Ra isotope distribution in river, estuarine waters and sediments of the Paranaguá Estuarine Complex (PEC). The stratification of the Ra isotopes along water columns indicate differing natural sources. In sediments, the radium isotope activities was inversely proportional to the particle size. The highest concentrations of (223)Ra, (224)Ra, (226)Ra and (228)Ra in the water column were found in the bottom more saline waters and towards the inner of the estuary. These relatively high concentrations towards the bottom of the estuary may be attributed to the influence of tidally driven groundwater source and desorption from particles at the maximum turbidity zone. The apparent river water ages from the radium isotope ratios, (223)Ra/(224)Ra and (223)Ra/(228)Ra, indicate that the principal rivers that flow into the estuary have residence times from between 6 and 11days. PMID:27422485

  19. De-repression of RaRF-mediated RAR repression by adenovirus E1A in the nucleolus.

    PubMed

    Um, Soo-Jong; Youn, Hye Sook; Kim, Eun-Joo

    2014-02-21

    Transcriptional activity of the retinoic acid receptor (RAR) is regulated by diverse binding partners, including classical corepressors and coactivators, in response to its ligand retinoic acid (RA). Recently, we identified a novel corepressor of RAR called the retinoic acid resistance factor (RaRF) (manuscript submitted). Here, we report how adenovirus E1A stimulates RAR activity by associating with RaRF. Based on immunoprecipitation (IP) assays, E1A interacts with RaRF through the conserved region 2 (CR2), which is also responsible for pRb binding. The first coiled-coil domain of RaRF was sufficient for this interaction. An in vitro glutathione-S-transferase (GST) pull-down assay was used to confirm the direct interaction between E1A and RaRF. Further fluorescence microscopy indicated that E1A and RaRF were located in the nucleoplasm and nucleolus, respectively. However, RaRF overexpression promoted nucleolar translocation of E1A from the nucleoplasm. Both the RA-dependent interaction of RAR with RaRF and RAR translocation to the nucleolus were disrupted by E1A. RaRF-mediated RAR repression was impaired by wild-type E1A, but not by the RaRF binding-defective E1A mutant. Taken together, our data suggest that E1A is sequestered to the nucleolus by RaRF through a specific interaction, thereby leaving RAR in the nucleoplasm for transcriptional activation.

  20. Inhibition of proliferation and induction of apoptosis in soft tissue sarcoma cells by interferon-α and retinoids

    PubMed Central

    Brodowicz, T; Wiltschke, C; Kandioler-Eckersberger, D; Grunt, T W; Rudas, M; Schneider, S M; Hejna, M; Budinsky, A; Zielinski, C C

    1999-01-01

    Uncontrolled proliferation and a defect of apoptosis constitute crucial elements in the development and progression of tumours. Among many other biological response modifiers known to influence these mechanisms, the efficacy of retinoids and interferons in the treatment of various malignant entities is currently matter of discussion. In the present study, we have investigated the effects of 9-cis-retinoic acid (9cRA), 13-cis-retinoic acid (13cRA), all-trans-retinoic acid (tRA) and interferon-α on proliferation and apoptosis of human soft tissue sarcoma (STS) cell lines HTB-82 (rhabdomyosarcoma), HTB-91 (fibrosarcoma), HTB-92 (liposarcoma), HTB-93 (synovial sarcoma) and HTB-94 (chondrosarcoma) in relation to p53 genotype as well as p53 expression. HTB-91, HTB-92 and HTB-94 STS cells exhibited mutant p53, whereas wild-type p53 was found in HTB-93 STS cells, and a normal p53 status in HTB-82 STS cells, carrying a silent point mutation only. Interferon-α, irrespective of p53 status, inhibited the proliferation of all five cell lines dose- and time-dependently. Similarly, 9cRA, 13cRA and tRA decreased the proliferation of HTB-82 and HTB-93 STS cells, whereas the proliferation of p53-mutated HTB-91, HTB-92 and HTB-94 STS cells remained unchanged. Furthermore, only 9cRA and tRA were capable of inducing apoptosis in HTB-82 and HTB-93 STS cells, whereas HTB-91, HTB-92 and HTB-94 STS cells did not undergo apoptosis under the influence of 9cRA or tRA. Retinoic acid receptor (RAR)-α and RAR-β mRNA were not detectable by Northern blot analysis in the five STS cell lines, whereas mRNA for the universal retinoic acid receptor, RAR-γ, was expressed in all STS cell lines indicating that retinoid resistance was not associated with a lack of RAR expression. Apoptosis was not induced by interferon-α or 13cRA in any of the five STS cell lines tested. Our results indicate that within the panel of tested STS cell lines, inhibition of proliferation and induction of apoptosis result

  1. Radium content and the 226Ra /228Ra activity ratio in groundwater from bedrock

    NASA Astrophysics Data System (ADS)

    Asikainen, Matti

    1981-08-01

    The relative abundance of 226Ra and 228Ra were determined in the groundwater from 125 drilled wells containing from < 0.1 to 51.3 pCi/l of 226Ra. The determination of 228Ra was carried out with a liquid scintillation counter by measuring only the weakly energetic β particles emitted from 228Ra. Thus the interference from the daughter nuclides of 226Ra was avoided, without specific separation of 228Ac. The direct measurement of 228Ra made the method decisively simpler and faster in terms of the chemistry involved. The concentration of 228Ra was found to be independent of the amount of 226Ra present in the samples. The concentrations of 228Ra were nearly the same over the whole range of 226Ra concentrations and the average sol 226Ra /228Ra ratio sharply increased as the 226Ra content of water increased. The 226Ra /228Ra ratio in the drilled wells varied from 0.3 to 26. Abnormally high 226Ra /228Ra ratios were found in areas with known uranium deposits as well as in several drilled wells at other locations. The abnormally high 226Ra /228Ra ratios present in groundwater suggest that the radioactivity anomaly is caused by uranium deposits and not by common rocks. In samples with a low radioactivity level the average 226Ra /228Ra ratio was slightly below unity, corresponding to the typical U/ Th ratio of granite, the most common kind of rock in the study area. The samples from the rapakivi area proved to be exceptional in that they had a low 226Ra /228Ra ratio independent of the concentration of 226Ra.

  2. Radiotherapy and temozolomide for anaplastic astrocytic gliomas

    PubMed Central

    Nayak, Lakshmi; Panageas, Katherine S.; Reiner, Anne S.; Huse, Jason T.; Pentsova, Elena; Braunthal, Stephanie G.; Abrey, Lauren E.; DeAngelis, Lisa M.

    2015-01-01

    We previously reported results of a phase II non-comparative trial that randomized patients with glioblastoma following radiotherapy to one of two different temozolomide schedules, followed by 13-cis-retinoic acid (RA) maintenance. Here we report the results of an exploratory cohort of patients accrued with anaplastic astrocytic tumors. Patients with newly diagnosed anaplastic astrocytoma (AA) or anaplastic oligo-astrocytoma (AOA) were treated with concurrent radiotherapy (60 Gy over 6 weeks) and temozolomide (75 mg/m2), and six adjuvant 28-day cycles of either dose-dense (150 mg/m2, days 1–7, 15–21) or metronomic (50 mg/m2, days 1–28) temozolomide. Subsequently, maintenance RA (100 mg/m2, days 1–21/28) was administered until disease progression. All outcome measures were descriptive without intention to compare between treatment arms. Survival was measured by the Kaplan–Meier method. There were 31 patients (21 men, 10 women) with median age 48 years (range 28–74), median KPS 90 (range 60–100). Extent of resection was gross-total in 35 %, subtotal 23 %, and biopsy 42 %. Histology was AA in 90 %, and AOA in 10 %. MGMT promoter methylation was methylated in 20 %, unmethylated in 50 %, and uninformative in 30 % of 30 tested. Median progression-free survival was 2.1 years (95 % CI 0.95–Not Reached), and overall survival 2.9 years (95 % CI 2.0–Not Reached). We report outcomes among a homogeneously treated population with anaplastic astrocytic tumors. Survival was unexpectedly short compared to other reports. These data may be useful as a contemporary historic control for other ongoing or future randomized trials. PMID:25920709

  3. Radiotherapy and temozolomide for anaplastic astrocytic gliomas.

    PubMed

    Nayak, Lakshmi; Panageas, Katherine S; Reiner, Anne S; Huse, Jason T; Pentsova, Elena; Braunthal, Stephanie G; Abrey, Lauren E; DeAngelis, Lisa M; Lassman, Andrew B

    2015-05-01

    We previously reported results of a phase II non-comparative trial that randomized patients with glioblastoma following radiotherapy to one of two different temozolomide schedules, followed by 13-cis-retinoic acid (RA) maintenance. Here we report the results of an exploratory cohort of patients accrued with anaplastic astrocytic tumors. Patients with newly diagnosed anaplastic astrocytoma (AA) or anaplastic oligo-astrocytoma (AOA) were treated with concurrent radiotherapy (60 Gy over 6 weeks) and temozolomide (75 mg/m(2)), and six adjuvant 28-day cycles of either dose-dense (150 mg/m(2), days 1-7, 15-21) or metronomic (50 mg/m(2), days 1-28) temozolomide. Subsequently, maintenance RA (100 mg/m(2), days 1-21/28) was administered until disease progression. All outcome measures were descriptive without intention to compare between treatment arms. Survival was measured by the Kaplan-Meier method. There were 31 patients (21 men, 10 women) with median age 48 years (range 28-74), median KPS 90 (range 60-100). Extent of resection was gross-total in 35%, subtotal 23%, and biopsy 42%. Histology was AA in 90%, and AOA in 10%. MGMT promoter methylation was methylated in 20%, unmethylated in 50%, and uninformative in 30% of 30 tested. Median progression-free survival was 2.1 years (95% CI 0.95-Not Reached), and overall survival 2.9 years (95 % CI 2.0-Not Reached). We report outcomes among a homogeneously treated population with anaplastic astrocytic tumors. Survival was unexpectedly short compared to other reports. These data may be useful as a contemporary historic control for other ongoing or future randomized trials. PMID:25920709

  4. Revealed: The spy who regulates neuroblastoma stem cells.

    PubMed

    Vora, Parvez; Venugopal, Chitra; Singh, Sheila K

    2014-11-30

    Neuroblastoma (NB), an embryonal tumour of the sympathetic nervous system, is thought to originate from undifferentiated neural crest cells and is known to exhibit extremely heterogeneous biological and clinical behaviors. Occurring in very young children, the median age at diagnosis is 17 months and it accounts for 10% of all pediatric cancer mortalities. The standard treatment regimen for patients with high-risk NB includes induction and surgery followed by isotretinoin or Accutane (13-cis retinoic acid) treatment, which is shown to induce terminal differentiation of NB cells. However, molecular regulators that maintain an undifferentiated phenotype in NB cells are still poorly understood. PMID:25483101

  5. Pneumocystis carinii pneumonia: a late presentation following treatment for stage IV neuroblastoma.

    PubMed

    Clarke, Edward; Glaser, Adam W; Picton, Susan V

    2003-09-01

    This report describes a child who develops Pneumocystis carinii pneumonia 7 months after high-dose chemotherapy for stage IV neuroblastoma. In addition to chemotherapy the child had also been treated with abdominal radiotherapy and 13-cis-retinoic acid. Standard practice has been to treat patients with prophylactic co-trimoxazole for 3 months after high-dose therapy, but this report highlights the intensity and complexity of current treatment for stage IV neuroblastoma and the need to be aware of prolonged lymphopenia after such treatment. PMID:14631621

  6. VELoCiRaPTORS.

    NASA Astrophysics Data System (ADS)

    Lundgren, J.; Esham, B.; Padalino, S. J.; Sangster, T. C.; Glebov, V.

    2007-11-01

    The Venting and Exhausting of Low Level Air Contaminants in the Rapid Pneumatic Transport of Radioactive Samples (VELoCiRaPTORS) system is constructed to transport radioactive materials quickly and safely at the NIF. A radioactive sample will be placed inside a carrier that is transported via an airflow system produced by controlled differential pressure. Midway through the transportation process, the carrier will be stopped and vented by a powered exhaust blower which will remove radioactive gases within the transport carrier. A Geiger counter will monitor the activity of the exhaust gas to ensure that it is below acceptable levels. If the radiation level is sufficient, the carrier will pass through the remainder of the system, pneumatically braking at the counting station. The complete design will run manually or automatically with control software. Tests were performed using an inactive carrier to determine possible transportation problems. The system underwent many consecutive trials without failure. VELoCiRaPTORS is a prototype of a system that could be installed at both the Laboratory for Laser Energetics at the University of Rochester and the National Ignition Facility at LLNL.

  7. Reflection asymmetric shape in sup 221 Ra

    SciTech Connect

    Liang, C.F.; Paris, P.; Briancon, C. ); Sheline, R.K. )

    1990-04-20

    This paper reports on mass separated sources of {sup 225}Th used to study the level structure of {sup 221}Ra following alpha decay. Fluorination techniques were used to obtain the selectivity in atomic number. The low lying levels in {sup 221}Ra are interpreted in terms of K = 5/2 {sup {plus minus}} and 3/2{sup {plus minus}} parity doublet bands which occur naturally from reflection asymmetric models. The anomalous spin sequences in the K = 3/2{sup {plus minus}} bands of {sup 221}Ra are interpreted in terms of their Coriolis coupling with K = 1/2{sup {plus minus}} bands with large decoupling parameters. The low-lying parity doublet bands in {sup 221}Ra, {sup 223}Ra and {sup 225}Ra, and particularly the Coriolis coupling of their K = 3/2{sup {plus minus}} bands, are compared and contrasted.

  8. Occurrence of 222Rn, 226Ra, 228Ra and U in groundwater in Fujian Province, China.

    PubMed

    Zhuo, W; Iida, T; Yang, X

    2001-01-01

    222Rn, 226Ra, 228Ra and U were determined in a total of 552 groundwater samples collected throughout Fujian Province of China. The geometric mean concentrations of 222Rn, 226Ra, 228Ra and total U in the groundwater were 147.8 kBq m-3, 12.7 Bq m-3, 30.2 Bq m-3 and 0.54 microgram kg-1, respectively. High groundwater 222Rn was explained by the predominantly granitic rock aquifers in Fujian. A lifetime risk of 1.7 x 10(-3) was estimated for the ingestion of groundwater 222Rn. High ratios of 228Ra to 226Ra contents (geometric mean of 2.4) and their disproportion suggest that 228Ra should also be measured in the assessment of population doses from drinking water in the regions of high rock or soil 232Th. No significant correlation between the 222Rn concentrations in groundwater and air was found.

  9. Cardiovascular risk factor management in patients with RA compared to matched non-RA patients

    PubMed Central

    Cawston, Helene; Bourhis, Francois; Al, Maiwenn; Rutten-van Mölken, Maureen P. M. H.; Liao, Katherine P.; Solomon, Daniel H.

    2016-01-01

    Objective. RA is associated with a 50–60% increase in risk of cardiovascular (CV) death. This study aimed to compare management of CV risk factors in RA and matched non-RA patients. Methods. A retrospective cohort study was conducted using UK clinical practice data. Patients presenting with an incident RA diagnosis were matched 1:4 to non-RA patients based on a propensity score for RA, entry year, CV risk category and treatment received at index date (date of RA diagnosis). Patients tested and treated for CV risk factors as well as those attaining CV risk factor management goals were evaluated in both groups. Results. Between 1987 and 2010, 24 859 RA patients were identified and matched to 87 304 non-RA patients. At index date, groups had similar baseline characteristics. Annual blood pressure, lipids and diabetes-related testing were similar in both groups, although CRP and ESR were higher in RA patients at diagnosis and decreased over time. RA patients prescribed antihypertensives increased from 38.2% at diagnosis to 45.7% at 5 years, from 14.0 to 20.6% for lipid-lowering treatments and from 5.1 to 6.4% for antidiabetics. Similar treatment percentages were observed in non-RA patients, although slightly lower for antihypertensives. Modest (2%) but significantly lower attainment of lipid and diabetes goals at 1 year was observed in RA patients. Conclusion. There were no differences between groups in the frequency of testing and treatment of CV risk factors. Higher CV risk in RA patients seems unlikely to be driven by differences in traditional CV risk factor management. PMID:26705329

  10. Nuclear Structure of {sup 231}Ra

    SciTech Connect

    Boutami, R.; Fraile, L.M.; Borge, M.J.G.; Aas, A.J.; Fogelberg, B.; Garcia-Raffi, L.M.; Grant, I.S.; Gulda, K.; Hagebo, E.; Kurcewicz, W.; Lopez-Jimenez, M.J.; Lovhoiden, G.; Mach, H.; Martinez, T.; Rubio, B.; Tain, J.L.; Teijeiro, A.G.; Tengblad, O.; Thorsteinsen, T.F.

    1999-12-31

    The study of the upper border of the octupole deformation region near A=225, where the octupole deformation vanishes in the presence of a well developed quadrupole field, is of great relevance in order to understand the interplay of octupole and quadrupole collectivities. Within the IS322 collaboration at CERN we carry out a systematic investigation of the heavy Fr - Th nuclei that presently includes {sup 227}Fr, {sup 227,228,229}Ra, {sup 229}Ac and {sup 229,231}Th. The heaviest Ra isotope we have studied so far and in which the fast timing {beta}{gamma}{gamma}(t) method has been applied is {sup 231}Ra.

  11. Nuclear structure of {sup 231}Ra

    SciTech Connect

    Boutami, R.; Fraile, L. M.; Borge, M. J. G.; Lopez-Jimenez, M. J.; Teijeiro, A. G.; Aas, A. J.; Hageboe, E.; Fogelberg, B.; Mach, H.; Garcia-Raffi, L. M.; Martinez, T.; Rubio, B.; Tain, J. L.; Grant, I. S.; Gulda, K.; Kurcewicz, W.; Loevhoeiden, G.; Tengblad, O.; Thorsteinsen, T. F.

    1999-11-16

    The study of the upper border of the octupole deformation region near A=225, where the octupole deformation vanishes in the presence of a well developed quadrupole field, is of great relevance in order to understand the interplay of octupole and quadrupole collectivities. Within the IS322 collaboration at CERN we carry out a systematic investigation of the heavy Fr-Th nuclei that presently includes {sup 227}Fr, {sup 227,228,229}Ra, {sup 229}Ac and {sup 229,231}Th. The heaviest Ra isotope we have studied so far and in which the fast timing {beta}{gamma}{gamma}(t) method has been applied is {sup 231}Ra.

  12. Surface water mixing estimated from 228Ra and 226Ra in the northwestern North Pacific.

    PubMed

    Kawakami, Hajime; Kusakabe, Masashi

    2008-08-01

    We investigated the horizontal distributions of (228)Ra and (226)Ra in surface waters of the northwestern North Pacific Ocean and Okhotsk Sea. Ratios of (228)Ra/(226)Ra were relatively large in the Tsugaru Current (0.6-0.8) and Okhotsk Sea (0.4-0.5), and small in the Western Subarctic Gyre (<0.2) and the Oyashio (0.25-0.3). (228)Ra/(226)Ra ratios in western Subarctic Water (SAW) rose slightly upon mixing with Okhotsk Water (OKW), before becoming the Oyashio Water (OYW). Also, ratios in the OYW increased during mixing with Tsugaru Current Water (TCW). Estimating from (228)Ra/(226)Ra ratios and (226)Ra activities with a simple two-end members-mixing model, we assumed that approximately 23% of the OYW originated from the OKW and the coastal region off northern Honshu (Japan) was strongly influenced by the TCW. From a diagram of (228)Ra activities against salinity, we could roughly divide surface seawater in the study area into the five water masses, which were SAW, OYW, OKW, TCW, and Subtropical Water (STW).

  13. SoRa first flight. Summer 2009

    NASA Astrophysics Data System (ADS)

    Pirrotta, S.; Flamini, E.

    The SoRa (Sounding Radar) experiment was successfully launched from Longyearbyen (Svalbard, Norway) during the summer 2009 campaign managed by the Italian/Norwegian "Nobile Amundsen / Stratospheric Balloon Centre" (NA/SBC). SoRa is part of the Italian Space Agency (ASI) programs for Long Duration Balloon Flights. Carried by the biggest balloon (800.000 m3) ever launched in polar regions, SoRa main experiment and its three piggyback payloads (DUSTER, ISA and SIDERALE) performed a nominal flight of almost 4 days over the North Sea and Greenland, until the separation, landing and recovery in Baffin Island (Canada). Despite the final destructive event that compromise the scientific main goal of SoRa, the 2009 ASI balloon campaign can be considered an important milestone, because of the obtained scientific and technical results but also for the lesson learned by the science, engineering and managerial teams looking at the future ASI scientific balloon-born activities.

  14. Laser trapping of Ra-225 and Ra-226 and progress towards an electric dipole moment measurement

    NASA Astrophysics Data System (ADS)

    Guest, J. R.; Scielzo, N. D.; Ahmad, I.; Bailey, K.; Greene, J. P.; Holt, R. J.; Lu, Z.-T.; O'Connor, T. P.; Potterveld, D. H.

    2006-10-01

    Permanent electric dipole moments (EDMs) in atoms or molecules are signatures of Time (T)-and Parity (P)-violation and represent an important window onto physics beyond the Standard Model. We are developing a next generation EDM search around laser-cooled and trapped Ra-225 (t1/2 = 15 d). Due to octupole deformation of the nucleus, Ra-225 is predicted to be two to three orders of magnitude more sensitive to T-violating interactions than Hg-199, which currently sets the most stringent limits in the nuclear sector. We will discuss our progress, including the successful laser cooling and trapping of Ra-225 and Ra-226 atoms. We have demonstrated transverse cooling, Zeeman slowing, and capture of Ra-225 and Ra-226 atoms in a magneto-optical trap (MOT). By driving a second atomic transition, we have extended the lifetime of the trap from milliseconds to seconds and performed necessary spectroscopic measurements.

  15. Removal of 226Ra and 228Ra from TENORM sludge waste using surfactants solutions.

    PubMed

    Attallah, M F; Hamed, Mostafa M; El Afifi, E M; Aly, H F

    2015-01-01

    The feasibility of using surfactants as extracting agent for the removal of radium species from TENORM sludge produced from petroleum industry is evaluated. In this investigation cationic and nonionic surfactants were used as extracting agents for the removal of radium radionuclides from the sludge waste. Two surfactants namely cetyltrimethylammonium bromide (CTAB) and Triton X-100 (TX100) were investigated as the extracting agents. Different parameters affecting the removal of both (226)Ra and (228)Ra by the two surfactants as well as their admixture were studied by the batch technique. These parameters include effect of shaking time, surfactants concentration and temperature as well as the effect of surfactants admixture. It was found that, higher solution temperature improves the removal efficiency of radium species. Combined extraction of nonionic and cationic surfactants produces synergistic effect in removal both (226)Ra and (228)Ra, where the removals reached 84% and 80% for (226)Ra and (228)Ra, respectively, were obtained using surfactants admixture.

  16. Removal of 226Ra and 228Ra from TENORM sludge waste using surfactants solutions.

    PubMed

    Attallah, M F; Hamed, Mostafa M; El Afifi, E M; Aly, H F

    2015-01-01

    The feasibility of using surfactants as extracting agent for the removal of radium species from TENORM sludge produced from petroleum industry is evaluated. In this investigation cationic and nonionic surfactants were used as extracting agents for the removal of radium radionuclides from the sludge waste. Two surfactants namely cetyltrimethylammonium bromide (CTAB) and Triton X-100 (TX100) were investigated as the extracting agents. Different parameters affecting the removal of both (226)Ra and (228)Ra by the two surfactants as well as their admixture were studied by the batch technique. These parameters include effect of shaking time, surfactants concentration and temperature as well as the effect of surfactants admixture. It was found that, higher solution temperature improves the removal efficiency of radium species. Combined extraction of nonionic and cationic surfactants produces synergistic effect in removal both (226)Ra and (228)Ra, where the removals reached 84% and 80% for (226)Ra and (228)Ra, respectively, were obtained using surfactants admixture. PMID:25464043

  17. The Mycobacterium tuberculosis H37Ra gene MRA_1916 causes growth defects upon down-regulation

    PubMed Central

    Singh, Kumar Sachin; Singh, Sudheer Kumar

    2015-01-01

    D-amino acid oxidases play an important role in converting D-amino acids to their corresponding α-keto acids. MRA_1916 of Mycobacterium tuberculosis H37Ra (Mtb-Ra) is annotated to be a D-amino acid oxidase (DAO). However, not much information is available about its physiological role during Mtb-Ra growth and survival. The present study was taken-up to understand the role of DAO during different stages of growth and effect of its down-regulation on growth. Recombinant Mtb-Ra strains with DAO and GlcB (malate synthase: MRA_1848) gene knockdown were developed and their growth was studied using Microtiter Alamar Blue Assay (MABA) with glycerol, acetate and glycine as a carbon source. Ethyl bromopyruvate (BrP) was used as an inhibitor of GlcB. MABA study showed inhibition of wild-type (WT) and knockdowns in the presence of BrP (2.5mM). However, growth inhibition of WT was less noticeable at lower concentrations of BrP. Mtb-Ra with DAO knockdown showed poor utilization of glycine in the presence of BrP. The DAO localization study showed its prominent distribution in cytosolic fraction and to some extent in cell wall and membrane fractions. Growth profile of WT under oxygen and nutritional stress showed changes in expression of DAO, GlcB, PckA (phosphoenolpyruvate carboxykinase: MRA_0219) and GlyA1 (serine hydroxymethyltransferase: MRA_1104). PMID:26531045

  18. Ra-226 and Pb-210/Ra-226 Activity Ratio in the Northern South China Sea

    NASA Astrophysics Data System (ADS)

    Chi-Ju, L.; Yu-Chia, C.; Tsung-En, W.

    2004-05-01

    The surface water distributions and vertical profiles of Ra-226 in the northern South China Sea (SCS) have been measured. Surface water Ra-226 varies between 10 and 16 dpm/100 kg with higher values at stations adjacent to the landmass. Each Ra-226 profile shows an increase from the surface toward the bottom. Above 1000m depth Ra-226 is systematically about 5 dpm/100kg higher in the northern South China Sea than in the western North Pacific. This difference may be attributed to a strong Ra-226 source from the shelf and slope area of the SCS. Below this depth Ra-226 displays large variation within some of the profiles with lower limits being comparable to the activities of the western North Pacific but higher limits being systematically about 5 dpm/100kg higher. These high Ra-226 activities may reflect effects of the longer isolation time for the deep water in the SCS basin and strong Ra input from the underlying sediments. The Pb-210/Ra-226 activity ratio ranges between 1.4 and 2.7 in the surface water with higher activity ratio at the station closer to the Luzon Strait. The Pb-210 in excess over Ra-226 in the surface water due to atmospheric input may penetrate to a depth of about 200 to 500m. Below this depth, Pb-210/Ra-226 activity ratio ranges between 0.5 and 0.7 because Pb-210 is scavenged by settling particulates. Box model calculations within a mixed layer of 50m in the area yield a mean residence time of about 1 yr for Pb-210 if an atmospheric Pb-210 flux of 1 dpm/cm2/y is adopted. The activity ratio of about 0.5 to 0.7 in the deep water corresponds to a Pb-210 mean residence time of about 30 to 70 yrs with respect to particulate scavenging.

  19. The Sophomore RA Experience: An Examination of Job Satisfaction, Turnover Intentions, and RA Self-Efficacy

    ERIC Educational Resources Information Center

    Brandt Brecheisen, Shannon M.

    2014-01-01

    The purpose of this national, quantitative study was to (1) provide psychometrics for the ACUHO-I/EBI RA Survey, a joint project between between Educational Benchmarking, Inc (EBI) and The Association of College and University Housing Officers--International (ACUHO-I), and (2) explore the sophomore resident assistant (RA) experience. This study…

  20. 228Ra/ 226Ra and 226Ra/Ba ratios in the Western Mediterranean Sea: Barite formation and transport in the water column

    NASA Astrophysics Data System (ADS)

    van Beek, P.; Sternberg, E.; Reyss, J.-L.; Souhaut, M.; Robin, E.; Jeandel, C.

    2009-08-01

    226Ra, 228Ra and Ba distributions as well as 228Ra/ 226Ra and 226Ra/Ba ratios were measured in seawater, suspended and sinking particles at the DYFAMED station in the Western Mediterranean Sea at different seasons of year 2003 in order to track the build-up and fate of barite through time. The study of the 228Ra ex/ 226Ra ex ratios (Ra ex = Ra activities corrected for the lithogenic Ra) of suspended particles suggests that Ba ex (Ba ex = Ba concentrations corrected for the lithogenic Ba, mostly barite) formation takes place not only in the upper 500 m of the water column but also deeper (i.e. throughout the mesopelagic layer). Temporal changes in the 228Ra ex/ 226Ra ex ratios of sinking particles collected at 1000 m depth likely reflect changes in the relative proportion of barite originating from the upper water column (with a high 228Ra/ 226Ra ratio) and formed in the mesopelagic layer (with a low 228Ra/ 226Ra ratio). 228Ra ex/ 226Ra ex ratios measured in sinking particles collected in the 1000 m-trap in April and May suggest that barite predominantly formed in the upper water column during that period, while barite found outside the phytoplankton bloom period (February and June) appears to form deeper in the water column. Combining ratios of both the suspended and sinking particles provides information on aggregation/disaggregation processes. High 226Ra ex/Ba ex ratios were also found in suspended particles collected in the upper 500 m of the water column. Because celestite is expected to be enriched in Ra [Bernstein R. E., Byrne R. H. and Schijf J. (1998) Acantharians: a missing link in the oceanic biogeochemistry of barium. Deep-Sea Res. II45, 491-505], acantharian skeletons may contribute to these high ratios in shallow waters. The formation of both acantharian skeletons and barite enriched in 226Ra may thus contribute to the decrease in the dissolved 226Ra activity and 226Ra/Ba ratios of surface waters observed between February and June 2003 at the DYFAMED

  1. Leaching of 226Ra from U mill tailings by sulfate-reducing bacteria.

    PubMed

    Landa, E R; Miller, C L; Updegraff, D M

    1986-10-01

    Relatively insoluble sulfate precipitates appear to be a major host for Ra in sulfuric acid-treated, U mill tailings. The dissolution of such precipitates by natural processes, such as metabolism by sulfate-reducing bacteria (SRB), creates the potential for release of Ra to contacting waters. Significant leaching of Ra by SRB was achieved in the laboratory during the anaerobic incubation (1 to 119 days) of U mill tailings with pure cultures of Desulfovibrio desulfuricans and mixed cultures containing SRB isolated from the tailings, all grown on a lactate medium at room temperature. While the maximum 226Ra concentration reached in a sterile media control was 0.44 Bq/L (12 pCi/L), that in the SRB systems was 61 Bq/L (1640 pCi/L) or about 20% of the total Ra inventory in the original tailings sample. The leaching of Ra in SRB systems was accompanied by a decrease in soluble sulfate concentration, an increase in total sulfide concentration, and an increase in the number of SRB. The observed leaching effect does not appear to be due to the action of microbial chelates or to binding to cell walls. Potential implications of these findings to the management of U mill tailings and other radioactive wastes are discussed. PMID:3759464

  2. Leaching of /sup 226/Ra from U mill tailings by sulfate-reducing bacteria

    SciTech Connect

    Landa, E.R.; Miller, C.L.; Updegraff, D.M.

    1986-10-01

    Relatively insoluble sulfate precipitates appear to be a major host for Ra in sulfuric acid-treated, U mill tailings. The dissolution of such precipitates by natural processes, such as metabolism by sulfate-reducing bacteria (SRB), creates the potential for release of Ra to contacting waters. Significant leaching of Ra by SRB was achieved in the laboratory during the anaerobic incubation (1 to 119 days) of U mill tailings with pure cultures of Desulfovibrio desulfuricans and mixed cultures containing SRB isolated from the tailings, all grown on a lactate medium at room temperature. While the maximum /sup 226/Ra concentration reached in a sterile media control was 0.44 Bq/L (12 pCi/L), that in the SRB systems was 61 Bq/L (1640 pCi/L) or about 20% of the total Ra inventory in the original tailings sample. The leaching of Ra in SRB systems was accompanied by a decrease in soluble sulfate concentration, an increase in total sulfide concentration, and an increase in the number of SRB. The observed leaching effect does not appear to be due to the action of microbial chelates or to binding to cell walls. Potential implications of these findings to the management of U mill tailings and other radioactive wastes are discussed.

  3. An alternative method for Ra determinations in water

    SciTech Connect

    Loyd, D.H.; Drake, E.N. 2d.

    1989-07-01

    Concentrations of /sup 226/Ra and /sup 224/Ra in 13 wells distributed throughout McCulloch and Mason counties in the Hickory Aquifer of the Llano Uplift Region of West-Central Texas are reported. Measurable alpha-particle activity is present in all wells, with seven wells having /sup 226/Ra radioactivity concentrations greater than 185 Bq m-3 (5 pCi L-1). An alternative methodology for measuring /sup 226/Ra, /sup 224/Ra and /sup 228/Ra is described. The EPA-approved methodology for estimating total Ra is shown to be invalid for aquifers containing significant levels of /sup 224/Ra. Alpha-particle activity measurements made in the interval of 12 to 300 h after Ra isolation lead to self-consistent solutions for radioactivity concentrations of /sup 226/Ra and /sup 224/Ra, with negligible contributions from /sup 228/Ra. Radioactivity concentrations of /sup 228/Ra can be calculated from grow-in terms for this isotope used with alpha-particle activity measurements at post-isolation times significantly longer than 800 h. Comparison of the /sup 226/Ra radioactivity concentration with that reported previously by the Texas Department of Health for a single well indicates acceptable agreement. However, the radioactivity concentration attributable to /sup 228/Ra for the same well was found to be in significant disagreement with the Texas Department of Health value.

  4. Discovery of radioactive decay of /sup 222/Ra and /sup 224/Ra by /sup 14/C emission

    SciTech Connect

    Price, P.B.; Stevenson, J.D.; Barwick, S.W.; Ravn, H.L.

    1985-01-28

    Using the ISOLDE on-line isotope separator at CERN to produce sources of /sup 221/Fr, /sup 221/Ra, /sup 222/Ra, /sup 223/Ra, and /sup 224/Ra, and using polycarbonate track-recording films sensitive to energetic carbon nuclei but not to alpha particles, we have discovered two new cases of the rare /sup 14/C decay mode: in /sup 222/Ra and /sup 224/Ra. Our results for branching ratios, B, relative to alpha decay are for /sup 221/Fr and /sup 221/Ra, B<4.4 x 10/sup -12/; for /sup 222/Ra, B = (3.7 +- 0.6) x 10/sup -10/; for /sup 223/Ra, B = (6.1 +- 1.0) x 10/sup -10/; for /sup 224/Ra, B = (4.3 +- 1.2) x 10/sup -11/. .AE

  5. Fine structure in sup 14 C emission from sup 223 Ra and sup 224 Ra

    SciTech Connect

    Hourani, E.; Rosier, L.; Berrier-Ronsin, G.; Elayi, A.; Mueller, A.C.; Rappenecker, G.; Rotbard, G.; Renou, G.; Liebe, A.; Stab, L. ); Ravn, H.L. )

    1991-10-01

    The measurement of the energy spectrum of {sup 14}C nuclei emitted in the spontaneous radioactivity of {sup 223}Ra and {sup 224}Ra has been carried out, using thin and intense sources (480 MBq for {sup 223}Ra and 3550 MBq for {sup 224}Ra). The sources were obtained by implanting mass-separated beams into Al and vitreous C catchers. The measurement was performed with a superconducting solenoidal spectrometer. Our discovery, previously reported, of fine structure in the energy spectrum of {sup 14}C emission from {sup 223}Ra, which is analogous to the one known for {alpha} emission, is confirmed. Only 13% of the branching ratio in {sup 14}C decay leads to the ground state of the residual nucleus, while 81% to the first excited state. For {sup 14}C emission from {sup 224}Ra, a lower limit of 2 for the hindrance factor has been measured for the transition to the first excited state in the residual nucleus. Also, a precise identification in {ital Z} with an {ital E}{times}{Delta}{ital E} telescope has been performed for the radiation from the {sup 223}Ra source. Our measurements of fine structure in {sup 14}C emissions open this field to nuclear structure studies.

  6. Neutron Resonance Parameters for Ra-226 (Radium)

    NASA Astrophysics Data System (ADS)

    Sukhoruchkin, S. I.; Soroko, Z. N.

    This document is part of the Supplement containing the complete sets of data of Volume 24 `Neutron Resonance Parameters' of Landolt-Börnstein - Group I `Elementary Particles, Nuclei and Atoms'. It provides the neutron resonance parameters for the isotope Ra-226 (Radium).

  7. Integrating Retinoic Acid Signaling with Brain Function

    ERIC Educational Resources Information Center

    Luo, Tuanlian; Wagner, Elisabeth; Drager, Ursula C.

    2009-01-01

    The vitamin A derivative retinoic acid (RA) regulates the transcription of about a 6th of the human genome. Compelling evidence indicates a role of RA in cognitive activities, but its integration with the molecular mechanisms of higher brain functions is not known. Here we describe the properties of RA signaling in the mouse, which point to…

  8. Extensive polymorphism of Ra86 genes in field populations of Rhipicephalus appendiculatus from Kenya.

    PubMed

    Kamau, L M; Skilton, R A; Githaka, N; Kiara, H; Kabiru, E; Shah, T; Musoke, Aj; Bishop, R P

    2016-07-01

    Commercial vaccines based on recombinant forms of the Bm86 tick gut antigen are used to control the southern cattle tick, Rhipicephalus microplus, a 1-host species, in Australia and Latin America. We describe herein sequence polymorphism in genes encoding Ra86 homologues of Bm86 in the brown ear tick, Rhipicephalus appendiculatus, isolated from four Kenyan field populations and one laboratory colony. Sequencing of 19 Ra86 sequences defined two alleles differentiated by indels, encoding 693 amino acids (aa) and 654 aa respectively, from the Muguga laboratory reference strain. Ra86 sequences were also determined from gut cDNA from four field populations of R. appendiculatus collected in different livestock production systems in Kenya. Analysis of approximately 20 Ra86 sequences from each of the four field sites in central and Western Kenya; Makuyu, Kiambu, Kakamega and Uasin Gishu, revealed three additional size types differentiated by 39-49 amino acid indels resulting in a total of 5 indel-defined genotypes. The 693 aa type 5 was isolated only from the laboratory tick stock; genotypes 1, 2 and 3 were identified in ticks from the four Kenyan field sites and appeared to be derivatives of the shorter RA86 genotype found in Muguga laboratory stock genotype 4. By contrast no large indels have yet been observed between R. microplus sequences from Australia, South America or Africa. Evidence that selection contributes to the observed sequence variation was provided by analysis of ratio of synonymous and non-synonymous substitutions and application of the selective neutrality and neutral evolution tests to the primary data. Phylogenetic analysis clustered sequences from all Ra86 size types and Bm86, into four major clades based on amino acid substitutions, but there was no evidence that these groupings correlated with geographical separation of R. appendiculatus populations. PMID:27051976

  9. An improved method for the simultaneous determination of /sup 224/Ra, /sup 226/Ra and /sup 228/Ra in water, soils and sediments

    SciTech Connect

    Lucas, H.F.

    1987-01-01

    The naturally occurring concentrations of radium (/sup 226/Ra and /sup 228/Ra) in public and private water supplies have been studied for many years. Both general surveys ad local studies have established the geographical regions where well waters exceed 3 pCi/L (1-17). In general, the /sup 226/Ra was determined by the emanation method, while the /sup 228/Ra was determined from the beta activity of the /sup 228/Ac daughter. In a recent review (18) of the methods used ''a number of approved analytic methods can bear improvement, especially the method for 228Ra.'' The purpose of the work described here was to develop an improved method for the simultaneous determination of /sup 226/Ra and /sup 228/Ra. 22 refs., 3 tabs.

  10. (228)Ra and (226)Ra measurement on a BaSO4 co-precipitation source.

    PubMed

    Medley, Peter; Martin, Paul; Bollhöfer, Andreas; Parry, David

    2014-10-14

    One of the most commonly-used methods for determination of (226)Ra, particularly in water samples, utilises co-precipitation of Ra with BaSO4, followed by microfiltration to produce a source for alpha counting. This paper describes two extensions to BaSO4 co-precipitation methods which enable determination of (228)Ra using the same source. The adaptations presented here do not introduce any contaminants that will affect the separation of radium or alpha counting for (226)Ra, and can be used for re-analysis of already existing sources prepared by BaSO4 co-precipitation. The first adaptation uses detection of (228)Ac on the source by gamma spectrometry. The detection efficiency is high, allowing analysis of water samples at sufficiently low activity to be suitable in testing for compliance with drinking water quality standards. As (228)Ac grows in quickly, taking less than 2 days to reach equilibrium with the (228)Ra parent, this can also be useful in radiological emergency response situations. The second adaptation incorporates a method for the digestion of BaSO4 sources, allowing separation of thorium and subsequent determination of (228)Th activity. Although ingrowth periods for (228)Th can be lengthy, very low detection limits for (228)Ra can be achieved with this technique.

  11. (228)Ra and (226)Ra measurement on a BaSO4 co-precipitation source.

    PubMed

    Medley, Peter; Martin, Paul; Bollhöfer, Andreas; Parry, David

    2014-10-14

    One of the most commonly-used methods for determination of (226)Ra, particularly in water samples, utilises co-precipitation of Ra with BaSO4, followed by microfiltration to produce a source for alpha counting. This paper describes two extensions to BaSO4 co-precipitation methods which enable determination of (228)Ra using the same source. The adaptations presented here do not introduce any contaminants that will affect the separation of radium or alpha counting for (226)Ra, and can be used for re-analysis of already existing sources prepared by BaSO4 co-precipitation. The first adaptation uses detection of (228)Ac on the source by gamma spectrometry. The detection efficiency is high, allowing analysis of water samples at sufficiently low activity to be suitable in testing for compliance with drinking water quality standards. As (228)Ac grows in quickly, taking less than 2 days to reach equilibrium with the (228)Ra parent, this can also be useful in radiological emergency response situations. The second adaptation incorporates a method for the digestion of BaSO4 sources, allowing separation of thorium and subsequent determination of (228)Th activity. Although ingrowth periods for (228)Th can be lengthy, very low detection limits for (228)Ra can be achieved with this technique. PMID:25464199

  12. Genetics of RA susceptibility, what comes next?

    PubMed Central

    Ding, James; Eyre, Stephen; Worthington, Jane

    2015-01-01

    Summary Genome-wide association studies (GWASs) have been used to great effect to identify genetic susceptibility loci for complex disease. A series of GWAS and meta-analyses have informed the discovery of over 100 loci for rheumatoid arthritis (RA). In common with findings in other autoimmune diseases the lead signals for the majority of these loci do not map to known gene sequences. In order to realise the benefit of investment in GWAS studies it is vital we determine how disease associated alleles function to influence disease processes. This is leading to rapid development in our knowledge as to the function of non-coding regions of the genome. Here we consider possible functional mechanisms for intergenic RA-associated variants which lie within lncRNA sequences. PMID:26509058

  13. Uranium series disequilibria in ground waters from a fractured bedrock aquifer (Morungaba Granitoids--Southern Brazil): implications to the hydrochemical behavior of dissolved U and Ra.

    PubMed

    Reyes, Erika; Marques, Leila S

    2008-10-01

    Activity concentrations of dissolved (234)U, (238)U, (226)Ra and (228)Ra were determined in ground waters from two deep wells drilled in Morungaba Granitoids (Southern Brazil). Sampling was done monthly for little longer than 1 year. Significant disequilibrium between (238)U, (234)U and (226)Ra were observed in all samples. The variation of (238)U and (234)U activity concentrations and (234)U/(238)U activity ratios is related to seasonal changes. Although the distance between the two wells is short (about 900 m), systematic differences of activity concentrations of U isotopes, as well as of (234)U/(238)U, (226)Ra/(234)U and (228)Ra/(226)Ra activity ratios were noticed, indicating distinct host rock-water interactions. Slightly acidic ground water percolation through heterogeneous host rock, associated with different recharge processes, may explain uranium and radium isotope behavior.

  14. Orally administered rosmarinic acid is present as the conjugated and/or methylated forms in plasma, and is degraded and metabolized to conjugated forms of caffeic acid, ferulic acid and m-coumaric acid.

    PubMed

    Baba, Seigo; Osakabe, Naomi; Natsume, Midori; Terao, Junji

    2004-05-28

    Rosmarinic acid (RA) is contained in various Lamiaceae herbs used commonly as culinary herbs. Although RA has various potent physiological actions, little is known on its bioavailability. We therefore investigated the absorption and metabolism of orally administered RA in rats. After being deprived of food for 12 h, RA (50 mg/kg body weight) or deionized water was administered orally to rats. Blood samples were collected from a cannula inserted in the femoral artery before and at designated time intervals after administration of RA. Urine excreted within 0 to 8 h and 8 to 18 h post-administration was also collected. RA and its related metabolites in plasma and urine were measured by LC-MS after treatment with sulfatase and/or beta-glucuronidase. RA, mono-methylated RA (methyl-RA) and m-coumaric acid (COA) were detected in plasma, with peak concentrations being reached at 0.5, 1 and 8 h after RA administration, respectively. RA, methyl-RA, caffeic acid (CAA), ferulic acid (FA) and COA were detected in urine after RA administration. These components in plasma and urine were present predominantly as conjugated forms such as glucuronide or sulfate. The percentage of the original oral dose of RA excreted in the urine within 18 h of administration as free and conjugated forms was 0.44 +/- 0.21% for RA, 1.60 +/- 0.74% for methyl-RA, 1.06 +/- 0.35% for CAA, 1.70 +/- 0.45% for FA and 0.67 +/- 0.29% for COA. Approximately 83% of the total amount of these metabolites was excreted in the period 8 to 18 h after RA administration. These results suggest that RA was absorbed and metabolized as conjugated and/or methylated forms, and that the majority of RA absorbed was degraded into conjugated and/or methylated forms of CAA, FA and COA before being excreted gradually in the urine. PMID:15120569

  15. Transgenic retinoic acid sensor lines in zebrafish indicate regions of available embryonic retinoic acid

    PubMed Central

    Mandal, Amrita; Rydeen, Ariel; Anderson, Jane; Sorrell, Mollie R.J.; Zygmunt, Tomas; Torres-Vázquez, Jesús; Waxman, Joshua S.

    2013-01-01

    Background Retinoic acid (RA) signaling plays a critical role in vertebrate development. Transcriptional reporters of RA signaling in zebrafish, thus far, have not reflected the broader availability of embryonic RA, necessitating additional tools to enhance our understanding of the spatial and temporal activity of RA signaling in vivo. Results We have generated novel transgenic RA sensors in which a RA receptor (RAR) ligand-binding domain (RLBD) is fused to the Gal4 DNA binding domain (GDBD) or a VP16-GDBD (VPBD) construct. Stable transgenic lines expressing these proteins when crossed with UAS reporter lines are responsive to RA. Interestingly, the VPBD RA sensor is significantly more sensitive than the GDBD sensor and demonstrates there may be almost ubiquitous availability of RA within the early embryo. Using confocal microscopy to compare the expression of the GDBD RA sensor to our previously established RA signaling transcriptional reporter line, Tg(12XRARE:EGFP), illustrates these reporters have significant overlap, but that expression from the RA sensor is much broader. We also identify previously unreported domains of expression for the Tg(12XRARE:EGFP) line. Conclusions Our novel RA sensor lines will be useful and complementary tools for studying RA signaling during development and anatomical structures independent of RA signaling. PMID:23703807

  16. Sorption of (226)Ra from oil effluents onto synthetic cation exchangers.

    PubMed

    Al Attar, Lina; Safia, Bassam

    2013-07-30

    Increasing environmental awareness is being urged for the safe disposal of (226)Ra-contaminated production water generated in the oil industry. Birnessite, antimony silicate and their cationic derivatives were studied for the take-up of (226)Ra using the batch-type method under experimentally determined parameters, viz. contact time, solution-solid ratio and (226)Ra concentration. Data was expressed in terms of distribution coefficients. Sorption experiments were performed in different concentrations of nitric acid in order to speculate the mechanism of (226)Ra uptake. Variation in the magnitude of sorption efficiency of the materials in the presence of the major components of waste streams, i.e. Na(+), K(+) and Ca(2+), revealed that K(+) was the greatest competitor and Na(+) the least. The application of the materials to sorb (226)Ra from actual oil co-production water samples, collected from Der Ezzor and Al Fourat petroleum companies (DEZPC and AFPC), was interpreted in terms of the exchange properties of the materials and water characterisation. Of the parameters studied, the selectivity of materials was shown to be greatly dependent on the pH of wastewater to be treated. PMID:23623032

  17. Error-control and processes optimization of (223/224)Ra measurement using Delayed Coincidence Counter (RaDeCC).

    PubMed

    Xiaoqing, Cheng; Lixin, Yi; Lingling, Liu; Guoqiang, Tang; Zhidong, Wang

    2015-11-01

    RaDeCC has proved to be a precise and standard way to measure (224)Ra and (223)Ra in water samples and successfully made radium a tracer of several environmental processes. In this paper, the relative errors of (224)Ra and (223)Ra measurement in water samples via a Radium Delayed Coincidence Count system are analyzed through performing coincidence correction calculations and error propagation. The calculated relative errors range of 2.6% ∼ 10.6% for (224)Ra and 9.6% ∼ 14.2% for (223)Ra. For different radium activities, effects of decay days and counting time on final radium relative errors are evaluated and the results show that these relative errors can decrease by adjusting the two measurement factors. Finally, to minimize propagated errors in Radium activity, a set of optimized RaDeCC measurement parameters are proposed.

  18. Error-control and processes optimization of (223/224)Ra measurement using Delayed Coincidence Counter (RaDeCC).

    PubMed

    Xiaoqing, Cheng; Lixin, Yi; Lingling, Liu; Guoqiang, Tang; Zhidong, Wang

    2015-11-01

    RaDeCC has proved to be a precise and standard way to measure (224)Ra and (223)Ra in water samples and successfully made radium a tracer of several environmental processes. In this paper, the relative errors of (224)Ra and (223)Ra measurement in water samples via a Radium Delayed Coincidence Count system are analyzed through performing coincidence correction calculations and error propagation. The calculated relative errors range of 2.6% ∼ 10.6% for (224)Ra and 9.6% ∼ 14.2% for (223)Ra. For different radium activities, effects of decay days and counting time on final radium relative errors are evaluated and the results show that these relative errors can decrease by adjusting the two measurement factors. Finally, to minimize propagated errors in Radium activity, a set of optimized RaDeCC measurement parameters are proposed. PMID:26233651

  19. A rapid and inexpensive method for 226Ra and 228Ra measurements of high TDS groundwaters.

    PubMed

    El-Shrakawy, A; Ebaid, Y Y; Burnett, W C; Aldaihan, Soaad K

    2013-07-01

    A series of laboratory-scale studies was conducted by preconcentrating (226)Ra from spiked water test samples using Purolite ion-exchange resin to evaluate the adsorption efficiency of the resin under varying conditions. After removing the resin from the columns, it was sealed in gas-tight containers and measured via gamma spectrometry. The Purolite resin showed high radium uptake and retention from natural waters in the presence of high iron and total dissolved solids (TDS). This procedure allowed us to process a large number of high TDS samples at a typical rate of 15 samples/day using three germanium detectors. Quality assurance and method validation have been achieved by analyzing selected groundwater samples, with different (226)Ra activities and high TDS values, and comparing the results to those using alpha spectrometry with a (133)Ba yield tracer. There was very good agreement between the obtained (226)Ra activities by both methods.

  20. IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging.

    PubMed

    Wakabayashi, Chisato; Numakawa, Tadahiro; Odaka, Haruki; Ooshima, Yoshiko; Kiyama, Yuji; Manabe, Toshiya; Kunugi, Hiroshi; Iwakura, Yoichiro

    2015-07-10

    Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus.

  1. sup 222 Rn, sup 226 Ra, and sup 228 Ra as tracers for the evolution of warm core rings

    SciTech Connect

    Orr, J.C.

    1988-01-01

    Naturally occurring levels of {sup 228}Ra, {sup 226}Ra, and {sup 222}Rn were measured in and around warm core rings to enhance interpretation provided by conventional conservative tracers. Surplus {sup 222}Rn was found in warm core ring 82B, thereby indicating penetration of rapidly advecting shelf water (transit time {le} 16 days). An in situ pumping system has been developed to rapidly extract {sup 228}Ra from seawater. This instrument may also simplify large-volume sampling for other trace species in seawater. Coincidence counting ({beta}-{gamma}) has been applied to analysis of oceanic {sup 228}Ra, providing precise, low-level determinations shortly after sampling with relatively high counting efficiency (5.3%), low background (0.0054 cpm) and reasonable ease of analytical processing. Results show, {sup 228}Ra activity within ring 82B increased with ring age, marking infiltration of surrounding waters. Also {sup 228}Ra must have been lost from ring 82B before it was 2 months old, an interpretation supported by physical evolution models of ring 82B and distributions of particulate Mn and {sup 228}Ra. Because {sup 226}Ra is not similarly lost, {sup 228}Ra could not have been scavenged. Particulate Mn is the only species found to correlate with {sup 228}Ra. Loss of both species in young ring 82B is attributed to their incorporation into rapidly sinking fecal material. Latter, enhanced zooplankton activity indirectly facilitated solubilization of adsorbed {sup 228}Ra; particles subsequently lost were deficient in {sup 228}Ra. Like warm core rings, the Gulf Stream loses {sup 228}Ra at a rate 60 times faster than explainable by radioactive decay, without corresponding loss of {sup 226}Ra or particulate Ba. Evaluation of counting methods reveals a fivefold sensitivity jump is feasible for {sup 228}Ra.

  2. Phytanic acid and docosahexaenoic acid increase the metabolism of all-trans-retinoic acid and CYP26 gene expression in intestinal cells.

    PubMed

    Lampen, A; Meyer, S; Nau, H

    2001-10-31

    Retinoids are essential for growth and cell differentiation of epithelial tissues. The effects of the food compounds phytol, the phytol metabolite phytanic acid, and the fatty acid docosahexaenoic acid (DHA) on the retinoid signaling pathway in intestinal cells were studied. Phytol inhibited the formation of all-trans-retinoic acid (RA) from dietary retinol in intestinal cells. Phytanic acid, a known retinoic X receptor (RXRalpha) and peroxisome proliferator activating receptor (PPARalpha) activator, also activated PPARdelta, and to a lesser degree PPARgamma, in a transactivation assay. Phytanic acid had no effect on intestinal RA hydroxylase CYP26 (also named P450RAI) gene expression and metabolism of all-trans-RA in intestinal Caco-2 cells. However, in combination with retinoic acid receptor (RAR)-ligands (all-trans-RA or synthetic Am580) phytanic acid enhanced the induction of CYP26 and RA-metabolism in comparison to treatments with all-trans-RA or Am580 alone. Also treatment with DHA did not affect CYP26 gene expression and RA-metabolism but cotreatment of the cells with DHA and all-trans-RA or Am580 enhanced the induction of CYP26, in comparison to the induction caused by all-trans-RA or Am580 alone. This study indicates that food compounds such as phytanic acid and DHA that are RXR-agonists and have an impact on intestinal CYP26 gene expression and metabolism of all-trans-RA in intestinal cells.

  3. A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist

    PubMed Central

    Xu, Wenfeng; Presnell, Scott R.; Parrish-Novak, Julia; Kindsvogel, Wayne; Jaspers, Steve; Chen, Zhi; Dillon, Stacey R.; Gao, Zeren; Gilbert, Teresa; Madden, Karen; Schlutsmeyer, Stacy; Yao, Lena; Whitmore, Theodore E.; Chandrasekher, Yasmin; Grant, Francis J.; Maurer, Mark; Jelinek, Laura; Storey, Harold; Brender, Ty; Hammond, Angie; Topouzis, Stavros; Clegg, Christopher H.; Foster, Donald C.

    2001-01-01

    IL-22 is an IL-10 homologue that binds to and signals through the class II cytokine receptor heterodimer IL-22RA1/CRF2–4. IL-22 is produced by T cells and induces the production of acute-phase reactants in vitro and in vivo, suggesting its involvement in inflammation. Here we report the identification of a class II cytokine receptor designated IL-22RA2 (IL-22 receptor-α 2) that appears to be a naturally expressed soluble receptor. IL-22RA2 shares amino acid sequence homology with IL-22RA1 (also known as IL-22R, zcytor11, and CRF2–9) and is physically adjacent to IL-20Rα and IFN-γR1 on chromosome 6q23.3–24.2. We demonstrate that IL-22RA2 binds specifically to IL-22 and neutralizes IL-22-induced proliferation of BaF3 cells expressing IL-22 receptor subunits. IL-22RA2 mRNA is highly expressed in placenta and spleen by Northern blotting. PCR analysis using RNA from various tissues and cell lines showed that IL-22RA2 was expressed in a range of tissues, including those in the digestive, female reproductive, and immune systems. In situ hybridization revealed the dominant cell types expressing IL-22RA2 were mononuclear cells and epithelium. Because IL-22 induces the expression of acute phase reactants, IL-22RA2 may play an important role as an IL-22 antagonist in the regulation of inflammatory responses. PMID:11481447

  4. Simultaneous determination of 226Ra and 210Pb in groundwater and soil samples by using the liquid scintillation counter-suspension gel method.

    PubMed

    Kim, Y J; Kim, C K; Lee, J I

    2001-02-01

    A method for the simultaneous determination of 226Ra and 210Pb in groundwater and soil samples by liquid scintillation counting was developed. Radium and lead were separated together from the samples as Ba(Ra) x PbSO4 co-precipitate, which was centrifuged and dissolved with 0.1 M EDTA solution (pH 9.0). Radium was separated as Ba(Ra)SO4 co-precipitate by adding ammonium sulfate and adjusting the pH of the solution to 4.2. Lead remaining in the solution was separated as PbSO4 precipitate by adding 9 M sulfuric acid. These Ba(Ra)SO4 and PbSO4 precipitates were purified with EDTA solution and used for measurement. To save time and to make counting samples simpler, direct counting of Ba(Ra)SO4 and PbSO4 precipitates instead of the phosphoric acid fusion method was attempted. Ba(Ra)SO4 and PbSO4 precipitates were suspended in the scintillation gel, and measured. Two liquid scintillation cocktails, Instagel XF and UltimaGold AB were used to prepare the counting samples. A mixture of water (40%), Instagel XF (40%) and UltimaGold AB (20%) formed a stable gel. Activities of 226Ra and 210Pb were calculated from the alpha spectrum of Ba(Ra)SO4 and beta spectrum of PbSO4, respectively. The long-term stability of the suspension gel was good. The analytical results of 226Ra and 210Pb in spiked groundwater samples were in good agreement with the known concentrations of 226Ra and 210Pb. The analytical values of 226Ra and 210Pb in the soil reference samples were within 11.5 and 1.6% of the relative error from the reference values, respectively.

  5. Environmental fate of Ra in cation-exchange regeneration brine waste disposed to septic tanks, New Jersey Coastal Plain, USA: migration to the water table.

    PubMed

    Szabo, Zoltan; Jacobsen, Eric; Kraemer, Thomas F; Parsa, Bahman

    2010-01-01

    Fate of radium (Ra) in liquid regeneration brine wastes from water softeners disposed to septic tanks in the New Jersey Coastal Plain was studied. Before treatment, combined Ra ((226)Ra plus (228)Ra) concentrations (maximum, 1.54 Bq L(-1)) exceeded the 0.185 Bq L(-1) Maximum Contaminant Level in 4 of 10 studied domestic-well waters (median pH, 4.90). At the water table downgradient from leachfields, combined Ra concentrations were low (commonly < or =0.019 Bq L(-1)) when pH was >5.3, indicating sequestration; when pH was < or =5.3 (acidic), concentrations were elevated (maximum, 0.985 Bq L(-1) - greater than concentrations in corresponding discharged septic-tank effluents (maximum, 0.243 Bq L(-1))), indicating Ra mobilization from leachfield sediments. Confidence in quantification of Ra mass balance was reduced by study design limitations, including synoptic sampling of effluents and ground waters, and large uncertainties associated with analytical methods. The trend of Ra mobilization in acidic environments does match observations from regional water-quality assessments.

  6. High-Speed RaPToRS

    NASA Astrophysics Data System (ADS)

    Henchen, Robert; Esham, Benjamin; Becker, William; Pogozelski, Edward; Padalino, Stephen; Sangster, Thomas; Glebov, Vladimir

    2008-11-01

    The High-Speed Rapid Pneumatic Transport of Radioactive Samples (HS-RaPToRS) system, designed to quickly and safely move radioactive materials, was assembled and tested at the Mercury facility of the Naval Research Laboratory (NRL) in Washington D.C. A sample, which is placed inside a four-inch-diameter carrier, is activated before being transported through a PVC tube via airflow. The carrier travels from the reaction chamber to the end station where it pneumatically brakes prior to the gate. A magnetic latch releases the gate when the carrier arrives and comes to rest. The airflow, optical carrier-monitoring devices, and end gate are controlled manually or automatically with LabView software. The installation and testing of the RaPToRS system at NRL was successfully completed with transport times of less than 3 seconds. The speed of the carrier averaged 16 m/s. Prospective facilities for similar systems include the Laboratory for Laser Energetics and the National Ignition Facility.

  7. Ra-224 and Ra-226: A New Method for Measuring Groundwater Seepage in Lake Michigan

    NASA Astrophysics Data System (ADS)

    Stevens, K. R.; Buyan, A. C.; Waples, J. T.

    2008-12-01

    Radium isotopes have been used to estimate groundwater discharge (GWD) in coastal marine waters for decades, but this technique has never before been used in the Laurentian Great Lakes. In this study, we used a RAD7 radon-in-air monitor to measure naturally-occurring radium isotopes Ra-224 (half-life= 3.64 d) and Ra-226 (half-life = 1600 a) in groundwater and three shallow water sites along Lake Michigan's Wisconsin coastline. Radium-224 activities in groundwater ranged from 1153 dpm m-3 in a deep aquifer (New Berlin well no.7) to 31 dpm m-3 in a shallow aquifer (Pryor well). Nearshore Lake Michigan measurements of Ra-224 were lowest at Red Arrow Beach (0.2 dpm m-3), higher in the Milwaukee harbor (GLWI slip, 1.1 dpm m-3) and highest at Harrington Beach (4.1 dpm m-3) and correspond well with groundwater seepage estimates made by Cherkauer et al. (1990) using alternate methods (i.e., where higher radium activity is indicative of higher GWD). These Ra-224 measurements are the first ever made in Lake Michigan (and presumably any of the Great Lakes) and we conclude that, by sampling offshore radium activity gradients, this RAD7 technique is a viable method for directly measuring GWD in Lake Michigan and other freshwater systems.

  8. Natural radioactivity of 226Ra and 228Ra in thermal and mineral waters in Croatia.

    PubMed

    Bituh, Tomislav; Marovic, Gordana; Petrinec, Branko; Sencar, Jasminka; Franulovic, Iva

    2009-01-01

    Thermal waters are known as valuable natural resources of a country. They contain certain degree of natural radioactivity attributable to the elements of the uranium and thorium natural decay series. Among these elements, the most radiotoxic and the most important is radium that exists in several isotopic forms (226Ra and 228Ra). The focus of attention was the content of radium in samples of thermal and mineral spring water from several spas in Croatia. These waters are mainly used for medical, bathing and recreational purposes, and some of them are used for drinking. Measured activity concentrations of 226Ra ranged from 87 to 6200 mBq l(-1) which, in some springs, exceed the maximal permissible level of 1 Bq l(-1) for drinking water. Measured activity concentrations of 228Ra ranged from 23 to 3480 mBq l(-1). The study showed that radium content for the investigated thermal and mineral waters is below the levels at which negative consequences would arise due to ingestion.

  9. Preparing concentrated carrier-free /sup 228/Ra

    SciTech Connect

    Volynskii, L.D.; Garbuzov, V.M.; Tsirlin, V.A.

    1988-05-01

    A scheme has been devised for processing large amounts of old thorium salts to obtain concentrated carrier-free /sup 228/Ra preparations. The process includes simple regeneration of the original thorium salt. The main stages in concentrating the /sup 228/Ra are precipitation and separation of thorium peroxide, isolating the radium with a carrier, ion-exchange separation of the radium from the carrier, and final purification by electrolysis. The /sup 228/Ra recovery is 70%.

  10. CMS calls a temporary halt to the RA program.

    PubMed

    2014-05-01

    The Recovery Auditors (RA) have been prohibited from issuing new post-payment Additional Document Requests since February but can conduct automated reviews until June 1. CMS is revamping the RA program and will award new contracts to auditors at an undetermined point in the future. Contract changes include fewer records requests for hospitals with low denial rates and postponing RA fees until the second level of appeal. Meanwhile, hospitals still have to comply with records requests issued before February.

  11. Exogenous IL-1Ra attenuates intestinal mucositis induced by oxaliplatin and 5-fluorouracil through suppression of p53-dependent apoptosis.

    PubMed

    Wang, Xia; Gao, Jin; Qian, Lan; Gao, Jing; Zhu, Shunying; Wu, Mingyuan; Zhang, Yang; Guan, Wen; Ye, Hao; Yu, Yan; Han, Wei

    2015-01-01

    Chemotherapy-induced intestinal mucositis (CIM) is a major dose-limiting side effect of many chemoagents, resulting in weight loss, diarrhea, and even death. The current treatments for CIM are palliative and have limited benefit. Interleukin-1 receptor antagonist is a natural antagonist of interleukin-1. Our previous studies showed the protective effect of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) on the intestine in mice after 5-fluorouracil chemotherapy. In this study, we further evaluated rhIL-1Ra in the treatment of CIM induced by different chemoagents and their combination. Normal as well as tumor-bearing mice were administered oxaliplatin (L-OHP), 5-fluorouracil, or their combination to induce intestinal mucositis and mortality. rhIL-1Ra administered after the chemotherapy, but not after the onset of diarrhea, significantly improved mouse survival, attenuated body weight loss, and reduced the incidence, severity, and duration of diarrhea. Histological examination showed that rhIL-1Ra-treated mice had a relatively intact mucosa structure, more proliferating crypt cells, and higher acid mucin content than the vehicle-treated mice. rhIL-1Ra suppressed crypt apoptosis by reducing the levels of proapoptotic proteins in wild-type, but not in IL-1RI or p53 mice. In addition, rhIL-1Ra was as effective as octreotide acetate in the treatment of chemotherapy-induced diarrhea, but with the advantage of reducing the epithelial apoptosis, the major cause of CIM. Importantly, the tumor sensitivity to chemotherapy was not affected by rhIL-1Ra. Thus, our data strongly suggest that rhIL-1Ra may be useful for the treatment of intestinal mucositis and improving the quality of life for cancer patients on chemotherapy.

  12. 228Ra, 226Ra, 224Ra and 223Ra in potential sources and sinks of land-derived material in the German Bight of the North Sea: implications for the use of radium as a tracer

    NASA Astrophysics Data System (ADS)

    Schmidt, Caroline; Hanfland, Claudia; Regnier, Pierre; van Cappellen, Philippe; Schlüter, Michael; Knauthe, Ulrich; Stimac, Ingrid; Geibert, Walter

    2011-08-01

    Activities of the naturally occurring radium nuclides 228Ra, 226Ra, 224Ra and 223Ra were determined in waters of the open German Bight and adjacent nearshore areas in the North Sea, in order to explore the potential use of radium isotopes as natural tracers of land-ocean interaction in an environment characterised by extensive tidal flats, as well as riverine and groundwater influx. Data collected at various tidal phases from the Weser Estuary (228Ra: 46.3 ± 4.6; 226Ra: 17.1 ± 1.1; 224Ra: 26.1 ± 8.2 to 36.5 ± 6.1; 223Ra: 1.8 ± 0.1 to 4.0 ± 0.4), tidal flats near Sahlenburg (228Ra: 39.3 ± 3.8 to 46.0 ± 4.5; 226Ra: 15.5 ± 1.5 to 16.5 ± 1.7; 224Ra: 34.3 ± 2.2 to 85.3 ± 6.3; 223Ra: 3.6 ± 0.5 to 8.0 ± 1.2), freshwater seeps on tidal flats near Sahlenburg (228Ra: 42.1 ± 4.1; 226Ra: 21.3 ± 2.2; 224Ra: 5.1 ± 0.9; 223Ra: 2.6 ± 1.3) and also in permanently inundated parts of the North Sea (228Ra: 23.0 ± 2.3 to 28.2 ± 2.8; 226Ra: 8.2 ± 0.8 to 11.8 ± 1.2; 224Ra: 3.1 ± 1.0 to 10.1 ± 0.9; 223Ra: 0.1 ± 0.02 to 0.9 ± 0.05; units: disintegrations per minute per 100 kg water sample) reveal that, except for the fresh groundwater, the potential end-members of nearshore water mass mixing have quite similar radium signatures, excluding a simple discrimination between the sources. However, the decreasing activities of the short-lived 224Ra and 223Ra isotopes recorded towards the island of Helgoland in the central German Bight show a potential to constrain fluxes of land-derived material to the open North Sea. The largest source for all radium isotopes is generally found on the vast tidal flats and in the Weser Estuary. Future work could meaningfully combine this so-called radium quartet approach with investigations of radon activity. Indeed, preliminary data from a tidal flat site with fresh groundwater seepage reveal a 222Rn signal that is clearly lower in seawater.

  13. Doses from 222Rn, 226Ra, and 228Ra in groundwater from Guarani aquifer, South America.

    PubMed

    Bonotto, D M

    2004-01-01

    Groundwater samples were analysed for 222Rn, 226Ra, and 228Ra in Guarani aquifer spreading around 1 million km2 within four countries in South America, and it was found that their activity concentrations are lognormally distributed. Population-weighted average activity concentration for these radionuclides allowed to estimate a value either slightly higher (0.13 mSv/year) than 0.1 mSv for the total effective dose or two times higher (0.21 mSv/year) than this limit, depending on the choice of the dose conversion factor. Such calculation adds useful information for the appropriate management of this transboundary aquifer that is socially and economically very important to about 15 million inhabitants living in Brazil, Argentina, Uruguay and Paraguay.

  14. Determination of the four natural Ra isotopes in thermal waters by gamma-ray spectrometry.

    PubMed

    Condomines, M; Rihs, S; Lloret, E; Seidel, J L

    2010-02-01

    Our method for the simultaneous determination of the four natural Ra isotopes ((226)Ra, (228)Ra, (224)Ra and (223)Ra) in thermal waters involves a separation of Ra on a selective filter (3M EMPORE Radium Rad disk), and a single counting using a broad-energy HPGe detector (BE Ge manufactured by CANBERRA). The calculation of (223)Ra and (228)Ra activities requires interference and cascade summing corrections. The (226)Ra activities in CO(2)-rich thermal waters of the Lodève Basin (South of France) range from 530 to 2240mBq/l. The low ((228)Ra/(226)Ra) activity ratios (0.19-0.29) suggest that Ra is mostly derived from the aquifer carbonates. The short-lived (224)Ra and (223)Ra are probably added to the water through recoil or desorption processes from Th-enriched coatings on the fracture walls.

  15. A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells

    PubMed Central

    Lo Cicero, Alessandra; Jaskowiak, Anne-Laure; Egesipe, Anne-Laure; Tournois, Johana; Brinon, Benjamin; Pitrez, Patricia R.; Ferreira, Lino; de Sandre-Giovannoli, Annachiara; Levy, Nicolas; Nissan, Xavier

    2016-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process and, among these, all-trans retinoic acid and 13-cis-retinoic acid, that also decreased progerin expression. This study highlights the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders. PMID:27739443

  16. Paraprofessional Staff in Transition: The Sophomore RA Experience

    ERIC Educational Resources Information Center

    Brandt Brecheisen, Shannon M.

    2015-01-01

    The sophomore resident assistant (RA) experience exists at the point where the sophomore experience and the RA position intersect. Sophomore students contend with specific transition struggles and challenges unique to their class standing as they make decisions about their sense of purpose and future career, and those who choose to become RAs face…

  17. Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).

    PubMed

    O'Dwyer, David N; Armstrong, Michelle E; Cooke, Gordon; Dodd, Jonathan D; Veale, Douglas J; Donnelly, Seamas C

    2013-10-01

    Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD.

  18. Activity concentrations of 224Ra, 226Ra, 228Ra and 40K radionuclides in refinery products and the additional radiation dose originated from oil residues in Turkey.

    PubMed

    Parmaksiz, A; Agus, Y; Bulgurlu, F; Bulur, E; Yildiz, Ç; Öncü, T

    2013-10-01

    A total of 56 crude oil, refinery product, waste water, sludge and scale samples collected from three refineries were measured by gamma-ray spectrometry. Except for nine samples, all refinery product samples were found to have activity concentrations below the minimum detectable activity (MDA) values. The maximum (224)Ra, (226)Ra, (228)Ra and (40)K activity concentrations in crude oil and refinery product samples were measured as 11.7 ± 4.5, 14.9 ± 3.5, 11.6 ± 4.5, 248.5 ± 18.5 Bq kg(-1), respectively. The maximum (224)Ra, (226)Ra, (228)Ra and (40)K activity concentrations in scale, sludge and water samples were measured as 343.7 ± 11.8, 809.2 ± 29.0, 302.5 ± 21.6, 623.0 ± 80.9 Bq kg(-1), respectively. Radium equivalent activities of the residue samples were calculated up to 1241.8 ± 42.4 Bq kg(-1). The maximum activity concentration index and the alpha index were found to be 4.2 and 4.0, respectively. The annual effective doses of residue samples were calculated below the permitted dose rate for the public, i.e. 1 mSv y(-1).

  19. Radium Ra 223 dichloride in castration-resistant prostate cancer.

    PubMed

    Joung, J Y; Ha, Y S; Kim, I Y

    2013-08-01

    Radium Ra 223 dichloride (Xofigo®, formerly Alpharadin) is one of the representative α-particle-emitting isotopes that delivers radiation with a higher biological effect to a more localized area. Preclinical studies in mouse, rat and canine models have demonstrated that radium Ra 223 dichloride has a definite skeletal affinity and antitumor effect with a relatively low toxicity on bone marrow. More recently, in a large randomized phase III trial (ALSYMPCA), patients with bone metastasis and castration-resistant prostate cancer (CRPC) received six cycles of 50 kBq/kg of radium Ra 223 dichloride in 4-week intervals. In these men, radium Ra 223 dichloride improved the median overall survival by 3.6 months when compared to the placebo group. Collectively, these results suggest that radium Ra 223 dichloride is a promising candidate for managing bone metastases in patients with CRPC.

  20. Decay of sup 226 Ra by sup 14 C emission

    SciTech Connect

    Weselka, D.; Hille, P.; Chalupka, A. )

    1990-02-01

    Previous observation of heavy-ion emission from {sup 226}Ra has been confirmed. Charge and energy of the emitted fragment were measured using thin {sup 226}Ra sources and polycarbonate track-recording films. Decay by {sup 14}C emission could be identified unambiguously. The track-detector was calibrated with tandem-accelerated {sup 14}C and {sup 16}O ions and tested by observing the {sup 14}C emission from {sup 223}Ra yielding a branching ratio of (5.0{plus minus}1.0){times}10{sup {minus}10}. In the case of {sup 226}Ra our result for the {sup 14}C/{alpha} ratio is (2.3{plus minus}0.8){times}10{sup {minus}11}. Estimates of partial half-lives of Ra isotopes for {sup 14}C emission are discussed.

  1. Rainfall Manipulation Plot Study (RaMPS)

    DOE Data Explorer

    Blair, John [Kansas State University; Fay, Phillip [USDA-ARS; Knapp, Alan [Colorado State University; Collins, Scott [University of New Mexico; Smith, Melinda [Yale University

    Rainfall Manipulation Plots facility (RaMPs) is a unique experimental infrastructure that allows us to manipulate precipitation events and temperature, and assess population community, and ecosystem responses in native grassland. This facility allows us to manipulate the amount and timing of individual precipitation events in replicated field plots at the Konza Prairie Long-Term Ecological Research (LTER) site. Questions we are addressing include: • What is the relative importance of more extreme precipitation patterns (increased climatic variability) vs. increased temperatures (increased climatic mean) with regard to their impact on grassland ecosystem structure and function? Both projected climate change factors are predicted to decrease soil water availability, but the mechanisms by which this resource depletion occurs differ. • Will altered precipitation patterns, increased temperatures and their interaction increase opportunities for invasion by exotic species? • Will long-term (6-10 yr) trajectories of community and ecosystem change in response to more extreme precipitation patterns continue at the same rate as initial responses from years 1-6? Or will non-linear change occur as potential ecological thresholds are crossed? And will increased temperatures accelerate these responses? Data sets are available as ASCII files, in Excel spreadsheets, and in SAS format. (Taken from http://www.konza.ksu.edu/ramps/backgrnd.html

  2. The atRA-responsive gene neuron navigator 2 functions in neurite outgrowth and axonal elongation.

    PubMed

    Muley, P D; McNeill, E M; Marzinke, M A; Knobel, K M; Barr, M M; Clagett-Dame, M

    2008-11-01

    Neuron navigator 2 (Nav2) was first identified as an all-trans retinoic acid (atRA)-responsive gene in human neuroblastoma cells (retinoic acid-induced in neuroblastoma 1, RAINB1) that extend neurites after exposure to atRA. It is structurally related to the Caenorhabditis elegans unc-53 gene that is required for cell migration and axonal outgrowth. To gain insight into NAV2 function, the full-length human protein was expressed in C. elegans unc-53 mutants under the control of a mechanosensory neuron promoter. Transgene expression of NAV2 rescued the defects in unc-53 mutant mechanosensory neuron elongation, indicating that Nav2 is an ortholog of unc-53. Using a loss-of-function approach, we also show that Nav2 induction is essential for atRA to induce neurite outgrowth in SH-SY5Y cells. The NAV2 protein is located both in the cell body and along the length of the growing neurites of SH-SY5Y cells in a pattern that closely mimics that of neurofilament and microtubule proteins. Transfection of Nav2 deletion constructs in Cos-1 cells reveals a region of the protein (aa 837-1065) that directs localization with the microtubule cytoskeleton. Collectively, this work supports a role for NAV2 in neurite outgrowth and axonal elongation and suggests this protein may act by facilitating interactions between microtubules and other proteins such as neurofilaments that are key players in the formation and stability of growing neurites.

  3. Measurement of 224Ra and 226Ra activities in natural waters using a radon-in-air monitor

    USGS Publications Warehouse

    Kim, G.; Burnett, W.C.; Dulaiova, H.; Swarzenski, P.W.; Moore, W.S.

    2001-01-01

    We report a simple new technique for measuring low-level radium isotopes (224Ra and 226Ra) in natural waters. The radium present in natural waters is first preconcentrated onto MnO2-coated acrylic fiber (Mn fiber) in a column mode. The radon produced from the adsorbed radium is then circulated through a closed air-loop connected to a commercial radon-in-air monitor. The monitor counts alpha decays of radon daughters (polonium isotopes) which are electrostatically collected onto a silicon semiconductor detector. Count data are collected in energy-specific windows, which eliminate interference and maintain very low backgrounds. Radium-224 is measured immediately after sampling via 220Rn (216Po), and 226Ra is measured via 222Rn (218Po) after a few days of ingrowth of 222Rn. This technique is rapid, simple, and accurate for measurements of low-level 224Ra and 226Ra activities without requiring any wet chemistry. Rapid measurements of short-lived 222Rn and 224Ra, along with long-lived 226Ra, may thus be made in natural waters using a single portable system for environmental monitoring of radioactivity as well as tracing of various geochemical and geophysical processes. The technique could be especially useful for the on-site rapid determination of 224Ra which has recently been found to occur at elevated activities in some groundwater wells.

  4. Measurement of 224Ra and 225Ra activities in natural waters using a radon-in-air monitor.

    PubMed

    Kim, G; Burnett, W C; Dulaiova, H; Swarzenski, P W; Moore, W S

    2001-12-01

    We report a simple new technique for measuring low-level radium isotopes (224Ra and 226Ra) in natural waters. The radium present in natural waters is first preconcentrated onto MnO2-coated acrylic fiber (Mn fiber) in a column mode. The radon produced from the adsorbed radium is then circulated through a closed air-loop connected to a commercial radon-in-air monitor. The monitor counts alpha decays of radon daughters (polonium isotopes) which are electrostatically collected onto a silicon semiconductor detector. Count data are collected in energy-specific windows, which eliminate interference and maintain very low backgrounds. Radium-224 is measured immediately after sampling via 220Rn (216Po), and 226Ra is measured via 222Rn 218Po) after a few days of ingrowth of 222Rn. This technique is rapid, simple, and accurate for measurements of low-level 224Ra and 226Ra activities without requiring any wet chemistry. Rapid measurements of short-lived 222Rn and 224Ra, along with long-lived 226Ra, may thus be made in natural waters using a single portable system for environmental monitoring of radioactivity as well as tracing of various geochemical and geophysical processes. The technique could be especially useful for the on-site rapid determination of 224Ra which has recently been found to occur at elevated activities in some groundwater wells.

  5. Seasonal variations in 228Ra/226Ra ratio within coastal waters of the Sea of Japan: implications for water circulation patterns in coastal areas.

    PubMed

    Inoue, M; Tanaka, K; Watanabe, S; Kofuji, H; Yamamoto, M; Komura, K

    2006-01-01

    In this study, low-background gamma-spectrometry was used to determine the (228)Ra/(226)Ra ratio of 131 coastal water samples from various environments around Honshu Island, Japan (mainly around Noto Peninsula) at 1-3 month intervals from April 2003 until September 2005. Spatial variation in (228)Ra/(226)Ra ratios was also assessed by analyzing 34 coastal water samples from five areas within the Sea of Japan during May and June 2004. The (228)Ra/(226)Ra ratio of coastal water from all sites around Noto Peninsula shows seasonal variation, with minimum values during summer ((228)Ra/(226)Ra=0.7) and maximum values during autumn-winter ((228)Ra/(226)Ra=1.7-2). This seasonal variation is similar to that recorded for coastal water between Tsushima Strait and Noto Peninsula. The measured lateral variation in (228)Ra/(226)Ra ratios within coastal water between Tsushima Strait and Noto Peninsula is only minor (0.5-0.7; May-June 2004). Coastal waters from two other sites (Pacific shore and Tsugaru Strait, north Honshu) show no clear seasonal variation in (228)Ra/(226)Ra ratio. These measured variations in (228)Ra/(226)Ra ratio, especially the temporal variations, have important implications for seasonal changes in patterns of coastal water circulation within the Sea of Japan.

  6. Progress toward an EDM measurement in {sup225}Ra.

    SciTech Connect

    Holt, R. J.; Ahmad, I.; Bailey, K.; Graner, B.; Greene, J. P.; Korsch, W.; Lu, Z.-T.; Mueller, P.; O'Connor, T. P.; Sulai, I. A.; Trimble, W. L.

    2010-11-01

    Permanent electric dipole moments (EDMs) in atoms or molecules are a signature of time-reversal and parity violation and represent an important window onto physics beyond the Standard Model. We are developing a next generation EDM search based on laser-cooled and trapped {sup 225}Ra atoms. Due to octupole deformation of the nucleus, {sup 225}Ra is predicted to be two to three orders of magnitude more sensitive to T-violating interactions than {sup 199}Hg, which currently sets the most stringent limits in the nuclear sector. We will discuss progress toward realizing a first EDM measurement for {sup 225}Ra.

  7. Concurrent determination of 224Ra, 226Ra, 228Ra, and unsupported 212Pb in a single analysis for drinking water and wastewater: dissolved and suspended fractions.

    PubMed

    Parsa, Bahman; Obed, Reynaldo N; Nemeth, William K; Suozzo, Gail

    2004-02-01

    A technique has been developed for the measurement of 224Ra, 226Ra, 228Ra, and unsupported 2t2Pb concurrently in a single analysis. The procedure can be applied to both drinking water and wastewater, including the dissolved and suspended fractions of a sample. For drinking water samples, using 3-L aliquots, the radium isotopes are isolated by a fast PbSO4 co-precipitation and then quantified by gamma-ray spectroscopy. The radium isotopes 224Ra, 226Ra, and 228Ra are measured through their gamma-ray-emitting decay products, 212Pb, 214Pb (and/or 214Bi), and 228Ac, respectively. Because of the short half-life of 224Ra (T1/2 = 3.66 d), the precipitate should be counted within 4 d of the sample collection date. In case the measurement of unsupported 212Pb (T1/2 = 10.64 h) is required, the gamma-ray analysis should be initiated as soon as possible, preferably on the same day of collection. The counting is repeated after about 21 d to ensure the 226Ra progeny are in equilibrium with their parent. At this point, the 228Ac equilibration with its 228Ra parent is already established. In the case of samples containing suspended materials, an aliquot of sample is filtered and then the filtrate is treated as described above for drinking water samples. The suspended fraction of sample, collected on the filter, is directly analyzed by gamma-ray spectroscopy with no further chemical separation. Aliquots of de-ionized water spiked with various radium standards were analyzed to check the accuracy and precision of the method. In addition, analysis results of actual samples using this method were compared with the ones performed using U.S. Environmental Protection Agency-approved procedures, and the measured values were in close agreement. This method simplifies the analytical procedures and reduces the labor while achieving the precision, accuracy, and minimum detection concentration requirements of EPA's Regulations.

  8. RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation

    PubMed Central

    Nishimoto, Satoko; Wilde, Susan M.; Wood, Sophie; Logan, Malcolm P.O.

    2015-01-01

    Summary The retinoic acid (RA)- and β-catenin-signaling pathways regulate limb bud induction and initiation; however, their mechanisms of action are not understood and have been disputed. We demonstrate that both pathways are essential and that RA and β-catenin/TCF/LEF signaling act cooperatively with Hox gene inputs to directly regulate Tbx5 expression. Furthermore, in contrast to previous models, we show that Tbx5 and Tbx4 expression in forelimb and hindlimb, respectively, are not sufficient for limb outgrowth and that input from RA is required. Collectively, our data indicate that RA signaling and Tbx genes act in a coherent feed-forward loop to regulate Fgf10 expression and, as a result, establish a positive feedback loop of FGF signaling between the limb mesenchyme and ectoderm. Our results incorporate RA-, β-catenin/TCF/LEF-, and FGF-signaling pathways into a regulatory network acting to recruit cells of the embryo flank to become limb precursors. PMID:26212321

  9. Anti-Diabetic Effects of Madecassic Acid and Rotundic Acid.

    PubMed

    Hsu, Yuan-Man; Hung, Yi-chih; Hu, Lihong; Lee, Yi-ju; Yin, Mei-chin

    2015-12-01

    Anti-diabetic effects of madecassic acid (MEA) and rotundic acid (RA) were examined. MEA or RA at 0.05% or 0.1% was supplied to diabetic mice for six weeks. The intake of MEA, not RA, dose-dependently lowered plasma glucose level and increased plasma insulin level. MEA, not RA, intake dose-dependently reduced plasminogen activator inhibitor-1 activity and fibrinogen level; as well as restored antithrombin-III and protein C activities in plasma of diabetic mice. MEA or RA intake decreased triglyceride and cholesterol levels in plasma and liver. Histological data agreed that MEA or RA intake lowered hepatic lipid droplets, determined by ORO stain. MEA intake dose-dependently declined reactive oxygen species (ROS) and oxidized glutathione levels, increased glutathione content and maintained the activity of glutathione reductase and catalase in the heart and kidneys of diabetic mice. MEA intake dose-dependently reduced interleukin (IL)-1β, IL-6, tumor necrosis factor-α and monocyte chemoattractant protein-1 levels in the heart and kidneys of diabetic mice. RA intake at 0.1% declined cardiac and renal levels of these inflammatory factors. These data indicated that MEA improved glycemic control and hemostatic imbalance, lowered lipid accumulation, and attenuated oxidative and inflammatory stress in diabetic mice. Thus, madecassic acid could be considered as an anti-diabetic agent. PMID:26633490

  10. Anti-Diabetic Effects of Madecassic Acid and Rotundic Acid

    PubMed Central

    Hsu, Yuan-Man; Hung, Yi-chih; Hu, Lihong; Lee, Yi-ju; Yin, Mei-chin

    2015-01-01

    Anti-diabetic effects of madecassic acid (MEA) and rotundic acid (RA) were examined. MEA or RA at 0.05% or 0.1% was supplied to diabetic mice for six weeks. The intake of MEA, not RA, dose-dependently lowered plasma glucose level and increased plasma insulin level. MEA, not RA, intake dose-dependently reduced plasminogen activator inhibitor-1 activity and fibrinogen level; as well as restored antithrombin-III and protein C activities in plasma of diabetic mice. MEA or RA intake decreased triglyceride and cholesterol levels in plasma and liver. Histological data agreed that MEA or RA intake lowered hepatic lipid droplets, determined by ORO stain. MEA intake dose-dependently declined reactive oxygen species (ROS) and oxidized glutathione levels, increased glutathione content and maintained the activity of glutathione reductase and catalase in the heart and kidneys of diabetic mice. MEA intake dose-dependently reduced interleukin (IL)-1β, IL-6, tumor necrosis factor-α and monocyte chemoattractant protein-1 levels in the heart and kidneys of diabetic mice. RA intake at 0.1% declined cardiac and renal levels of these inflammatory factors. These data indicated that MEA improved glycemic control and hemostatic imbalance, lowered lipid accumulation, and attenuated oxidative and inflammatory stress in diabetic mice. Thus, madecassic acid could be considered as an anti-diabetic agent. PMID:26633490

  11. Ra: The Sun for Science and Humanity

    NASA Technical Reports Server (NTRS)

    1996-01-01

    To guide the development of the Ra Strategic Framework, we defined scientific and applications objectives. For our primary areas of scientific interest, we choose the corona, the solar wind, the Sun's effect on the Earth, and solar theory and model development. For secondary areas of scientific interest, we selected sunspots, the solar constant, the Sun's gravitational field, helioseismology and the galactic cosmic rays. We stress the importance of stereoscopic imaging, observations at high spatial, spectral, and temporal resolutions, as well as of long duration measurements. Further exploration of the Sun's polar regions is also important, as shown already by the Ulysses mission. From an applications perspective, we adopted three broad objectives that would derive complementary inputs for the Strategic Framework. These were to identify and investigate: possible application spin-offs from science missions, possible solar-terrestrial missions dedicated to a particular application, and possible future applications that require technology development. The Sun can be viewed as both a source of resources and of threats. Our principal applications focus was that of threat mitigation, by examining ways to improve solar threat monitoring and early warning systems. We compared these objectives to the mission objectives of past, current, and planned international solar missions. Past missions (1962-1980) seem to have been focused on improvement of scientific knowledge, using multiple instrument spacecraft. A ten year gap followed this period, during which the results from previous missions were analyzed and solar study programmes were prepared in international organizations. Current missions (1990-1996) focus on particular topics such as the corona, solar flares, and coronal mass ejections. In planned missions, Sun/Earth interactions and environmental effects of solar activity are becoming more important. The corona is the centre of interest of almost all planned missions

  12. Seasonal changes in submarine groundwater discharge to coastal salt ponds estimated using 226Ra and 228Ra as tracers

    USGS Publications Warehouse

    Hougham, A.L.; Moran, S.B.; Masterson, J.P.; Kelly, R.P.

    2008-01-01

    Submarine groundwater discharge (SGD) to coastal southern Rhode Island was estimated from measurements of the naturally-occurring radioisotopes 226Ra (t1/2 = 1600??y) and 228Ra (t1/2 = 5.75??y). Surface water and porewater samples were collected quarterly in Winnapaug, Quonochontaug, Ninigret, Green Hill, and Pt. Judith-Potter Ponds, as well as nearly monthly in the surface water of Rhode Island Sound, from January 2002 to August 2003; additional porewater samples were collected in August 2005. Surface water activities ranged from 12-83??dpm 100??L- 1 (60??dpm = 1??Bq) and 21-256??dpm 100??L- 1 for 226Ra and 228Ra, respectively. Porewater 226Ra activities ranged from 16-736??dpm 100??L- 1 (2002-2003) and 95-815??dpm 100??L- 1 (2005), while porewater 228Ra activities ranged from 23-1265??dpm 100??L- 1. Combining these data with a simple box model provided average 226Ra-based submarine groundwater fluxes ranging from 11-159??L m- 2 d- 1 and average 228Ra-derived fluxes of 15-259??L m- 2 d- 1. Seasonal changes in Ra-derived SGD were apparent in all ponds as well as between ponds, with SGD values of 30-472??L m- 2 d- 1 (Winnapaug Pond), 6-20??L m- 2 d- 1 (Quonochontaug Pond), 36-273??L m- 2 d- 1 (Ninigret Pond), 29-76??L m- 2 d- 1 (Green Hill Pond), and 19-83??L m- 2 d- 1 (Pt. Judith-Potter Pond). These Ra-derived fluxes are up to two orders of magnitude higher than results predicted by a numerical model of groundwater flow, estimates of aquifer recharge for the study period, and values published in previous Ra-based SGD studies in Rhode Island. This disparity may result from differences in the type of flow (recirculated seawater versus fresh groundwater) determined using each technique, as well as variability in porewater Ra activity. ?? 2007 Elsevier B.V. All rights reserved.

  13. An early "Atkins' Diet": RA Fisher analyses a medical "experiment".

    PubMed

    Senn, Stephen

    2006-04-01

    A study on vitamin absorption which RA Fisher analysed for WRG Atkins and co-authored with him is critically examined. The historical background as well as correspondence between Atkins and Fisher is presented.

  14. Dynamics and precision in retinoic acid morphogen gradients

    PubMed Central

    Schilling, Thomas F.; Nie, Qing; Lander, Arthur D.

    2013-01-01

    Summary Retinoic acid (RA) regulates many cellular behaviors during embryonic development and adult homeostasis. Like other morphogens, RA forms gradients through the use of localized sources and sinks, feedback, and interactions with other signals; this has been particularly well studied in the context of hindbrain segmentation in vertebrate embryos. Yet, as a small lipophilic molecule derived from a dietary source—vitamin A—RA differs markedly from better-studied polypeptide morphogens in its mechanisms of transport, signaling, and removal. Computational models suggest that the distinctive features of RA gradients make them particularly robust to large perturbations. Such features include combined positive and negative feedback effects via intracellular fatty acid binding proteins and RA-degrading enzymes. Here, we discuss how these features, together with feedback interactions among RA target genes, help enable RA to specify multiple, accurate pattern elements in the developing hindbrain, despite operating in an environment of high cellular and biochemical uncertainty and noise. PMID:23266215

  15. Rapid determination of 226Ra in emergency urine samples

    DOE PAGES

    Maxwell, Sherrod L.; Culligan, Brian K.; Hutchison, Jay B.; Utsey, Robin C.; McAlister, Daniel R.

    2014-02-27

    A new method has been developed at the Savannah River National Laboratory (SRNL) that can be used for the rapid determination of 226Ra in emergency urine samples following a radiological incident. If a radiological dispersive device event or a nuclear accident occurs, there will be an urgent need for rapid analyses of radionuclides in urine samples to ensure the safety of the public. Large numbers of urine samples will have to be analyzed very quickly. This new SRNL method was applied to 100 mL urine aliquots, however this method can be applied to smaller or larger sample aliquots as needed.more » The method was optimized for rapid turnaround times; urine samples may be prepared for counting in <3 h. A rapid calcium phosphate precipitation method was used to pre-concentrate 226Ra from the urine sample matrix, followed by removal of calcium by cation exchange separation. A stacked elution method using DGA Resin was used to purify the 226Ra during the cation exchange elution step. This approach combines the cation resin elution step with the simultaneous purification of 226Ra with DGA Resin, saving time. 133Ba was used instead of 225Ra as tracer to allow immediate counting; however, 225Ra can still be used as an option. The rapid purification of 226Ra to remove interferences using DGA Resin was compared with a slightly longer Ln Resin approach. A final barium sulfate micro-precipitation step was used with isopropanol present to reduce solubility; producing alpha spectrometry sources with peaks typically <40 keV FWHM (full width half max). This new rapid method is fast, has very high tracer yield (>90 %), and removes interferences effectively. The sample preparation method can also be adapted to ICP-MS measurement of 226Ra, with rapid removal of isobaric interferences.« less

  16. Concentration of {sup 226}Ra in human teeth

    SciTech Connect

    Yamamoto, Masayoishi; Ueno, Kaoru; Hinoide, Moriyo; Ohkubo, Yoshiteru

    1994-11-01

    {sup 226}Ra concentrations in human teeth from several cities, mainly Tokyo, Japan, were determined with emphasis on the measurement of low-level {sup 226}Ra by alpha-ray spectrometry following chemical separation. No appreciable differences in {sup 226}Ra concentration were found among various permanent teeth samples of different age groups in Tokyo. The mean {sup 226}Ra concentration for Tokyo was 0.51 {+-} 0.06 mBq (g CA){sup -1}. {sup 226}Ra concentration [mean: 0.67 {+-} 0.11 mBq (g Ca){sup -1}] in teeth in western regions of the country was statistically higher than that [mean: 0.48 {+-} 0.09 mBq (g Ca){sup -1}] in eastern ones. The mean {sup 226}Ra concentration [0.51 mBq (g CA){sup -1}] in teeth from Tokyo was less than the concentration [1.11 mBq (g CA){sup -1}] reported for vertebral bone samples of this city. 27 refs., 1 fig., 5 tabs.

  17. Determining groundwater Ra end-member values for the estimation of the magnitude of submarine groundwater discharge using Ra isotope tracers

    NASA Astrophysics Data System (ADS)

    Cho, Hyung-Mi; Kim, Guebuem

    2016-04-01

    Radium isotopes (228Ra and 226Ra) are excellent tracers of submarine groundwater discharge (SGD). To estimate SGD magnitudes, information on the end-member values of Ra concentrations in groundwater is critical; however, the distribution characteristics of Ra in coastal aquifers are poorly understood. In this study, we show that Ra concentrations in coastal groundwater are primarily dependent on salinity based on the data (n > 500) obtained from global coastal aquifers, although previous end-member calculations averaged all Ra concentrations without considering salinity. If we assume that SGD is composed mainly of seawater infiltrating the aquifer, previous estimates of SGD for the Atlantic Ocean and the global ocean were overestimated twofold to threefold. This may be similar for other applications using different Ra isotopes. Our study highlights that the end-members of Ra isotopes in groundwater should be carefully considered when estimating SGD using Ra isotope mass balances in the ocean.

  18. Coelimination and Survival in Gene Network Evolution: Dismantling the RA-Signaling in a Chordate.

    PubMed

    Martí-Solans, Josep; Belyaeva, Olga V; Torres-Aguila, Nuria P; Kedishvili, Natalia Y; Albalat, Ricard; Cañestro, Cristian

    2016-09-01

    The bloom of genomics is revealing gene loss as a pervasive evolutionary force generating genetic diversity that shapes the evolution of species. Outside bacteria and yeast, however, the understanding of the process of gene loss remains elusive, especially in the evolution of animal species. Here, using the dismantling of the retinoic acid metabolic gene network (RA-MGN) in the chordate Oikopleura dioica as a case study, we combine approaches of comparative genomics, phylogenetics, biochemistry, and developmental biology to investigate the mutational robustness associated to biased patterns of gene loss. We demonstrate the absence of alternative pathways for RA-synthesis in O. dioica, which suggests that gene losses of RA-MGN were not compensated by mutational robustness, but occurred in a scenario of regressive evolution. In addition, the lack of drastic phenotypic changes associated to the loss of RA-signaling provides an example of the inverse paradox of Evo-Devo. This work illustrates how the identification of patterns of gene coelimination-in our case five losses (Rdh10, Rdh16, Bco1, Aldh1a, and Cyp26)-is a useful strategy to recognize gene network modules associated to distinct functions. Our work also illustrates how the identification of survival genes helps to recognize neofunctionalization events and ancestral functions. Thus, the survival and extensive duplication of Cco and RdhE2 in O. dioica correlated with the acquisition of complex compartmentalization of expression domains in the digestive system and a process of enzymatic neofunctionalization of the Cco, while the surviving Aldh8 could be related to its ancestral housekeeping role against toxic aldehydes. PMID:27406791

  19. HLA-D region genes and rheumatoid arthritis (RA): importance of DR and DQ genes in conferring susceptibility to RA.

    PubMed Central

    Singal, D P; Green, D; Reid, B; Gladman, D D; Buchanan, W W

    1992-01-01

    The distribution of HLA-D region antigens was studied in three groups (I, IIa, and IIb) of patients with rheumatoid arthritis (RA): group I comprised 43 patients with mild, non-progressive RA, controlled by non-steroidal anti-inflammatory drugs without progression or erosions; group II comprised 94 patients with severe disease, who had earlier been treated with non-steroidal anti-inflammatory drugs and all had incomplete response requiring treatment with gold (sodium aurothiomalate). Of these, 46 patients (group IIa) responded to gold and the disease was well controlled, and the remaining 48 patients (group IIb) did not respond to gold and developed gold induced toxic reactions, including thrombocytopenia or proteinuria, or both. HLA-D region antigens were defined by serological and molecular (Southern blot analysis and oligonucleotide typing) techniques. The results show that DR4 was significantly increased in all three groups of patients. The prevalence of DR1, or DR1 in DR4 negative patients, and DR3 and DR4 associated DQw7 specificities, however, showed differences in these three groups of patients. The prevalence of DR1 and of DR1 in DR4 negative patients was increased only in patients with mild (group I) RA, but not in patients with severe (groups IIa and IIb) disease. On the other hand, the prevalence of DR4 associated DQw7 was significantly increased in patients with severe disease, but not in patients with mild RA. In addition, DR3 was significantly increased only in patients with severe disease who developed gold induced toxic reactions (group IIb). These data suggest that the HLA-D region genes which cause susceptibility to mild RA may be different from those causing susceptibility to severe RA. The results suggest that both DR and DQ (A, B) genes may be important in conferring susceptibility to RA: DR in mild disease and DQ in severe RA. Images PMID:1371662

  20. Radium isotopes ((226)Ra and (228)Ra) in Na-Cl type groundwaters from Tohoku District (Aomori, Akita and Yamagata Prefectures) in Japan.

    PubMed

    Tomita, Jumpei; Zhang, Jing; Yamamoto, Masayoshi

    2014-11-01

    A total of 28 Na-Cl type groundwater samples were collected from Aomori, Akita and Yamagata Prefectures, in the Tohoku District of Japan, and their radium isotope ((226)Ra and (228)Ra) concentrations were measured along with their chemical components and stable isotope ratios (δ(2)H and δ(18)Os). The (226)Ra concentrations in groundwater samples varied widely, ranging from 8.8 to 1587 mBq kg(-1). These concentrations showed an increasing tendency with the increase of the total dissolved solid (TDS) contents. The (228)Ra/(226)Ra activity ratios were in the range from 0.3 to 4.2, with most data being around 0.5-2. These ratios were within those of (232)Th/(238)U found in granitic and related rocks and so on in Japan, indicating that Ra isotopes mainly ejected into the groundwater by the alpha-recoil process. The relationship between (226)Ra and other parameters suggested that Ra isotopes in groundwater samples in this study were mainly constrained by adsorption-desorption reactions depending on salinity with wide variation. Clear correlation between (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS observed in sulfate-free groundwater samples indicated that Ra isotopes of them were constrained by adsorption-desorption reactions depending on salinity under reducing condition. In contrast, relationship of (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS in sulfate-containing groundwater samples varied widely, and then, removal or enhanced mobility of Ra isotopes of them were observed.

  1. Radium isotopes ((226)Ra and (228)Ra) in Na-Cl type groundwaters from Tohoku District (Aomori, Akita and Yamagata Prefectures) in Japan.

    PubMed

    Tomita, Jumpei; Zhang, Jing; Yamamoto, Masayoshi

    2014-11-01

    A total of 28 Na-Cl type groundwater samples were collected from Aomori, Akita and Yamagata Prefectures, in the Tohoku District of Japan, and their radium isotope ((226)Ra and (228)Ra) concentrations were measured along with their chemical components and stable isotope ratios (δ(2)H and δ(18)Os). The (226)Ra concentrations in groundwater samples varied widely, ranging from 8.8 to 1587 mBq kg(-1). These concentrations showed an increasing tendency with the increase of the total dissolved solid (TDS) contents. The (228)Ra/(226)Ra activity ratios were in the range from 0.3 to 4.2, with most data being around 0.5-2. These ratios were within those of (232)Th/(238)U found in granitic and related rocks and so on in Japan, indicating that Ra isotopes mainly ejected into the groundwater by the alpha-recoil process. The relationship between (226)Ra and other parameters suggested that Ra isotopes in groundwater samples in this study were mainly constrained by adsorption-desorption reactions depending on salinity with wide variation. Clear correlation between (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS observed in sulfate-free groundwater samples indicated that Ra isotopes of them were constrained by adsorption-desorption reactions depending on salinity under reducing condition. In contrast, relationship of (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS in sulfate-containing groundwater samples varied widely, and then, removal or enhanced mobility of Ra isotopes of them were observed. PMID:25113929

  2. A simple differential diffusion model to account for the discrepancy between 223Ra- and 224Ra-based eddy diffusivities

    NASA Astrophysics Data System (ADS)

    Stachelhaus, Scott L.; Moran, S. Bradley

    2012-03-01

    A series of 223Ra (t1/2 = 11.4 d) and 224Ra (t1/2 = 3.66 d) measurements made in the Mid-Atlantic Bight yield eddy diffusivity (K) estimates of 1.2 ± 0.3 × 102 m2 s-1 and 1.4 ± 0.2 × 102 m2 s-1, respectively. These results fall in line with previous studies from multiple locations throughout the ocean, in which 224Ra-based eddy diffusivities invariably exceed those determined using 223Ra. Such a pattern conflicts with the Fickian model for eddy diffusivity, in which K is constant. Moreover, this trend runs counter to the length scale-dependent view of eddy diffusion, which suggests that K values estimated using 223Ra should exceed those of 224Ra, because the length scale of the former is greater than that of the latter. A finite mixing-length model based on the concept of differential diffusion is used to provide an explanation for this discrepancy.

  3. Leaching of radionuclides from uranium ore and mill tailings ( Ra- 226, Tn-230).

    USGS Publications Warehouse

    Landa, E.R.

    1982-01-01

    The major part of the extractable uranium is associated with a readily acid-soluble fraction in both ore and tailings. The major part of the extractable 226Ra was associated with an iron, manganese hydrous-oxide fraction in the ore and tailings. Thorium-230 was the least leachable of the radionuclides studied. The major portion of the extractable 230Th was associated with alkaline-earth sulphate precipitates, organic matter, or both. The specific effects of milling on each of the nuclides are discussed.-Author

  4. Induction of the oxidative catabolism of retinoid acid in MCF-7 cells.

    PubMed Central

    Krekels, M. D.; Verhoeven, A.; van Dun, J.; Cools, W.; Van Hove, C.; Dillen, L.; Coene, M. C.; Wouters, W.

    1997-01-01

    Cytochrome P450-dependent oxidation is a pathway for all-trans-retinoic acid (all-trans-RA) catabolism. Induction of this catabolic pathway was studied in MCF-7 breast cancer cells. MCF-7 cells showed low constitutive all-trans-RA catabolism. Concentration-dependent induction was obtained by preincubation of the cells with all-trans-RA (10(-9) to 10(-6) M). Onset of induction was fast, being detectable within 60 min, with maximal induction (45-fold) obtained after 16 h. Enzymatic characterization of induced all-trans-RA catabolism showed an estimated Km value (Michaelis-Menten constant) of 0.33 microM and a Vmax value (maximal velocity of an enzyme-catalysed reaction) of 54.5 fmol polar all-trans-RA metabolites 10(6) cells(-1) h(-1). These kinetic parameters represent the overall formation of polar metabolites from all-trans-RA. Induction of all-trans-RA catabolism was also obtained with other retinoids, CH55 >> 13-cis-RA = all-trans-RA > 9-cis-RA > 4-keto-all-trans-RA > 4-keto-13-cis-RA > retinol. The potency of the retinoids to induce all-trans-RA catabolism was correlated to their retinoic acid receptor affinity (Crettaz et al, 1990; Repa et al, 1990; Sani et al, 1990). Induction of all-trans-RA catabolism was inhibited by actinomycin D. Furthermore, all-trans-RA did not increase cytosolic retinoic acid-binding protein (CRABP) mRNA levels. These data suggest that induction of all-trans-RA catabolism in MCF-7 cells is a retinoic acid receptor-mediated gene transcriptional event. Induced all-trans-RA catabolism was inhibited by various retinoids with decreasing potency in the order: all-trans-RA > 4-keto-all-trans-RA > 13-cis-RA > 9-cis-RA > 4-keto-13-cis-RA > retinol > CH55. The antitumoral compound liarozole-fumarate inhibited all-trans-RA catabolism with a potency similar to that of all-trans-RA. Images Figure 4 PMID:9099955

  5. The role of CYP26 enzymes in defining appropriate retinoic acid exposure during embryogenesis.

    PubMed

    Pennimpede, Tracie; Cameron, Don A; MacLean, Glenn A; Li, Hui; Abu-Abed, Suzan; Petkovich, Martin

    2010-10-01

    Retinoic acid (RA) is a pleiotropic derivative of vitamin A, or retinol, which is responsible for all of the bioactivity associated with this vitamin. The teratogenic influences of vitamin A deficiency and excess RA in rodents were first observed more than 50 years ago. Efforts over the last 15-20 years have refined these observations by defining the molecular mechanisms that control RA availability and signaling during murine embryonic development. This review will discuss our current understanding of the role of RA in teratogenesis, with specific emphasis on the essential function of the RA catabolic CYP26 enzymes in preventing teratogenic consequences caused by uncontrolled distribution of RA. Particular focus will be paid to the RA-sensitive tissues of the caudal and cranial regions, the limb, and the testis, and how genetic mutation of factors controlling RA distribution have revealed important roles for RA during embryogenesis.

  6. Ra-226 and Ra-226/Ba Signatures of Intermediate and Deep Water Masses of the Labrador Sea

    NASA Astrophysics Data System (ADS)

    Pons-Branchu, E.; Hillaire-Marcel, C.; Ghaleb, B.

    2004-05-01

    The Labrador sea plays an important role in the formation of intermediate North Atlantic water, (cf. Labrador Sea Water -LSW) and subsequently, in the general thermohaline circulation of the ocean. In addition, water masses originating from the Norwegian and Greenland seas are present below the LSW, in the deeper part of the basin. Investigations on the geochemistry of radium have been undertaken as a mean to document these deep and intermediate circulation processes. The vertical distribution of Ra-226 and Ba contents has been established for 8 stations located along 2 sections from 48°44 N; 52°58W to 52°23 N 45°17W and from 53.59°N to 60.34°N, 48.13°W. Thermo-Ionization Mass Spectrometry coupled with a new radium extraction and purification technique permitted the measurement of Ra-226 using 200 ml samples (i.e., appr. 10 femtograms of Ra). In parallel, Ba contents were determined using M-C-ICP-MS in order to normalize Ra-226 concentrations, since Ba is often seen as a subrogate stable isotope of Ra, due to their almost similar geochemical behaviour. Large variations in Ra-226 concentrations are observed. They range from 51 fg/g in intermediate and deep water samples to 31 fg/g in surface waters. When normalised to a salinity of 35 or to the Ba contents large discrepancies are still observed. They suggest a specific Ra-signature for each of the major water masses present in the basin. Particular attention has been paid to Ra-226 contents in the LSW in relation to its production rate as well as to the influence of the Western Boundary Under Current (WBUC), which carries the North Atlantic Deep water masses into their gyre along the lower slopes of the Labrador sea. Based on the presently available data set, a peak in Ra-226 and Ba contents seems to characterise the high velocity axis of the WBUC. These data suggest moreover a lower Ra-226 content for the LSW than for the deeper water masses.

  7. The "RA" Expeditions: The Archaeological and Anthropological Background. The "RA" Expeditions: The Coriolis Effect. The "RA" Expeditions: The Papyrus Reed. Learning Experiences for Coastal and Oceanic Awareness Studies, Nos. 211, 212, 213. [Project COAST].

    ERIC Educational Resources Information Center

    Delaware Univ., Newark. Coll. of Education.

    Included are three units related to coastal and oceanic awareness. These are: (1) The "RA" Expeditions: The Archaeological and Anthropological Background; (2) The "RA" Expeditions: The Coriolis Effect; and (3) The "RA" Expeditions: The Papyrus Reed. Each of the three units are designed for students in grades 6-12. Each unit contains teacher…

  8. Seasonal variation of 228Ra/226Ra ratio in seaweed: implications for water circulation patterns in coastal areas of the Noto Peninsula, Japan.

    PubMed

    Inoue, M; Kofuji, H; Yamamoto, M; Komura, K

    2005-01-01

    To examine water circulation patterns of coastal water, 72 seaweed (Sargasso) samples and 27 coastal water samples were collected from coastal areas of the Noto Peninsula, Japan, during the period from December 1998 to June 2002. The (228)Ra and (226)Ra activities of those samples were measured by low-background gamma-ray spectrometry. There was a wide range of activities of (228)Ra (0.5-2Bq/kg-fresh) and (226)Ra (0.5-1.2Bq/kg-fresh) in the Sargasso samples. The (228)Ra/(226)Ra activity ratio of Sargasso samples exhibited seasonal variation with minimum values in June ((228)Ra/(226)Ra= approximately 1) and maximum values in December (1.5-2.5), which was mainly governed by changes in (228)Ra activity. It is also notable that the seasonal variation of the (228)Ra/(226)Ra ratio of Sargasso is in approximate agreement with that of the ambient coastal water. Sargasso samples appear to have retained the (228)Ra/(226)Ra ratio of the ambient coastal waters, and the temporal variations in that ratio provide insight into seasonal changes in water circulation in the Noto Peninsula coastal area.

  9. An efficient and simple method for measuring (226)Ra using the scintillation cell in a delayed coincidence counting system (RaDeCC).

    PubMed

    Waska, Hannelore; Kim, Seolwon; Kim, Guebuem; Peterson, Richard N; Burnett, William C

    2008-12-01

    A delayed coincidence counter (RaDeCC), developed to determine ultra-low levels of (223)Ra (half life = 11.1 days) and (224)Ra (half life = 3.6 days) in seawater, was adapted to measure (226)Ra (half life = 1622 years). After pre-concentration of Ra from seawater onto MnO(2)-coated fiber we show in this study that the (226)Ra activity can be determined using the RaDeCC's ability to record alpha decay of its daughters as total counts. For sufficient ingrowth of (222)Rn, the Mn-fiber is hermetically sealed in a column for a few days. Then, the ingrown (222)Rn is circulated through the RaDeCC air-loop system followed by shutting down of the pump and closure of the scintillation cell for equilibration. Counting may be completed within a few hours for seawater samples. Sample measurements with this method agreed well with data obtained using gamma-ray spectrometry. This proves that a set of Ra isotopes ((223)Ra, (224)Ra, and (226)Ra), commonly used for geophysical studies such as mixing rates of different water masses and submarine groundwater discharge, can be efficiently and rapidly measured using the RaDeCC.

  10. Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for 223Ra and 225Ra for targeted alpha therapy

    DOE PAGES

    Rojas, J. V.; Woodward, J. D.; Chen, N.; Rondinone, A. J.; Castano, C. H.; Mirzadeh, S.

    2015-03-19

    Targeted alpha therapy (TAT) has the potential for killing specific tumor cells with minimum collateral damage to surrounding healthy tissue. Radionuclides such as 223Ra, 225Ra, and 225Ac are of special interest for radiotherapeutic applications as they emit multiple -particles during their decay. Utilizing appropriate carriers capable of retaining both the parent radioisotope as well as daughter products is important for the effective delivery of the radioisotope to the tumor site while mitigating global in vivo radiotoxicity. Methods. In this work, core and core+2 shells (NPs with 2 additional layers of cold LaPO4 deposited on the core surfaces) LaPO4 nanoparticles (NPs)more » were synthesized containing either 223Ra or 225Ra/225Ac and the retention of the parents and daughters within the NPs in vitro was investigated. Results. The NPs crystallized in rhabdophane phase with mean diameters of 3.4 and 6.3 nm for core and core+2 shells, respectively. The core LaPO 4 NPs retained up to 88% of 223Ra over 35 days. However, in the core+2 shell NPs, the retention of 223Ra and its daughter, 211Pb, was improved to > 99.9% over 27 days. Additionally, the retention of 225Ra/225Ac parents was > 99.98% and ~80% for the 221Fr and 213Bi daughters over 35 days for the core+2 shell NPs. Conclusions. These results suggest that LaPO4 NPs are potentially effective carriers of radium isotopes.« less

  11. Microbiota and bile acid profiles in retinoic acid-primed mice that exhibit accelerated liver regeneration

    PubMed Central

    Liu, Hui-Xin; Hu, Ying; Wan, Yu-Jui Yvonne

    2016-01-01

    Background & Aims All-trans Retinoic acid (RA) regulates hepatic lipid and bile acid homeostasis. Similar to bile acid (BA), RA accelerates partial hepatectomy (PHx)-induced liver regeneration. Because there is a bidirectional regulatory relationship between gut microbiota and BA synthesis, we examined the effect of RA in altering the gut microbial population and BA composition and established their relationship with hepatic biological processes during the active phases of liver regeneration. Methods C57BL/6 mice were treated with RA orally followed by 2/3 PHx. The roles of RA in shifting gut microbiota and BA profiles as well as hepatocyte metabolism and proliferation were studied. Results RA-primed mice exhibited accelerated hepatocyte proliferation revealed by higher numbers of Ki67-positive cells compared to untreated mice. Firmicutes and Bacteroidetes phyla dominated the gut microbial community (>85%) in both control and RA-primed mice after PHx. RA reduced the ratio of Firmicutes to Bacteroidetes, which was associated with a lean phenotype. Consistently, RA-primed mice lacked transient lipid accumulation normally found in regenerating livers. In addition, RA altered BA homeostasis and shifted BA profiles by increasing the ratio of hydrophilic to hydrophobic BAs in regenerating livers. Accordingly, metabolic regulators fibroblast growth factor 21, Sirtuin1, and their downstream targets AMPK and ERK1/2 were more robustly activated in RA-primed than unprimed regenerating livers. Conclusions Priming mice with RA resulted in a lean microbiota composition and hydrophilic BA profiles, which were associated with facilitated metabolism and enhanced cell proliferation. PMID:26701854

  12. Rapid determination of 226Ra in environmental samples

    SciTech Connect

    Maxwell, Sherrod L.; Culligan, Brian K.

    2012-02-04

    A new rapid method for the determination of {sup 228}Ra in natural water samples has been developed at the SRNL/EBL (Savannah River National Lab/ Environmental Bioassay Laboratory) that can be used for emergency response or routine samples. While gamma spectrometry can be employed with sufficient detection limits to determine {sup 228}Ra in solid samples (via {sup 228}Ac) , radiochemical methods that employ gas flow proportional counting techniques typically provide lower MDA (Minimal Detectable Activity) levels for the determination of {sup 228}Ra in water samples. Most radiochemical methods for {sup 228}Ra collect and purify {sup 228}Ra and allow for {sup 228}Ac daughter ingrowth for ~36 hours. In this new SRNL/EBL approach, {sup 228}Ac is collected and purified from the water sample without waiting to eliminate this delay. The sample preparation requires only about 4 hours so that {sup 228}Ra assay results on water samples can be achieved in < 6 hours. The method uses a rapid calcium carbonate precipitation enhanced with a small amount of phosphate added to enhance chemical yields (typically >90%), followed by rapid cation exchange removal of calcium. Lead, bismuth, uranium, thorium and protactinium isotopes are also removed by the cation exchange separation. {sup 228}Ac is eluted from the cation resin directly onto a DGA Resin cartridge attached to the bottom of the cation column to purify {sup 228}Ac. DGA Resin also removes lead and bismuth isotopes, along with Sr isotopes and {sup 90}Y. La is used to determine {sup 228}Ac chemical yield via ICP-MS, but {sup 133}Ba can also be used instead if ICP-MS assay is not available. Unlike some older methods, no lead or strontium holdback carriers or continual readjustment of sample pH is required.

  13. Effect of retinoic acid and ethanol on retinoic acid receptor beta and glial fibrillary acidic protein mRNA expression in human astrocytoma cells.

    PubMed

    Grummer, M A; Salih, Z N; Zachman, R D

    2000-11-17

    This work explores the hypothesis that perturbations caused by ethanol on the regulatory role of retinoids in brain development may be a mechanism involved in the neuropathology of fetal alcohol syndrome. The interaction of ethanol and retinoic acid (RA) on RA receptor (RAR) beta and glial fibrillary acidic protein (GFAP) mRNA expression is evaluated. In the U-373 MG astrocytoma, mRNA expression of RAR beta was increased and GFAP was decreased by RA. Ethanol decreased the expression of RAR beta mRNA, but increased that of GFAP. The RA-stimulated increase in RAR beta was not affected by the presence of ethanol. RA prevented the ethanol-induced increase in GFAP mRNA. Cycloheximide abolished only the GFAP response to ethanol. This work shows that an interrelationship between ethanol and RA exists in the astrocyte. PMID:11058790

  14. Process waste assessment: Color print processing (RA-4)

    SciTech Connect

    Catlett, P.

    1994-05-01

    The Kodak RA-4 process is used to develop prints and overhead transparencies from photographic negatives. The assessment was based on usage, effluent discharge, and final disposition of waste generated by the process. Two options explored were bleach-fix regeneration and the conversion to a digital image processing system. The RA-4 process is process is environmentally sound and generates a relatively small amount of waste. The bleach-fix option would provide only a small effluent reduction. The digital imaging conversion option, if fully implemented, could greatly reduce waste generated in the photo lab.

  15. RAPID DETERMINATION OF RA-226 IN ENVIRONMENTAL SAMPLES

    SciTech Connect

    Maxwell, S.

    2012-01-03

    A new rapid method for the determination of {sup 226}Ra in environmental samples has been developed at the Savannah River Site Environmental Lab (Aiken, SC, USA) that can be used for emergency response or routine sample analyses. The need for rapid analyses in the event of a Radiological Dispersive Device or Improvised Nuclear Device event is well-known. In addition, the recent accident at Fukushima Nuclear Power Plant in March, 2011 reinforces the need to have rapid analyses for radionuclides in environmental samples in the event of a nuclear accident. {sup 226}Ra (T1/2 = 1,620 years) is one of the most toxic of the long-lived alpha-emitters present in the environment due to its long life and its tendency to concentrate in bones, which increases the internal radiation dose of individuals. The new method to determine {sup 226}Ra in environmental samples utilizes a rapid sodium hydroxide fusion method for solid samples, calcium carbonate precipitation to preconcentrate Ra, and rapid column separation steps to remove interferences. The column separation process uses cation exchange resin to remove large amounts of calcium, Sr Resin to remove barium and Ln Resin as a final purification step to remove {sup 225}Ac and potential interferences. The purified {sup 226}Ra sample test sources are prepared using barium sulfate microprecipitation in the presence of isopropanol for counting by alpha spectrometry. The method showed good chemical recoveries and effective removal of interferences. The determination of {sup 226}Ra in environmental samples can be performed in less than 16 h for vegetation, concrete, brick, soil, and air filter samples with excellent quality for emergency or routine analyses. The sample preparation work takes less than 6 h. {sup 225}Ra (T1/2 = 14.9 day) tracer is used and the {sup 225}Ra progeny {sup 217}At is used to determine chemical yield via alpha spectrometry. The rapid fusion technique is a rugged sample digestion method that ensures that any

  16. The meninges is a source of retinoic acid for the late-developing hindbrain.

    PubMed

    Zhang, Jinghua; Smith, Deborah; Yamamoto, Miyuki; Ma, Lanhua; McCaffery, Peter

    2003-08-20

    One general function for retinoic acid (RA) is pattern organization in the CNS. This regulatory factor has an essential role in spinal cord motor neuron and early posterior hindbrain development. In the anterior CNS, however, there is only a limited number of foci of RA synthesis, and less attention has been placed on regions such as the anterior hindbrain where RA synthesizing enzymes are absent. This study shows that a rich source of RA lies around the hindbrain from the RA synthetic enzyme retinaldehyde dehydrogenase-2 (RALDH2) present in the surrounding meninges and mesenchyme by embryonic day 13. RALDH2 is not distributed uniformly throughout the meninges but is restricted to territories over the developing hindbrain, suggesting that RA signaling may be localized to those regions. Further regulation of RA signaling is provided by the presence of a RA sink in the form of the CYP26B1 RA catabolic enzyme expressed in deeper regions of the brain. As a guide to the neural anatomy of hindbrain RA signaling, we used a mouse transgenic for a lacZ reporter gene driven by a RA response element (RAREhsplacZ) to identify regions of RA signaling. This reporter mouse provides evidence that RA signaling in the hindbrain after embryonic day 13 occurs in the regions of the cerebellum and precerebellar system adjacent to sources of RA, including the inferior olive and the pontine nuclei.

  17. Importance of ALDH1A enzymes in determining human testicular retinoic acid concentrations

    PubMed Central

    Arnold, Samuel L.; Kent, Travis; Hogarth, Cathryn A.; Schlatt, Stefan; Prasad, Bhagwat; Haenisch, Michael; Walsh, Thomas; Muller, Charles H.; Griswold, Michael D.; Amory, John K.; Isoherranen, Nina

    2015-01-01

    Retinoic acid (RA), the active metabolite of vitamin A, is required for spermatogenesis and many other biological processes. RA formation requires irreversible oxidation of retinal to RA by aldehyde dehydrogenase enzymes of the 1A family (ALDH1A). While ALDH1A1, ALDH1A2, and ALDH1A3 all form RA, the expression pattern and relative contribution of these enzymes to RA formation in the testis is unknown. In this study, novel methods to measure ALDH1A protein levels and intrinsic RA formation were used to accurately predict RA formation velocities in individual human testis samples and an association between RA formation and intratesticular RA concentrations was observed. The distinct localization of ALDH1A in the testis suggests a specific role for each enzyme in controlling RA formation. ALDH1A1 was found in Sertoli cells, while only ALDH1A2 was found in spermatogonia, spermatids, and spermatocytes. In the absence of cellular retinol binding protein (CRBP)1, ALDH1A1 was predicted to be the main contributor to intratesticular RA formation, but when CRBP1 was present, ALDH1A2 was predicted to be equally important in RA formation as ALDH1A1. This study provides a comprehensive novel methodology to evaluate RA homeostasis in human tissues and provides insight to how the individual ALDH1A enzymes mediate RA concentrations in specific cell types. PMID:25502770

  18. Initiating Meiosis: The Case for Retinoic Acid1

    PubMed Central

    Griswold, Michael D.; Hogarth, Cathryn A.; Bowles, Josephine; Koopman, Peter

    2011-01-01

    ABSTRACT The requirement for vitamin A in reproduction and development was first determined from studies of nutritional deficiencies. Subsequent research has shown that embryonic development and both male and female reproduction are modulated by retinoic acid (RA), the active form of vitamin A. Because RA is active in multiple developmental systems, its synthesis, transport, and degradation are tightly regulated in different tissues. A growing body of evidence implicates RA as a requirement for the initiation of meiosis in both male and female mammals, resulting in a mechanistic model involving the interplay of RA, RA synthesis enzymes, RA receptors, and degradative cytochrome P450 enzymes in this system. Recently, that model has been challenged, prompting a review of the established paradigm. While it remains possible that additional molecules may be involved in regulating entry into meiosis, the weight of evidence supporting a key role for RA is incontrovertible. PMID:22075477

  19. Effect of surfactants on Ra-sHSPI - A small heat shock protein from the cattle tick Rhipicephalus annulatus

    NASA Astrophysics Data System (ADS)

    Siddiqi, Mohammad Khursheed; Shahein, Yasser E.; Hussein, Nahla; Khan, Rizwan H.

    2016-09-01

    Electrostatic interaction plays an important role in protein aggregation phenomenon. In this study, we have checked the effect of anionic - Sodium Dodecyl Sulfate (SDS) and cationic-Cetyltrimethyl Ammonium Bromide (CTAB) surfactant on aggregation behavior of Ra-sHSPI, a small heat shock protein purified from Rhipicephalus annulatus tick. To monitor the effect of these surfactants, we have employed several spectroscopic methods such as Rayleigh light scattering measurements, ANS (8-Anilinonaphthalene-1-sulfonic acid) fluorescence measurements, ThT (Thioflavin T) binding assays, Far-UV CD (Circular Dichroism) and dynamic light scattering measurements. In the presence of anionic surfactant-SDS, Ra-sHSPI forms amyloid fibrils, in contrast, no amyloid formation was observed in presence of cationic surfactant at low pH. Enhancement of ANS fluorescence intensity confirms the exposition of more hydrophobic patches during aggregation. ThT binding assay confirms the amyloid fibrillar nature of the SDS induced Ra-sHSPI aggregates and supported by PASTA 2.0 (prediction of amyloid structural aggregation) software. This study demonstrates the crucial role of charge during amyloid fibril formation at low pH in Ra-sHSPI.

  20. Feasibility and Domain Validation of RA Flare Core Domain Set: A Report of the OMERACT 2014 RA Flare Group Plenary

    PubMed Central

    Bartlett, Susan J.; Bykerk, Vivian P.; Cooksey, Roxanne; Choy, Ernest H.; Alten, Rieke; Christensen, Robin; Furst, Daniel E.; Guillemin, Francis; Halls, Serena; Hewlett, Sarah; Leong, Amye L.; Lyddiatt, Anne; March, Lyn; Montie, Pamela; Orbai, Ana Maria; Pohl, Christoph; Voshaar, Marieke Scholte; Woodworth, Thasia G.; Bingham, Clifton O.

    2015-01-01

    Objective The OMERACT RA Flare Group was established to develop an approach to identify and measure rheumatoid arthritis (RA) flares. Here, we provide an overview of our OMERACT 2014 plenary. Methods Feasibility and validity of flare domains endorsed at OMERACT 11 (2012) were described based on initial data from three international studies collected using a common set of questions specific to RA flare. Mean flare frequency, severity, and duration data were presented, and domain scores were compared by flare status to examine known-groups validity. Breakout groups provided input for stiffness, self-management, contextual factors, and measurement considerations. Results Flare data from 501 patients in a observational study indicated 39% were in a flare, with mean (SD) severity of 6.0 (2.6) and 55% lasting > 14 days. Pain, physical function, fatigue, participation and stiffness scores averaged ≥ 2 times higher (2 of 11 points) in flaring individuals. Correlations between flare domains and corresponding legacy instruments were r’s from 0.46 to 0.93. A combined definition (patient-report of flare and DAS28 increase) was evaluated in two other trials with similar results. Breakout groups debated specific measurement issues. Conclusion These data contribute initial evidence of feasibility and content validation of the OMERACT RA Flare Core Domain Set. Our research agenda for OMERACT 2016 includes establishing duration/intensity criteria and developing criteria to identify RA flares using existing disease activity measures. Ongoing work will also address discordance between patients and physician ratings, facilitate applications to clinical care, elucidate the role of self-management and help finalize recommendations for RA flare measurement. PMID:25684764

  1. Diapycnal nutrient fluxes across the benthic boundary layers at the continental slopes off Peru and Mauritania based on 224Ra/223Ra-ratios

    NASA Astrophysics Data System (ADS)

    Reichert, P.; Scholten, J. C.; Eisenhauer, A.; Miquel, J. C.; Gasser, B.; Liebetrau, V.; Sommer, S.; Dengler, M.; Bryant, L. D.

    2014-12-01

    Marine sediments may act as sources and/or sinks of nutrients in oxygen minimum zones (OMZs) where solute fluxes between sediments and the above water column are believed to be an important component for the bioproductivity in the mixed layer. However, solute fluxes between sediments and the water column above are difficult to obtain. We determined the diapycnal nutrient fluxes across the benthic boundary layer at the OMZs off Peru and Mauritania using nutrient concentration profiles and vertical diffusion coefficients derived from 224Ra/223Ra isotope ratios. The radium isotopes 223Ra (half-life: 11.4 days) and 224Ra (half-life: 3.66 days) are produced in sediments by radioactive decay of 227Th and 228Th ,respectively: Diffusion of radium out of the sediments results in gradients of 224Ra/223Ra above the sediments; and these gradients may be used to estimate vertical diffusion coefficients. We determined 224Ra/223Ra along two transects at the continental slopes off Peru (12° S) and off Mauritania (18° N) in water depths between 65m - 1000mand 53m - 1100m, respectively. For the 223Ra/224Ra sampling we used acrylic fibers/cartridges coated with MnO2. The Mn-fibers were attached to benthic landers (moored for ~ 24 hours at the sea floor) and the Mn-cartridges were placed in series on several in-situ filtration pumps (Challenger Oceanic and McLane pumps). 223Ra and 224Ra were measured on-board using a delayed coincidence counting system (RaDeCC). In our presentation we will present the 224Ra/223Ra distribution along these transects investigated and we will compare the diapycnal radium-derived nutrient fluxes with those determined using benthic chambers and microstructure measurements.

  2. On RA Abstracts: From Rhetorical Structure to Thematic Organisation

    ERIC Educational Resources Information Center

    Lores, Rosa

    2004-01-01

    This paper reports an analysis of research article (RA) abstracts from linguistics journals from two related angles: rhetorical organisation and thematic structure. Based on a small scale study it reveals two major types of rhetorical organisation, here called the IMRD type and the CARS type. When thematic analysis, in terms of thematic…

  3. Observation of the negative ions: Ra[sup [minus

    SciTech Connect

    Zhao, X.; Nadeau, M.; Garwan, M.A.; Kilius, L.R.; Litherland, A.E. )

    1993-11-01

    The negative ions of the isotopes [sup 226]Ra, [sup 231]Pa, and [sup 244]Pu have been observed by means of accelerator mass spectrometry and their properties compared with the negative ions of Th and U. The electron affinities of all these elements have been estimated to be similar and greater than 50 meV.

  4. Improved experimental limit on the EDM of 225Ra

    NASA Astrophysics Data System (ADS)

    Bishof, Michael; Bailey, Kevin; Dietrich, Matthew R.; Greene, John P.; Holt, Roy J.; Kalita, Mukut R.; Korsch, Wolfgang; Lemke, Nathan D.; Lu, Zheng-Tian; Mueller, Peter; O'Connor, Tom P.; Parker, Richard H.; Rabga, Tenzin; Singh, Jaideep T.

    2015-10-01

    Searches for permanent electric dipole moments (EDMs) in fundamental and composite particles are sensitive probes of beyond-standard-model symmetry violation that could explain the dominance of matter over anti-matter. The 225Ra (t1/2 = 15d, I = 1/2) atom is a particularly attractive system to use for an EDM measurement because its large nuclear octupole deformation, closely spaced ground-state parity doublet, and large atomic mass make 225Ra uniquely sensitive to symmetry-violating interactions in the nuclear medium. We have developed an experiment to measure the EDM of 225Ra and demonstrated the first ``proof-of-principle'' measurement, giving a 95% confidence upper limit of 5E-22 e-cm. After implementing a vacuum upgrade, we have observed nuclear spin coherence after 20 s of free evolution - a factor of ten improvement over our earlier results - and have lowered the 225Ra EDM limit by over an order of magnitude. Upcoming experimental upgrades have the potential to further improve our EDM sensitivity by many orders of magnitude, allowing us to test symmetry violation at an unprecedented level. This work is supported by U.S. DOE, Office of Science, Office of Nuclear Physics, under Contract DE-AC02-06CH11357.

  5. Improved limit on the 225Ra electric dipole moment

    NASA Astrophysics Data System (ADS)

    Bishof, Michael; Parker, Richard H.; Bailey, Kevin G.; Greene, John P.; Holt, Roy J.; Kalita, Mukut R.; Korsch, Wolfgang; Lemke, Nathan D.; Lu, Zheng-Tian; Mueller, Peter; O'Connor, Thomas P.; Singh, Jaideep T.; Dietrich, Matthew R.

    2016-08-01

    Background: Octupole-deformed nuclei, such as that of 225Ra, are expected to amplify observable atomic electric dipole moments (EDMs) that arise from time-reversal and parity-violating interactions in the nuclear medium. In 2015 we reported the first "proof-of-principle" measurement of the 225Ra atomic EDM. Purpose: This work reports on the first of several experimental upgrades to improve the statistical sensitivity of our 225Ra EDM measurements by orders of magnitude and evaluates systematic effects that contribute to current and future levels of experimental sensitivity. Method: Laser-cooled and trapped 225Ra atoms are held between two high-voltage electrodes in an ultrahigh-vacuum chamber at the center of a magnetically-shielded environment. We observe Larmor precession in a uniform magnetic field using nuclear-spin-dependent laser light scattering and look for a phase shift proportional to the applied electric field, which indicates the existence of an EDM. The main improvement to our measurement technique is an order-of-magnitude increase in spin-precession time, which is enabled by an improved vacuum system and a reduction in trap-induced heating. Results: We have measured the 225Ra atomic EDM to be less than 1.4 ×10-23e cm (95 % confidence upper limit), which is a factor of 36 improvement over our previous result. Conclusions: Our evaluation of systematic effects shows that this measurement is completely limited by statistical uncertainty. Combining this measurement technique with planned experimental upgrades, we project a statistical sensitivity at the 1 ×10-28e cm level and a total systematic uncertainty at the 4 ×10-29e cm level.

  6. Protective Effect of RA on Myocardial Infarction-Induced Cardiac Fibrosis via AT1R/p38 MAPK Pathway Signaling and Modulation of the ACE2/ACE Ratio.

    PubMed

    Liu, Qiaofeng; Tian, Jingwei; Xu, Yanan; Li, Chunmei; Meng, Xiangjing; Fu, Fenghua

    2016-09-01

    Rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyllactic acid, RA) is a major active constituent of Rosmarinus officinalis Linn. (rosemary) having significant anti-inflammatory, anti-apoptotic, and antioxidant effects. However, the cardioprotection of RA is still not understood. The present study was designed, for the first time, to investigate the cardioprotection of RA on myocardial infarction (MI)-induced cardiac fibrosis and to clarify the possible mechanisms. MI was induced in adult rats by left anterior descending coronary artery ligation, and animals were then administered RA (50, 100, or 200 mg/kg) by gavage. Compared with the model group, RA treatment ameliorated changes in the left ventricular systolic pressure (LVSP), +dp/dtmax, and -dp/dtmax after 4 weeks. This was associated with attenuation of infarct size, collagen volume fraction (CVF), expression of collagen I, collagen III, alpha smooth muscle actin (α-SMA), and hydroxyproline (Hyp) concentrations. RA treatment was also associated with decreased angiotensin-converting enzyme (ACE) expression and increased ACE2 expression, as well as decreased expression of angiotensin type 1 receptor (AT1R) and phospho-p38 mitogen-activated protein kinase (p38 MAPK). Thus, RA can protect against cardiac dysfunction and fibrosis following MI, likely due to decreasing ACE expression and increasing ACE2 expression via the AT1R/p38 MAPK pathway. PMID:27538767

  7. Factors influencing the distribution of 223Ra and 224Ra in the coastal waters off Tanggu and Qikou in Bohai bay

    NASA Astrophysics Data System (ADS)

    Tang, Guoqiang; Yi, Lixin; Liu, Lingling; Cheng, Xiaoqing

    2015-10-01

    The naturally occurring 223Ra and 224Ra isotopes have become an established tool for investigating water mixing and submarine groundwater discharge (SGD). In this paper, we used the radium delayed coincidence counter (RaDeCC) to measure 223Ra and 224Ra activities, the distributions of 223Ra and 224Ra in two coastal waters with different hydrographical conditions and its influence factors were explored in Bohai bay. The results indicated that the Ra concentration was constrained by coastal land use patterns, the type of water and the geochemical environment. The Ra concentrations in groundwater and beach water were generally higher than the Ra concentrations in offshore waters. In the highly urbanized and industrialized Tanggu area, both of 223Ra in coastal water (average 3.74 dpm/100 L) and 224Ra (average 41.3 dpm/100 L) were lower than that in the undeveloped Qikou area (average 9.65 dpm/100 L and 148.9 dpm/100 L for 223Ra and 224Ra, respectively). Urbanization and Marine reclamations have modified local hydrogeological conditions, and then reduced SGD fluxes. Human activities have poured much more contaminants into coastal oceans and changed local aqueous environments, thus resulted all chemical compositions were richer in the urbanized coastal waters. With respect to the relationships between radium and the chemical compositions of the waters, radium was negatively related to salinity, nitrate and sulfate but was positively related to the concentration of cations such as calcium and magnesium. The apparent residence ages and SGD fluxes were also estimated from the radium distributions. There were more SGD fluxes into the coastal water off Qikou (9.88×107 m3/d) than into the water off Tanggu (1.22×107 m3/d).

  8. Depletion of Retinoic Acid Receptors Initiates a Novel Positive Feedback Mechanism that Promotes Teratogenic Increases in Retinoic Acid

    PubMed Central

    D'Aniello, Enrico; Rydeen, Ariel B.; Anderson, Jane L.; Mandal, Amrita; Waxman, Joshua S.

    2013-01-01

    Normal embryonic development and tissue homeostasis require precise levels of retinoic acid (RA) signaling. Despite the importance of appropriate embryonic RA signaling levels, the mechanisms underlying congenital defects due to perturbations of RA signaling are not completely understood. Here, we report that zebrafish embryos deficient for RA receptor αb1 (RARαb1), a conserved RAR splice variant, have enlarged hearts with increased cardiomyocyte (CM) specification, which are surprisingly the consequence of increased RA signaling. Importantly, depletion of RARαb2 or concurrent depletion of RARαb1 and RARαb2 also results in increased RA signaling, suggesting this effect is a broader consequence of RAR depletion. Concurrent depletion of RARαb1 and Cyp26a1, an enzyme that facilitates degradation of RA, and employment of a novel transgenic RA sensor line support the hypothesis that the increases in RA signaling in RAR deficient embryos are the result of increased embryonic RA coupled with compensatory RAR expression. Our results support an intriguing novel mechanism by which depletion of RARs elicits a previously unrecognized positive feedback loop that can result in developmental defects due to teratogenic increases in embryonic RA. PMID:23990796

  9. Retinoic acid and meiosis induction in adult versus embryonic gonads of medaka

    PubMed Central

    Adolfi, Mateus C.; Herpin, Amaury; Regensburger, Martina; Sacquegno, Jacopo; Waxman, Joshua S.; Schartl, Manfred

    2016-01-01

    In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage. PMID:27677591

  10. Affinity of rosmarinic acid to human serum albumin and its effect on protein conformation stability.

    PubMed

    Peng, Xin; Wang, Xiangchao; Qi, Wei; Su, Rongxin; He, Zhimin

    2016-02-01

    Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants with promising biological activities. The interaction between RA and human serum albumin (HSA) was investigated by multi-spectroscopic, electrochemistry, molecular docking and molecular dynamics simulation methods. The fluorescence emission of HSA was quenched by RA through a combined static and dynamic quenching mechanism, but the static quenching was the major constituent. Fluorescence experiments suggested that RA was bound to HSA with moderately strong binding affinity through hydrophobic interaction. The probable binding location of RA was located near site I of HSA. Additionally, as shown by the Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra, RA can result in conformational and structural alterations of HSA. Furthermore, the molecular dynamics studies were used to investigate the stability of the HSA and HSA-RA system. Altogether, the results can provide an important insight for the applications of RA in the food industry.

  11. Affinity of rosmarinic acid to human serum albumin and its effect on protein conformation stability.

    PubMed

    Peng, Xin; Wang, Xiangchao; Qi, Wei; Su, Rongxin; He, Zhimin

    2016-02-01

    Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants with promising biological activities. The interaction between RA and human serum albumin (HSA) was investigated by multi-spectroscopic, electrochemistry, molecular docking and molecular dynamics simulation methods. The fluorescence emission of HSA was quenched by RA through a combined static and dynamic quenching mechanism, but the static quenching was the major constituent. Fluorescence experiments suggested that RA was bound to HSA with moderately strong binding affinity through hydrophobic interaction. The probable binding location of RA was located near site I of HSA. Additionally, as shown by the Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra, RA can result in conformational and structural alterations of HSA. Furthermore, the molecular dynamics studies were used to investigate the stability of the HSA and HSA-RA system. Altogether, the results can provide an important insight for the applications of RA in the food industry. PMID:26304336

  12. Mechanisms of retinoic acid signalling and its roles in organ and limb development

    PubMed Central

    Cunningham, Thomas J.; Duester, Gregg

    2015-01-01

    Retinoic acid (RA) signalling has a central role during vertebrate development. RA synthesized in specific locations regulates transcription by interacting with nuclear RA receptors (RARs) bound to RA response elements (RAREs) near target genes. RA was first implicated in signalling on the basis of its teratogenic effects on limb development. Genetic studies later revealed that endogenous RA promotes forelimb initiation by repressing fibroblast growth factor 8 (Fgf8). Insights into RA function in the limb serve as a paradigm for understanding how RA regulates other developmental processes. In vivo studies have identified RAREs that control repression of Fgf8 during body axis extension or activation of homeobox (Hox) genes and other key regulators during neuronal differentiation and organogenesis. PMID:25560970

  13. Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-31RA Expression*

    PubMed Central

    Edukulla, Ramakrishna; Singh, Brijendra; Jegga, Anil G.; Sontake, Vishwaraj; Dillon, Stacey R.; Madala, Satish K.

    2015-01-01

    Interleukin 31 receptor α (IL-31RA) is a novel Type I cytokine receptor that pairs with oncostatin M receptor to mediate IL-31 signaling. Binding of IL-31 to its receptor results in the phosphorylation and activation of STATs, MAPK, and JNK signaling pathways. IL-31 plays a pathogenic role in tissue inflammation, particularly in allergic diseases. Recent studies demonstrate IL-31RA expression and signaling in non-hematopoietic cells, but this receptor is poorly studied in immune cells. Macrophages are key immune-effector cells that play a critical role in Th2-cytokine-mediated allergic diseases. Here, we demonstrate that Th2 cytokines IL-4 and IL-13 are capable of up-regulating IL-31RA expression on both peritoneal and bone marrow-derived macrophages from mice. Our data also demonstrate that IL-4Rα-driven IL-31RA expression is STAT6 dependent in macrophages. Notably, the inflammation-associated genes Fizz1 and serum amyloid A (SAA) are significantly up-regulated in M2 macrophages stimulated with IL-31, but not in IL-4 receptor-deficient macrophages. Furthermore, the absence of Type II IL-4 receptor signaling is sufficient to attenuate the expression of IL-31RA in vivo during allergic asthma induced by soluble egg antigen, which may suggest a role for IL-31 signaling in Th2 cytokine-driven inflammation and allergic responses. Our study reveals an important counter-regulatory role between Th2 cytokine and IL-31 signaling involved in allergic diseases. PMID:25847241

  14. Enrichment of Vitamin D response elements in RA associated loci supports a role for vitamin D in the pathogenesis of RA

    PubMed Central

    Yarwood, Annie; Martin, Paul; Bowes, John; Lunt, Mark; Worthington, Jane; Barton, Anne; Eyre, Steve

    2013-01-01

    The aim of this study was to explore the role of vitamin-D in rheumatoid arthritis (RA) pathogenesis by investigating enrichment of vitamin-D response elements (VDREs) in confirmed RA susceptibility loci and testing variants associated with vitamin-D levels for association with RA. Bioinformatically, VDRE genomic positions were overlaid with non HLA confirmed RA susceptibility regions. The number of VDREs at RA loci was compared to a randomly selected set of genomic loci to calculate an average relative risk (RR). SNPs in the DHCR7/NADSYN1 and CYP2R1 loci, previously associated with circulating vitamin-D levels, were tested in UK RA cases (n = 3870) and controls (n = 8430). Significant enrichment of VDREs was seen at RA loci (p=9.23×10−8) when regions were defined either by gene (RR 5.50) or position (RR 5.86). SNPs in the DHCR7/NADSYN1 locus showed evidence of positive association with RA, rs4944076 (p=0.008, OR 1.14 95% CI 1.03-1.24). The significant enrichment of VDREs at RA associated loci and the modest association of variants in loci controlling levels of circulating vitamin-D, supports the hypothesis that vitamin-D plays a role in the development of RA. PMID:23636220

  15. Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide

    PubMed Central

    Liu, Shenping; Desharnais, Joel; Sahasrabudhe, Parag V.; Jin, Ping; Li, Wei; Oates, Bryan D.; Shanker, Suman; Banker, Mary Ellen; Chrunyk, Boris A.; Song, Xi; Feng, Xidong; Griffor, Matt; Jimenez, Judith; Chen, Gang; Tumelty, David; Bhat, Abhijit; Bradshaw, Curt W.; Woodnutt, Gary; Lappe, Rodney W.; Thorarensen, Atli; Qiu, Xiayang; Withka, Jane M.; Wood, Lauren D.

    2016-01-01

    IL-17A is a pro-inflammatory cytokine that has been implicated in autoimmune and inflammatory diseases. Monoclonal antibodies inhibiting IL-17A signaling have demonstrated remarkable efficacy, but an oral therapy is still lacking. A high affinity IL-17A peptide antagonist (HAP) of 15 residues was identified through phage-display screening followed by saturation mutagenesis optimization and amino acid substitutions. HAP binds specifically to IL-17A and inhibits the interaction of the cytokine with its receptor, IL-17RA. Tested in primary human cells, HAP blocked the production of multiple inflammatory cytokines. Crystal structure studies revealed that two HAP molecules bind to one IL-17A dimer symmetrically. The N-terminal portions of HAP form a β-strand that inserts between two IL-17A monomers while the C-terminal section forms an α helix that directly blocks IL-17RA from binding to the same region of IL-17A. This mode of inhibition suggests opportunities for developing peptide antagonists against this challenging target. PMID:27184415

  16. Investigation of Retinoic Acid Function During Embryonic Brain Development Using Retinaldehyde-Rescued Rdh10 Knockout Mice

    PubMed Central

    Chatzi, Christina; Cunningham, Thomas J.; Duester, Gregg

    2013-01-01

    Background Retinoic acid (RA) signaling controls patterning and neuronal differentiation within the hindbrain, but forebrain RA function remains controversial. RA is produced from metabolism of retinol to retinaldehyde by retinol dehydrogenase (RDH), followed by metabolism of retinaldehyde to RA by retinaldehyde dehydrogenase (RALDH). Previous studies on Raldh2−/− and Raldh3−/− mice demonstrated an RA requirement for γ-aminobutyric acid (GABA)ergic and dopaminergic differentiation in forebrain basal ganglia, but no RA requirement was observed during early forebrain patterning or subsequent fore-brain cortical expansion. However, other studies suggested that RA controls forebrain patterning, and analysis of ethylnitrosourea-induced Rdh10 mutants suggested that RA synthesized in the meninges stimulates forebrain cortical expansion. Results We generated Rdh10−/− mouse embryos that lack RA activity early in the head and later in the meninges. We observed defects in hindbrain patterning and eye RA signaling, but early forebrain patterning was unaffected. Retinaldehyde treatment of Rdh10−/− embryos from E7–E9 rescues a cranial skeletal defect, resulting in E14.5 embryos lacking meningeal RA activity but maintaining normal forebrain shape and cortical expansion. Conclusions Rdh10−/− embryos demonstrate that RA controls hindbrain but not early forebrain patterning, while studies on retinaldehyde-rescued Rdh10−/− embryos show that meningeal RA synthesis is unnecessary to stimulate forebrain cortical expansion. PMID:23765990

  17. Excessive feedback of Cyp26a1 promotes cell non-autonomous loss of retinoic acid signaling

    PubMed Central

    Rydeen, Ariel; Voisin, Norine; D’Aniello, Enrico; Ravisankar, Padmapriyadarshini; Devignes, Claire-Sophie; Waxman, Joshua S.

    2015-01-01

    Teratogenic levels of retinoic acid (RA) signaling can cause seemingly contradictory phenotypes indicative of both increases and decreases of RA signaling. However, the mechanisms underlying these contradictory phenotypes are not completely understood. Here, we report that using a hyperactive RA receptor to enhance RA signaling in zebrafish embryos leads to defects associated with gain and loss of RA signaling. While the gain-of-function phenotypes arise from an initial increase in RA signaling, using genetic epistasis analysis we found that the loss-of-function phenotypes result from a clearing of embryonic RA that requires a rapid and dramatic increase in cyp26a1 expression. Thus, the sensitivity of cyp26a1 expression to increased RA signaling causes an overcompensation of negative feedback and loss of embryonic RA signaling. Additionally, we used blastula transplantation experiments to test if Cyp26a1, despite its cellular localization, can limit RA exposure to neighboring cells. We find that enhanced Cyp26a1 expression limits RA signaling in the local environment, thus providing the first direct evidence that Cyp26 enzymes can have cell non-autonomous consequences on RA levels within tissues. Therefore, our results provide novel insights into the teratogenic mechanisms of RA signaling and the cellular mechanisms by which Cyp26a1 expression can shape a RA gradient. PMID:26116175

  18. 76 FR 63701 - Culturally Significant Objects Imported for Exhibition Determinations: “Johan Zoffany RA: Society...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Culturally Significant Objects Imported for Exhibition Determinations: ``Johan Zoffany RA: Society Observed... determine that the objects to be included in the exhibition ``Johan Zoffany RA: Society Observed,''...

  19. Fast electric dipole transitions in Ra-Ac nuclei

    SciTech Connect

    Ahmad, I.

    1985-01-01

    Lifetime of levels in /sup 225/Ra, /sup 225/Ac, and /sup 227/Ac have been measured by delayed coincidence techniques and these have been used to determine the E1 gamma-ray transition probabilities. The reduced E1 transition probabilities. The reduced E1 transition probabilities in /sup 225/Ra and /sup 225/Ac are about two orders of magnitude larger than the values in mid-actinide nuclei. On the other hand, the E1 rate in /sup 227/Ac is similar to those measured in heavier actinides. Previous studies suggest the presence of octupole deformation in all the three nuclei. The present investigation indicates that fast E1 transitions occur for nuclei with octupole deformation. However, the studies also show that there is no one-to-one correspondence between E1 rate and octupole deformation. 13 refs., 4 figs.

  20. The biological effects of {sup 224}Ra injected into dogs

    SciTech Connect

    Muggenburg, B.A.; Lloyd, R.D.; Hahn, F.F.; Griffith, W.C.; Boecker, B.B.

    1994-11-01

    The purpose of this study was to investigate the toxicity of injected {sup 224}Ra in the dog. Radium-224 is a short-lived isotope of radium with a half-life of 3.62 d. When administered parenterally, it deposits on bone surfaces; because of its short half-life, most of its energy is deposited on bone surfaces, in a manner similar to plutonium. The experimental design included a comparison to the exposed human population. Instead of using a single injection of {sup 224}Ra, groups were included in which dogs were injected once, 10 times, or 50 times. This design provided groups that could be compared to the multiple injections often used in people for the treatment of ankylosing spondylitis.

  1. Emergency Radiobioassay Method for Determination of ⁹⁰Sr and ²²⁶Ra in a Spot Urine Sample.

    PubMed

    Sadi, Baki B; Fontaine, Allison; McAlister, Daniel; Li, Chunsheng

    2015-08-01

    A new radiobioassay method has been developed for simultaneous determination of (90)Sr and (226)Ra in a spot urine sample. The method is based on a matrix removal procedure to purify the target radionuclides from a urine sample followed by an automated high performance ion chromatographic (HPIC) separation of (90)Sr and (226)Ra and offline radiometric detection by liquid scintillation counting (LSC). A Sr-resin extraction chromatographic cartridge was used for matrix removal and purification of (90)Sr and (226)Ra from a urine sample prior to its introduction to the HPIC system. The HPIC separation was carried out through cation exchange chromatography using methanesulfonic acid (75 mM) as the mobile phase at 0.25 mL/min flow rate. The performance criteria of the method was evaluated against the American National Standard Institute ANSI/HPS N13.30-2011 standard for the root mean squared error (RMSE) of relative bias (Br) and relative precision (SB) at two different spiked activity levels. The RMSE of Br and SB for (90)Sr and (226)Ra were found to be satisfactory (≤0.25). The minimum detectable activity (MDA) of the method for (90)Sr and (226)Ra are 2 Bq/L and 0.2 Bq/L, respectively. The MDA values are at least 1/10th of the concentrations of (90)Sr (190 Bq/L) and (226)Ra (2 Bq/L) excreted in urine on the third day following an acute exposure (inhalation) that would lead to an effective dose of 0.1 Sv in the first year. The sample turnaround time is less than 8 h for simultaneous determination of (90)Sr and (226)Ra.

  2. An Excess 226Ra Geochronology for Saanich Inlet

    NASA Astrophysics Data System (ADS)

    Grayson, R. P.; Plater, A. J.; Boyle, J. F.; Appleby, P. G.

    2004-12-01

    When examining past environmental and climatic change the ability to date both freshwater and marine sediments is essential. Numerous methods are currently available, however where present techniques fail, novel dating techniques are required to overcome these obstacles. In particular the use of 14C to date sediments over the Holocene period can be severely limited where there are significant hard-water and reservoir effects and where reworking of organic matter occurs. The use of unsupported or excess 226Ra offers a potential dating tool in such depositional contexts over the Holocene time period as a result of its half-life of 1600 years. Indeed, the technique has been applied to a number of environments since first being proposed by Koide et al. (1976). However, numerous question marks still surround the application of the technique, particularly with reference to the dating of sub-aqueous sediment deposits. As part of wider research into the applicability of excess 226Ra to date lake sedimentary environments, deep-sea samples from Saanich Inlet were obtained from the ODP (Leg 169S) in order to validate the dating technique. Saanich Inlet is an anoxic fjord located on the coastline of Vancouver Island, British Colombia, the sediments of which have been shown to be comprised of lamina-scale alternations between diatom-rich and diatom-poor clays and silts representing annual. Using digital sediment colour analysis Nederbragt and Thurow (2001) constructed a varve chronology for the last 6000 years. Alpha-spectrometry was successfully used to measure 226Ra, 230Th and 234U in sediment samples collected from Saanich Inlet during ODP Leg 169S. These activities were used to determine an excess 226Ra geochronology for Saanich Inlet. This radiometric chronology compares well with dates obtained from the varve record, and spans two different phases of sediment accumulation.

  3. An improved limit on the EDM of 225 Ra

    NASA Astrophysics Data System (ADS)

    Bishof, Michael; Bailey, Kevin; Dietrich, Matthew R.; Greene, John P.; Holt, Roy J.; Kalita, Mukut R.; Korsch, Wolfgang; Lemke, Nathan D.; Lu, Zheng-Tian; Mueller, Peter; O'Connor, Thomas P.; Parker, Richard H.; Rabga, Tenzin; Singh, Jaideep T.

    2016-05-01

    Searches for permanent electric dipole moments (EDMs) are sensitive probes of symmetry violation that could explain the dominance of matter over anti-matter. The 225 Ra (t1/2 = 15 days, I = 1/2) atom is a particularly attractive system to use for an EDM measurement because its octupole-deformed nucleus, closely spaced ground-state parity doublet, and large nuclear charge make 225 Ra uniquely sensitive to symmetry-violating interactions in the nuclear medium. In 2015, we reported the first ``proof of principle'' measurement of the 225 Ra EDM, giving a 95% confidence upper limit of 5* 10-22 e-cm; representing the first EDM measurement using laser-trapped atoms as well as the first EDM measurement of an atom with an octupole-deformed nucleus. After implementing upgrades to our apparatus, we now observe nuclear spin coherence after 20 s of free evolution - a factor of ten improvement. A new EDM measurement based on the upgraded system improved the 95% confidence upper limit by a factor of 36. We also report on the progress of current experimental upgrades that have the potential to further improve our EDM sensitivity by many orders of magnitude, allowing us to test symmetry violation at an unprecedented level. This work is supported by U.S. DOE, Office of Science, Office of Nuclear Physics, under Contract DE-AC02-06CH11357.

  4. Search for a Permanent Electric Dipole Moment of 225Ra

    NASA Astrophysics Data System (ADS)

    Kalita, Mukut Ranjan

    The observation of a permanent electric dipole moment (EDM) in a non-degenerate system would indicate the violation of discrete symmetries of Time reversal (T) or combined application of Charge (C) and Parity (P) symmetry violation through the CPT theorem. The diamagnetic 225Ra atom with nuclear spin I=1/2 is a favorable candidate for an EDM search. Experimental sensitivity to its EDM is enhanced due to its high atomic mass and the increased Schiff moment of its octupole deformed nucleus. An experimental setup is developed where laser cooled neutral radium atoms are collected in a magneto-optical trap (MOT). The collected atoms are transported 1 meter with a far off-resonant optical dipole trap (ODT) and then the atoms are transferred to a second standing-wave ODT in an experimental chamber. The atoms are then optically polarized and allowed to Larmor precess in parallel and antiparallel electric and magnetic fields. The difference between the Larmor precession frequency for parallel and antiparallel fields is experimentally determined to measure the EDM. This thesis is about the first measurement of the EDM of the 225Ra atom where an upper limit of |d(225Ra)| < 5.0 x 10-22 e·cm (95% confidence) is reached. Keywords: Permanent EDM, CP violation, laser cooling and trapping, rare isotopes, radium.

  5. An evaluation of ²²⁶Ra and ²²⁸Ra in drinking water in several counties in Texas, USA.

    PubMed

    Landsberger, S G; George, G

    2013-11-01

    Naturally Occurring Radioactive Material (NORM) or Technology Enhanced Naturally Occurring Radioactive Material (TENORM) can be a potential health risk. It is now well known that the underlying geology in many parts of Texas has given rise to levels of (226)Ra and (228)Ra that often exceed the limits set by the US Environmental Protection Agency. A detailed literature search was undertaken to assess the levels of (226)Ra and (228)Ra in all of the Texas counties. Several statistical evaluations of the data were performed. The Hickory aquifer in the Llano Uplift region of Texas has consistently had the highest number of (226)Ra and (228)Ra concentrations above the legal limit. As well many of the affected rural communities may not have the financial resources to rectify the problem.

  6. Immunodiagnostic Significance of Anti-RA33 Autoantibodies in Saudi Patients with Rheumatoid Arthritis

    PubMed Central

    Al-Mughales, Jamil A.

    2015-01-01

    The primary objective of this study was to evaluate and compare the immunodiagnostic significance and utility of anti-RA33 with anti-CCP, RF, and CRP in Saudi patients with rheumatoid arthritis. Methods. This was a prospective controlled clinical study conducted at King Abdul Aziz University Tertiary Medical Centre. The sera of 41 RA patients, 31 non-RA patients, and 29 healthy controls were collected. Anti-RA33 and anti-CCP were measured using commercially available ELISA principle kits. RF and CRP were measured using nephelometry. Results. Anti-RA33 antibodies had the lowest positive and negative predictive values and showed a sensitivity of 7.32% with 95.12% specificity. Of the other three markers (including anti-CCP antibodies, CRP, and RF), only anti-CCP showed specificity of 90.46% with sensitivity of 63.41% compared to non-RA patients + healthy control. There was a significant correlation with rheumatoid factor positivity with anti-CCP. With respect to CRP, a notable correlation was seen only with anti-RA33. Conclusion. Compared to rheumatoid factor, anti-CCP antibodies, and C-reactive proteins, the anti-RA33 autoantibodies seem to be not representing as an important additional immunodiagnostic marker in Saudi patients with established RA. RA33 may have more interest in early RA or less severe RA and other systemic connective tissue disorders. PMID:25883991

  7. Composition and Antioxidant Activity of Geopropolis Collected by Melipona subnitida (Jandaíra) Bees

    PubMed Central

    Alves de Souza, Silvana; Camara, Celso Amorim; Monica Sarmento da Silva, Eva; Silva, Tania Maria Sarmento

    2013-01-01

    An investigation of the geopropolis collected by Melipona subnitida (jandaíra) stingless bee led to the isolation and characterization of two phenylpropanoids, 6-O-p-coumaroyl-D-galactopyranose (1) and 6-O-cinnamoyl-1-O-p-coumaroyl-β-D-glucopyranose (2), and seven flavonoids, 7-O-methyl-naringenin (3), 7-O-methyl aromadendrin (4), 7,4′-di-O-methyl aromadendrin (5), 4′-O-methyl kaempferol (6), 3-O-methyl quercetin (7), 5-O-methyl aromadendrin (8), and 5-O-methyl kaempferol (9). The structure of the new phenylpropanoid (1) was established from IR, LC-ESI-MS, and NMR spectral data, including 2D NMR experiments. The extract and fractions demonstrated significant antioxidant activity in DPPH, ABTS, and β-carotene/linoleic acid tests. PMID:23935683

  8. Composition and Antioxidant Activity of Geopropolis Collected by Melipona subnitida (Jandaíra) Bees.

    PubMed

    Alves de Souza, Silvana; Camara, Celso Amorim; Monica Sarmento da Silva, Eva; Silva, Tania Maria Sarmento

    2013-01-01

    An investigation of the geopropolis collected by Melipona subnitida (jandaíra) stingless bee led to the isolation and characterization of two phenylpropanoids, 6-O-p-coumaroyl-D-galactopyranose (1) and 6-O-cinnamoyl-1-O-p-coumaroyl- β -D-glucopyranose (2), and seven flavonoids, 7-O-methyl-naringenin (3), 7-O-methyl aromadendrin (4), 7,4'-di-O-methyl aromadendrin (5), 4'-O-methyl kaempferol (6), 3-O-methyl quercetin (7), 5-O-methyl aromadendrin (8), and 5-O-methyl kaempferol (9). The structure of the new phenylpropanoid (1) was established from IR, LC-ESI-MS, and NMR spectral data, including 2D NMR experiments. The extract and fractions demonstrated significant antioxidant activity in DPPH, ABTS, and β -carotene/linoleic acid tests.

  9. Opening of the closed water area and consequent changes of ²²⁸Ra/²²⁶Ra activity ratios in coastal lagoon Nakaumi, southwest Japan.

    PubMed

    Nomura, Ritsuo; Nakamura, Kosaku; Seto, Koji; Inoue, Mutsuo; Kofuji, Hisaki

    2013-11-01

    In Lake Nakaumi, the second largest coastal lagoon in Japan, artificially closed (Honjyo) area, which was left untouched for 28 years, was partly opened in May, 2009. (228)Ra/(226)Ra ratio of waters in Honjyo area and Lake Nakaumi showed a well-tuned seasonal variation exhibiting high value in summer. After the opening event, however, the (228)Ra/(226)Ra ratios in the Honjyo water showed an unclear seasonal variation in both surface and deep water. This opening event caused the change of active movement of lake and marine water.

  10. Retinoic acid in alveolar development, maintenance and regeneration.

    PubMed Central

    Maden, Malcolm; Hind, Matthew

    2004-01-01

    Recent data suggest that exogenous retinoic acid (RA), the biologically active derivative of vitamin A, can induce alveolar regeneration in a rat model of experimental emphysema. Here, we describe a mouse model of disrupted alveolar development using dexamethasone administered postnatally. We show that the effects of dexamethasone are concentration dependent, dose dependent, long lasting and result in a severe loss of alveolar surface area. When RA is administered to these animals as adults, lung architecture and the surface area per unit of body weight are completely restored to normal. This remarkable effect may be because RA is required during normal alveolar development and administering RA re-awakens gene cascades used during development. We provide evidence that RA is required during alveologenesis in the mouse by showing that the levels of the retinoid binding proteins, the RA receptors and two RA synthesizing enzymes peak postnatally. Furthermore, an inhibitor of RA synthesis, disulphiram, disrupts alveologenesis. We also show that RA is required throughout life for the maintenance of lung alveoli because when rats are deprived of dietary retinol they lose alveoli and show the features of emphysema. Alveolar regeneration with RA may therefore be an important novel therapeutic approach to the treatment of respiratory diseases characterized by a reduced gas-exchanging surface area such as bronchopulmonary dysplasia and emphysema for which there are currently no treatments. PMID:15293808

  11. Fate of retinoic acid-activated embryonic cell lineages.

    PubMed

    Dollé, Pascal; Fraulob, Valérie; Gallego-Llamas, Jabier; Vermot, Julien; Niederreither, Karen

    2010-12-01

    Retinoic acid (RA), a vitamin A derivative, is synthesized by specific cell populations and acts as a diffusible embryonic signal activating ligand-inducible transcription factors, the RA receptors (RARs). RA-activatable transgenic systems have revealed many discrete, transient sites of RA action during development. However, there has been no attempt to permanently label the RA-activated cell lineages during mouse ontogenesis. We describe the characterization of a RA-activatable Cre transgene, which through crosses with a conditional reporter strain (the ROSA26R lacZ reporter), leads to a stable labeling of the cell populations experiencing RA signaling during embryogenesis. RA response-element (RARE)-driven Cre activity mimics at early stages the known activity of the corresponding RARE-lacZ transgene (Rossant et al.,1991). Stable labeling of the Cre-excised cell populations allows to trace the distribution of the RA-activated cell lineages at later stages. These are described in relationship with current models of RA activity in various developmental systems, including the embryonic caudal region, limb buds, hindbrain, sensory organs, and heart. PMID:21046629

  12. In vitro effects of retinoic acid on mouse incisor development.

    PubMed

    Bloch-Zupan, A; Mark, M P; Weber, B; Ruch, J V

    1994-10-01

    The developing dentition is known to express the complete set of retinoic acid (RA) nuclear receptors and cytoplasmic RA-binding proteins (CRABPI and II), and RA is required for in vitro mouse molar morphogenesis, so the role of RA during in vitro mouse incisor development was investigated. Histological procedures, immunocytochemical detection of proliferating cells, immunofluorescence detection of laminin, and in situ hybridization with RNA probes for CRABPI and II were done on the tooth-germ cultures either in the presence or in the absence of RA. RA appeared to control initial morphogenesis, particularly the asymmetrical growth of the cervical loop, and to regulate required differential mitotic activity. RA seemed also to be involved in asymmetrical laminin deposition. The distribution of the CRABP gene transcripts was similar during in vivo and in vitro incisor development. However, CRABPI gene transcript distribution in the labial part of the epithelial loop was detected in vitro only in the presence of RA. A direct role of the CRABPs during tooth development is, however, unlikely because Ch55, a synthetic RA analogue that does not bind to CRABP, had the same effects as RA on in vitro incisor development. PMID:7741659

  13. Influence of the IL-1Ra gene polymorphism on in vivo synthesis of IL-1Ra and IL-1β after live yellow fever vaccination

    PubMed Central

    Hacker, U T; Erhardt, S; Tschöp, K; Jelinek, T; Endres, S

    2001-01-01

    The inflammatory response in infectious and autoimmune diseases is regulated by the balance between pro- and anti-inflammatory cytokines. The IL-1 complex contains polymorphic genes coding for IL-1α, IL-1β and IL-1Ra. The IL-1Ra (variable number of tanden repeat) VNTR polymorphism has been shown to influence the capacity to produce IL-1β and IL-1Ra after in vitro stimulation. Allele 2 of this polymorphism is associated with a number of inflammatory diseases. To determine the impact of the IL-1Ra polymorphism on in vivo human cytokine synthesis, we used a yellow fever vaccination model for the induction of cytokine synthesis in healthy volunteers. Two different yellow fever vaccines were used. After administration of the RKI vaccine (34 volunteers), plasma TNF-α concentration increased from 13·4 ± 0·9 pg/ml to 23·3 ± 1·1 pg/ml (P < 0·001), and plasma IL-1Ra concentration increased from 308 ± 25 pg/ml to 1019 ± 111 pg/ml (P < 0·001), on day 2. Using Stamaril® vaccine, no increase in the plasma concentrations of either TNF-α or IL-1Ra could be detected (n = 17). Only the RKI vaccine induced TNF-α synthesis after in vitro stimulation of MNC. Carriers of allele 2 of the IL-1Ra polymorphism had increased baseline concentrations of IL-1Ra (350 ± 32 pg/ml) compared with non-carriers (222 ± 18 pg/ml, P < 0·001), and decreased concentrations of IL-1β (0·9 ± 0·2 pg/ml for carriers versus 2·8 ± 0·7 pg/ml for non-carriers, P = 0·017). After yellow fever vaccination (RKI vaccine), no significant differences in the increase of IL-1Ra plasma levels were detected between carriers and non-carriers of allele 2 of the IL-1Ra gene polymorphism. This is the first study to examine the influence of this genetic polymorphism on in vivo-induced human IL-1β and IL-1Ra synthesis. Baseline concentrations of IL-1Ra and IL-1β were significantly influenced by the IL-1Ra polymorphism. No influence of the IL-1Ra polymorphism on the in vivo-induced production of IL-1Ra

  14. Bone-seeking radiopharmaceuticals for treatment of osseous metastases, Part 1: α therapy with 223Ra-dichloride.

    PubMed

    Pandit-Taskar, Neeta; Larson, Steven M; Carrasquillo, Jorge A

    2014-02-01

    Metastatic disease to bone is commonly seen in the advanced stages of many cancers. The cardinal symptom, pain, is often the cause of significant morbidity and reduced quality of life. Treatment of bone pain includes nonsteroidal analgesics and opiates; however, long-term use of these drugs is commonly associated with significant side effects, and tolerance is common. External-beam radiation therapy is effective mainly in localized disease sites. Bone-targeting radiopharmaceuticals are beneficial in the management of patients with multiple metastatic lesions. This article focuses on the 3 most commonly used agents: the Food and Drug Administration-approved (89)Sr-chloride, (153)Sm-ethylenediaminetetramethylene phosphonic acid (EDTMP), and (223)Ra-dichloride. We will discuss the physical characteristics, clinical data, dosage, and administration of these agents, including optimal patient selection and toxicity associated with their use. These radioactive agents have proven efficacy in the treatment of painful osseous metastases from prostate cancer and breast cancer. Significant recent advances include use of these agents in combination with chemotherapy and the use of the α emitter (223)Ra-dichloride in prostate cancer, primarily to improve survival and skeletal related events. The review is presented in 2 parts. The first will discuss the characteristics and clinical use of (223)Ra-dichloride, and the second will discuss the β emitters (89)Sr and (153)Sm-EDTMP.

  15. MRA_1571 is required for isoleucine biosynthesis and improves Mycobacterium tuberculosis H37Ra survival under stress

    PubMed Central

    Sharma, Rishabh; Keshari, Deepa; Singh, Kumar Sachin; Yadav, Shailendra; Singh, Sudheer Kumar

    2016-01-01

    Threonine dehydratase is a pyridoxal 5-phosphate dependent enzyme required for isoleucine biosynthesis. Threonine dehydratase (IlvA) participates in conversion of threonine to 2-oxobutanoate and ammonia is released as a by-product. MRA_1571 is annotated to be coding for IlvA in Mycobacterium tuberculosis H37Ra (Mtb-Ra). We developed a recombinant (KD) Mtb-Ra strain by down-regulating IlvA. The growth studies on different carbon sources suggested reduced growth of KD compared to wild-type (WT), also, isoleucine concentration dependent KD growth restoration was observed. The expression profiling of IlvA suggested increased expression of IlvA during oxygen, acid and oxidative stress. In addition, KD showed reduced survival under pH, starvation, nitric oxide and peroxide stresses. KD was more susceptible to antimycobacterial agents such as streptomycin (STR), rifampicin (RIF) and levofloxacin (LVF), while, no such effect was noticeable when exposed to isoniazid. Also, an increase in expression of IlvA was observed when exposed to STR, RIF and LVF. The dye accumulation studies suggested increased permeability of KD to ethidium bromide and Nile Red as compared to WT. TLC and Mass studies confirmed altered lipid profile of KD. In summary down-regulation of IlvA affects Mtb growth, increases its susceptibility to stress and leads to altered cell wall lipid profile. PMID:27353854

  16. MRA_1571 is required for isoleucine biosynthesis and improves Mycobacterium tuberculosis H37Ra survival under stress.

    PubMed

    Sharma, Rishabh; Keshari, Deepa; Singh, Kumar Sachin; Yadav, Shailendra; Singh, Sudheer Kumar

    2016-01-01

    Threonine dehydratase is a pyridoxal 5-phosphate dependent enzyme required for isoleucine biosynthesis. Threonine dehydratase (IlvA) participates in conversion of threonine to 2-oxobutanoate and ammonia is released as a by-product. MRA_1571 is annotated to be coding for IlvA in Mycobacterium tuberculosis H37Ra (Mtb-Ra). We developed a recombinant (KD) Mtb-Ra strain by down-regulating IlvA. The growth studies on different carbon sources suggested reduced growth of KD compared to wild-type (WT), also, isoleucine concentration dependent KD growth restoration was observed. The expression profiling of IlvA suggested increased expression of IlvA during oxygen, acid and oxidative stress. In addition, KD showed reduced survival under pH, starvation, nitric oxide and peroxide stresses. KD was more susceptible to antimycobacterial agents such as streptomycin (STR), rifampicin (RIF) and levofloxacin (LVF), while, no such effect was noticeable when exposed to isoniazid. Also, an increase in expression of IlvA was observed when exposed to STR, RIF and LVF. The dye accumulation studies suggested increased permeability of KD to ethidium bromide and Nile Red as compared to WT. TLC and Mass studies confirmed altered lipid profile of KD. In summary down-regulation of IlvA affects Mtb growth, increases its susceptibility to stress and leads to altered cell wall lipid profile.

  17. 226Ra or 226Ra/Ba dating of Holocene volcanic rocks: application to Mt. Etna and Merapi volcanoes

    NASA Astrophysics Data System (ADS)

    Condomines, M.; Gauthier, P. J.; Tanguy, J. C.; Gertisser, R.; Thouret, J. C.; Berthommier, P.; Camus, G.

    2005-02-01

    This paper shows how 226Ra- 230Th disequilibria can be used to date Holocene volcanic rocks from some well selected volcanoes. A systematic study of these disequilibria on historical or well-dated volcanic samples is indeed first required to test the applicability of this method. Two examples are described here to illustrate its potential. In the case of Mt. Etna, the good correlation observed between ( 226Ra) 0 activities at the time of eruption and Th contents in lava flows from the last two millennia [M. Condomines, J.C. Tanguy, V. Michaud, Magma dynamics at Mt. Etna: constraints from U-Th-Ra-Pb radioactive disequilibria and Sr isotopes in historical lavas, Earth Planet. Sci. Lett. 132 (1995) 25-41] is used to infer the ages of several newly analysed lava flows. The calculated ages are in good agreement with those deduced from the archaeomagnetic curve describing the variation of the geomagnetic field direction in southern Italy [J.C. Tanguy, I. Bucur, J.F.C. Thompson, Geomagnetic secular variation in Sicily and revised ages of historic lavas from Mt. Etna, Nature 318 (1985) 453-455, J.C. Tanguy, M. Le Goff, V. Chillemi, A. Paiotti, C. Principe, S. La Delfa, G. Patane, Variation séculaire de la direction du champ géomagnétique enregistrée par les laves de l'Etna et du Vésuve pendant les deux derniers millénaires, C. R. Acad. Sci. Paris 329 (1999) 557-564, J.C. Tanguy, M. Le Goff, C. Principe, S. Arrighi, V. Chillemi, A. Paiotti, S. La Delfa, G. Patane, Archaeomagnetic dating of Mediterranean volcanics of the last 2100 years: validity and limits. Earth Planet. Sci. Lett. 211 (2003) 111-124]. We also present a whole set of new U-series data on historical, recent, and older samples from Merapi (Indonesia), and show that the ( 226Ra)/Ba ratio has probably maintained a quasi-steady state value during at least the past four millennia, and can be used to infer the ( 226Ra) 0/Ba ratio of old volcanics at the time of eruption, and thus their ages. Comparison with

  18. Retinoic acid alleviates Con A-induced hepatitis and differentially regulates effector production in NKT cells.

    PubMed

    Lee, Kyoo-A; Song, You Chan; Kim, Ga-Young; Choi, Gyeyoung; Lee, Yoon-Sook; Lee, Jung-Mi; Kang, Chang-Yuil

    2012-07-01

    Retinoic acid (RA) is a diverse regulator of immune responses. Although RA promotes natural killer T (NKT) cell activation in vitro by increasing CD1d expression on antigen-presenting cells (APCs), the direct effects of RA on NKT-cell responses in vivo are not known. In the present study, we demonstrated the effect of RA on the severity of Con A-induced hepatitis and molecular changes of NKT cells. First, we demonstrated that Con A-induced liver damage was ameliorated by RA. In correlation with cytokine levels in serum, RA regulated the production of IFN-γ and IL-4 but not TNF-α by NKT cells without influencing the NKT-cell activation status. However, RA did not alleviate α-GalCer-induced liver injury, even though it reduced IFN-γ and IL-4 but not TNF-α levels in serum. This regulation was also detected when liver mononuclear cells (MNCs) or NKT hybridoma cells were treated with RA in vitro. The regulatory effect of RA on NKT cells was mediated by RAR-α, and RA reduced the phosphorylation of MAPK. These results suggest that RA differentially modulates the production of effector cytokines by NKT cells in hepatitis, and the suppressive effect of RA on hepatitis varies with the pathogenic mechanism of liver injury.

  19. Silybin from Silybum Marianum Seeds Inhibits Confluent-Induced Keratinocytes Differentiation as Effectively as Retinoic Acid without Inducing Inflammatory Cytokine.

    PubMed

    Kitajima, Seiji; Yamaguchi, Kohji

    2009-09-01

    Retinoic acid (RA) has been effective for improving wrinkles. However, it has also been reported that RA induces skin irritation. In this study, we explored new botanical compounds that show RA-like activity, but do not induce inflammation in vitro. Keratinocytes were maintained in a confluent condition and induced differentiation. Under this condition keratinocytes were treated with many botanical extracts and their morphological change were observed and compared with RA-treated. We found that silybin, which is a major flavonolignan from Silybum Marianum seeds, induced RA-like morphological change and prevented differentiation. We showed that silybin, like RA, reduced the expression of keratinocyte terminal differentiation markers and stimulated the expression of basement membrane component proteins. In contrast, silybin, unlike RA, did not stimulate the secretion of IL-1alpha, which is a skin irritation mediator. These results suggest that silybin has RA-like activity on keratinocytes and has the potential to improve winkle without inducing skin irritation.

  20. Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rosmarinic acid (RA), a caffeic acid derivative found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be of benefit t...

  1. Physiological insights into all-trans-retinoic acid biosynthesis

    PubMed Central

    Napoli, Joseph L.

    2011-01-01

    All-trans-retinoic acid (atRA) provides essential support to diverse biological systems and physiological processes. Epithelial differentiation and its relationship to cancer and embryogenesis have typified intense areas of interest into atRA function. Recently, however, interest in atRA action in the nervous system, the immune system, energy balance and obesity has increased considerably, especially concerning postnatal function. atRA action depends on atRA biosynthesis: defects in retinoid-dependent processes increasingly relate to defects in atRA biogenesis. Considerable evidence indicates that physiological atRA biosynthesis occurs via a regulated process, consisting of a complex interaction of retinoid binding-proteins and retinoid recognizing enzymes. An accrual of biochemical, physiological and genetic data have identified specific functional outcomes for the retinol dehydrogenases, RDH1, RDH10, and DHRS9, as physiological catalysts of the first step in atRA biosynthesis, and for the retinal dehydrogenases RALDH1, RALDH2, and RALDH3, as catalysts of the second and irreversible step. Each of these enzymes associates with explicit biological processes mediated by atRA. Redundancy occurs, but seems limited. Cumulative data supports a model of interactions among these enzymes with retinoid binding-proteins, with feedback regulation and/or control by atRA via modulating gene expression of multiple participants. The ratio apo-CRBP1/holo-CRBP1 participates by influencing retinol flux into and out of storage as retinyl esters, thereby modulating substrate to support atRA biosynthesis. atRA biosynthesis requires presence of both an RDH and an RALDH: conversely, absence of one isozyme of either step does not indicate lack of atRA biosynthesis at the site. PMID:21621639

  2. Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis

    PubMed Central

    Arendt, Kristin L.; Zhang, Zhenjie; Ganesan, Subhashree; Hintze, Maik; Shin, Maggie M.; Tang, Yitai; Cho, Ahryon; Graef, Isabella A.; Chen, Lu

    2015-01-01

    Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca2+ levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca2+-levels to RA synthesis remains unknown. Here we identify the Ca2+-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca2+-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity. PMID:26443861

  3. Complex Regulation of cyp26a1 Creates a Robust Retinoic Acid Gradient in the Zebrafish Embryo

    PubMed Central

    White, Richard J; Nie, Qing; Lander, Arthur D; Schilling, Thomas F

    2007-01-01

    Positional identities along the anterior–posterior axis of the vertebrate nervous system are assigned during gastrulation by multiple posteriorizing signals, including retinoic acid (RA), fibroblast growth factors (Fgfs), and Wnts. Experimental evidence has suggested that RA, which is produced in paraxial mesoderm posterior to the hindbrain by aldehyde dehydrogenase 1a2 (aldh1a2/raldh2), forms a posterior-to-anterior gradient across the hindbrain field, and provides the positional information that specifies the locations and fates of rhombomeres. Recently, alternative models have been proposed in which RA plays only a permissive role, signaling wherever it is not degraded. Here we use a combination of experimental and modeling tools to address the role of RA in providing long-range positional cues in the zebrafish hindbrain. Using cell transplantation and implantation of RA-coated beads into RA-deficient zebrafish embryos, we demonstrate that RA can directly convey graded positional information over long distances. We also show that expression of Cyp26a1, the major RA-degrading enzyme during gastrulation, is under complex feedback and feedforward control by RA and Fgf signaling. The predicted consequence of such control is that RA gradients will be both robust to fluctuations in RA synthesis and adaptive to changes in embryo length during gastrulation. Such control also provides an explanation for the fact that loss of an endogenous RA gradient can be compensated for by RA that is provided in a spatially uniform manner. PMID:18031199

  4. Atomic Mass and Nuclear Binding Energy for Ra-226 (Radium)

    NASA Astrophysics Data System (ADS)

    Sukhoruchkin, S. I.; Soroko, Z. N.

    This document is part of the Supplement containing the complete sets of data of Subvolume B `Nuclei with Z = 55 - 100' of Volume 22 `Nuclear Binding Energies and Atomic Masses' of Landolt-Börnstein - Group I `Elementary Particles, Nuclei and Atoms', and additionally including data for nuclei with Z = 101 - 130. It provides atomic mass, mass excess, nuclear binding energy, nucleon separation energies, Q-values, and nucleon residual interaction parameters for atomic nuclei of the isotope Ra-226 (Radium, atomic number Z = 88, mass number A = 226).

  5. Atomic Mass and Nuclear Binding Energy for Ra-287 (Radium)

    NASA Astrophysics Data System (ADS)

    Sukhoruchkin, S. I.; Soroko, Z. N.

    This document is part of the Supplement containing the complete sets of data of Subvolume B `Nuclei with Z = 55 - 100' of Volume 22 `Nuclear Binding Energies and Atomic Masses' of Landolt-Börnstein - Group I `Elementary Particles, Nuclei and Atoms', and additionally including data for nuclei with Z = 101 - 130. It provides atomic mass, mass excess, nuclear binding energy, nucleon separation energies, Q-values, and nucleon residual interaction parameters for atomic nuclei of the isotope Ra-287 (Radium, atomic number Z = 88, mass number A = 287).

  6. Spin of the sup 219 Ra ground state

    SciTech Connect

    Hackett, E.D.; Kuehner, J.A.; Waddington, J.C. ); Jones, G.D.

    1989-09-01

    The {sup 208}Pb({sup 18}O,3{ital n}){sup 223}Th reaction at 83 MeV bombarding energy was used to populate the alpha-radioactive nucleus {sup 223}Th. Out-of-beam alpha-gamma coincidences were recorded at correlation angles of 90{degree} and 180{degree}. The {ital a}{sub 2} angular correlation coefficient was extracted for an alpha-gamma cascade to the {sup 215}Rn ground state via the 0.316 MeV excited state. This limited the assignment of the ground-state spin of {sup 219}Ra to ((7/2, 11) / 2 ){sup +}. .AE

  7. Atomic Mass and Nuclear Binding Energy for Ra-223 (Radium)

    NASA Astrophysics Data System (ADS)

    Sukhoruchkin, S. I.; Soroko, Z. N.

    This document is part of the Supplement containing the complete sets of data of Subvolume B `Nuclei with Z = 55 - 100' of Volume 22 `Nuclear Binding Energies and Atomic Masses' of Landolt-Börnstein - Group I `Elementary Particles, Nuclei and Atoms', and additionally including data for nuclei with Z = 101 - 130. It provides atomic mass, mass excess, nuclear binding energy, nucleon separation energies, Q-values, and nucleon residual interaction parameters for atomic nuclei of the isotope Ra-223 (Radium, atomic number Z = 88, mass number A = 223).

  8. Atomic Mass and Nuclear Binding Energy for Ra-186 (Radium)

    NASA Astrophysics Data System (ADS)

    Sukhoruchkin, S. I.; Soroko, Z. N.

    This document is part of the Supplement containing the complete sets of data of Subvolume B `Nuclei with Z = 55 - 100' of Volume 22 `Nuclear Binding Energies and Atomic Masses' of Landolt-Börnstein - Group I `Elementary Particles, Nuclei and Atoms', and additionally including data for nuclei with Z = 101 - 130. It provides atomic mass, mass excess, nuclear binding energy, nucleon separation energies, Q-values, and nucleon residual interaction parameters for atomic nuclei of the isotope Ra-186 (Radium, atomic number Z = 88, mass number A = 186).

  9. Dominant negative mutant of retinoic acid receptor alpha inhibits retinoic acid-induced P19 cell differentiation by binding to DNA.

    PubMed

    Costa, S L; McBurney, M W

    1996-05-25

    Retinoic acid (RA) is a potent inducer of P19 cell differentiation. RA activity is thought to be mediated by nuclear RA receptors (RARs), transcription factors whose activity is dependent on RA. There are three RARs called alpha, beta, and gamma. We created truncated versions of the three RARs and compared their activities as inhibitors of RA-mediated gene transcription and of P19 cell differentiation. Only mutants of the RAR alpha were inhibitory in these assays. A mutant of RAR alpha carrying a 10-amino-acid insert was able to heterodimerize with RXRbeta or with the normal RAR alpha and the inhibitory activity of this mutant was dependent on an intact DNA binding domain. We conclude that dominant negative mutants of RAR alpha act by heterodimerizing with RXRs or RARs and binding to RA response elements on DNA, thereby preventing binding of the normal receptors to those sites. PMID:8635515

  10. (226) RA AND (228) RA ACTIVITIES ASSOCIATED WITH AGRICULTURAL DRAINAGE PONDS AND WETLAND PONDS IN THE KANKAKEE WATERSHED, IL-IN, USA

    EPA Science Inventory

    Background radioactivity is elevated in many agricultural drainage ponds and also constructed wetland ponds in the Kankakee watershed. During 1995-1999, gross-a and -B activities were measured up to 455 and 1650 mBq L-1, respectively. 226Ra and 228Ra averaged 139 and 192 mBq L-01...

  11. Protective effect of rosmarinic acid against oxidative stress biomarkers in liver and kidney of strepotozotocin-induced diabetic rats.

    PubMed

    Mushtaq, Nadia; Schmatz, Roberta; Ahmed, Mushtaq; Pereira, Luciane Belmonte; da Costa, Pauline; Reichert, Karine Paula; Dalenogare, Diéssica; Pelinson, Luana Paula; Vieira, Juliano Marchi; Stefanello, Naiara; de Oliveira, Lizielle Souza; Mulinacci, Nadia; Bellumori, Maria; Morsch, Vera Maria; Schetinger, Maria Rosa

    2015-12-01

    In the present study, we investigated the efficiency of rosmarinic acid (RA) in preventing the alteration of oxidative parameters in the liver and kidney of diabetic rats induced by streptozotocin (STZ). The animals were divided into six groups (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol, and diabetic/RA 10 mg/kg. After 3 weeks of treatment, we found that TBARS levels in liver and kidney were significantly increased in the diabetic/saline group and the administration of RA prevented this increase in the liver and kidney (P < 0.05). Diabetes caused a significant decrease in the activity of superoxide dismutase (SOD) and catalase (CAT) in the diabetes/saline group (P < 0.05). However, the treatment with 10 mg/kg RA (antioxidant) prevented this alteration in SOD and CAT activity in the diabetic RA group (P < 0.05). In addition, RA reverses the decrease in ascorbic acid and non-protein-thiol (NPSH) levels in diabetic rats. The treatment with RA also prevented the decrease in the Delta-aminolevulinic acid dehydratase (ALA-D) activity in the liver and kidney of diabetic rats. Furthermore, RA did not have any effect on glycemic levels. These results indicate that RA effectively reduced the oxidative stress induced by STZ, suggesting that RA is a potential candidate for the prevention and treatment of pathological conditions in diabetic models.

  12. Protective effect of rosmarinic acid against oxidative stress biomarkers in liver and kidney of strepotozotocin-induced diabetic rats.

    PubMed

    Mushtaq, Nadia; Schmatz, Roberta; Ahmed, Mushtaq; Pereira, Luciane Belmonte; da Costa, Pauline; Reichert, Karine Paula; Dalenogare, Diéssica; Pelinson, Luana Paula; Vieira, Juliano Marchi; Stefanello, Naiara; de Oliveira, Lizielle Souza; Mulinacci, Nadia; Bellumori, Maria; Morsch, Vera Maria; Schetinger, Maria Rosa

    2015-12-01

    In the present study, we investigated the efficiency of rosmarinic acid (RA) in preventing the alteration of oxidative parameters in the liver and kidney of diabetic rats induced by streptozotocin (STZ). The animals were divided into six groups (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol, and diabetic/RA 10 mg/kg. After 3 weeks of treatment, we found that TBARS levels in liver and kidney were significantly increased in the diabetic/saline group and the administration of RA prevented this increase in the liver and kidney (P < 0.05). Diabetes caused a significant decrease in the activity of superoxide dismutase (SOD) and catalase (CAT) in the diabetes/saline group (P < 0.05). However, the treatment with 10 mg/kg RA (antioxidant) prevented this alteration in SOD and CAT activity in the diabetic RA group (P < 0.05). In addition, RA reverses the decrease in ascorbic acid and non-protein-thiol (NPSH) levels in diabetic rats. The treatment with RA also prevented the decrease in the Delta-aminolevulinic acid dehydratase (ALA-D) activity in the liver and kidney of diabetic rats. Furthermore, RA did not have any effect on glycemic levels. These results indicate that RA effectively reduced the oxidative stress induced by STZ, suggesting that RA is a potential candidate for the prevention and treatment of pathological conditions in diabetic models. PMID:26452500

  13. Effects of in utero retinoic acid exposure on mouse pelage hair follicle development.

    PubMed

    García-Fernández, Rosa A; Pérez-Martínez, Claudia; Escudero-Diez, Alfredo; García-Iglesias, Maria J

    2002-06-01

    We investigated in vivo the histological and immunohistochemical responses of mouse hair pelage follicle morphogenesis to prenatal exposure to a potentially nonteratogenic dose of all-trans-retinoic acid (RA), as a basis studying the preventive effect of RA on adult mouse skin carcinogenesis. In pregnant mice, a single oral dose of RA at 30 mg kg-1 body weight given on day 11.5 of gestation caused no RA-induced changes in the morphology or temporal expression patterns of keratins during pelage hair follicle morphogenesis. The only differential effect of RA was a statistically significant increase in the number of BrdU-positive nuclei in hair bulbs from RA exposed fetuses compared with nonexposed mice. The absence of adverse RA effects suggests that this experimental design may represent a valuable protocol for use in studies on the in vivo effects of this retinoid on different skin diseases.

  14. Investigations On The EnviSAT RA2 Tropospheric Correction

    NASA Astrophysics Data System (ADS)

    Blarel, F.; Legresy, B.

    2013-12-01

    The Center for the Topography of Oceans and the Hydrosphere (CTOH), the Altimeter Data Service of the LEGOS laboratory pursue an effort to validate and improve ENVISAT RA2 altimetry. We investigate the stability and reliability of different corrections for the altimetric measurements. With the one before last ENVISAT RA2 processing (v1.0), the ICE Validation chain of the CTOH detected some issues with the Dry Tropospheric Correction (DTC) over the Cryosphere. Here we present the validation of the latest reprocessing (v2.1) of ENVISAT data. We observe the limitation of this re-processed DTC, especially the jump observed at cycle 44 over Antarctica which causes significant local trend and suspect changes in the variability of this correction over time. We investigated a solution and re- compute this correction all over the globe with the ERA Interim ECMWF pressure fields and using directly the altimetric range measurement rather than any external digital elevation model (DEM). We present the results of this investigation, the statistics of previous (DTC_v2.1) and new corrections (DTC_ctoh) and in the context of different surfaces. The improvement is significant, and we discuss the aspects and impacts of this improvement, in terms of meteorological-fields, procedure, and location.

  15. The Bayo Canyon/radioactive lanthanum (RaLa) program

    SciTech Connect

    Dummer, J.E.; Taschner, J.C.; Courtright, C.C.

    1996-04-01

    LANL conducted 254 radioactive lanthanum (RaLa) implosion experiments Sept. 1944-March 1962, in order to test implosion designs for nuclear weapons. High explosives surrounding common metals (surrogates for Pu) and a radioactive source containing up to several thousand curies of La, were involved in each experiment. The resulting cloud was deposited as fallout, often to distances of several miles. This report was prepared to summarize existing records as an aid in evaluating the off-site impact, if any, of this 18-year program. The report provides a historical setting for the program, which was conducted in Technical Area 10, Bayo Canyon about 3 miles east of Los Alamos. A description of the site is followed by a discussion of collateral experiments conducted in 1950 by US Air Force for developing an airborne detector for tracking atmospheric nuclear weapons tests. All known off-site data from the RaLa program are tabulated and discussed. Besides the radiolanthanum, other potential trace radioactive material that may have been present in the fallout is discussed and amounts estimated. Off-site safety considerations are discussed; a preliminary off-site dose assessment is made. Bibliographical data on 33 persons important to the program are presented as footnotes.

  16. AXIAL SKELETAL AND HOX EXPRESSION DOMAIN ALTERATIONS INDUCED BY RETINOIC ACID, VALPROIC ACID AND BROMOXYNIL DURING MURINE DEVELOPMENT

    EPA Science Inventory

    ABSTRACT

    Retinoic acid (RA) alters the developmental fate of the axial skeletal anlage. "Anteriorizations" or "posteriorizations", the assumption of characteristics of embryonic areas normally anterior or posterior to the affected tissues, are correlated with altered emb...

  17. Prolong Exposure of NSAID in Patients With RA Will Decrease the Risk of Dementia

    PubMed Central

    Chang, Kuang-Hsi; Hsu, Yi-Chao; Hsu, Chih-Chao; Lin, Cheng-Li; Hsu, Chung Y.; Lee, Chang-Yin; Chong, Lee-Won; Liu, Hui-Chuan; Lin, Ming-Chia; Kao, Chia-Hung

    2016-01-01

    Abstract Rheumatoid arthritis (RA), a chronic, systemic inflammatory disorder, primarily affects joints. Several studies have indicated that early inflammation, cardiovascular disease, and depression in patients were associated with a considerably increased risk of dementia. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for treating RA. NSAIDs facilitate alleviating RA-associated chronic pain, inflammation, and swelling. Therefore, we conducted this nationwide study for evaluating the association between the dementia risk and NSAID treatment in patients with RA. The RA cohort comprised patients aged 20 years and older who were newly diagnosed with RA between 2000 and 2011, with data obtained from the Registry of Catastrophic Illnesses Patient Database (RCIPD). Patients without RA were frequency matched with the RA cohort at a 1:4 ratio according to age, sex, and year of RA diagnosis. The relative risks of dementia were estimated using Cox proportional hazard models. The risk of dementia in the RA cohort was not significantly higher than that in the non-RA cohort (adjusted HR [hazard ratio] = 0.95, 95% confidence interval [CI] = 0.87–1.02). Regarding the duration of NSAID treatment, the risk of dementia was significantly lower when the RA cohort used NSAIDs for >2191 days (HR = 0.56, 95% CI = 0.45–0.68). A longer duration of NSAID treatment possibly reduces the risk of dementia. Additional studies are warranted for verifying the association of dementia risk with NSAID treatment in patients with RA. PMID:26962833

  18. PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation

    SciTech Connect

    Qiao, Jingbo; Paul, Pritha; Lee, Sora; Qiao, Lan; Josifi, Erlena; Tiao, Joshua R.; Chung, Dai H.

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Retinoic acid (RA) induces neuroblastoma cells differentiation, which is accompanied by G0/G1 cell cycle arrest. Black-Right-Pointing-Pointer RA resulted in neuroblastoma cell survival and inhibition of DNA fragmentation; this is regulated by PI3K pathway. Black-Right-Pointing-Pointer RA activates PI3K and ERK1/2 pathway; PI3K pathway mediates RA-induced neuroblastoma cell differentiation. Black-Right-Pointing-Pointer Upregulation of p21 is necessary for RA-induced neuroblastoma cell differentiation. -- Abstract: Neuroblastoma, the most common extra-cranial solid tumor in infants and children, is characterized by a high rate of spontaneous remissions in infancy. Retinoic acid (RA) has been known to induce neuroblastoma differentiation; however, the molecular mechanisms and signaling pathways that are responsible for RA-mediated neuroblastoma cell differentiation remain unclear. Here, we sought to determine the cell signaling processes involved in RA-induced cellular differentiation. Upon RA administration, human neuroblastoma cell lines, SK-N-SH and BE(2)-C, demonstrated neurite extensions, which is an indicator of neuronal cell differentiation. Moreover, cell cycle arrest occurred in G1/G0 phase. The protein levels of cyclin-dependent kinase inhibitors, p21 and p27{sup Kip}, which inhibit cell proliferation by blocking cell cycle progression at G1/S phase, increased after RA treatment. Interestingly, RA promoted cell survival during the differentiation process, hence suggesting a potential mechanism for neuroblastoma resistance to RA therapy. Importantly, we found that the PI3K/AKT pathway is required for RA-induced neuroblastoma cell differentiation. Our results elucidated the molecular mechanism of RA-induced neuroblastoma cellular differentiation, which may be important for developing novel therapeutic strategy against poorly differentiated neuroblastoma.

  19. Modulation of human stratum corneum properties by salicylic acid and all-trans-retinoic acid.

    PubMed

    Piérard-Franchimont, C; Goffin, V; Piérard, G E

    1998-01-01

    Topical all-trans-retinoic acid (RA) has been reported to decrease the in vivo skin response to sodium lauryl sulfate (SLS). The converse was also shown with a synergistic effect of RA following prior applications of SLS. The reason for such effects is not clear. We employed measures of transepidermal water loss (TEWL), squamometry and sequential corneosurfametry to explore the protective activity of a 0.05% RA cream at the level of the stratum corneum. Nonionic oil-in-water emulsions with or without 5% salicylic acid (SA) served as test product references. Data indicated that the RA formulation was responsible for a stochastic impairment in the TEWL and for an increased intercorneocyte cohesion. SA and the unmedicated emulsion did not lead to similar TEWL changes. The squamometry test proved to be very sensitive to disclose the effects of SA and RA without, however, allowing to distinguish the difference in the physiological processes involved. The corneosurfametry bioassay did not show any protection or synergistic effect between RA or SA and SLS challenge on the stratum corneum. This is in contrast to a previous work showing a positive protective effect afforded by retinol against SLS. The combined effects of irritant compounds affecting the stratum corneum are complex. The precise reason for some of their biological consequences remains a conundrum. On balance, products such as SA and RA do not appear to afford protection or impairment to a surfactant challenge at the level of the stratum corneum. PMID:9885411

  20. Modulation of human stratum corneum properties by salicylic acid and all-trans-retinoic acid.

    PubMed

    Piérard-Franchimont, C; Goffin, V; Piérard, G E

    1998-01-01

    Topical all-trans-retinoic acid (RA) has been reported to decrease the in vivo skin response to sodium lauryl sulfate (SLS). The converse was also shown with a synergistic effect of RA following prior applications of SLS. The reason for such effects is not clear. We employed measures of transepidermal water loss (TEWL), squamometry and sequential corneosurfametry to explore the protective activity of a 0.05% RA cream at the level of the stratum corneum. Nonionic oil-in-water emulsions with or without 5% salicylic acid (SA) served as test product references. Data indicated that the RA formulation was responsible for a stochastic impairment in the TEWL and for an increased intercorneocyte cohesion. SA and the unmedicated emulsion did not lead to similar TEWL changes. The squamometry test proved to be very sensitive to disclose the effects of SA and RA without, however, allowing to distinguish the difference in the physiological processes involved. The corneosurfametry bioassay did not show any protection or synergistic effect between RA or SA and SLS challenge on the stratum corneum. This is in contrast to a previous work showing a positive protective effect afforded by retinol against SLS. The combined effects of irritant compounds affecting the stratum corneum are complex. The precise reason for some of their biological consequences remains a conundrum. On balance, products such as SA and RA do not appear to afford protection or impairment to a surfactant challenge at the level of the stratum corneum.

  1. Laser-trapping of {sup 225}Ra and {sup 226}Ra with repumping by room-temperature blackbody radiation.

    SciTech Connect

    Guest, J. R.; Scielzo, N. D.; Ahmad, I.; Bailey, K.; Greene, J. P.; Holt, R. J.; Lu, Z.-T.; O'Connor, T. P.; Potterveld, D. H.; Physics; Enrico Fermi Inst.; Univ. of Chicago

    2007-02-27

    We have demonstrated Zeeman slowing and capture of neutral {sup 225}Ra and {sup 226}Ra atoms in a magneto-optical trap. The intercombination transition {sup 1}S{sub 0} {yields} {sup 3}P{sub 1} is the only quasicycling transition in radium and was used for laser-cooling and trapping. Repumping along the {sup 3}D{sub 1} {yields} {sup 1}P{sub 1} transition extended the lifetime of the trap from milliseconds to seconds. Room-temperature blackbody radiation was demonstrated to provide repumping from the metastable {sup 3}P{sub 0} level. We measured the isotope shift and hyperfine splittings on the {sup 3}D{sub 1} {yields} {sup 1}P{sub 1} transition with the laser-cooled atoms, and set a limit on the lifetime of the {sup 3}D{sub 1} level based on the measured blackbody repumping rate. Laser-cooled and trapped radium is an attractive system for studying fundamental symmetries.

  2. Spatiotemporal manipulation of retinoic acid activity in zebrafish hindbrain development via photo-isomerization.

    PubMed

    Xu, Lijun; Feng, Zhiping; Sinha, Deepak; Ducos, Bertrand; Ebenstein, Yuval; Tadmor, Arbel D; Gauron, Carole; Le Saux, Thomas; Lin, Shuo; Weiss, Shimon; Vriz, Sophie; Jullien, Ludovic; Bensimon, David

    2012-09-01

    All-trans retinoic acid (RA) is a key player in many developmental pathways. Most methods used to study its effects in development involve continuous all-trans RA activation by incubation in a solution of all-trans RA or by implanting all-trans RA-soaked beads at desired locations in the embryo. Here we show that the UV-driven photo-isomerization of 13-cis RA to the trans-isomer (and vice versa) can be used to non-invasively and quantitatively control the concentration of all-trans RA in a developing embryo in time and space. This facilitates the global or local perturbation of developmental pathways with a pulse of all-trans RA of known concentration or its inactivation by UV illumination. In zebrafish embryos in which endogenous synthesis of all-trans RA is impaired, incubation for as little as 5 minutes in 1 nM all-trans RA (a pulse) or 5 nM 13-cis RA followed by 1-minute UV illumination is sufficient to rescue the development of the hindbrain if performed no later than bud stage. However, if subsequent to this all-trans RA pulse the embryo is illuminated (no later than bud stage) for 1 minute with UV light (to isomerize, i.e. deactivate, all-trans RA), the rescue of hindbrain development is impaired. This suggests that all-trans RA is sequestered in embryos that have been transiently exposed to it. Using 13-cis RA isomerization with UV light, we further show that local illumination at bud stage of the head region (but not the tail) is sufficient to rescue hindbrain formation in embryos whose all-trans RA synthetic pathway has been impaired. PMID:22874920

  3. Shifting boundaries of retinoic acid activity control hindbrain segmental gene expression.

    PubMed

    Sirbu, Ioan Ovidiu; Gresh, Lionel; Barra, Jacqueline; Duester, Gregg

    2005-06-01

    Retinoic acid (RA) generated by Raldh2 in paraxial mesoderm is required for specification of the posterior hindbrain, including restriction of Hoxb1 expression to presumptive rhombomere 4 (r4). Hoxb1 expression requires 3' and 5' RA response elements for widespread induction up to r4 and for r3/r5 repression, but RA has previously been detected only from r5-r8, and vHnf1 is required for repression of Hoxb1 posterior to r4 in zebrafish. We demonstrate in mouse embryos that an RA signal initially travels from the paraxial mesoderm to r3, forming a boundary next to the r2 expression domain of Cyp26a1 (which encodes an RA-degrading enzyme). After Hoxb1 induction, the RA boundary quickly shifts to r4/r5, coincident with induction of Cyp26c1 in r4. A functional role for Cyp26c1 in RA degradation was established through examination of RA-treated embryos. Analysis of Raldh2-/- and vHnf1-/- embryos supports a direct role for RA in Hoxb1 induction up to r4 and repression in r3/r5, as well as an indirect role for RA in Hoxb1 repression posterior to r4 via RA induction of vHnf1 up to the r4/r5 boundary. Our findings suggest that Raldh2 and Cyp26 generate shifting boundaries of RA activity, such that r3-r4 receives a short pulse of RA and r5-r8 receives a long pulse of RA. These two pulses of RA activity function to establish expression of Hoxb1 and vHnf1 on opposite sides of the r4/r5 boundary.

  4. Retinoic Acid-mediated Nuclear Receptor Activation and Hepatocyte Proliferation

    PubMed Central

    Bushue, Nathan; Wan, Yu-Jui Yvonne

    2016-01-01

    Due to their well-known differentiation and apoptosis-inducing abilities, retinoic acid (RA) and its analogs have strong anti-cancer efficacy in human cancers. However, in vivo RA is a liver mitogen. While speculation has persisted that RA-mediated signaling is likely involved in hepatocyte proliferation during liver regeneration, direct evidence is still required. Findings in support of this proposition include observations that a release of retinyl palmitate (the precursor of RA) occurs in liver stellate cells following liver injury. Nevertheless, the biological action of this released vitamin A is virtually unknown. More likely is that the released vitamin A is converted to RA, the biological form, and then bound to a specific receptor (retinoid x receptor; RXRα), which is most abundantly expressed in the liver. Considering the mitogenic effects of RA, the RA-activated RXRα would likely then influence hepatocyte proliferation and liver tissue repair. At present, the mechanism by which RA stimulates hepatocyte proliferation is largely unknown. This review summarizes the activation of nuclear receptors (peroxisome proliferator activated receptor-α, pregnane x receptor, constitutive androstane receptor, and farnesoid x receptor) in an RXRα dependent manner to induce hepatocyte proliferation, providing a link between RA and its proliferative role.

  5. Ethanol Effects On Physiological Retinoic Acid Levels

    PubMed Central

    Napoli, Joseph L.

    2011-01-01

    Summary All-trans-retinoic acid (atRA) serves essential functions during embryogenesis and throughout post-natal vertebrate life. Insufficient or excess atRA causes teratogenic and/or toxic effects in the developing embryo: interference with atRA biosynthesis or signaling likely underlies some forms of cancer. Many symptoms of vitamin A (atRA precursor) deficiency and/or toxicity overlap with those of another pleiotropic agent—ethanol. These overlapping symptoms have prompted research to understand whether interference with atRA biosynthesis and/or action may explain (in part) pathology associated with excess ethanol consumption. Ethanol affects many aspects of retinoid metabolism and mechanisms of action site-specifically, but no robust data support inhibition of vitamin A metabolism, resulting in decreased atRA in vivo during normal vitamin A nutriture. Actually, ethanol either has no effect on or increases atRA at select sites. Despite this realization, insight into whether interactions between ethanol and retinoids represent cause vs. effect requires additional research. PMID:21766417

  6. Visualization of an endogenous retinoic acid gradient across embryonic development.

    PubMed

    Shimozono, Satoshi; Iimura, Tadahiro; Kitaguchi, Tetsuya; Higashijima, Shin-Ichi; Miyawaki, Atsushi

    2013-04-18

    In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain and paraxial mesoderm. RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes. However, gradients of endogenous morphogens in live embryos have not been directly observed; indeed, their existence, distribution and requirement for correct patterning remain controversial. Here we report a family of genetically encoded indicators for RA that we have termed GEPRAs (genetically encoded probes for RA). Using the principle of fluorescence resonance energy transfer we engineered the ligand-binding domains of RA receptors to incorporate cyan-emitting and yellow-emitting fluorescent proteins as fluorescence resonance energy transfer donor and acceptor, respectively, for the reliable detection of ambient free RA. We created three GEPRAs with different affinities for RA, enabling the quantitative measurement of physiological RA concentrations. Live imaging of zebrafish embryos at the gastrula and somitogenesis stages revealed a linear concentration gradient of endogenous RA in a two-tailed source-sink arrangement across the embryo. Modelling of the observed linear RA gradient suggests that the rate of RA diffusion exceeds the spatiotemporal dynamics of embryogenesis, resulting in stability to perturbation. Furthermore, we used GEPRAs in combination with genetic and pharmacological perturbations to resolve competing hypotheses on the structure of the RA gradient during hindbrain formation and somitogenesis. Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and

  7. Retinoic acid expands the evolutionarily reduced dentition of zebrafish

    PubMed Central

    Seritrakul, Pawat; Samarut, Eric; Lama, Tenzing T. S.; Gibert, Yann; Laudet, Vincent; Jackman, William R.

    2012-01-01

    Zebrafish lost anterior teeth during evolution but retain a posterior pharyngeal dentition that requires retinoic acid (RA) cell-cell signaling for its development. The purposes of this study were to test the sufficiency of RA to induce tooth development and to assess its role in evolution. We found that exposure of embryos to exogenous RA induces a dramatic anterior expansion of the number of pharyngeal teeth that later form and shifts anteriorly the expression patterns of genes normally expressed in the posterior tooth-forming region, such as pitx2 and dlx2b. After RA exposure, we also observed a correlation between cartilage malformations and ectopic tooth induction, as well as abnormal cranial neural crest marker gene expression. Additionally, we observed that the RA-induced zebrafish anterior teeth resemble in pattern and number the dentition of fish species that retain anterior pharyngeal teeth such as medaka but that medaka do not express the aldh1a2 RA-synthesizing enzyme in tooth-forming regions. We conclude that RA is sufficient to induce anterior ectopic tooth development in zebrafish where teeth were lost in evolution, potentially by altering neural crest cell development, and that changes in the location of RA synthesis correlate with evolutionary changes in vertebrate dentitions.—Seritrakul, P., Samarut, E., Lama, T. T. S., Gibert, Y., Laudet, V., Jackman, W. R. Retinoic acid expands the evolutionarily reduced dentition of zebrafish. PMID:22942074

  8. Rosmarinic acid prevents against memory deficits in ischemic mice.

    PubMed

    Fonteles, Analu Aragão; de Souza, Carolina Melo; de Sousa Neves, Julliana Catharina; Menezes, Ana Paula Fontenele; Santos do Carmo, Marta Regina; Fernandes, Francisco Diego Pinheiro; de Araújo, Patrícia Rodrigues; de Andrade, Geanne Matos

    2016-01-15

    Polyphenols have neuroprotective effects after brain ischemia. It has been demonstrated that rosmarinic acid (RA), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties. To evaluate the effectiveness of RA against memory deficits induced by permanent middle cerebral artery occlusion (pMCAO) mice were treated with RA (0.1, 1, and 20mg/kg/day, i.p. before ischemia and during 5 days). Animals were evaluated for locomotor activity and working memory 72 h after pMCAO, and spatial and recognition memories 96 h after pMCAO. In addition, in another set of experiments brain infarction, neurological deficit score and myeloperoxidase (MPO) activity were evaluates 24h after the pMCAO. Finally, immunohistochemistry, and western blot, and ELISA assay were used to analyze glial fibrillary acidic protein (GFAP), and synaptophysin (SYP) expression, and BDNF level, respectively. The working, spatial, and recognition memory deficits were significantly improved with RA treatment (20mg/kg). RA reduced infarct size and neurological deficits caused by acute ischemia. The mechanism for RA neuroprotection involved, neuronal loss suppression, and increase of synaptophysin expression, and increase of BDNF. Furthermore, the increase of MPO activity and GFAP immunireactivity were prevented in MCAO group treated with RA. These results suggest that RA exerts memory protective effects probably due to synaptogenic activity and anti-inflammatory action.

  9. Redox control of retinoic acid receptor activity: a novel mechanism for retinoic acid resistance in melanoma cells.

    PubMed

    Demary, K; Wong, L; Liou, J S; Faller, D V; Spanjaard, R A

    2001-06-01

    Retinoic acid (RA) slows growth and induces differentiation of tumor cells through activation of RA receptors (RARs). However, melanoma cell lines display highly variable responsiveness to RA, which is a poorly understood phenomenon. By using Northern and Western blot analyses, we show that RA-resistant A375 and RA-responsive S91 melanoma cells express comparable levels of major components of RAR-signaling pathways. However, A375 cells have substantially higher intracellular reactive oxygen species (ROS) levels than S91 cells. Lowering ROS levels in A375 cells through hypoxic culture conditions restores RAR-dependent trans-activity, which could be further enhanced by addition of the antioxidant N-acetyl-cysteine. Hypoxia also enhances RAR activity in the moderately RA-responsive C32 cells, which have intermediate ROS levels. Conversely, increasing oxidative stress in highly RA-responsive S91 and B16 cells, which have low ROS levels, by treatment with H(2)O(2) impairs RAR activity. Consistent with these observations, RA more potently inhibited the proliferation of hypoxic A375 cells than that of normoxic cells. Oxidative states diminish, whereas reducing conditions enhance, DNA binding of retinoid X receptor/RAR heterodimers in vitro, providing a molecular basis for the observed inverse correlation between RAR activity and ROS levels. The redox state of melanoma cells provides a novel, epigenetic control mechanism of RAR activity and RA resistance. PMID:11356710

  10. Production of Ra225 precursor for Ac225/Bi213 generators. Final CRADA Report.

    SciTech Connect

    Ehst, D. A.; Nuclear Engineering Division

    2009-10-02

    Russian subcontractors shipped two small deliveries of Ra225 to PNNL for evaluation. The activity was close to the requisite amount in the subcontract. The first labeled properly; the second did not. This showed that the Russians could supply Ra225 to the US; however they proved unable to meet future demands for larger amounts of activity. The US DOE attempts to get Ra225 from Russian should be terminated; the Russians, under Rosatom, are not interested in this business.

  11. Flow rates and reaction rates in the Galapagos Rise spreading center hydrothermal system as inferred from 228Ra/226Ra in vesicomyid clam shells

    PubMed Central

    Turekian, Karl K.; Cochran, J. Kirk

    1986-01-01

    The 228Ra/226Ra ratios in a previously dated vesicomyid clam shell were used to determine that seawater was in contact with mid-oceanic-ridge basalt glass for 22-45 years prior to arrival to the surface at 350°C at the Galapagos Rise Spreading Center. The minimum rate of reaction for the 45-year sojourn time, based on a water/rock ratio of 2.8 derived from 226Ra concentrations, is 8 g of basalt altered per kg of seawater per year. PMID:16593746

  12. All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver.

    PubMed

    Tripathy, Sasmita; Chapman, John D; Han, Chang Y; Hogarth, Cathryn A; Arnold, Samuel L M; Onken, Jennifer; Kent, Travis; Goodlett, David R; Isoherranen, Nina

    2016-05-01

    All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. The liver is the main storage organ of vitamin A, but activation of the retinoic acid receptors (RARs) in mouse liver and in human liver cell lines has also been shown. AlthoughatRA treatment improves mitochondrial function in skeletal muscle in rodents, its role in modulating mitochondrial function in the liver is controversial, and little data are available regarding the human liver. The aim of this study was to determine whetheratRA regulates hepatic mitochondrial activity.atRA treatment increased the mRNA and protein expression of multiple components of mitochondrialβ-oxidation, tricarboxylic acid (TCA) cycle, and respiratory chain. Additionally,atRA increased mitochondrial biogenesis in human hepatocytes and in HepG2 cells with and without lipid loading based on peroxisome proliferator activated receptor gamma coactivator 1αand 1βand nuclear respiratory factor 1 mRNA and mitochondrial DNA quantification.atRA also increasedβ-oxidation and ATP production in HepG2 cells and in human hepatocytes. Knockdown studies of RARα, RARβ, and PPARδrevealed that the enhancement of mitochondrial biogenesis andβ-oxidation byatRA requires peroxisome proliferator activated receptor delta. In vivo in mice,atRA treatment increased mitochondrial biogenesis markers after an overnight fast. Inhibition ofatRA metabolism by talarozole, a cytochrome P450 (CYP) 26 specific inhibitor, increased the effects ofatRA on mitochondrial biogenesis markers in HepG2 cells and in vivo in mice. These studies show thatatRA regulates mitochondrial function and lipid metabolism and that increasingatRA concentrations in human liver via CYP26 inhibition may increase mitochondrial biogenesis and fatty acidβ-oxidation and provide therapeutic benefit in diseases associated with mitochondrial dysfunction. PMID:26921399

  13. Ra-2 In-flight - Verification and Calibration Preliminary Results

    NASA Astrophysics Data System (ADS)

    Roca, M.; Laxon, S.; Martini, A.; Celani, C.; Zelli, C.; Francis, R.; Jackson, H.; Levrini, G.

    The EnviSat-1 satellite embarks an innovative radar altimeter, the RA-2, which rep- resents a new generation of radar altimeters compared the earlier ERS altimeters and TOPEX/Poseidon. This is due to its integration of many advanced features such as au- tonomous resolution selection a robust Smodel freeT tracker and its ability to telemeter & cedil;individual echo samples. Before the measurements from the RA-2 may be exploited the instrument and the data processing system have to be commissioned and a verification activity has to be performed. During this activity the correctness of the instrument in-flight operation is verified and its functionality optimised. In this paper we will outline the strategy and procedures adopted to tune the parameters used on-board. We will describe the algo- rithms and identify the those on-board parameters which play a key role in controlling the tracking and resolution selection. The strategy and procedures adopted to tune on- board parameters and hence maximise scientific return from the instrument will then be outlined. We will show results before and after the optimisation activities as well as comparison with pre-flight simulations. Also, we will show the RA-2 measurement performance of range and sigma-0 as well as the performance of its tracker. In par- ticular the tuning of the autonomous range resolution selection logic is a challenging task and we will show the results of this activity. The measurement performance of the instrument and the overall system are also evaluated, including verification of the instrument auxiliary data retrieval and correct usage of these data in the ground pro- cessing algorithms. Finally, these data is ready to be used for calibration purposes, as the Absolute Range and Sigma-0 Calibrations: The RA-2 altimeter is intended to continue an uninterrupted series of measurements of sea-level and ice-sheet elevation started by ERS-1 in 1991. To fully exploit these measurements, an absolute reference in

  14. Rapid method for the determination of 226Ra in hydraulic fracturing wastewater samples

    DOE PAGES

    Maxwell, Sherrod L.; Culligan, Brian K.; Warren, Richard A.; McAlister, Daniel R.

    2016-03-24

    A new method that rapidly preconcentrates and measures 226Ra from hydraulic fracturing wastewater samples was developed in the Savannah River Environmental Laboratory. The method improves the quality of 226Ra measurements using gamma spectrometry by providing up to 100x preconcentration of 226Ra from this difficult sample matrix, which contains very high levels of calcium, barium, strontium, magnesium and sodium. The high chemical yield, typically 80-90%, facilitates a low detection limit, important for lower level samples, and indicates method ruggedness. Ba-133 tracer is used to determine chemical yield and correct for geometry-related counting issues. The 226Ra sample preparation takes < 2 hours.

  15. Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor alpha (RAR alpha) and PLZF-RAR alpha fusion proteins on retinoic acid signalling.

    PubMed Central

    Ruthardt, M; Testa, U; Nervi, C; Ferrucci, P F; Grignani, F; Puccetti, E; Grignani, F; Peschle, C; Pelicci, P G

    1997-01-01

    Fusion proteins involving the retinoic acid receptor alpha (RAR alpha) and the PML or PLZF nuclear protein are the genetic markers of acute promyelocytic leukemias (APLs). APLs with the PML-RAR alpha or the PLZF-RAR alpha fusion protein are phenotypically indistinguishable except that they differ in their sensitivity to retinoic acid (RA)-induced differentiation: PML-RAR alpha blasts are sensitive to RA and patients enter disease remission after RA treatment, while patients with PLZF-RAR alpha do not. We here report that (i) like PML-RAR alpha expression, PLZF-RAR alpha expression blocks terminal differentiation of hematopoietic precursor cell lines (U937 and HL-60) in response to different stimuli (vitamin D3, transforming growth factor beta1, and dimethyl sulfoxide); (ii) PML-RAR alpha, but not PLZF-RAR alpha, increases RA sensitivity of hematopoietic precursor cells and restores RA sensitivity of RA-resistant hematopoietic cells; (iii) PML-RAR alpha and PLZF-RAR alpha have similar RA binding affinities; and (iv) PML-RAR alpha enhances the RA response of RA target genes (those for RAR beta, RAR gamma, and transglutaminase type II [TGase]) in vivo, while PLZF-RAR alpha expression has either no effect (RAR beta) or an inhibitory activity (RAR gamma and type II TGase). These data demonstrate that PML-RAR alpha and PLZF-RAR alpha have similar (inhibitory) effects on RA-independent differentiation and opposite (stimulatory or inhibitory) effects on RA-dependent differentiation and that they behave in vivo as RA-dependent enhancers or inhibitors of RA-responsive genes, respectively. Their different activities on the RA signalling pathway might underlie the different responses of PML-RAR alpha and PLZF-RAR alpha APLs to RA treatment. The PLZF-RAR alpha fusion protein contains an approximately 120-amino-acid N-terminal motif (called the POZ domain), which is also found in a variety of zinc finger proteins and a group of poxvirus proteins and which mediates protein

  16. U, Ra and Ba incorporation during precipitation of hydrothermal carbonates: Implications for {sup 226}Ra-Ba dating of impure travertines

    SciTech Connect

    Rihs, S.; Condomines, M.; Sigmarsson, O.

    2000-02-01

    The authors studied U, Ra and Ba incorporation in calcite in a natural CO{sub 2}-rich hydrothermal area from the French Massif Central. Along the western border of the Limagne graben, several springs are exploited for the petrification of various artifacts with calcite. These sites offer the opportunity to sample the water and the calcite layers downflow from the spring, and thus to follow the evolution of their U, Ra and Ba contents as precipitation proceeds. Results show that the apparent partition coefficients of U, Ra and Ba between water and calcite decrease during precipitation for the three elements. The authors found no direct relation between this variation and the main factors able to influence the partition coefficient, such as precipitation rate, which suggests that the incorporation of these trace elements could result from a composite process of adsorption and coprecipitation. Ra and Ba have a similar behavior, with an apparent partition coefficient decreasing from 0.80 to 0.47 for Ra and 0.96 to 0.68 for Ba, resulting in a small ({le}10%) variation of the Ra/Ba ratio. The apparent partition coefficient of U decreases from 0.38 to 0.20. These apparent coefficients are much higher than equilibrium values but might be applicable to natural systems with high precipitation rates. The authors also investigated the possibility of using the decay of the {sup 226}Ra-excess, or the decrease of the ({sup 226}Ra)/Ba ratio to date older deposits. Whereas the {sup 226}Ra initial activity at the time of deposition has not remained constant, and cannot be used for dating, the ({sup 226}Ra)/Ba method gives better results, when appropriate corrections for detrital contamination in Ba are made. Mixing diagrams using Th as an indicator of contamination allow calculation of the ({sup 226}Ra)/Ba ratio of the pure carbonate component. The calculated ages of five travertine layers range from 330 to 800 years, suggesting a mean deposition rate of about 1 cm/yr. The

  17. Tracking suspended particle transport via radium isotopes ((226)Ra and (228)Ra) through the Apalachicola-Chattahoochee-Flint River system.

    PubMed

    Peterson, Richard N; Burnett, William C; Opsahl, Stephen P; Santos, Isaac R; Misra, Sambuddha; Froelich, Philip N

    2013-02-01

    Suspended particles in rivers can carry metals, nutrients, and pollutants downstream which can become bioactive in estuaries and coastal marine waters. In river systems with multiple sources of both suspended particles and contamination sources, it is important to assess the hydrologic conditions under which contaminated particles can be delivered to downstream ecosystems. The Apalachicola-Chattahoochee-Flint (ACF) River system in the southeastern United States represents an ideal system to study these hydrologic impacts on particle transport through a heavily-impacted river (the Chattahoochee River) and one much less impacted by anthropogenic activities (the Flint River). We demonstrate here the utility of natural radioisotopes as tracers of suspended particles through the ACF system, where particles contaminated with arsenic (As) and antimony (Sb) have been shown to be contributed from coal-fired power plants along the Chattahoochee River, and have elevated concentrations in the surficial sediments of the Apalachicola Bay Delta. Radium isotopes ((228)Ra and (226)Ra) on suspended particles should vary throughout the different geologic provinces of this river system, allowing differentiation of the relative contributions of the Chattahoochee and Flint Rivers to the suspended load delivered to Lake Seminole, the Apalachicola River, and ultimately to Apalachicola Bay. We also use various geochemical proxies ((40)K, organic carbon, and calcium) to assess the relative composition of suspended particles (lithogenic, organic, and carbonate fractions, respectively) under a range of hydrologic conditions. During low (base) flow conditions, the Flint River contributed 70% of the suspended particle load to both the Apalachicola River and the bay, whereas the Chattahoochee River became the dominant source during higher discharge, contributing 80% of the suspended load to the Apalachicola River and 62% of the particles entering the estuary. Neither of these hydrologic

  18. Tracking suspended particle transport via radium isotopes ((226)Ra and (228)Ra) through the Apalachicola-Chattahoochee-Flint River system.

    PubMed

    Peterson, Richard N; Burnett, William C; Opsahl, Stephen P; Santos, Isaac R; Misra, Sambuddha; Froelich, Philip N

    2013-02-01

    Suspended particles in rivers can carry metals, nutrients, and pollutants downstream which can become bioactive in estuaries and coastal marine waters. In river systems with multiple sources of both suspended particles and contamination sources, it is important to assess the hydrologic conditions under which contaminated particles can be delivered to downstream ecosystems. The Apalachicola-Chattahoochee-Flint (ACF) River system in the southeastern United States represents an ideal system to study these hydrologic impacts on particle transport through a heavily-impacted river (the Chattahoochee River) and one much less impacted by anthropogenic activities (the Flint River). We demonstrate here the utility of natural radioisotopes as tracers of suspended particles through the ACF system, where particles contaminated with arsenic (As) and antimony (Sb) have been shown to be contributed from coal-fired power plants along the Chattahoochee River, and have elevated concentrations in the surficial sediments of the Apalachicola Bay Delta. Radium isotopes ((228)Ra and (226)Ra) on suspended particles should vary throughout the different geologic provinces of this river system, allowing differentiation of the relative contributions of the Chattahoochee and Flint Rivers to the suspended load delivered to Lake Seminole, the Apalachicola River, and ultimately to Apalachicola Bay. We also use various geochemical proxies ((40)K, organic carbon, and calcium) to assess the relative composition of suspended particles (lithogenic, organic, and carbonate fractions, respectively) under a range of hydrologic conditions. During low (base) flow conditions, the Flint River contributed 70% of the suspended particle load to both the Apalachicola River and the bay, whereas the Chattahoochee River became the dominant source during higher discharge, contributing 80% of the suspended load to the Apalachicola River and 62% of the particles entering the estuary. Neither of these hydrologic

  19. Distribution of (223)Ra and (224)Ra in the Bo Sea embayment in Tianjin and its implication of submarine groundwater discharge.

    PubMed

    Liu, Lingling; Yi, Lixin; Cheng, Xiaoqing; Tang, Guoqiang

    2015-12-01

    Submarine groundwater discharge (SGD) is now recognized as an important pathway between land and sea. In this study, in order to analyze the distribution of naturally occurring short-lived radium isotopes and the relative SGD effect in Bo Sea embayment, (223)Ra and (224)Ra were measured in three parts of the embayment with the radium-delayed coincidence counting (RaDeCC) system. Subsequently, the mixing process was studied by the calculation of diffusion coefficients (Kx and Kz) and advection velocities (Vx and Vz) based on the 2D advection-diffusion model. Additionally, the apparent residence ages and SGD flux were quantified based on the (224)Ra and (223)Ra activities. The results showed that the Ra activities exponentially decreased with the distance offshore, and both the Kx and Vx took the order of northern part > southern part > middle part. In vertical direction, there was the maximum value of Vz and minimum Kz in middle part and the maximum Kz and minimum Vz in southern part. The average ages for the northern, middle and southern parts were 4.28, 7.38 and 3.73 days, respectively. The final SGD flux yielded by (224)Ra was 0.09, 0.01 and 0.03 m d(-1) in the northern, middle and southern parts, respectively. The SGD flux yielded by (223)Ra was 0.08, 0.01 and 0.03 m d(-1) in northern, middle and southern parts, respectively. The result indicates that there is the fastest exchange rate and the biggest SGD flux in the southern part in Bo Sea embayment.

  20. Distribution of (223)Ra and (224)Ra in the Bo Sea embayment in Tianjin and its implication of submarine groundwater discharge.

    PubMed

    Liu, Lingling; Yi, Lixin; Cheng, Xiaoqing; Tang, Guoqiang

    2015-12-01

    Submarine groundwater discharge (SGD) is now recognized as an important pathway between land and sea. In this study, in order to analyze the distribution of naturally occurring short-lived radium isotopes and the relative SGD effect in Bo Sea embayment, (223)Ra and (224)Ra were measured in three parts of the embayment with the radium-delayed coincidence counting (RaDeCC) system. Subsequently, the mixing process was studied by the calculation of diffusion coefficients (Kx and Kz) and advection velocities (Vx and Vz) based on the 2D advection-diffusion model. Additionally, the apparent residence ages and SGD flux were quantified based on the (224)Ra and (223)Ra activities. The results showed that the Ra activities exponentially decreased with the distance offshore, and both the Kx and Vx took the order of northern part > southern part > middle part. In vertical direction, there was the maximum value of Vz and minimum Kz in middle part and the maximum Kz and minimum Vz in southern part. The average ages for the northern, middle and southern parts were 4.28, 7.38 and 3.73 days, respectively. The final SGD flux yielded by (224)Ra was 0.09, 0.01 and 0.03 m d(-1) in the northern, middle and southern parts, respectively. The SGD flux yielded by (223)Ra was 0.08, 0.01 and 0.03 m d(-1) in northern, middle and southern parts, respectively. The result indicates that there is the fastest exchange rate and the biggest SGD flux in the southern part in Bo Sea embayment. PMID:26318773

  1. Deciphering the binding patterns and conformation changes upon the bovine serum albumin-rosmarinic acid complex.

    PubMed

    Peng, Xin; Wang, Xiangchao; Qi, Wei; Huang, Renliang; Su, Rongxin; He, Zhimin

    2015-08-01

    Rosmarinic acid (RA) is an importantly and naturally occurring polyphenol from plants of the mint family with potent biological activities. Here, the in vitro interaction of RA with bovine serum albumin (BSA) has been investigated using various biophysical approaches as well as molecular modeling methods, to ascertain its binding mechanism and conformational changes. The fluorescence results demonstrated that the fluorescence quenching of BSA by RA was mainly the result of the formation of a ground state BSA-RA complex, and BSA had one high affinity RA binding site with a binding constant of 4.18 × 10(4) mol L(-1) at 298 K. Analysis of thermodynamic parameters revealed that hydrophobic and hydrogen bond interactions were the dominant intermolecular force in the complex formation. The primary binding site of RA in BSA (site I) had been identified by site marker competitive experiments. The distance between RA and the tryptophan residue of BSA was evaluated at 3.12 nm based on Förster's theory of non-radiation energy transfer. The UV-vis absorption, synchronous fluorescence, three-dimensional fluorescence, 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectra confirmed that the conformation and structure of BSA were altered in the presence of RA. Moreover, the nuclear magnetic spectroscopy showed that the aromatic groups of RA took part in the binding reaction during the BSA-RA complexation. In addition, the molecular picture of the interaction mechanism between BSA and RA at the atomic level was well examined by molecular docking and dynamics studies. In brief, RA can bind to BSA with noncovalent bonds in a relatively stable way, and these findings will be beneficial to the functional food research of RA.

  2. Role of Acinus in Regulating Retinoic Acid-Responsive Gene Pre-mRNA Splicing

    PubMed Central

    Wang, Fang; Soprano, Kenneth J.; Soprano, Dianne Robert

    2014-01-01

    Acinus-S’ is a co-repressor for retinoic acid receptor (RAR)-dependent gene transcription and has been suggested to be involved in RNA processing. In this study the role of Acinus isoforms in regulating pre-mRNA splicing was explored using in vivo splicing assays. Both Acinus-L and Acinus-S’, with the activity of Acinus-L higher than that of Acinus-S’, increase the splicing of a retinoic acid (RA)-responsive minigene containing a weak 5′ splice site but not a RA-responsive minigene containing a strong 5′ splice site. RA treatment further enhances the splicing of the weak 5′ splice site by Acinus in a dose- and time-dependent manner, suggesting a RA-dependent activity in addition to a RA-independent activity of Acinus. The RA-independent effect of Acinus occurs to varying degrees using minigene constructs containing several different promoters while the RA-dependent splicing activity of Acinus is specific for transcripts derived from the minigene driven by a RA response element (RARE)-containing promoter. This suggests that the ligand-dependent splicing activity of Acinus is related to the RA-activated RAR bound to the RARE. The RRM domain is necessary for the RA-dependent splicing activity of Acinus and the RA-independent splicing activity of Acinus is repressed by RNPS1. Importantly, measurement of the splicing of endogenous human RARβ and Bcl-x in vivo demonstrates that Acinus stimulates the use of the weaker alternative 5′ splice site of these two genes in a RA-dependent manner for RARβ and a RA-independent manner for Bcl-x. Taken together, these studies demonstrate that Acinus functions in both RAR-dependent splicing and RAR-dependent transcription. PMID:25205379

  3. Deciphering the binding patterns and conformation changes upon the bovine serum albumin-rosmarinic acid complex.

    PubMed

    Peng, Xin; Wang, Xiangchao; Qi, Wei; Huang, Renliang; Su, Rongxin; He, Zhimin

    2015-08-01

    Rosmarinic acid (RA) is an importantly and naturally occurring polyphenol from plants of the mint family with potent biological activities. Here, the in vitro interaction of RA with bovine serum albumin (BSA) has been investigated using various biophysical approaches as well as molecular modeling methods, to ascertain its binding mechanism and conformational changes. The fluorescence results demonstrated that the fluorescence quenching of BSA by RA was mainly the result of the formation of a ground state BSA-RA complex, and BSA had one high affinity RA binding site with a binding constant of 4.18 × 10(4) mol L(-1) at 298 K. Analysis of thermodynamic parameters revealed that hydrophobic and hydrogen bond interactions were the dominant intermolecular force in the complex formation. The primary binding site of RA in BSA (site I) had been identified by site marker competitive experiments. The distance between RA and the tryptophan residue of BSA was evaluated at 3.12 nm based on Förster's theory of non-radiation energy transfer. The UV-vis absorption, synchronous fluorescence, three-dimensional fluorescence, 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectra confirmed that the conformation and structure of BSA were altered in the presence of RA. Moreover, the nuclear magnetic spectroscopy showed that the aromatic groups of RA took part in the binding reaction during the BSA-RA complexation. In addition, the molecular picture of the interaction mechanism between BSA and RA at the atomic level was well examined by molecular docking and dynamics studies. In brief, RA can bind to BSA with noncovalent bonds in a relatively stable way, and these findings will be beneficial to the functional food research of RA. PMID:26146359

  4. Measurement of (238)U, (228)Ra, (226)Ra, (40)K and (137)Cs in foodstuffs samples collected from coastal areas of China.

    PubMed

    Tuo, Fei; Zhang, Qing; Zhou, Qiang; Xu, Cuihua; Zhang, Jing; Li, Wenhong; Zhang, Jianfeng; Su, Xu

    2016-05-01

    This study represents a total of 245 samples collected. The activities of (238)U, (228)Ra, (226)Ra, (40)K and (137)Cs were determined in samples of vegetables, tea, cereal (rice, wheat and corn), meat, poultry, freshwater product, seafood and seaweed that collected from the 30km safety zone of the Nuclear Power Plants (NPPs) area. All the samples radionuclide activities were quantified by using High Purity Germanium (HPGe) gamma spectrometry. The geometric mean concentrations (Bqkg(-1) wet weight) for (238)U, (228)Ra, (226)Ra, (40)K, and (137)Cs in all investigated foodstuffs samples, are 0.13, 0.16, 0.11, 68 and 0.02, respectively. The arithmetic mean concentrations (Bqkg(-1) wet weight) for (238)U, (228)Ra, (226)Ra, (40)K, and (137)Cs in all investigated foodstuffs samples, are 0.34, 0.65, 0.32, 111 and 0.09, respectively. Results of this study were compared with others, the measured values are the same with those of a previous investigation. Radiation doses due to the consumption of these foodstuffs to humans are estimated to comprise around 37-46% of the annual dose limit for public.

  5. 226Ra, 228Ra and 228Th in scale and sludge samples from the Campos Basin oilfield E&P activities.

    PubMed

    Matta, L E; Godoy, J M; Reis, M C

    2002-01-01

    More than 40 scale and sludge samples from the Campos Basin oilfield were analysed in terms of 226Ra, 228Ra and 228Th. Although the exact origin of the samples was not known, scale samples derived from production pipes and sludge samples from water-oil separation units. Reported values ranged from 0.13 to 331 kBq.kg(-1) for 226Ra, from 0.10 to 245 kBq.kg(-1) for 228Ra and <0.10 to 272 kBq.kg(-1) for 228Th in sludge samples. The concentrations in scales were much more regular than in sludges and ranged from 16.2 to 93.2 kBq.kg(-1) for 226Ra, from 4.0 to 36.9 kBq.kg(-1) for 228Ra and from 4.5 to 18.5 kBq.kg(-1) for 228Th. Based on the Basic Safety Standards recommendations and on the derived results, these activities cannot be regarded as exempted and specific procedures should be designed for their radiological control.

  6. Analysis of the distribution characteristics of 226Ra and 228Ra and their sources in the western part of Qinghai Lake

    NASA Astrophysics Data System (ADS)

    Kong, Fancui; Sha, Zhanjiang; Du, Jinzhou; Su, Weigang; Yu, Chenguang; Zhao, Shunli; Hu, Jufang; Ye, Mei

    2015-11-01

    The 226Ra and 228Ra activities of Qinghai Lake surface water, groundwater, river water, suspended particles, and bottom sediments were measured in a gamma-ray spectrometer. The sources of 226Ra and 228Ra were discussed according to their distribution characteristics. 226Ra and 228Ra activities (dpm/(100 L)) ranged from 14.13±0.22 to 19.22±0.42 and 17.72±0.66 to 30.96±1.47 in the surface water of the North Bay, respectively, and from 7.88±0.24 to 33.80±0.47 and 15.73±0.74 to 57.31±1.44, respectively, in the South Bay. The surface water near the estuary had a lower salinity and had a higher concentration of radium isotopes than the samples collected further away. The farther offshore the sample, the higher the salinity was, and the lower the radium isotope activity. The distribution of radium activities in the western part of Qinghai Lake is controlled by several factors, including Buha River runoff, desorption from suspended particles derived from the river, groundwater discharge, and a small amount of diffusion from the sediment.

  7. Measurement of (238)U, (228)Ra, (226)Ra, (40)K and (137)Cs in foodstuffs samples collected from coastal areas of China.

    PubMed

    Tuo, Fei; Zhang, Qing; Zhou, Qiang; Xu, Cuihua; Zhang, Jing; Li, Wenhong; Zhang, Jianfeng; Su, Xu

    2016-05-01

    This study represents a total of 245 samples collected. The activities of (238)U, (228)Ra, (226)Ra, (40)K and (137)Cs were determined in samples of vegetables, tea, cereal (rice, wheat and corn), meat, poultry, freshwater product, seafood and seaweed that collected from the 30km safety zone of the Nuclear Power Plants (NPPs) area. All the samples radionuclide activities were quantified by using High Purity Germanium (HPGe) gamma spectrometry. The geometric mean concentrations (Bqkg(-1) wet weight) for (238)U, (228)Ra, (226)Ra, (40)K, and (137)Cs in all investigated foodstuffs samples, are 0.13, 0.16, 0.11, 68 and 0.02, respectively. The arithmetic mean concentrations (Bqkg(-1) wet weight) for (238)U, (228)Ra, (226)Ra, (40)K, and (137)Cs in all investigated foodstuffs samples, are 0.34, 0.65, 0.32, 111 and 0.09, respectively. Results of this study were compared with others, the measured values are the same with those of a previous investigation. Radiation doses due to the consumption of these foodstuffs to humans are estimated to comprise around 37-46% of the annual dose limit for public. PMID:26926376

  8. Antibacterial synergy between rosmarinic acid and antibiotics against methicillin-resistant Staphylococcus aureus

    PubMed Central

    Ekambaram, Sanmuga Priya; Perumal, Senthamil Selvan; Balakrishnan, Ajay; Marappan, Nathiya; Gajendran, Sabari Srinivasan; Viswanathan, Vinodhini

    2016-01-01

    Aim/Background: Medicinal plants have ability to resist microorganisms by synthesizing secondary metabolites such as phenols. Rosmarinic acid (RA) is a phenylpropanoid widely distributed in plants and well known as therapeutic and cosmetic agent. Methicillin-resistant Staphylococcus aureus (MRSA) which is resistant to all kinds of β-lactams, threatens even most potent antibiotics. To improve the efficiency of antibiotics against multi-drug resistant bacteria and to reduce the antibiotic dose, the antibacterial activity and the synergistic effect of RA with standard antibiotics against S. aureus and MRSA was investigated. Materials and Methods: Antibacterial activity of RA against S. aureus and a clinical isolate of MRSA was evaluated by agar well diffusion method. Minimum inhibitory concentration (MIC) of RA was determined by broth dilution method. Synergism of RA with various antibiotics against S. aureus and MRSA was studied by broth checkerboard method and time-kill kinetic assay. Effect of RA on microbial surface components recognizing adhesive matrix molecules (MSCRAMM’s) of S. aureus and MRSA was studied using sodium dodecyl sulfate - polyacrylamide gel electrophoresis. Results: MIC of RA was found to be 0.8 and 10 mg/ml against S. aureus and MRSA, respectively. RA was synergistic with vancomycin, ofloxacin, and amoxicillin against S. aureus and only with vancomycin against MRSA. The time-kill analysis revealed that synergistic combinations were a more effective than individual antibiotics. MSCRAMM’s protein expression of S. aureus and MRSA was markedly suppressed by RA + vancomycin combination rather than RA alone. Conclusion: The synergistic effects of RA with antibiotics were observed against S. aureus and MRSA. RA showed inhibitory effect on the surface proteins MSCRAMM’s. Even though RA was shown to exhibit a synergistic effect with antibiotics, the MIC was found to be higher. Thus, further studies on increasing the efficacy of RA can develop it

  9. Retinoic Acid Attenuates Ileitis by Restoring the Balance between T-Helper 17 and T

    PubMed Central

    Collins, Colm B.; Aherne, Carol M.; Kominsky, Douglas; McNamee, Eóin N.; Lebsack, Matthew D.P.; Eltzschig, Holger; Jedlicka, Paul; Rivera-Nieves, Jesús

    2013-01-01

    Background & Aims Retinoic acid (RA), produced by intestinal epithelial cells (IECs) and dendritic cells (DCs) and regulated by transforming growth factor (TGF)-β, controls the enteric immune response by activating regulatory T (Treg) cells and preventing activation of T-helper (Th)17 cells Methods We studied the roles of RA in mice that overproduce tumor necrosis factor (TNF) and develop chronic ileitis (TNFΔARE mice). We assessed the frequency and function of CD103+ DCs and Th17 and Treg cells by flow cytometry; we measured expression of cytokines and retinaldehyde dehydrogenase (RALDH) enzymes in ileum samples, DCs, and IECs by real-time PCR. We quantified RA by electrochemical analysis and examined the effect of RA supplementation on TNF-induced ileitis using histologic, co-culture, and suppression assays and flow cytometry Results Numbers of CD103+ DCs decreased in the inflamed ilea of mice with chronic disease; RA synthetic machinery (RALDH1,2) was downregulated. Nevertheless, the proportion of CD4+, CD25+, FoxP3+ Treg cells increased, indicating an alternate source for RA. IECs responded to reduced levels of RA by upregulating RALDH3 in vivo and in vitro. Net tissue levels of RA levels remained lower in TNFΔARE than wild-type mice, indicating that epithelial up-regulation of RALDH3 could not maintain adequate concentrations of RA, probably because of loss of IEC mass. RA supplementation significantly attenuated disease by increasing the number and function of CD103+ DCs and Treg cells and reducing Th17 cells Conclusions Reduced levels of RA appear to induce IEC to upregulate synthesis of RA. RA supplementation attenuates ileitis through its effects on CD103+ DCs and Treg and Th17 cells. RA supplementation might used to treat patients with Crohn's disease PMID:22027263

  10. Testing of organic acids in engine coolants

    SciTech Connect

    Weir, T.W.

    1999-08-01

    The effectiveness of 30 organic acids as inhibitors in engine coolants is reported. Tests include glassware corrosion of coupled and uncoupled metals. FORD galvanostatic and cyclic polarization electrochemistry for aluminum pitting, and reserve alkalinity (RA) measurements. Details of each test are discussed as well as some general conclusions. For example, benzoic acid inhibits coupled metals well but is ineffective on cast iron when uncoupled. In benzoic acid inhibits coupled metals well but is ineffective on cast iron when uncoupled. In general, the organic acids provide little RA when titrated to a pH of 5.5, titration to a pH of 4.5 can result in precipitation of the acid. Trends with respect to acid chain length are reported also.

  11. A correlation between soil descriptions and {sup 226}Ra concentrations in Florida soils

    SciTech Connect

    Harrison, D.P.

    1992-12-31

    The soil radium content in Florida is highly variable. The range in radium concentrations, where the samples involved in this study are concerned, is from 0.1 pCi/g to 18.5 pCi/g. Low {sup 226}Ra concentrations (0.1 to 5 pCi/g) are evidenced in sands, moderate concentrations (5 to 11 pCi/g) are found in silt and gravel, and high {sup 226}Ra concentrations (>11 pCi/g) are found in soil horizons with shell, clay, and strata with phosphate. Strata containing phosphate yields a high concentration of {sup 226}Ra. The information obtained in this study, soil descriptions with their corresponding {sup 226}Ra concentrations, comes from geological cores drilled by geotechnical consultants with gamma spectrometry analysis performed by high resolution gamma spectroscopy. Concentration; of {sup 226}Ra generally increase with depth. These cores are usually terminated at 20 feet deep, with some cores being shallower than this due to hitting bedrock or encountering the water table. These frequency distributions give the core-logging geologist an approximate concentration of {sup 226}Ra based on the description of the soil. Since the correlation of {sup 226}Ra and soil descriptions can be used as a tool in assigning indoor radon potential, this study is of importance to land managers, contractors, developers, and regulating agencies who are attempting to place standards on tracts of land with {sup 226}Ra concentration used as a criterion.

  12. Leachable 226Ra in Philippine phosphogypsum and its implication in groundwater contamination in Isabel, Leyte, Philippines.

    PubMed

    Cañete, Socrates Jose P; Palad, Lorna Jean H; Enriquez, Eliza B; Garcia, Teofilo Y; Yulo-Nazarea, Teresa

    2008-07-01

    Phosphogypsum (PG), the major waste material in phosphate fertilizer processing, has been known to contain enhanced levels of naturally-occurring radionuclides especially (226)Ra. The lack of radioactivity data regarding Philippine phosphogypsum and its environmental behavior in the Philippine setting has brought concern on possible contamination of groundwater beneath the phosphogypsum ponds in Isabel, Leyte, Philippines. The radioactivity of Philippine phosphogypsum was determined and the leaching of (226)Ra from phosphogypsum and through local soil was quantified. Level of (226)Ra in groundwater samples in Isabel, Leyte, Philippines was also quantified to address the primary concern. It was found that the (226)Ra activity in Philippine phosphogypsum is distributed in a wide range from 91.5 to 935 Bq/kg. As much as 5% of (226)Ra can be leached from Philippine PG with deionized water. In vitro soil leach experiments suggest that the soil in the phosphate fertilizer plant area would be able to deter the intrusion of (226)Ra into the water table. Compared to reported values of natural groundwater levels of (226)Ra, the concentration of this radionuclide in Isabel, Leyte groundwater suggest that there is no (226)Ra intrusion brought about by the presence of phosphogypsum ponds in the area.

  13. IL-1Ra and its delivery strategies: inserting the association in perspective.

    PubMed

    Akash, Muhammad Sajid Hamid; Rehman, Kanwal; Chen, Shuqing

    2013-11-01

    Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory antagonist of interleukin-1 family of pro-inflammatory cytokines. The broad spectrum anti-inflammatory effects of IL-1Ra have been investigated against various auto-immune diseases such as diabetes mellitus, rheumatoid arthritis. Despite of its outstanding broad spectrum anti-inflammatory effects, IL-1Ra has short biological half-life (4-6 h) and to cope with this problem, up till now, many delivery strategies have been applied either to extend the half-life and/or prolong the steady-state sustained release of IL-1Ra from its target site. Here in our present paper, we have provided an overview of all approaches attempted to prolong the duration of therapeutic effects of IL-1Ra either by fusing IL-1Ra using fusion protein technology to extend the half-life and/or development of new dosage forms using various biodegradable polymers to prolong its steady-state sustained release at the site of administration. These approaches have been characterized by their intended impact on either in vitro release characteristics and/or pharmacokinetic and pharmacodynamic parameters of IL-1Ra. We have also compared these delivery strategies with each other on the basis of bioactivity of IL-1Ra after fusion with fusion protein partner and/or encapsulation with biodegradable polymer. PMID:23794040

  14. [Uptake of radionuclides from soil to plant and the discovery of 226Ra, 232Th hyperaccumulator].

    PubMed

    Zhang, Zhi-Qiang; Chen, Di-Yun; Song, Gang; Yue, Yu-Mei

    2011-04-01

    11 sorts of plant samples and corresponding soil samples were collected in Conghua and Taishan, Pearl River Delta. The specific activity of 238U, 226Ra, 232Th and 40K of samples were investigated by using HPGe-gamma-ray spectra analysis. The results showed that the average specific activity of 238U, 226Ra, 232Th and 40K in soil samples were 151.8, 146.3, 226.6, 665.5 Bq/kg, which were higher than the average values of China and the world. The concentration of 238U in all sort of plants are very low and most of them are lower than detection limit, while the values of 226Ra, 232Th and 40K were high. The contents of 226Ra and 232Th in Dicranopteris dichotoma were the highest, whose average specific activity is 285.9, 986.2 Bq/kg respectively. The average bioconcentration factors (BFs)of 26Ra, 232Th of Dicranopteris dichotoma were 2.20, 4.23, respectively, the other 10 sort of plants have BFs of 2266Ra, 232Th were in the range of 10(-1)-10(-2). The bioconcentration factors and the translocation factors of 226Ra, 232Th of Dicranopteris dichotoma. were all bigger than 1, so Dicranopteris dichotoma can be defined as hyperaccumulator of 226Ra and 232Th. PMID:21717763

  15. Antioxidant activity and sensory evaluation of a rosmarinic acid-enriched extract of Salvia officinalis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An extract of S. officinalis (garden sage) was developed using supercritical fluid extraction, followed by hot water extraction. The resulting extract was enriched in polyphenols, including rosmarinic acid (RA), which has shown promising health benefits in animals. The extract contained RA at a conc...

  16. Use of Ra isotopes to deduce rapid transfer of sediment-derived inputs off Kerguelen

    NASA Astrophysics Data System (ADS)

    Sanial, V.; van Beek, P.; Lansard, B.; Souhaut, M.; Kestenare, E.; d'Ovidio, F.; Zhou, M.; Blain, S.

    2015-03-01

    The Southern Ocean is known to be the largest high-nutrient, low-chlorophyll (HNLC) region of the global ocean due to iron limitation. However, a large phytoplankton bloom develops annually downstream of the Kerguelen Islands, a bloom which is sustained partly by iron released from the sediments deposited onto the shelves. In the framework of the KEOPS-2 project, we used radium isotopes (224Ra, T1/2 = 3.66 d; 223Ra, T1/2 = 11.4 d; 228Ra, T1/2 = 5.75 yr) to provide information on the origin of iron fertilization and on the timescales of the transfer of sediment-derived inputs (including iron and other micronutrients) towards offshore waters. Significant 224Ra and 223Ra activities were found in the near vicinity of the Kerguelen Islands, in agreement with the short half-lives of these isotopes. Significant 224Ra and 223Ra activities were also detected up to 200 km downstream of the islands and more unexpectedly in offshore waters south of the polar front. These observations thus clearly indicate (i) that the sediment-derived inputs are rapidly transferred towards offshore waters (on timescales on the order of several days up to several weeks) and (ii) that the polar front is not a physical barrier for the chemical elements released from the sediments of the Kerguelen Plateau. The Ra data set suggests that iron and other micronutrients released by the shelves of the Kerguelen Islands may contribute to fueling the phytoplankton bloom downstream of the islands, despite the presence of the polar front. However, the heterogeneous distribution of the 224Ra and 223Ra activities in surface waters suggests that this supply across the front is not a continuous process but rather a process that is highly variable in space and time.

  17. Use of Ra isotopes to deduce rapid transfer of sediment-derived inputs off Kerguelen

    NASA Astrophysics Data System (ADS)

    Sanial, V.; van Beek, P.; Lansard, B.; Souhaut, M.; Kestenare, E.; d'Ovidio, F.; Zhou, M.; Blain, S.

    2014-09-01

    The Southern Ocean is known as the largest High-Nutrient, Low-Chlorophyll (HNLC) region of the global ocean due to iron limitation. However, a large phytoplankton bloom develops annually downstream of the Kerguelen Islands, which is sustained partly by iron released from the sediments deposited onto the margins. In the framework of the KEOPS-2 project, we used radium isotopes (224Ra, T1/2 = 3.66 d; 223Ra, T1/2 = 11.4 d; 228Ra, T1/2 = 5.75 yr) to provide information on the origin of iron fertilization and on the timescales of the transfer of sediment-derived inputs (including iron and other micronutrients) towards offshore waters. Significant 223Ra and 223Ra activities were found in the near vicinity of the Kerguelen Islands, in agreement with the short half-lives of these isotopes. Significant 224Ra and 223Ra activities were also detected up to 200 km downstream of the islands and more unexpectedly in offshore waters south of the Polar Front. These observations thus clearly indicate (i) that the sediment-derived inputs are rapidly transferred towards offshore waters (on timescales in the order of several days up to several weeks) and (ii) that the Polar Front is not a physical barrier for the chemical elements released from the sediments of Kerguelen Plateau. The Ra dataset suggests that iron and other micronutrients released by the shallow sediments of the Kerguelen margins may contribute to fuel the phytoplankton bloom downstream of the islands, despite the presence of the Polar Front. However, the heterogeneous distribution of the 224Ra and 223Ra activities in surface waters suggests that this supply across the front is not a continuous process, but rather a process that is highly variable in space and time.

  18. atRA-induced apoptosis of mouse embryonic palate mesenchymal cells involves activation of MAPK pathway

    SciTech Connect

    Yu Zengli . E-mail: yuzengli@263.net; Xing Ying . E-mail: xingy@zzu.edu.cn

    2006-08-15

    Our previous studies have shown that atRA treatment resulted in cell-cycle block and growth inhibition in mouse embryonic palatal mesenchymal (MEPM). In the current study, gestation day (GD) 13 MEPM cells were used to test the hypothesis that the growth inhibition by atRA is due to apoptosis. The effects of atRA on apoptosis were assessed by performing MTT assay, Cell Death Detection ELISA and flow cytometry, respectively. Data analysis confirmed that atRA treatment induced apoptosis-like cell death, as shown by decreased cell viability and increased fragmented DNA and sub-G1 fraction. atRA-induced apoptosis was associated with upregulation of bcl-2, translocation of bax protein to the mitochondria from the cytosol, activation of caspase-3 and cytochrome c release into cytosol. atRA-induced apoptosis was abrogated by z-DEVD-fmk, a caspase-3 specific inhibitor, and z-VAD-fmk, a general caspase inhibitor, suggesting that the atRA-induced cell death of MEPM cells occurs through the cytochrome c- and caspase-3-dependent pathways. In addition, atRA treatment caused a strong and sustained activation of c-Jun N-terminal kinase (JNK) and p38 kinase (p38), as well as an early but transient activation of extracellular signal-regulated kinase (ERK). Importantly, atRA-induced DNA fragmentation and capase-3 activation were prevented by pretreatment with the JNK inhibitor (SP600125) and the p38 MAPK inhibitor (SB202190), but not by pretreatment with MEK inhibitor (U0126). From these results, we suggest that mitogen-activated protein kinase-dependent pathways is involved in the atRA-induced apoptosis of MEPM cells.

  19. The CpxRA two-component system is essential for Citrobacter rodentium virulence.

    PubMed

    Thomassin, Jenny-Lee; Giannakopoulou, Natalia; Zhu, Lei; Gross, Jeremy; Salmon, Kristiana; Leclerc, Jean-Mathieu; Daigle, France; Le Moual, Hervé; Gruenheid, Samantha

    2015-05-01

    Citrobacter rodentium is a murine intestinal pathogen used as a model for the foodborne human pathogens enterohemorrhagic Escherichia coli and enteropathogenic E. coli. During infection, these pathogens use two-component signal transduction systems to detect and adapt to changing environmental conditions. In E. coli, the CpxRA two-component signal transduction system responds to envelope stress by modulating the expression of a myriad of genes. Quantitative real-time PCR showed that cpxRA was expressed in the colon of C57BL/6J mice infected with C. rodentium. To determine whether CpxRA plays a role during C. rodentium infection, a cpxRA deletion strain was generated and found to have a colonization defect during infection. This defect was independent of an altered growth rate or a defective type III secretion system, and single-copy chromosomal complementation of cpxRA restored virulence. The C. rodentium strains were then tested in C3H/HeJ mice, a lethal intestinal infection model. Mice infected with the ΔcpxRA strain survived infection, whereas mice infected with the wild-type or complemented strains succumbed to infection. Furthermore, we found that the cpxRA expression level was higher during early infection than at a later time point. Taken together, these data demonstrate that the CpxRA two-component signal transduction system is essential for the in vivo virulence of C. rodentium. In addition, these data suggest that fine-tuned cpxRA expression is important for infection. This is the first study that identifies a C. rodentium two-component transduction system required for pathogenesis. This study further indicates that CpxRA is an interesting target for therapeutics against enteric pathogens.

  20. Direct protein-protein interactions and substrate channeling between cellular retinoic acid binding proteins and CYP26B1.

    PubMed

    Nelson, Cara H; Peng, Chi-Chi; Lutz, Justin D; Yeung, Catherine K; Zelter, Alex; Isoherranen, Nina

    2016-08-01

    Cellular retinoic acid binding proteins (CRABPs) bind all-trans-retinoic acid (atRA) tightly. This study aimed to determine whether atRA is channeled directly to cytochrome P450 (CYP) CYP26B1 by CRABPs, and whether CRABPs interact directly with CYP26B1. atRA bound to CRABPs (holo-CRABP) was efficiently metabolized by CYP26B1. Isotope dilution experiments showed that delivery of atRA to CYP26B1 in solution was similar with or without CRABP. Holo-CRABPs had higher affinity for CYP26B1 than free atRA, but both apo-CRABPs inhibited the formation of 4-OH-RA by CYP26B1. Similar protein-protein interactions between soluble binding proteins and CYPs may be important for other lipophilic CYP substrates.

  1. RA induces the neural-like cells generated from epigenetic modified NIH/3T3 cells.

    PubMed

    Zhang, Xi-Mei; Li, Qiu-Ming; Su, Dong-Ju; Wang, Ning; Shan, Zhi-Yan; Jin, Lian-Hong; Lei, Lei

    2010-03-01

    Recently, differentiated somatic cells had been reprogrammed to pluripotential state in vitro, and various tissue cells had been elicited from those cells. Epigenetic modifications allow differentiated cells to perpetuate the molecular memory needed for the cells to retain their identity. DNA methylation and histone deacetylation are important patterns involved in epigenetic modification, which take critical roles in regulating DNA expression. In this study, we dedifferentiated NIH/3T3 fibroblasts by 5-aza-2-deoxycytidine (5-aza-dC) and Trichstatin A (TSA) combination, and detected gene expression pattern, DNA methylation level, and differentiation potential of reprogrammed cells. As the results, embryonic marker Sox2, klf4, c-Myc and Oct4 were expressed in reprogrammed NIH/3T3 fibroblasts. Total DNA methylation level was significant decreased after the treatment. Moreover, exposure of the reprogrammed cells to all trans-retinoic acid (RA) medium elicited the generation of neuronal class IIIbeta-tubulin-positive, neuron-specific enolase (NSE)-positive, nestin-positive, and neurofilament light chain (NF-L)-positive neural-like cells. PMID:19263240

  2. Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for 223Ra and 225Ra for targeted alpha therapy

    SciTech Connect

    Rojas, J. V.; Woodward, J. D.; Chen, N.; Rondinone, A. J.; Castano, C. H.; Mirzadeh, S.

    2015-03-19

    Targeted alpha therapy (TAT) has the potential for killing specific tumor cells with minimum collateral damage to surrounding healthy tissue. Radionuclides such as 223Ra, 225Ra, and 225Ac are of special interest for radiotherapeutic applications as they emit multiple -particles during their decay. Utilizing appropriate carriers capable of retaining both the parent radioisotope as well as daughter products is important for the effective delivery of the radioisotope to the tumor site while mitigating global in vivo radiotoxicity. Methods. In this work, core and core+2 shells (NPs with 2 additional layers of cold LaPO4 deposited on the core surfaces) LaPO4 nanoparticles (NPs) were synthesized containing either 223Ra or 225Ra/225Ac and the retention of the parents and daughters within the NPs in vitro was investigated. Results. The NPs crystallized in rhabdophane phase with mean diameters of 3.4 and 6.3 nm for core and core+2 shells, respectively. The core LaPO 4 NPs retained up to 88% of 223Ra over 35 days. However, in the core+2 shell NPs, the retention of 223Ra and its daughter, 211Pb, was improved to > 99.9% over 27 days. Additionally, the retention of 225Ra/225Ac parents was > 99.98% and ~80% for the 221Fr and 213Bi daughters over 35 days for the core+2 shell NPs. Conclusions. These results suggest that LaPO4 NPs are potentially effective carriers of radium isotopes.

  3. Early mouse caudal development relies on crosstalk between retinoic acid, Shh and Fgf signalling pathways.

    PubMed

    Ribes, Vanessa; Le Roux, Isabelle; Rhinn, Muriel; Schuhbaur, Brigitte; Dollé, Pascal

    2009-02-01

    The progressive generation of embryonic trunk structures relies on the proper patterning of the caudal epiblast, which involves the integration of several signalling pathways. We have investigated the function of retinoic acid (RA) signalling during this process. We show that, in addition to posterior mesendoderm, primitive streak and node cells transiently express the RA-synthesizing enzyme Raldh2 prior to the headfold stage. RA-responsive cells (detected by the RA-activated RARE-lacZ transgene) are additionally found in the epiblast layer. Analysis of RA-deficient Raldh2(-/-) mutants reveals early caudal patterning defects, with an expansion of primitive streak and mesodermal markers at the expense of markers of the prospective neuroepithelium. As a result, many genes involved in neurogenesis and/or patterning of the embryonic spinal cord are affected in their expression. We demonstrate that RA signalling is required at late gastrulation stages for mesodermal and neural progenitors to respond to the Shh signal. Whole-embryo culture experiments indicate that the proper response of cells to Shh requires two RA-dependent mechanisms: (1) a balanced antagonism between Fgf and RA signals, and (2) a RA-mediated repression of Gli2 expression. Thus, an interplay between RA, Fgf and Shh signalling is likely to be an important mechanism underpinning the tight regulation of caudal embryonic development. PMID:19168680

  4. Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism

    PubMed Central

    Ross, A. Catharine; Zolfaghari, Reza

    2013-01-01

    The active metabolite of vitamin A, retinoic acid (RA), is a powerful regulator of gene transcription. RA is also a therapeutic drug. The oxidative metabolism of RA by certain members of the cytochrome P450 (CYP) superfamily helps to maintain tissue RA concentrations within appropriate bounds. The CYP26 family—CYP26A1, CYP26B1, and CYP26C1—is distinguished by being both regulated by and active toward all-trans-RA (at-RA) while being expressed in different tissue-specific patterns. The CYP26A1 gene is regulated by multiple RA response elements. CYP26A1 is essential for embryonic development, whereas CYP26B1 is essential for postnatal survival as well as germ cell development. Enzyme kinetic studies have demonstrated that several CYP proteins are capable of metabolizing at-RA; however, it is likely that CYP26A1 plays a major role in RA clearance. Thus, pharmacological approaches to limiting the activity of CYP26 enzymes may extend the half-life of RA and could be useful clinically in the future. PMID:21529158

  5. Retinoic acid treatment of fibroblasts causes a rapid decrease in ( sup 3 H)inositol uptake

    SciTech Connect

    Sinha, R.; Creek, K.E.; Silverman-Jones, C.; de Luca, L.M. )

    1989-04-01

    NIH 3T3 fibroblasts treated with all-trans-retinoic acid (RA) showed a dramatic decrease in the uptake of ({sup 3}H)inositol compared to solvent-treated controls. The onset of RA-induced inhibition of ({sup 3}H)inositol uptake was rapid with a 10-15% decrease occurring after 2-3 h of RA exposure and 60-70% reduction after 16 h of RA treatment. A progressive dose-dependent decrease in inositol uptake was found as the concentration of RA increased from 10{sup {minus}8} to 10{sup {minus}5} M and the effect was fully reversible within 48 h after RA removal. RA inhibition of inositol uptake was also observed in 3T3-Swiss and Balb/3T3 cells but not in two virally transformed 3T3 cell lines. Phlorizin, amiloride, and monensin inhibited inositol uptake by 66, 74, and 58%, respectively, and this inhibition was additive when the cells were treated with RA as well as these inhibitors. A decreased incorporation of ({sup 3}H)inositol into polyphosphoinositides was also observed in RA-treated cells but not to the same extent as for ({sup 3}H)inositol uptake. In conclusion, RA treatment of 3T3 fibroblasts decreases the uptake of ({sup 3}H)inositol by up to 70% within 8 to 10 h at near physiological concentrations in a reversible and specific manner.

  6. Determination of (210)Pb and (226)Ra/(228)Ra in continental water using HIDEX 300SL LS-spectrometer with TDCR efficiency tracing and optimized α/β-discrimination.

    PubMed

    Eikenberg, J; Beer, H; Jäggi, M

    2014-11-01

    An analytical method for determination of (210)Pb, (226)Ra and (228)Ra is presented based on adsorption on 3M Empore RadDiscs, and measurement applying liquid scintillation spectrometry (LSC) after elution. The LSC measurement was performed with optimized α/β-discrimination and isotope standardization using the triple to double coincidence ratio (TDCR). The consistency of measurement results between radioactive parent-daughter pairs (210)Pb/(210)Bi, (226)Ra/(222)Rn and (228)Ra/(228)Ac was checked in long-term counting experiments and the influence ofinterference of in-growing daughters from (226)Ra into the β-spectrum of (228)Ra+(228)Ac was studied as well. Recommendations for optimized LSC (228)Ra measurement besides presence of (226)Ra are given.

  7. Determination of (210)Pb and (226)Ra/(228)Ra in continental water using HIDEX 300SL LS-spectrometer with TDCR efficiency tracing and optimized α/β-discrimination.

    PubMed

    Eikenberg, J; Beer, H; Jäggi, M

    2014-11-01

    An analytical method for determination of (210)Pb, (226)Ra and (228)Ra is presented based on adsorption on 3M Empore RadDiscs, and measurement applying liquid scintillation spectrometry (LSC) after elution. The LSC measurement was performed with optimized α/β-discrimination and isotope standardization using the triple to double coincidence ratio (TDCR). The consistency of measurement results between radioactive parent-daughter pairs (210)Pb/(210)Bi, (226)Ra/(222)Rn and (228)Ra/(228)Ac was checked in long-term counting experiments and the influence ofinterference of in-growing daughters from (226)Ra into the β-spectrum of (228)Ra+(228)Ac was studied as well. Recommendations for optimized LSC (228)Ra measurement besides presence of (226)Ra are given. PMID:24637085

  8. Preparative separation and purification of rosmarinic acid from perilla seed meal via combined column chromatography.

    PubMed

    Tang, Weizhuo; Sun, Baoshan; Zhao, Yuqing

    2014-02-01

    In this study, the preparative separation and purification of rosmarinic acid (RA) from perilla seed meal (PSM), which is a by-product of edible oil production, was achieved using combined column chromatography over macroporous and polyamide resins. To optimize the RA enrichment process, the performance and separation characteristics of nine selected macroporous resins with different chemical and physical properties were investigated. SP825 resin was the most effective: the content of RA increased from 0.27% in the original extract to 16.58% in the 50% ethanol fraction (a 61.4-fold increase). During further purification treatment on polyamide resin, 90.23% pure RA could be obtained in the 70% ethanol fraction. RA with a higher purity (>95%) could also be easily obtained using one crystallization operation. The proposed method is simple, easily operated, cost-effective, and environmentally friendly and is suitable for both large-scale RA production and waste management.

  9. Release of rosmarinic acid from semisolid formulations and its penetration through human skin ex vivo.

    PubMed

    Stelmakienė, Ada; Ramanauskienė, Kristina; Briedis, Vitalis

    2015-06-01

    The aim of this study was to evaluate the release of rosmarinic acid (RA) from the experimental topical formulations with the Melissa officinalis L. extract and to evaluate its penetration through undamaged human skin ex vivo. The results of the in vitro release study showed that higher amounts of RA were released from the emulsion vehicle when lemon balm extract was added in its dry form. An inverse correlation was detected between the released amount of RA and the consistency index of the formulation. Different penetration of RA into the skin may be influenced by the characteristics of the vehicle as well as by the form of the extract. The results of penetration assessment showed that the intensity of RA penetration was influenced by its lipophilic properties: RA was accumulating in the epidermis, while the dermis served as a barrier, impeding its deeper penetration. PMID:26011936

  10. Release of rosmarinic acid from semisolid formulations and its penetration through human skin ex vivo.

    PubMed

    Stelmakienė, Ada; Ramanauskienė, Kristina; Briedis, Vitalis

    2015-06-01

    The aim of this study was to evaluate the release of rosmarinic acid (RA) from the experimental topical formulations with the Melissa officinalis L. extract and to evaluate its penetration through undamaged human skin ex vivo. The results of the in vitro release study showed that higher amounts of RA were released from the emulsion vehicle when lemon balm extract was added in its dry form. An inverse correlation was detected between the released amount of RA and the consistency index of the formulation. Different penetration of RA into the skin may be influenced by the characteristics of the vehicle as well as by the form of the extract. The results of penetration assessment showed that the intensity of RA penetration was influenced by its lipophilic properties: RA was accumulating in the epidermis, while the dermis served as a barrier, impeding its deeper penetration.

  11. Preparative separation and purification of rosmarinic acid from perilla seed meal via combined column chromatography.

    PubMed

    Tang, Weizhuo; Sun, Baoshan; Zhao, Yuqing

    2014-02-01

    In this study, the preparative separation and purification of rosmarinic acid (RA) from perilla seed meal (PSM), which is a by-product of edible oil production, was achieved using combined column chromatography over macroporous and polyamide resins. To optimize the RA enrichment process, the performance and separation characteristics of nine selected macroporous resins with different chemical and physical properties were investigated. SP825 resin was the most effective: the content of RA increased from 0.27% in the original extract to 16.58% in the 50% ethanol fraction (a 61.4-fold increase). During further purification treatment on polyamide resin, 90.23% pure RA could be obtained in the 70% ethanol fraction. RA with a higher purity (>95%) could also be easily obtained using one crystallization operation. The proposed method is simple, easily operated, cost-effective, and environmentally friendly and is suitable for both large-scale RA production and waste management. PMID:24381020

  12. Increased mucociliary differentiation and aquaporins formation of respiratory epithelial cells on retinoic acid-loaded hyaluronan-derivative membranes.

    PubMed

    Huang, Tsung-Wei; Chan, Yen-Hui; Su, Huang-Wei; Chou, Ya-Shuan; Young, Tai-Horng

    2013-06-01

    While playing a major role in maintaining the mucociliary phenotype of respiratory epithelial cells (RECs), retinoids are critical determinants of their normal function. However, despite being a powerful biological agent, retinoic acid (RA) is generally not used in regenerative medicine due to its scarce bioavailability via conventional administration. Therefore, the ability to incorporate RA into biomaterials allows for a combination of the biological effects of RA and biomaterials in influencing cellular behavior. This study attempts to develop RA-loaded hyaluronan-derivative membrane (RA-HAm) and investigates how this membrane affects the mucociliary differentiation and aquaporins (AQP) formation of RECs. In a simulated in vitro culture condition, the RA release from membranes is maintained for 7days. On the seventh day, the cumulative release rate of RA from supportive biomaterials is ~87% under detect limitation. RECs cultured on RA-HAm reveal numerous mature ciliated cells and microvilli compared to aggregated cilia-like structures on hyaluronan-derivative membrane (HAm). Moreover, the expression levels of MUC5AC and AQP on RA-HAm are higher than those on HAm. The proposed model elucidates the release of hydrophobic RA from hyaluronan-derivative biomaterials. We believe that RA-loaded hyaluronan biomaterials are highly promising biomaterials for use in sinonasal surgery and tissue engineering of the respiratory system.

  13. Retinoic acid regulates CD1d gene expression at the transcriptional level in human and rodent monocytic cells.

    PubMed

    Chen, Qiuyan; Ross, A Catharine

    2007-04-01

    CD1d belongs to a group of nonclassical antigen-presenting molecules that present glycolipid antigens and thereby activate natural killer T (NKT) cells, a subset of bifunctional T cells. Little is known so far regarding the expression and physiologic regulation of CD1d. Here we show that all-trans-retinoic acid (RA), the active metabolite of vitamin A, rapidly (1 hr after treatment) increases CD1d mRNA in human and rodent monocytic cells at a physiologic dose (10 nM). The induction is RA specific and RA receptor (RAR) dependent-RA and an RARalpha agonist, Am580, both had a pronounced positive effect, whereas the addition of RARalpha antagonist partially blocked the increase in CD1d mRNA induced by RA and Am580. The induction was also completely blocked by the presence of actinomycin D. A putative RA-response element was identified in the distal 5' flanking region of the CD1d gene, which binds nuclear retinoid receptors and was responsive to RA in both gel mobility shift assay and transient transfection assay in THP-1 cells. These results further confirmed the transcriptional regulation of RA in CD1d gene expression. Moreover, RA significantly increased alpha-galactosylceramide-induced spleen cell proliferation. These studies together provide evidence for a previously unknown mechanism of CD1d gene expression regulation by RA and suggest that RA is a significant modulator of NKT cell activation.

  14. Ra-228, Ra-226, Pb-210 and Po-210 variations in the water columns and the surface water plankton in the Luzon Strait and northern South China Sea

    NASA Astrophysics Data System (ADS)

    Chung, Y.; Lin, C.; Wang, P.; Su, Y.

    2006-12-01

    Profiles of Ra-228, Ra-226, Pb-210 and Po-210 were measured in the Luzon Strait (LS) and northern South China Sea (SCS) areas to delineate the exchanges between the western Philippine Sea (WPS) and the northern SCS waters across the LS. Plankton samples were also collected for Po-210 and Pb-210 measurements to assess the balance between the Po-210 excess over Pb-210 in the plankton and the deficit in the surface water. Profiles of Ra-228 and Ra-226 seem to indicate the out flow of the SCS water below the salinity minimum and above around 1500m depth, below which the WPS water flows into the SCS through the LS above a sill depth of about 2600m. This is consistent with previous studies conducted in the area. All the Pb-210 profiles show a strong subsurface maximum with higher activity in the LS area. This maximum is in large excess over its parent, Ra-226 due to atmospheric input. Po-210 profiles generally follow the associated Pb-210 profiles but with lower activities, showing Po-210 deficiency. Po-210 is strongly enriched over Pb-210 in the plankton samples with an activity ratio generally over 10 and up to 40. Both nuclides in the plankton are higher in the LS area, a trend similar to the surface water. The Po-210 excess in the plankton can account for at least 70 percent of the surface water deficit, part of which may be removed by sinking particles.

  15. Metrological Determination of Natural Radioactive Isotopes {sup 226}Ra, {sup 228}Ra and {sup 210}Pb by Means of Ge Detector

    SciTech Connect

    Almeida, Maria Candida M. de; Delgado, Jose U.; Poledna, Roberto; Oliveira, Estela Maria de; Silva, Ronaldo L. da

    2008-08-07

    A metrological method to determine the activity per mass unity (activity concentration) of {sup 226}Ra and {sup 210}Pb ({sup 238}U decay series) and {sup 228}Ra ({sup 232}Th series) by gamma-ray spectrometers based on hyper-pure coaxial germanium detector was developed. In the soil the {sup 22}Ra (half-life = 1600 years) exhibits the same level of radioactivity as {sup 238}U (half-life 4.5x10{sup 9} years) because of a natural phenomenon called secular equilibrium. {sup 226}Ra decays into {sup 222}Rn (half-life = 3.8 days), a radioactive inert gas. After several days, the {sup 222}Rn naturally decays to {sup 218}Po (half-life = 3 minutes), where finally {sup 210}Pb (half-life = 22 years) is produced. The metrological capability of high-resolution gamma-ray spectrometry for naturally occurring radionuclides at environmental levels is showed, with emphasis on the use of 2 mL standard sources volume in a glass ampoule. Source preparation and calibration procedures are described. Radionuclide standards in an activity range of 10 to 250 Bq/g were produced which can be applied in a variety of environmental sample analysis (water, plant material, sediment, etc.). Uncertainties for {sup 226}Ra and {sup 210}Pb around 3% (k = 1) were obtained.

  16. U-238 - Th-230 - Ra-226 disequilibria in volcanics: A new insight into melting conditions

    NASA Astrophysics Data System (ADS)

    Chabaux, Francois; Allegre, Claude J.

    1994-08-01

    Using new mass spectrometry techniques developed for the analysis of Ra isotopes, we present U-238 - Th-230 - Ra-226 disequilibria data from a variety of volcanic settings, and compare them with previously published data. Two correlations are observed with alkali volcanic data, one between (Th-230/U-238) and (Th-230/Ra-226) and another between the intensity of the disequilibria and the buoyancy flux of the underlying plume. These two correlations prove that partial melting is the major cause of U-Th-Ra fractionations in this volcanic context. The U-238 - Th-230 - Ra-226 disequilibria then place new constraints on some parameters of the classical melting models (batch melting and dynamic melting). The comparison of U-238 - Th-230 - Ra-226 disequilibria in alkali volcanics, carbonatites and subduction zones shows a clear parallel between the disequilibria value and the type of volcanic context. Such a parallel reflects the diversity of the conditions of magma generation, and shows that the U-238 - Th-230 - Ra-226 disequilibria systematics are very dependent on the chemical composition of liquids produced during magmatic processes. A systematic difference is observed between disequilibria in MORB and in alkali volcanics, which could indicate that the melting processes in these two volcanic contexts are very different.

  17. The CpxRA two-component system contributes to Legionella pneumophila virulence.

    PubMed

    Tanner, Jennifer R; Li, Laam; Faucher, Sébastien P; Brassinga, Ann Karen C

    2016-06-01

    The bacterium Legionella pneumophila is capable of intracellular replication within freshwater protozoa as well as human macrophages, the latter of which results in the serious pneumonia Legionnaires' disease. A primary factor involved in these host cell interactions is the Dot/Icm Type IV secretion system responsible for translocating effector proteins needed to establish and maintain the bacterial replicative niche. Several regulatory factors have been identified to control the expression of the Dot/Icm system and effectors, one of which is the CpxRA two-component system, suggesting essentiality for virulence. In this study, we generated cpxR, cpxA and cpxRA in-frame null mutant strains to further delineate the role of the CpxRA system in bacterial survival and virulence. We found that cpxR is essential for intracellular replication within Acanthamoeba castellanii, but not in U937-derived macrophages. Transcriptome analysis revealed that CpxRA regulates a large number of virulence-associated proteins including Dot/Icm effectors as well as Type II secreted substrates. Furthermore, the cpxR and cpxRA mutant strains were more sodium resistant than the parental strain Lp02, and cpxRA expression reaches maximal levels during postexponential phase. Taken together, our findings suggest the CpxRA system is a key contributor to L. pneumophila virulence in protozoa via virulence factor regulation. PMID:26934669

  18. Radium Ra 223 dichloride injection: U.S. Food and Drug Administration drug approval summary.

    PubMed

    Kluetz, Paul G; Pierce, William; Maher, V Ellen; Zhang, Hui; Tang, Shenghui; Song, Pengfei; Liu, Qi; Haber, Martin T; Leutzinger, Eldon E; Al-Hakim, Ali; Chen, Wei; Palmby, Todd; Alebachew, Elleni; Sridhara, Rajeshwari; Ibrahim, Amna; Justice, Robert; Pazdur, Richard

    2014-01-01

    On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Ra-223; Xofigo injection; Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease. The FDA review was based on clinical trial BC1-06, which randomly allocated patients (2:1) to either Ra-223 plus best standard of care (BSoC) or placebo plus BSoC. The primary endpoint was overall survival (OS) with a key secondary endpoint of time to first symptomatic skeletal event (SSE). A statistically significant improvement in OS was demonstrated [HR, 0.70; 95% confidence interval, 0.55-0.88, P = 0.0019]. At the prespecified interim analysis, the median OS durations were 14.0 and 11.2 months in the Ra-223 and placebo arms, respectively. The improvement in OS was supported by a delay in time to first SSE favoring the Ra-223 arm. The most common (>10%) adverse reactions in patients receiving Ra-223 were nausea, diarrhea, vomiting, and peripheral edema. The most common (>10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Ra-223 is the first α-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer.

  19. Carbachol-Induced Reduction in the Activity of Adult Male Zebra Finch RA Projection Neurons.

    PubMed

    Meng, Wei; Wang, Song-Hua; Li, Dong-Feng

    2016-01-01

    Cholinergic mechanism is involved in motor behavior. In songbirds, the robust nucleus of the arcopallium (RA) is a song premotor nucleus in the pallium and receives cholinergic inputs from the basal forebrain. The activity of projection neurons in RA determines song motor behavior. Although many evidences suggest that cholinergic system is implicated in song production, the cholinergic modulation of RA is not clear until now. In the present study, the electrophysiological effects of carbachol, a nonselective cholinergic receptor agonist, were investigated on the RA projection neurons of adult male zebra finches through whole-cell patch-clamp techniques in vitro. Our results show that carbachol produced a significant decrease in the spontaneous and evoked action potential (AP) firing frequency of RA projection neurons, accompanying a hyperpolarization of the membrane potential, an increase in the evoked AP latency, afterhyperpolarization (AHP) peak amplitude, and AHP time to peak, and a decrease in the membrane input resistance, membrane time constant, and membrane capacitance. These results indicate that carbachol reduces the activity of RA projection neurons by hyperpolarizing the resting membrane potential and increasing the AHP and the membrane conductance, suggesting that the cholinergic modulation of RA may play an important role in song production. PMID:26904300

  20. Behavior of /sup 226/Ra in the Mississippi River mixing zone

    SciTech Connect

    Moore, D.G.; Scott, M.R.

    1986-12-15

    The behavior of /sup 226/Ra in the Mississippi River mixing zone is strongy nonconservative and includes desorption similar to that for the Hudson, Pee Dee, and Amazon rivers. However, dissolved and desorbed /sup 226/Ra concentrations in the Mississippi are 2 to 5 times greater than in the other rivers at the same salinity. Radium concentrations vary inversely with the water discharge rate. The /sup 226/Ra desorption maximum occurs at a salinity of 5.0, much lower than the 18 to 28 salinity values for the maxima of the other three rivers. High concentrations of dissolved /sup 226/Ra (up to 82 dpm per 100 L) and the low salinity values for the desorption maximum in the Mississippi River result from three major factors. Suspended sediments include a large fraction of montmorillonite, which gives the sediment a high cation exchange capacity. 0.54 meq/g. The average suspended sediment load is large, about 510 mg/L, and contains 1.9 dpm g desorbable /sup 226/Ra. The dissolved /sup 226/Ra river water end-member (9.6 dpm per 100 L) is higher than in surface seawater. The annual contribution of /sup 226/Ra to the ocean from the Mississippi River is 3.7 x 10/sup 14/ dmp/yr based on data from three cruises. Evidence of flux of /sup 226/Ra from estuarine and shelf sediments is common in vertical profile sampling of the deltaic waters but is not reflected in calculations made with an ''apparent'' river water Ra value extrapolated to zero salinity.

  1. Role of retinoic acid metabolizing cytochrome P450s, CYP26, in inflammation and cancer

    PubMed Central

    Stevison, Faith; Jing, Jing; Tripathy, Sasmita; Isoherranen, Nina

    2016-01-01

    Vitamin A (retinol) and its active metabolite, all-trans-retinoic acid (atRA), play critical roles in regulating the differentiation, growth and migration of immune cells. Similarly, as critical signaling molecules in the regulation of the cell cycle, retinoids are important in cancers. Concentrations of atRA are tightly regulated in tissues, predominantly by the availability of retinol, synthesis of atRA by ALDH1A enzymes and metabolism and clearance of atRA by CYP26 enzymes. The ALDH1A and CYP26 enzymes are expressed in several cell types in the immune system and in cancer cells. In the immune system the ALDH1A and CYP26 enzymes appear to modulate RA concentrations. Consequently, alterations in the activity of ALDH1A and CYP26 enzymes are expected to change disease outcomes in inflammation. There is increasing evidence from various disease models of intestinal and skin inflammation that treatment with atRA has a positive effect on disease markers. However, whether aberrant atRA concentrations or atRA synthesis and metabolism play a role in inflammatory disease development and progression is not well understood. In cancers, especially in acute promyelocytic leukemia and neuroblastoma, increasing intracellular concentrations of atRA appears to provide clinical benefit. Inhibition of the CYP26 enzymes to increase atRA concentrations and combat therapy resistance has been pursued as a drug target in these cancers. This chapter covers the current knowledge of how atRA and retinol regulate the immune system and inflammation, how retinol and atRA metabolism is altered in inflammation and cancer and what roles atRA metabolizing enzymes have in immune responses and cancers. PMID:26233912

  2. Retinoic Acid and Histone Deacetylases Regulate Epigenetic Changes in Embryonic Stem Cells*

    PubMed Central

    Urvalek, Alison M.; Gudas, Lorraine J.

    2014-01-01

    All-trans-retinoic acid (RA) is a vitamin A metabolite that plays major roles in regulating stem cell differentiation and development. RA is the ligand of the retinoic acid receptor (RAR) family of transcription factors, which interact with retinoic acid response elements (RAREs) within target gene proximal promoters and enhancers. Although RA-mediated gene activation is well understood, less is known about the mechanisms for repression at RA-regulated genes. Using chromatin immunoprecipitation experiments, we show that in embryonic stem cells in the absence of RA, histone deacetylases (HDACs) differentially bind to various RAREs in proximal promoters or enhancer regions of RA-regulated genes; HDAC1, HDAC2, and HDAC3 bind at RAREs in the Hoxa1 and Cyp26a1 gene regulatory regions, whereas only HDAC1 binds at the RARβ2 RARE. shRNA knockdown of HDAC1, HDAC2, or HDAC3 differentially increases the deposition of the histone 3 lysine 27 acetylation (H3K27ac) epigenetic mark associated with increases in these three transcripts. Importantly, RA treatment differentially mediates the removal of HDACs from the Hoxa1, Cyp26a1, and RARβ2 genes and promotes the deposition of the H3K27ac mark at these genes. Overall, we show that HDACs differentially bind to RA-regulated genes to control key epigenetic marks involved in stem cell differentiation. PMID:24821725

  3. A shared HLA-DRB1 sequence confers RA susceptibility in Greeks.

    PubMed

    Carthy, D; Ollier, W; Papasteriades, C; Pappas, H; Thomson, W

    1993-10-01

    Previous serological studies of Greek rheumatoid arthritis (RA) patients have failed to demonstrate an association with DR4. Using sequence specific oligonucleotide typing we have identified the DRB1 alleles in panels of Greek RA patients and controls. When patient and control HLA-DRB1 frequencies were compared, significantly higher frequencies of DRB1*0101 (23.3% vs. 7.0%, odds ratio [OR] 4.0, 95% confidence intervals [CI] 1.4-12.0) and DRB1*1001 (20.9% vs. 5.8%, OR 4.3, 95% CI 1.3-13.7) were found in RA patients compared with controls. No association of DRB1*04 with RA was observed (20.9% vs. 14.0% in controls) confirming earlier reports. However DRB1*04 subtyping demonstrated a small but significant increase of DRB1*0405 in patients (14.0% vs. 3.5%, OR 4.5, 95% CI 1.1-18.9). When the frequency of individuals carrying the shared RA susceptibility epitope was compared between patients and controls it was found to be significantly higher in RA patients (60.5% vs. 22.1%, OR 5.4, 95% CI 2.4-12.0). We conclude that the shared epitope is significantly associated with RA in this population, but that it is predominantly accounted for by DRB1*0101 and DRB1*1001. Previous studies of UK RA patients have demonstrated a negative association of DR2 with disease and articular erosions. HLA-DR2 variants, DRB1*1501 and *1502 are not at reduced frequency in Greek RA patients (DRB1*1501, 14.0% in patients vs. 7.0% in controls; DRB1*1502, 7.0% in patients vs. 7.0% in controls). Genes conferring RA resistance may be in linkage disequilibrium with DR2 in UK patients. This does not appear to be the case in Greek RA patients. No association was seen between RA and HLA-DPB1 type.

  4. Rosmarinic acid mitigates signs of systemic oxidative stress in streptozotocin-induced diabetes in rats.

    PubMed

    Sotnikova, Ruzena; Kaprinay, Barbara; Navarova, Jana

    2015-10-01

    The aim of the work was to study the effect of rosmarinic acid (RA) on markers of oxidative stress in rats with diabetes. Diabetes was induced by streptozotocin (STZ), RA was administered orally for ten weeks. Water consumption was measured daily. Ten weeks after the first RA administration, urine was collected over 15 hours. N-acetyl-β-D-glucosaminidase (NAGA) activity, levels of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) were determined in the pancreas, kidney, and plasma. RA administration to diabetic rats ameliorated markers of oxidative stress, as well as water consumption and urination. We assume that RA may mitigate STZ-induced diabetic manifestations by protecting rat tissues against damaging effect of free radicals. PMID:26374995

  5. 210Pb- 226Ra and 228Ra- 232Th systematics in young arc lavas: implications for magma degassing and ascent rates

    NASA Astrophysics Data System (ADS)

    Turner, Simon; Black, Stuart; Berlo, Kim

    2004-10-01

    New data show that island arc rocks have ( 210Pb/ 226Ra) o ratios which range from as low as 0.24 up to 2.88. In contrast, ( 228Ra/ 232Th) appears always within error of 1 suggesting that the large 226Ra-excesses observed in arc rocks were generated more than 30 years ago. This places a maximum estimate on melt ascent velocities of around 4000 m/year and provides further confidence that the 226Ra excesses reflect deep (source) processes rather than shallow level alteration or seawater contamination. Conversely, partial melting must have occurred more than 30 years prior to eruption. The 210Pb deficits are most readily explained by protracted magma degassing. Using published numerical models, the data suggest that degassing occurred continuously for periods up to several decades just prior to eruption but no link with eruption periodicity was found. Longer periods are required if degassing is discontinuous, less than 100% efficient or if magma is recharged or stored after degassing. The long durations suggest much of this degassing occurs at depth with implications for the formation of hydrothermal and copper-porphyry systems. A suite of lavas erupted in 1985-1986 from Sangeang Api volcano in the Sunda arc are characterised by deficits of 210Pb relative to 226Ra from which 6-8 years of continuous 222Rn degassing would be inferred from recent numerical models. These data also form a linear ( 210Pb)/Pb-( 226Ra)/Pb array which might be interpreted as a 71-year isochron. However, the array passes through the origin suggesting displacement downwards from the equiline in response to degassing and so the slope of the array is inferred not to have any age significance. Simple modelling shows that the range of ( 226Ra)/Pb ratios requires thousands of years to develop consistent with differentiation occurring in response to cooling at the base of the crust. Thus, degassing post-dated, and was not responsible for magma differentiation. The formation, migration and extraction

  6. Effects of 13 developmentally toxic chemicals on the migration of rat cephalic neural crest cells in vitro.

    PubMed

    Usami, Makoto; Mitsunaga, Katsuyoshi; Miyajima, Atsuko; Takamatu, Mina; Kazama, Shugo; Irie, Tomohiko; Doi, Osamu; Takizawa, Tatsuya

    2016-03-01

    The inhibition of neural crest cell (NCC) migration has been considered as a possible pathogenic mechanism underlying chemical developmental toxicity. In this study, we examined the effects of 13 developmentally toxic chemicals on the migration of rat cephalic NCCs (cNCCs) by using a simple in vitro assay. cNCCs were cultured for 48 h as emigrants from rhombencephalic neural tubes explanted from rat embryos at day 10.5 of gestation. The chemicals were added to the culture medium at 24 h of culture. Migration of cNCCs was measured as the change in the radius (radius ratio) calculated from the circular spread of cNCCs between 24 and 48 h of culture. Of the chemicals examined, 13-cis-retinoic acid, ethanol, ibuprofen, lead acetate, salicylic acid, and selenate inhibited the migration of cNCCs at their embryotoxic concentrations; no effects were observed for acetaminophen, caffeine, indium, phenytoin, selenite, tributyltin, and valproic acid. In a cNCC proliferation assay, ethanol, ibuprofen, salicylic acid, selenate, and tributyltin inhibited cell proliferation, suggesting the contribution of the reduced cell number to the inhibited migration of cNCCs. It was determined that several developmentally toxic chemicals inhibited the migration of cNCCs, the effects of which were manifested as various craniofacial abnormalities. PMID:26175014

  7. Relative developmental toxicity potencies of retinoids in the embryonic stem cell test compared with their relative potencies in in vivo and two other in vitro assays for developmental toxicity.

    PubMed

    Louisse, Jochem; Gönen, Süleyman; Rietjens, Ivonne M C M; Verwei, Miriam

    2011-05-30

    The present study determines the relative developmental toxicity potencies of retinoids in the embryonic stem (ES)-D3 cell differentiation assay of the embryonic stem cell test, and compares the outcomes with their relative potencies in in vivo and two other in vitro assays for developmental toxicity. The results reveal that the potency ranking obtained in the ES-D3 cell differentiation assay is similar to the reported potency rankings in the two other in vitro assays for developmental toxicity. TTNPB ((E)-4[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid) was the most potent retinoid, whereas etretinate and retinol had the lowest potency. All-trans-retinoic acid, 13-cis-retinoic acid, 9-cis-retinoic acid and acitretin showed an intermediate potency. In vivo potency rankings of the developmental toxicity of retinoids appear to be dependent on the species and/or exposure regimens used. The obtained in vitro potency ranking does not completely correspond with the in vivo potency rankings, although TTNPB is correctly predicted to be the most potent and retinol the least potent congener. The lack of in vivo kinetic processes in the ES-D3 cell differentiation assay might explain the deviating potency predictions of some retinoids. Therefore, knowledge on the species-dependent in vivo kinetics is essential when using in vitro toxicity data for the estimation of in vivo developmental toxicity potencies within series of related compounds.

  8. Laser-cooled RaF as a promising candidate to measure molecular parity violation

    NASA Astrophysics Data System (ADS)

    Isaev, T. A.; Hoekstra, S.; Berger, R.

    2010-11-01

    The parameter Wa, which characterizes nuclear-spin-dependent parity violation (PV) in the molecular spin-rotational Hamiltonian, was computed with a quasirelativistic Hartree-Fock approach for radium fluoride (RaF) and found to be one of the largest absolute values predicted so far. The peculiar electronic structure of RaF leads to highly diagonal Franck-Condon matrices between the energetically lowest two electronic states, which qualifies RaF for direct laser cooling. A subset of diatomic molecules with a wide range of internal structures suitable for this cooling technique is also indicated. As trapped cold molecules offer superior coherence times, RaF can be considered promising for high-precision experiments aimed at molecular PV.

  9. 112. HISTORIC AMERICAN BUILDINGS SURVEY R.A. Waugh, Photographer October 1936 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    112. HISTORIC AMERICAN BUILDINGS SURVEY R.A. Waugh, Photographer October 1936 NOTCHING in STUDS for OLD WINDOW FRAMES, NORTH WALL, ORIGINAL KITCHEN, LOOKING NORTH - Colonel Paul Wentworth House, Dover Street (moved to MA, Dover), Dover, Strafford County, NH

  10. 100. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    100. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 STUDS & SLOTS for FORMER WINDOW, SOUTH WALL, WEST BAY, 2nd FLOOR LOOKING SOUTH - Colonel Paul Wentworth House, Dover Street (moved to MA, Dover), Dover, Strafford County, NH

  11. A Study on Sorption of (226)Ra on Different Clay Matrices.

    PubMed

    Alhajji, E; Al-Masri, M S; Khalily, H; Naoum, B E; Khalil, H S; Nashawati, A

    2016-08-01

    The sorption of radium 226 ((226)Ra) on different clay materials (bentonite, illite and a mixture of bentonite-illite) was studied. Clay materials are used in the construction of disposal pits for technically enhanced naturally occurring radioactive materials (TENORM) wastes (i.e., contaminated soil and sludge) generated by the oil and gas industry operations. Experimental conditions (pH, clay materials quantity, and activity concentrations of (226)Ra) were changed in order to determine the optimal state for adsorption of (226)Ra. The results showed that the concentration of adsorbed (226)Ra on clay materials increased with time to reach an equilibrium state after approximately 5 h. More than 95 % of the radium was adsorbed. The mixture of bentonite-illite (1/9) exhibited the greatest adsorption of radium under all experimental conditions. PMID:27329110

  12. 124. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    124. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 CHAIR RAIL FOUND AS HOUSE WAS BEING TORN DOWN - Colonel Paul Wentworth House, Dover Street (moved to MA, Dover), Dover, Strafford County, NH

  13. 123. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    123. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 LOOM STRETCHER FOUND AS HOUSE WAS BEING TORN DOWN - Colonel Paul Wentworth House, Dover Street (moved to MA, Dover), Dover, Strafford County, NH

  14. 126. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    126. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 REVERSE of BUTTON FOUND BETWEEN SILLS of MAIN HOUSE AND LEAN-TO - Colonel Paul Wentworth House, Dover Street (moved to MA, Dover), Dover, Strafford County, NH

  15. 153. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    153. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 CLOSE-UP OF WATTLE FOUND ON OLD CHIMNEY HAUNCH - Colonel Paul Wentworth House, Dover Street (moved to MA, Dover), Dover, Strafford County, NH

  16. 125. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    125. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 OBVERSE of BUTTON FOUND BETWEEN SILLS of MAIN HOUSE AND LEAN-TO - Colonel Paul Wentworth House, Dover Street (moved to MA, Dover), Dover, Strafford County, NH

  17. Laser-cooled RaF as a promising candidate to measure molecular parity violation

    SciTech Connect

    Isaev, T. A.; Berger, R.; Hoekstra, S.

    2010-11-15

    The parameter W{sub a}, which characterizes nuclear-spin-dependent parity violation (PV) in the molecular spin-rotational Hamiltonian, was computed with a quasirelativistic Hartree-Fock approach for radium fluoride (RaF) and found to be one of the largest absolute values predicted so far. The peculiar electronic structure of RaF leads to highly diagonal Franck-Condon matrices between the energetically lowest two electronic states, which qualifies RaF for direct laser cooling. A subset of diatomic molecules with a wide range of internal structures suitable for this cooling technique is also indicated. As trapped cold molecules offer superior coherence times, RaF can be considered promising for high-precision experiments aimed at molecular PV.

  18. 134. Historic American Buildings Survey R.A. WAUGH, Photographer October 1936 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    134. Historic American Buildings Survey R.A. WAUGH, Photographer October 1936 ELEVATION 1st. FLOOR WEST FIREPLACE AS IT WAS BEING TORN OUT - Colonel Paul Wentworth House, Dover Street (moved to MA, Dover), Dover, Strafford County, NH

  19. 142. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    142. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 LEAN-TO OVENS-SECTION WITH FRONT WALL TORN DOWN - Colonel Paul Wentworth House, Dover Street (moved to MA, Dover), Dover, Strafford County, NH

  20. A Study on Sorption of (226)Ra on Different Clay Matrices.

    PubMed

    Alhajji, E; Al-Masri, M S; Khalily, H; Naoum, B E; Khalil, H S; Nashawati, A

    2016-08-01

    The sorption of radium 226 ((226)Ra) on different clay materials (bentonite, illite and a mixture of bentonite-illite) was studied. Clay materials are used in the construction of disposal pits for technically enhanced naturally occurring radioactive materials (TENORM) wastes (i.e., contaminated soil and sludge) generated by the oil and gas industry operations. Experimental conditions (pH, clay materials quantity, and activity concentrations of (226)Ra) were changed in order to determine the optimal state for adsorption of (226)Ra. The results showed that the concentration of adsorbed (226)Ra on clay materials increased with time to reach an equilibrium state after approximately 5 h. More than 95 % of the radium was adsorbed. The mixture of bentonite-illite (1/9) exhibited the greatest adsorption of radium under all experimental conditions.

  1. 97. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    97. Historic American Buildings Survey R.A. Waugh, Photographer October 1936 FRAMING of SUMMER BEAM INTO SILL ALSO FLOOR TIMBERS INTO SUMMER BEAM - Colonel Paul Wentworth House, Dover Street (moved to MA, Dover), Dover, Strafford County, NH

  2. Release of 226Ra from uranium mill tailings by microbial Fe(III) reduction

    USGS Publications Warehouse

    Landa, E.R.; Phillips, E.J.P.; Lovley, D.R.

    1991-01-01

    Uranium mill tailings were anaerobically incubated in the presence of H2 with Alteromonas putrefaciens, a bacterium known to couple the oxidation of H2 and organic compounds to the reduction of Fe(III) oxides. There was a direct correlation between the extent of Fe(III) reduction and the accumulation of dissolved 226Ra. In sterile tailings in which Fe(III) was not reduced, there was negligible leaching of 226Ra. The behavior of Ba was similar to that of Ra in inoculated and sterile systems. These results demonstrate that under anaerobic conditions, microbial reduction of Fe(III) may result in the release of dissolved 226Ra from uranium mill tailings. ?? 1991.

  3. Rapid determination of 226Ra in emergency urine samples

    SciTech Connect

    Maxwell, Sherrod L.; Culligan, Brian K.; Hutchison, Jay B.; Utsey, Robin C.; McAlister, Daniel R.

    2014-02-27

    A new method has been developed at the Savannah River National Laboratory (SRNL) that can be used for the rapid determination of 226Ra in emergency urine samples following a radiological incident. If a radiological dispersive device event or a nuclear accident occurs, there will be an urgent need for rapid analyses of radionuclides in urine samples to ensure the safety of the public. Large numbers of urine samples will have to be analyzed very quickly. This new SRNL method was applied to 100 mL urine aliquots, however this method can be applied to smaller or larger sample aliquots as needed. The method was optimized for rapid turnaround times; urine samples may be prepared for counting in <3 h. A rapid calcium phosphate precipitation method was used to pre-concentrate 226Ra from the urine sample matrix, followed by removal of calcium by cation exchange separation. A stacked elution method using DGA Resin was used to purify the 226Ra during the cation exchange elution step. This approach combines the cation resin elution step with the simultaneous purification of 226Ra with DGA Resin, saving time. 133Ba was used instead of 225Ra as tracer to allow immediate counting; however, 225Ra can still be used as an option. The rapid purification of 226Ra to remove interferences using DGA Resin was compared with a slightly longer Ln Resin approach. A final barium sulfate micro-precipitation step was used with isopropanol present to reduce solubility; producing alpha spectrometry sources with peaks typically <40 keV FWHM (full width half max). This new rapid method is fast, has very high tracer yield (>90 %), and removes interferences effectively. The sample preparation method can also be adapted to ICP-MS measurement of 226Ra, with rapid removal of isobaric interferences.

  4. 210Pb-226Ra disequilibria in Icelandic basalts and implications for melt transport time

    NASA Astrophysics Data System (ADS)

    Sigmarsson, O.

    2003-04-01

    Primitive basalts with radioactive disequilibrium between isotopes of the 238U decay chain may provide constraints on the timescales of mantle melt migration. The disequilibria between 238U, 230Th and 226Ra have been studied in several Recent basalts whereas very few results exist on the 210Pb-226Ra disequilibria. Only basalts significantly younger than 100 years old can be studied for 210Pb-226Ra disequilibria due to the short half-live of 210Pb (22.3 years). Most lavas measured so far show either 210Pb-226Ra equilibria or 210Pb-deficit which have been attributed to the degassing of 222Rn in shallow magma chambers. Icelandic tholeiites from the last century are in radioactive equilibrium with (210Pb/226Ra) equal to unity. These basalts are fed from shallow magma chambers having residence time exceeding 100 years. In contrast, primitive alkaline basalts (MgO =7-12%) from Surtsey island had (210Pb/226Ra) ranging from 0.45±0.04 to 0.82±0.06 at the time of eruption. These large 210Pb deficits are unlikely to result from shallow magma degassing since no magma chamber existed beneath this volcanic island which was born during the 1963-67 eruption. The 210Pb-226Ra disequilibria increase from the beginning towards the end of the eruption when the most primitive basalts were produced, and decreases systematically with increasing Th content. These same basalts show a negative correlation between Pb and Cu abundances which are inconsistent with exsolution of sulfur rich liquid or crystallisation of sulphides as a fractionation mechanism of 210Pb and 226Ra. The large deficit of 210Pb in Surtsey lavas were thus most likely generated during mantle partial melting. In such a case, the time of melt transport from the source region to surface is constrained to be significantly shorter than 100 years.

  5. U-Th-Ra variations in Himalayan river sediments (Gandak river, India): Weathering fractionation and/or grain-size sorting?

    NASA Astrophysics Data System (ADS)

    Bosia, Clio; Chabaux, François; Pelt, Eric; France-Lanord, Christian; Morin, Guillaume; Lavé, Jérôme; Stille, Peter

    2016-11-01

    Understanding the origin of U-Th-Ra variations in the Ganga river sediments is a prerequisite for correctly using U-series nuclides to constrain the sediment transport times in Himalayan rivers. For this purpose, U, Th, and Ra concentrations, along with 238U-234U-230Th-226Ra radioactive disequilibria, were analyzed in bank, bedload and suspended sediments from the Gandak river, one of the main tributaries of the Ganga river. The data confirm that U and Th budgets of the Himalayan sediments are significantly influenced by minor resistant minerals, such as zircon, garnet and Ti-bearing minerals, the dissolution of which required the use of a high-pressure acid digestion process. Most importantly, the results indicate that the variations in (238U/232Th) and (230Th/232Th) activity ratios and 238U-234U-230Th-226Ra disequilibria in sediments along the river alluvial plain mainly reflect modifications in the mineralogical and grain-size compositions rather than the degree of weathering during transport. The (238U/232Th) and (230Th/232Th) activity ratios in the bank and bed sediments are related to variations in the minor primary minerals strongly enriched in U and Th (i.e., zircon, REE-bearing minerals and Ti-bearing minerals), whereas the activity ratios in the suspended load are related to variations in the proportions of clay, Fe-oxyhydroxides and the silt-sand fraction, which contains U- and Th-bearing minor minerals. The data also indicate that 238U-234U-230Th-226Ra disequilibria are strongly influenced by secondary mineral phases: the 230Th budget is likely mainly controlled by Fe-oxyhydroxides, and the 226Ra budget is likely mainly controlled by clay minerals. Therefore, the variations in the 238U-234U-230Th-232Th system in the sediments of the Gandak river cannot simply be interpreted as the result of fractionation due to chemical transformation of the bulk sediment during its transport within the alluvial plain and/or the result of radioactive decay. Consequently

  6. Exogenous Carbon Applications Enhance the Simultaneous Occurrence of Growth, Morphogenesis and Rosmarinic Acid Levels in Spearmint Plantelets In Vitro

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The caffeoyl ester rosmarinic acid (RA) synthesized in the phenylpropanoid pathway exhibits several proven medicinal properties. RA is constitutively synthesized in spearmint (Mentha spicata L.) plantlets grown in vitro and its content can be manipulated by nutritional and physical treatments. Car...

  7. An easy method for Ra-226 determination in river waters by liquid-scintillation counting

    NASA Astrophysics Data System (ADS)

    Moreno, H. P.; Vioque, I.; Manjón, G.; García-Tenorio, R.

    1999-01-01

    226Ra activity concentration in river water was determined using a low background liquid scintillation counter. Radium was extracted from the samples as Ra-BaSO4 precipitate which, afterwards, was dissolved with EDTA in ammonia medium. Solution was transferred into a low potassium glass vial and then mixed with a scintillation cocktail. Two different scintillation cocktails were selected for comparison. Efficiency, recovery yield and α/β separation were studied with both liquid scintillation cocktails. One single measurement, made one month after radium separation, allows to calculate the226Ra concentration as well as to assess the presence of alpha contamination of the sample. In the case of negligible interferences,224Ra concentrations can be subsequently evaluated in the same sample by the measurement made just after chemical separation of radium. This method has been applied for the determination of226Ra and224Ra activity concentrations in river water collected from different locations along the Odiel river estuary area (South-west of Spain). The presence of chemical industry, the wastes of which are released into the river, could be connected with radium activity concentration enhancements in the water.

  8. Distribution and retention in bone of /sup 226/Ra and comparison with the ICRP 20 model

    SciTech Connect

    Holtzman, R.B.; Rundo, J.; Sha, J.Y.; Spaletto, M.I.

    1981-01-01

    Analyses are presented of the ratios of /sup 226/Ra to calcium in over 650 samples of compact and cancellous bone from 66 female and 26 male subjects who had died from less than one to 60 years after first exposure to radium. The /sup 226/Ra/Ca ratios were normalized to the terminal /sup 226/Ra skeletal content. The /sup 226/Ra/Ca ratios for vertebrae were essentialy identical to those for other cancellous bone for a given subject. Comparisons of the data with predictions of the ICRP model of alkaline earth metabolism show that for female cancellous bone the normalized /sup 226/Ra/Ca ratios tended to be greater than predicted, while those for female cortical bone (femoral and tibial shaft) tended to be less. The data for males were fitted better by the model. A modification of the model to reduce the amount of radium deposited in soft tissue fitted the data better in some respects. A straight line linear least squares fit to the data appeared to fit as well as, or better than, the models. A radiation effect was suggested in that the normalized /sup 226/Ra/Ca ratio for vertebrae relative to the ratio expected increased with skeletal absorbed dose for vertebra. However, no such effect was apparent for compact bone or for the cancellous bone as a whole.

  9. Determination of (226)Ra in produced water by liquid scintillation counting.

    PubMed

    Godoy, José Marcus; Vianna, Lucas M; Godoy, Maria Luiza D P; Almeida, Ana Cristina

    2016-08-01

    It is proposed a method for the determination of (226)Ra in offshore platform liquid effluent samples (produced water). The method is based on a two-phase liquid scintillation counting system and allows for the direct and simple determination of (226)Ra content. Samples with high barium content may also have high (226)Ra concentration. Therefore, the sample volume is based on the barium concentration and ranges from 10 mL to 100 mL. Our new method was tested using multiple real samples and was compared with the BaSO4 precipitation method. The results based on the LSC were 30% higher than the precipitation method, which is attributed to the self-absorption of alpha particles in the BaSO4 precipitate. The determination of both (226)Ra and (228)Ra in the liquid effluent of offshore oil platforms is mandatory in Brazil. Thus, a second method of accurately assessing (228)Ra content remains necessary. PMID:27116402

  10. Argonne-Utah studies of /sup 224/Ra endosteal surface dosimetry

    SciTech Connect

    Schlenker, R.A.; Smith, J.M.

    1984-01-01

    The activities of /sup 212/Pb relative to /sup 224/Ra and of /sup 222/Rn relative to /sup 226/Ra were measured in bone surface deposits 24 h after radium injection into beagles. The fractional retention of /sup 220/Rn atoms was measured in vitro with hydrated and dehydrated bone samples to determine the effect of water content on the escape of radon from bone surfaces. The experimental data suggest that substantial /sup 224/Ra daughter product disequilibrium exists in bone surface deposits. Estimates for the lower and upper limits on the fractional retention of /sup 220/Rn in vivo are 0.05 and 0.25, respectively. The average bone surface activity of /sup 212/Pb relative to /sup 224/Ra ranged from 0.34 to 0.71 for four dogs, with the majority of the values toward the low end of the range. Only a small portion of the deposited /sup 212/Pb came from lead in the injection solution despite near equilibrium between /sup 224/Ra and its daughters at the time of injection. The retention data indicate that the endosteal tissue dose rate in the dogs at one day was actually one-third to about one-half that which would be calculated assuming equilibrium of /sup 224/Ra daughter products in bone surface deposits. 11 references, 2 figures, 7 tables.

  11. Teratogenicity of benzoic acid derivatives of retinoic acid in cultured mouse embryos.

    PubMed

    Goulding, E H; Jetten, A M; Abbott, B D; Pratt, R M

    1988-01-01

    Isotretinoin (13-cis-RA) is a human teratogen and mouse embryos exposed to 13-cis-RA in vivo exhibit many of the same defects as humans. Early postimplantation mouse embryos exposed to 13-cis-RA in culture exhibit developmental alterations of the visceral arches, similar to those seen after in vivo exposure. Certain benzoic acid derivatives of retinoic acid have been shown to possess activity equal to or greater than retinoic acid in several in vitro systems. This study examines the teratogenic effects of some of these retinoids on mouse embryos in vitro. Day 8 CD-1 mouse embryos were cultured for 48 hours in the presence of these benzoic acid derivatives. With the exception of Ro-15-0778, all compounds produced visceral arch malformations similar to those seen in embryos exposed to 13-cis-RA, but at dramatically different effective concentrations. Extremely low concentrations of the retinoic acid-related compounds tested appear to have detrimental effects on embryonic development and these compounds may be poor candidates for therapeutic use.

  12. First In Vivo Evaluation of Liposome-encapsulated 223Ra as a Potential Alpha-particle-emitting Cancer Therapeutic Agent

    SciTech Connect

    Jonasdottir, Thora J.; Fisher, Darrell R.; Borrebaek, Jorgen; Bruland, Oyvind S.; Larsen, Roy H.

    2006-09-13

    Liposomes carrying chemotherapeutics have had some success in cancer treatment and may be suitable carriers for therapeutic radionuclides. This study was designed to evaluate the biodistribution of and to estimate the radiation doses from the alpha emitter 223Ra loaded into pegylated liposomes in selected tissues. 223Ra was encapsulated in pegylated liposomal doxorubicin by ionophore-mediated loading. The biodistribution of liposomal 223Ra was compared to free cationic 223Ra in Balb/C mice. We showed that liposomal 223 Ra circulated in the blood with an initial half-time in excess of 24 hours, which agreed well with that reported for liposomal doxorubicin in rodents, while the blood half-time of cationic 223Ra was considerably less than one hour. When liposomal 223 Ra was catabolized, the released 223Ra was either excreted or taken up in the skeleton. This skeletal uptake increased up to 14 days after treatment, but did not reach the level seen with free 223Ra. Pre-treatment with non-radioactive liposomal doxorubicin 4 days in advance lessened the liver uptake of liposomal 223 Ra. Dose estimates showed that the spleen, followed by bone surfaces, received the highest absorbed doses. Liposomal 223 Ra was relatively stable in vivo and may have potential for radionuclide therapy and combination therapy with chemotherapeutic agents.

  13. Quantification of epidermal histological changes induced by topical retinoids and CD271 in the rhino mouse model using a standardized image analysis technique.

    PubMed

    Bouclier, M; Chatelus, A; Ferracin, J; Delain, C; Shroot, B; Hensby, C N

    1991-01-01

    The rhino mouse has been used as an experimental model to screen topically active comedolytic agents. Adult rhino mice were treated on the back once daily for 5 consecutive days per week during 3 weeks. Skin histological preparations were analyzed by image analysis techniques to quantify the number of epidermal comedones, comedo profile and epidermal thickness. Using both a negative (treated with acetone) and a positive (treated with Aberel gel 0.025%) control group of animals in all experiments conducted over a period of about 3 years, we defined the upper and lower limit of acceptability of the results. Topical treatment with an acetone solution of all-trans retinoic acid (0.01, 0.03, 0.1%) and 13-cis-retinoic acid (0.1%) induced comedolysis and a marked increase in epidermal thickness. Commercial preparations of all-trans retinoic acid (Aberel lotion, gel and cream, Retin A cream, Retacnyl cream) presented a similar comedolytic activity. However, the epidermal thickening was higher with Retin A and weaker with Retacnyl. CD271, a new modulator of cell differentiation, applied either in acetone solution (0.01, 0.1%) or in lotion, gel or cream formulations (0.1%) also demonstrated a marked activity (i.e. comedolysis and epidermal thickening). These data confirm that the rhino mouse model can be used to assay drugs applied either in solvent or in topical formulations. Activity in this model compares favorably with published clinical observations in the treatment of acne.

  14. Combination therapies improve the anticancer activities of retinoids in neuroblastoma

    PubMed Central

    Cheung, Belamy B

    2015-01-01

    Most therapeutic protocols for child cancers use cytotoxic agents which have a narrow therapeutic index, and resulting in severe acute and chronic toxicities to normal tissues. Despite the fact that most child cancer patients achieve complete remission after chemotherapy, death still occurs due to relapse of persistent minimal residual disease (MRD) which remaining after initial cytotoxic chemotherapy. Advanced neuroblastoma (NB) is a leading cause of cancer deaths in young children. Retinoids are an important component of advanced NB therapy at the stage of MRD, yet half of all patients treated with 13-cis-retinoic acid still relapse and die. More effective combination therapies, with a lower side-effect profile, are required to improve outcomes for NB. Fenretinide or N-4-hydroxyphenyl retinamide is a synthetic derivative of retinoic acid which works on cancer cells through nuclear receptor-dependent and -independent signalling mechanisms. Moreover, several histone deacetylase inhibitors have entered early phase trials, and, suberoylanilide hydroxamic acid has been approved for use in adult cutaneous T cell lymphoma. A number of studies suggest that retinoid signal activation is necessary for histone deacetylase inhibitor activity. A better understanding of their mechanism of actions will lead to more evidence-based retinoid combination therapies. PMID:26677433

  15. Chemoprevention of Lung Cancer

    PubMed Central

    Szabo, Eva; Mao, Jenny T.; Lam, Stephen; Reid, Mary E.

    2013-01-01

    Background: Lung cancer is the most common cause of cancer death in men and women in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk of developing lung cancer compared with lifetime never smokers. Chemoprevention refers to the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. Results: None of the phase 3 trials with the agents β-carotene, retinol, 13-cis-retinoic acid, α-tocopherol, N-acetylcysteine, acetylsalicylic acid, or selenium has demonstrated beneficial and reproducible results. To facilitate the evaluation of promising agents and to lessen the need for a large sample size, extensive time commitment, and expense, surrogate end point biomarker trials are being conducted to assist in identifying the most promising agents for later-stage chemoprevention trials. With the understanding of important cellular signaling pathways and the expansion of potentially important targets, agents (many of which target inflammation and the arachidonic acid pathway) are being developed and tested which may prevent or reverse lung carcinogenesis. Conclusions: By integrating biologic knowledge, additional early-phase trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. PMID:23649449

  16. Embryonic retinoic acid synthesis is essential for early mouse post-implantation development.

    PubMed

    Niederreither, K; Subbarayan, V; Dollé, P; Chambon, P

    1999-04-01

    A number of studies have suggested that the active derivative of vitamin A, retinoic acid (RA), may be important for early development of mammalian embryos. Severe vitamin A deprivation in rodents results in maternal infertility, precluding a thorough investigation of the role of RA during embryogenesis. Here we show that production of RA by the retinaldehyde dehydrogenase-2 (Raldh2) enzyme is required for mouse embryo survival and early morphogenesis. Raldh2 is an NAD-dependent aldehyde dehydrogenase with high substrate specificity for retinaldehyde. Its pattern of expression during mouse development has suggested that it may be responsible for embryonic RA synthesis. We generated a targeted disruption of the mouse Raldh2 gene and found that Raldh2-/- embryos, which die at midgestation without undergoing axial rotation (body turning), exhibit shortening along the anterioposterior axis and do not form limb buds. Their heart consists of a single, medial, dilated cavity. Their frontonasal region is truncated and their otocysts are severely reduced. These defects result from a block in embryonic RA synthesis, as shown by the lack of activity of RA-responsive transgenes, the altered expression of an RA-target homeobox gene and the near full rescue of the mutant phenotype by maternal RA administration. Our data establish that RA synthesized by the post-implantation mammalian embryo is an essential developmental hormone whose lack leads to early embryo death. PMID:10192400

  17. Regulation by retinoic acid of acylation-stimulating protein and complement C3 in human adipocytes.

    PubMed Central

    Scantlebury, T; Sniderman, A D; Cianflone, K

    2001-01-01

    Acylation-stimulating protein (ASP), a product of complement C3, stimulates triacylglycerol synthesis in adipocytes. Previous studies have identified transthyretin, associated with chylomicrons, as a stimulator of C3 and ASP production. Since both transthyretin and chylomicrons transport retinyl ester/retinol, our goal was to investigate whether retinoic acid (RA) could be a potential hormonal mediator of the effect. Inhibitors of protein synthesis and protein secretion eliminated the stimulatory effects of chylomicrons on both C3 and ASP production in human differentiated adipocytes, suggesting that de novo protein synthesis and secretion are both required. Incubation with chylomicrons increased C3 mRNA levels (37+/-1.5%). RA alone or with chylomicrons had a stimulatory effect on C3 production (29-fold at 16.6 nM RA) and ASP production. An RA receptor antagonist blocked stimulation of C3 mRNA and C3 secretion by both RA and chylomicrons. Finally, RA and chylomicrons activated a 1.8 kb C3-promoter-luciferase construct transfected into 3T3-F442 and 3T3-L1 cells (by 41+/-0.2% and 69+/-0.3% respectively), possibly via RA receptor half-sites identified by sequence analysis. This is the first evidence documenting stimulation by RA of the C3 gene. Thus we propose RA as a novel cellular trigger in chylomicrons that subsequently results in increased ASP production by adipocytes after a meal. PMID:11368771

  18. Interleukin 1 (IL-1) and IL-1-receptor antagonist (IL-1-RA) in middle ear cholesteatoma: an analysis of protein production and biological activity.

    PubMed

    Bujía, J; Kim, C; Ostos, P; Sudhoff, H; Kastenbauer, E; Hültner, L

    1996-01-01

    Cytokine networks are now presumed to play an essential role in the pathogenesis of middle ear cholesteatoma. Of the factors identified in cholesteatoma, interleukin-I (IL-1)-alpha appears to be especially important because of its stimulation of keratinocyte proliferation as well induction of bone resorption. To further characterize the possible role of IL-1 in the pathogenesis of cholesteatoma, we quantified the levels of IL-1 and IL-1-receptor antagonist (IL-1-RA) present using the bicinchonic acid protein assay and enzyme-linked immunosorbent assay (ELISA) on tissue extracts from 20 cholesteatoma specimens. The presence of biologically active IL-1 was also analyzed, using the cell line LBRM-33 and an ELISA for the detection of interleukin-2 (IL-2). Human skin obtained from the external ear canal was used as control. The amounts of IL-1-alpha in cholesteatoma (34.9 +/- 19.5) were higher than in human skin (6.7 +/- 2.8). The observed differences were statistically significant by Student's t-test (P < 0.01). Skin samples showed elevated concentrations of IL-1-RA (248.3 +/- 30.2) in comparison to that in the cholesteatoma (80.8 +/- 13.5). This was also statistically significant (P < 0.01). Whereas IL-1 activity was not detected in skin samples, all cholesteatoma specimens studied showed a stimulation effect on the production of IL-2 when incubated with the cell line LBRM-33. The results point to an over-expression of IL-1 concurrent with a decreased secretion of IL-1-RA in middle ear cholesteatoma. Furthermore IL-1-RA production is deficient relative to total IL-1 production, resulting in the presence of active IL-1.

  19. Substrate Specificity and Ligand Interactions of CYP26A1, the Human Liver Retinoic Acid Hydroxylase

    PubMed Central

    Thatcher, Jayne E.; Buttrick, Brian; Shaffer, Scott A.; Shimshoni, Jakob A.; Goodlett, David R.; Nelson, Wendel L.

    2011-01-01

    All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. atRA is also used as a drug, and synthetic atRA analogs and inhibitors of retinoic acid (RA) metabolism have been developed. The hepatic clearance of atRA is mediated primarily by CYP26A1, but design of CYP26A1 inhibitors is hindered by lack of information on CYP26A1 structure and structure-activity relationships of its ligands. The aim of this study was to identify the primary metabolites of atRA formed by CYP26A1 and to characterize the ligand selectivity and ligand interactions of CYP26A1. On the basis of high-resolution tandem mass spectrometry data, four metabolites formed from atRA by CYP26A1 were identified as 4-OH-RA, 4-oxo-RA, 16-OH-RA and 18-OH-RA. 9-cis-RA and 13-cis-RA were also substrates of CYP26A1. Forty-two compounds with diverse structural properties were tested for CYP26A1 inhibition using 9-cis-RA as a probe, and IC50 values for 10 inhibitors were determined. The imidazole- and triazole-containing inhibitors [S-(R*,R*)]-N-[4-[2-(dimethylamino)-1-(1H-imidazole-1-yl)propyl]-phenyl]2-benzothiazolamine (R116010) and (R)-N-[4-[2-ethyl-1-(1H-1,2,4-triazol-1-yl)butyl]phenyl]-2-benzothiazolamine (R115866) were the most potent inhibitors of CYP26A1 with IC50 values of 4.3 and 5.1 nM, respectively. Liarozole and ketoconazole were significantly less potent with IC50 values of 2100 and 550 nM, respectively. The retinoic acid receptor (RAR) γ agonist CD1530 was as potent an inhibitor of CYP26A1 as ketoconazole with an IC50 of 530 nM, whereas the RARα and RARβ agonists tested did not significantly inhibit CYP26A1. The pan-RAR agonist 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid and the peroxisome proliferator-activated receptor ligands rosiglitazone and pioglitazone inhibited CYP26A1 with IC50 values of 3.7, 4.2, and 8.6 μM, respectively. These data demonstrate that CYP26A1 has high ligand selectivity but accepts structurally related nuclear

  20. Normalizing Microbiota-Induced Retinoic Acid Deficiency Stimulates Protective CD8(+) T Cell-Mediated Immunity in Colorectal Cancer.

    PubMed

    Bhattacharya, Nupur; Yuan, Robert; Prestwood, Tyler R; Penny, Hweixian Leong; DiMaio, Michael A; Reticker-Flynn, Nathan E; Krois, Charles R; Kenkel, Justin A; Pham, Tho D; Carmi, Yaron; Tolentino, Lorna; Choi, Okmi; Hulett, Reyna; Wang, Jinshan; Winer, Daniel A; Napoli, Joseph L; Engleman, Edgar G

    2016-09-20

    Although all-trans-retinoic acid (atRA) is a key regulator of intestinal immunity, its role in colorectal cancer (CRC) is unknown. We found that mice with colitis-associated CRC had a marked deficiency in colonic atRA due to alterations in atRA metabolism mediated by microbiota-induced intestinal inflammation. Human ulcerative colitis (UC), UC-associated CRC, and sporadic CRC specimens have similar alterations in atRA metabolic enzymes, consistent with reduced colonic atRA. Inhibition of atRA signaling promoted tumorigenesis, whereas atRA supplementation reduced tumor burden. The benefit of atRA treatment was mediated by cytotoxic CD8(+) T cells, which were activated due to MHCI upregulation on tumor cells. Consistent with these findings, increased colonic expression of the atRA-catabolizing enzyme, CYP26A1, correlated with reduced frequencies of tumoral cytotoxic CD8(+) T cells and with worse disease prognosis in human CRC. These results reveal a mechanism by which microbiota drive colon carcinogenesis and highlight atRA metabolism as a therapeutic target for CRC.

  1. Molecular mechanism of 9-cis-retinoic acid inhibition of adipogenesis in 3T3-L1 cells

    SciTech Connect

    Sagara, Chiaki; Takahashi, Katsuhiko; Kagechika, Hiroyuki; Takahashi, Noriko

    2013-03-29

    Highlights: ► We examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1. ► 9-cis-RA inhibited lipid accumulation in adipogenetically-induced 3T3-L1 cells. ► A RXR pan-antagonist suppressed the inhibitory effects of 9-cis-RA on adipogenesis. ► This antagonist had no effects on RXRα and PPARγ levels in 9-cis-RA-treated cells. ► 9-cis-RA-induced decrease in both RXRα and PPARγ was independent of RXR activation. -- Abstract: Retinoic acid (RA) signaling is mediated by specific nuclear hormone receptors. Here we examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1 cells. 9-cis-RA inhibits the lipid accumulation of adipogenetically induced 3T3-L1 cells. The complex of retinoid X receptor α (RXRα) with peroxisome proliferator-activated receptor γ (PPARγ) is a major transcription factor in the process of adipogenesis, and the levels of these molecules were decreased by 9-cis-RA treatment. A RXR pan-antagonist suppressed 9-cis-RA’s inhibitory effects on adipogenesis, but not on the intracellular levels of both RXRα and PPARγ. These results suggest that 9-cis-RA could inhibit adipogenesis by activating RXR, and decrease both RXR and PPARγs levels in a RXR activation-independent manner.

  2. Normalizing Microbiota-Induced Retinoic Acid Deficiency Stimulates Protective CD8(+) T Cell-Mediated Immunity in Colorectal Cancer.

    PubMed

    Bhattacharya, Nupur; Yuan, Robert; Prestwood, Tyler R; Penny, Hweixian Leong; DiMaio, Michael A; Reticker-Flynn, Nathan E; Krois, Charles R; Kenkel, Justin A; Pham, Tho D; Carmi, Yaron; Tolentino, Lorna; Choi, Okmi; Hulett, Reyna; Wang, Jinshan; Winer, Daniel A; Napoli, Joseph L; Engleman, Edgar G

    2016-09-20

    Although all-trans-retinoic acid (atRA) is a key regulator of intestinal immunity, its role in colorectal cancer (CRC) is unknown. We found that mice with colitis-associated CRC had a marked deficiency in colonic atRA due to alterations in atRA metabolism mediated by microbiota-induced intestinal inflammation. Human ulcerative colitis (UC), UC-associated CRC, and sporadic CRC specimens have similar alterations in atRA metabolic enzymes, consistent with reduced colonic atRA. Inhibition of atRA signaling promoted tumorigenesis, whereas atRA supplementation reduced tumor burden. The benefit of atRA treatment was mediated by cytotoxic CD8(+) T cells, which were activated due to MHCI upregulation on tumor cells. Consistent with these findings, increased colonic expression of the atRA-catabolizing enzyme, CYP26A1, correlated with reduced frequencies of tumoral cytotoxic CD8(+) T cells and with worse disease prognosis in human CRC. These results reveal a mechanism by which microbiota drive colon carcinogenesis and highlight atRA metabolism as a therapeutic target for CRC. PMID:27590114

  3. SB-RA-2001 Inhibits Bacterial Proliferation by Targeting FtsZ Assembly

    PubMed Central

    2015-01-01

    FtsZ has been recognized as a promising antimicrobial drug target because of its vital role in bacterial cell division. In this work, we found that a taxane SB-RA-2001 inhibited the proliferation of Bacillus subtilis 168 and Mycobacterium smegmatis cells with minimal inhibitory concentrations of 38 and 60 μM, respectively. Cell lengths of these microorganisms increased remarkably in the presence of SB-RA-2001, indicating that it inhibits bacterial cytokinesis. SB-RA-2001 perturbed the formation of the FtsZ ring in B. subtilis 168 cells and also affected the localization of the late cell division protein, DivIVA, at the midcell position. Flow cytometric analysis of the SB-RA-2001-treated cells indicated that the compound did not affect the duplication of DNA in B. subtilis 168 cells. Further, SB-RA-2001 treatment did not affect the localization of the chromosomal partitioning protein, Spo0J, along the two ends of the nucleoids and also had no discernible effect on the nucleoid segregation in B. subtilis 168 cells. The agent also did not appear to perturb the membrane potential of B. subtilis 168 cells. In vitro, SB-RA-2001 bound to FtsZ with modest affinity, promoted the assembly and bundling of FtsZ protofilaments, and reduced the GTPase activity of FtsZ. GTP did not inhibit the binding of SB-RA-2001 to FtsZ, suggesting that it does not bind to the GTP binding site on FtsZ. A computational analysis indicated that SB-RA-2001 binds to FtsZ in the cleft region between the C-terminal domain and helix H7, and the binding site of SB-RA-2001 on FtsZ resembled that of PC190723, a well-characterized inhibitor of FtsZ. The findings collectively suggested that SB-RA-2001 inhibits bacterial proliferation by targeting the assembly dynamics of FtsZ, and this can be exploited further to develop potent FtsZ-targeted antimicrobials. PMID:24749867

  4. A newborn lethal defect due to inactivation of retinaldehyde dehydrogenase type 3 is prevented by maternal retinoic acid treatment

    PubMed Central

    Dupé, Valérie; Matt, Nicolas; Garnier, Jean-Marie; Chambon, Pierre; Mark, Manuel; Ghyselinck, Norbert B.

    2003-01-01

    The retinoic acid (RA) signal, produced locally from vitamin A by retinaldehyde dehydrogenase (Raldh) and transduced by the nuclear receptors for retinoids (RA receptor and 9-cis-RA receptor), is indispensable for ontogenesis and homeostasis of numerous tissues. We demonstrate that Raldh3 knockout in mouse suppresses RA synthesis and causes malformations restricted to ocular and nasal regions, which are similar to those observed in vitamin A-deficient fetuses and/or in retinoid receptor mutants. Raldh3 knockout notably causes choanal atresia (CA), which is responsible for respiratory distress and death of Raldh3-null mutants at birth. CA is due to persistence of nasal fins, whose rupture normally allows the communication between nasal and oral cavities. This malformation, which is similar to isolated congenital CA in humans and may result from impaired RA-controlled down-regulation of Fgf8 expression in nasal fins, can be prevented by a simple maternal treatment with RA. PMID:14623956

  5. Molecular mechanism of 9-cis-retinoic acid inhibition of adipogenesis in 3T3-L1 cells.

    PubMed

    Sagara, Chiaki; Takahashi, Katsuhiko; Kagechika, Hiroyuki; Takahashi, Noriko

    2013-03-29

    Retinoic acid (RA) signaling is mediated by specific nuclear hormone receptors. Here we examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1 cells. 9-cis-RA inhibits the lipid accumulation of adipogenetically induced 3T3-L1 cells. The complex of retinoid X receptor α (RXRα) with peroxisome proliferator-activated receptor γ (PPARγ) is a major transcription factor in the process of adipogenesis, and the levels of these molecules were decreased by 9-cis-RA treatment. A RXR pan-antagonist suppressed 9-cis-RA's inhibitory effects on adipogenesis, but not on the intracellular levels of both RXRα and PPARγ. These results suggest that 9-cis-RA could inhibit adipogenesis by activating RXR, and decrease both RXR and PPARγs levels in a RXR activation-independent manner. PMID:23485459

  6. Retinoic acid attenuates O2-induced inhibition of lung septation.

    PubMed

    Veness-Meehan, Kathleen A; Pierce, Richard A; Moats-Staats, Billie M; Stiles, Alan D

    2002-11-01

    Exposure of the newborn lung to hyperoxia is associated with impaired alveolar development. In newborn rats exposed to hyperoxia and studied at day 14 of life, retinoic acid (RA) treatment improved survival and increased lung collagen but did not improve alveolar development. To determine whether RA treatment during exposure to hyperoxia results in late improvement in alveolarization, we treated newborn rats with RA and hyperoxia from day 3 to day 14 and then weaned O2 to room air by day 20, and studied the animals on day 42. O2-exposed animals had larger mean lung volumes, larger alveoli, and decreased gas-exchange tissue relative to air-exposed animals, whereas RA-treated O2-exposed animals were not statistically different from air-exposed controls. Relative to control animals, elastin staining at day 14 was decreased in hyperoxia-exposed lung independent of RA treatment, and, at day 42, elastin staining was similar in all treatment groups. At day 14, elastin gene expression was similar in all treatment groups, whereas at day 42 lung previously exposed to hyperoxia showed increased elastin signal independent of RA treatment. These results indicate that RA treatment during hyperoxia exposure promotes septal formation without evidence of effects on elastin gene expression after 4 wk of recovery. PMID:12376350

  7. Retinoic acid triggers meiosis initiation via stra8-dependent pathway in Southern catfish, Silurus meridionalis.

    PubMed

    Li, Minghui; Feng, Ruijuan; Ma, He; Dong, Ranran; Liu, Zhilong; Jiang, Wentao; Tao, Wenjing; Wang, Deshou

    2016-06-01

    Existing studies demonstrated that retinoic acid (RA) regulates meiotic initiation via stra8-independent pathway in teleosts which lack stra8 in their genomes. However, stra8 was recently identified from several fish species including Southern catfish (Silurus meridionalis). To explore the existence of stra8-dependent pathway in RA mediated meiotic initiation in fishes, in the present study, the genes encoding RA synthase aldh1a2 and catabolic enzyme cyp26a1 and cyp26b1 were cloned from the Southern catfish. By immunohistochemistry, Aldh1a2 signal was observed in gonads of both sexes during the meiotic initiation period. By real-time PCR, differentially expressed gene was observed for cyp26a1, but not for cyp26b1, in gonads during the meiotic initiation. Administration of exogenous RA or inhibition of endogenous RA degradation by either KET (RA catabolic enzyme inhibitor) or cyp26a1 knockdown using CRISPR/Cas9 induced advanced meiotic initiation in the ovaries as demonstrated by increased Stra8/stra8 expression and appearance of oocytes. In contrast, treatment with RA synthase inhibitor DEAB resulted in delayed meiotic initiation and Stra8/stra8 expression in the ovaries, which was rescued by exogenous RA administration. These results indicated that (1) RA triggers the onset of meiosis via stra8-dependent pathway in stra8 existing teleosts, as it does in tetrapods; (2) exogenous RA can rescue the endogenous RA deficiency; (3) Cyp26a1, instead of Cyp26b1, is the key catabolic enzyme involved in meiosis initiation in teleosts. Taken together, RA might trigger meiotic initiation via stra8-dependent and -independent pathway in different teleosts.

  8. Quantitative Measurement of Relative Retinoic Acid Levels in E8.5 Embryos and Neurosphere Cultures Using the F9 RARE-Lacz Cell-based Reporter Assay.

    PubMed

    Ababon, Myka R; Li, Bo I; Matteson, Paul G; Millonig, James H

    2016-01-01

    Retinoic acid (RA) is an important developmental morphogen that coordinates anteroposterior and dorsoventral axis patterning, somitic differentiation, neurogenesis, patterning of the hindbrain and spinal cord, and the development of multiple organ systems. Due to its chemical nature as a small amphipathic lipid, direct detection and visualization of RA histologically remains technically impossible. Currently, methods used to infer the presence and localization of RA make use of reporter systems that detect the biological activity of RA. Most established reporter systems, both transgenic mice and cell lines, make use of the highly potent RA response element (RARE) upstream of the RAR-beta gene to drive RA-inducible expression of reporter genes, such as beta-galactosidase or luciferase. The transgenic RARE-LacZ mouse is useful in visualizing spatiotemporal changes in RA signaling especially during embryonic development. However, it does not directly measure overall RA levels. As a reporter system, the F9 RARE-LacZ cell line can be used in a variety of ways, from simple detection of RA to quantitative measurements of RA levels in tissue explants. Here we describe the quantitative determination of relative RA levels generated in embryos and neurosphere cultures using the F9 RARE-LacZ reporter cell line. PMID:27684594

  9. Mutations in the interleukin receptor IL11RA cause autosomal recessive Crouzon-like craniosynostosis.

    PubMed

    Keupp, Katharina; Li, Yun; Vargel, Ibrahim; Hoischen, Alexander; Richardson, Rebecca; Neveling, Kornelia; Alanay, Yasemin; Uz, Elif; Elcioğlu, Nursel; Rachwalski, Martin; Kamaci, Soner; Tunçbilek, Gökhan; Akin, Burcu; Grötzinger, Joachim; Konas, Ersoy; Mavili, Emin; Müller-Newen, Gerhard; Collmann, Hartmut; Roscioli, Tony; Buckley, Michael F; Yigit, Gökhan; Gilissen, Christian; Kress, Wolfram; Veltman, Joris; Hammerschmidt, Matthias; Akarsu, Nurten A; Wollnik, Bernd

    2013-11-01

    We have characterized a novel autosomal recessive Crouzon-like craniosynostosis syndrome in a 12-affected member family from Antakya, Turkey, the presenting features of which include: multiple suture synostosis, midface hypoplasia, variable degree of exophthalmos, relative prognathism, a beaked nose, and conductive hearing loss. Homozygosity mapping followed by targeted next-generation sequencing identified a c.479+6T>G mutation in the interleukin 11 receptor alpha gene (IL11RA) on chromosome 9p21. This donor splice-site mutation leads to a high percentage of aberrant IL11RA mRNA transcripts in an affected individual and altered mRNA splicing determined by in vitro exon trapping. An extended IL11RA mutation screen was performed in a cohort of 79 patients with an initial clinical diagnosis of Crouzon syndrome, pansynostosis, or unclassified syndromic craniosynostosis. We identified mutations segregating with the disease in five families: a German patient of Turkish origin and a Turkish family with three affected sibs all of whom were homozygous for the previously identified IL11RA c.479+6T>G mutation; a family with pansynostosis with compound heterozygous missense mutations, p.Pro200Thr and p.Arg237Pro; and two further Turkish families with Crouzon-like syndrome carrying the homozygous nonsense mutations p.Tyr232* and p.Arg292*. Using transient coexpression in HEK293T and COS7 cells, we demonstrated dramatically reduced IL11-mediated STAT3 phosphorylation for all mutations. Immunofluorescence analysis of mouse Il11ra demonstrated specific protein expression in cranial mesenchyme which was localized around the coronal suture tips and in the lambdoidal suture. In situ hybridization analysis of adult zebrafish also detected zfil11ra expression in the coronal suture between the overlapping frontal and parietal plates. This study demonstrates that mutations in the IL11RA gene cause an autosomal recessive Crouzon-like craniosynostosis. PMID:24498618

  10. Effects of retinoids on differentiation, lipid metabolism, epidermal growth factor, and low-density lipoprotein binding in squamous carcinoma cells

    SciTech Connect

    Ponec, M.; Weerheim, A. ); Havekes, L. ); Boonstra, J. )

    1987-08-01

    The relationship among keratinocyte differentiation capacity, lipid synthesis, low-density lipoprotein (LDL) metabolism, plasma membrane composition, and epidermal growth factor (EGF) binding has been studied in SCC-12F2 cells. The differentiation capacity of the cells, i.e., ionophore-induced cornified envelope formation, was inhibited by various retinoids and stimulated by hydrocortisone. Retinoids that caused a significant reduction of cornified envelope formation, i.e., retinoic acid and 13-cis-retinoic acid, caused only minor changes in lipid synthesis and plasma membrane composition. Arotinoid ethylsulfone, having a minor effect on cornified envelope formation, caused a drastic inhibition of cholesterol synthesis resulting in changes in the plasma membrane composition. Hydrocortisone stimulated cornified envelope formation but had only minor effects on lipid synthesis and plasma membrane composition. Of all retinoids tested, only arotinoid ethylsulfone caused a drastic increase in EGF binding, while hydrocortisone had no effect. These results clearly demonstrate that the plasma membrane composition is not related to keratinocyte differentiation capacity, but most likely does determine EGF binding. Furthermore, EGF binding does not determine keratinocyte differentiation capacity.

  11. Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes.

    PubMed

    Song, Xiuzu; Xu, Aie; Pan, Wei; Wallin, Brittany; Kivlin, Rebecca; Lu, Shan; Cao, Cong; Bi, Zhigang; Wan, Yinsheng

    2008-08-01

    The most common adverse effects that are related to all-trans retinoic acid (atRA) treatment are irritation and dryness of the skin. atRA therapy is reported to impair barrier function as achieved by trans-epidermal water loss (TEWL). Treatment with nicotinamide prior to initiation of atRA therapy provides additional barrier protection and thus reduces susceptibility of retinoic acid. Our previous studies showed that atRA upregulates aquaporin 3 (AQP3) in cultured human skin keratinocytes and fibroblasts. Others have demonstrated that in atopic dermatitis, overexpression of AQP3 is linked to elevated TEWL and that nicotinamide treatment reduces skin TEWL. In this study, we observed that while atRA upregulates AQP3 expression in cultured human skin keratinocytes (HaCaT cells), nicotinamide attenuates the effect of atRA in a concentration-dependent manner. atRA treatment induces EGFR and ERK activation. PD153035, an EGFR inhibitor, and U0126, an ERK inhibitor, inhibit atRA-induced upregulation of AQP3. Nicotinamide also inhibits atRA-induced activation of EGFR/ERK signal transduction and decreases water permeability by downregulating AQP3 expression. Collectively, our results indicate that the effect of atRA on AQP3 expression is at least partly mediated by EGFR/ERK signaling in cultured human skin keratinocytes. Nicotinamide attenuates atRA-induced AQP3 expression through inhibition of EGFR/ERK signal transduction and eventually decreases water permeability and water loss. Our study provides insights into the molecular mechanism through which nicotinamide reverses the side effects of dryness in human skin after treatment with atRA.

  12. Uptake and metabolism of (11-/sup 3/H) all-trans retinoic acid by rabbit tracheal epithelial cells

    SciTech Connect

    Bhat, P.V.; Jetten, A.M.

    1986-01-01

    Retinoic acid (RA) inhibits squamous cell differentiation of rabbit tracheal epithelial cells in culture at concentrations as low as 10/sup -9/ - 10/sup -10/ M. These cells take up 11-(/sup 3/H)-RA readily when added to the cells either as free RA or as RA complexed to serum retinol binding protein (SRBP) or albumin. The uptake of RA by RTE cells as SRBP or albumin complexes was significantly lower than that of free RA. Metabolites were analyzed by high pressure liquid chromatography. This analysis showed that RTE cells metabolized RA to polar metabolites (Peak I) and to a less polar metabolite (Peak III). The metabolite in Peak III constituted 13-20% of the cell-associated radioactivity after 24 hrs. incubation with RA. Formation of the Peak I and Peak III metabolites from RA was observed both in undifferentiated as well as in cells that underwent terminal differentiation to squamous cells and their synthesis appeared constitutive. When cells were treated for 6 hrs with /sup 3/H-RA and then further in the absence of RA 75% of the cell-associated radioactivity was released in the medium within 24 hrs, thereafter the release was slow. Analysis of the metabolites secreted by the cells into the medium showed only the presence of Peak I metabolites. The authors data show that RTE cells metabolize RA into polar metabolites which are rapidly released into the medium and into a less polar metabolite, possibly an ester of retinoic acid, which is retained by the cell.

  13. Correlated accumulation of anthocyanins and rosmarinic acid in mechanically stressed red cell suspensions of basil (Ocimum basilicum).

    PubMed

    Strazzer, Pamela; Guzzo, Flavia; Levi, Marisa

    2011-02-15

    A red basil cell line (T2b) rich in rosmarinic acid (RA) was selected for the stable production of anthocyanins (ACs) in the dark. Cell suspension cultures were subjected to mechanical stress through increased agitation (switch from 90 to 150 rpm) to determine the relationship between AC and RA accumulation. Cell extracts were analyzed by HPLC and LC-MS, and the resulting data were processed with multivariate statistical analysis. MS and MS/MS spectra facilitated the putative annotation of several complex cyanidin-based ACs, which were esterified with coumaric acid and, in some cases, also with malonic acid. It was also possible to identify various RA-related molecules, some caffeic and coumaric acid derivatives and some flavanones. Mechanical stress increased the total AC and RA contents, but reduced biomass accumulation. Many metabolites were induced by mechanical stress, including RA and some of its derivatives, most ACs, hydroxycinnamic acids and flavonoids, whereas the abundance of some RA dimers was reduced. Although AC and RA share a common early biosynthetic pathway (from phenylalanine to 4-coumaroyl-CoA) and could have similar or overlapping functions providing antioxidant activity against stress-generated reactive oxygen species, there appeared to be no competition between their individual pathways.

  14. Expression of the retinoic acid catabolic enzyme CYP26B1 in the human brain to maintain signaling homeostasis.

    PubMed

    Stoney, Patrick N; Fragoso, Yara D; Saeed, Reem Bu; Ashton, Anna; Goodman, Timothy; Simons, Claire; Gomaa, Mohamed S; Sementilli, Angelo; Sementilli, Leonardo; Ross, Alexander W; Morgan, Peter J; McCaffery, Peter J

    2016-07-01

    Retinoic acid (RA) is a potent regulator of gene transcription via its activation of a set of nuclear receptors controlling transcriptional activation. Precise maintenance of where and when RA is generated is essential and achieved by local expression of synthetic and catabolic enzymes. The catabolic enzymes Cyp26a1 and Cyp26b1 have been studied in detail in the embryo, where they limit gradients of RA that form patterns of gene expression, crucial for morphogenesis. This paracrine role of RA has been assumed to occur in most tissues and that the RA synthetic enzymes release RA at a site distant from the catabolic enzymes. In contrast to the embryonic CNS, relatively little is known about RA metabolism in the adult brain. This study investigated the distribution of Cyp26a1 and Cyp26b1 transcripts in the rat brain, identifying several novel regions of expression, including the cerebral cortex for both enzymes and striatum for Cyp26b1. In vivo use of a new and potent inhibitor of the Cyp26 enzymes, ser 2-7, demonstrated a function for endogenous Cyp26 in the brain and that hippocampal RA levels can be raised by ser 2-7, altering the effect of RA on differential patterning of cell proliferation in the hippocampal region of neurogenesis, the subgranular zone. The expression of CYP26A1 and CYP26B1 was also investigated in the adult human brain and colocalization of CYP26A1 and the RA synthetic enzyme RALDH2 indicated a different, autocrine role for RA in human hippocampal neurons. Studies with the SH-SY5Y human neuroblastoma cell line implied that the co-expression of RA synthetic and catabolic enzymes maintains retinoid homeostasis within neurons. This presents a novel view of RA in human neurons as part of an autocrine, intracellular signaling system.

  15. Liver-specific cytochrome P450 CYP2C22 is a direct target of retinoic acid and a retinoic acid-metabolizing enzyme in rat liver.

    PubMed

    Qian, Linxi; Zolfaghari, Reza; Ross, A Catharine

    2010-07-01

    Several cytochrome P450 (CYP) enzymes catalyze the C4-hydroxylation of retinoic acid (RA), a potent inducer of cell differentiation and an agent in the treatment of several diseases. Here, we have characterized CYP2C22, a member of the rat CYP2C family with homology to human CYP2C8 and CYP2C9. CYP2C22 was expressed nearly exclusively in hepatocytes, where it was one of the more abundant mRNAs transcripts. In H-4-II-E rat hepatoma cells, CYP2C22 mRNA was upregulated by all-trans (at)-RA, and Am580, a nonmetabolizable analog of at-RA. In comparison, in primary human hepatocytes, at-RA increased CYP2C9 but not CYP2C8 mRNA. Analysis of the CYP2C22 promoter region revealed a RA response element (5'-GGTTCA-(n)5-AGGTCA-3') in the distal flanking region, which bound the nuclear hormone receptors RAR and RXR and which was required for transcriptional activation response of this promoter to RA in CYP2C22-luciferase-transfected RA-treated HepG2 cells. The cDNA-expressed CYP2C22 protein metabolized [3H]at-RA to more polar metabolites. While long-chain polyunsaturated fatty acids competed, 9-cis-RA was a stronger competitor. Our studies demonstrate that CYP2C22 is a high-abundance, retinoid-inducible, hepatic P450 with the potential to metabolize at-RA, providing additional insight into the role of the CYP2C gene family in retinoid homeostasis.

  16. Induction of carnitine palmitoyl transferase 1 and fatty acid oxidation by retinoic acid in HepG2 cells.

    PubMed

    Amengual, Jaume; Petrov, Petar; Bonet, M Luisa; Ribot, Joan; Palou, Andreu

    2012-11-01

    The vitamin A derivative retinoic acid (RA) is an important regulator of mammalian adiposity and lipid metabolism, primarily acting at the gene expression level through nuclear receptors of the RA receptor (RAR) and retinoid X receptor (RXR) subfamilies. Here, we studied cell-autonomous effects of RA on fatty acid metabolism, particularly fatty acid oxidation, in human hepatoma HepG2 cells. Exposure to all-trans RA (ATRA) up-regulated the expression of carnitine palmitoyl transferase-1 (CPT1-L) in HepG2 cells in a dose- and time-dependent manner, and increased cellular oxidation rate of exogenously added radiolabeled palmitate. The effect of ATRA on gene expression of CPT1-L was: dependent on ongoing transcription, reproduced by both 9-cis RA and a pan-RXR agonist (but not a pan-RAR agonist) and abolished following RXRα partial siRNA-mediated silencing. CPT1-L gene expression was synergistically induced in HepG2 cells simultaneously exposed to ATRA and a selective peroxisome proliferator-activated receptor α agonist. We conclude that ATRA treatment enhances fatty acid catabolism in hepatocytes through RXR-mediated mechanisms that likely involve the transactivation of the PPARα:RXR heterodimer. Knowledge of agents and nutrient-derivatives capable of enhancing substrate oxidation systemically and specifically in liver, and their mechanisms of action, may contribute to new avenues of prevention and treatment of fatty liver, obesity and other metabolic syndrome-related disorders. PMID:22871568

  17. An emergency radiobioassay method for 226Ra in human urine samples.

    PubMed

    Sadi, Baki B; Li, Chunsheng; Kramer, Gary H

    2012-08-01

    A new radioanalytical method was developed for rapid determination of (226)Ra in human urine samples. The method is based on organic removal and decolourisation of a urine sample by a polymeric (acrylic ester) solid phase sorbent material followed by extraction and preconcentration of (226)Ra in an organic solvent using a dispersive liquid-liquid microextraction technique. Radiometric measurement of (226)Ra was carried out using a liquid scintillation counting instrument. The minimum detectable activity for the method (0.15 Bq l(-1)) is lower than the required sensitivity of 0.2 Bq l(-1) for (226)Ra in human urine samples as defined in the requirements for radiation emergency bioassay techniques for the public and first responders based on the dose threshold for possible medical attention recommended by the International Commission on Radiological Protection (ICRP). The accuracy (expressed as relative bias, B(r)) and repeatability of the method (expressed as relative precision, S(B)) evaluated at the reference level (2 Bq l(-1)) were found to be -4.5 and 2.6 %, respectively. The sample turnaround time was <5 h for a single urine sample and <20 h for a batch of six urine samples. With the fast sample turnaround time combined with the potential to carry out the analysis in a field deployable mobile laboratory, the newly developed method can be used for emergency radiobioassay of (226)Ra in human urine samples following a radiological or nuclear accident.

  18. PADI4 haplotypes in association with RA Mexican patients, a new prospect for antigen modulation.

    PubMed

    Zavala-Cerna, Maria Guadalupe; Gonzalez-Montoya, Norma Guadalupe; Nava, Arnulfo; Gamez-Nava, Jorge I; Moran-Moguel, Maria Cristina; Rosales-Gomez, Roberto Carlos; Gutierrez-Rubio, Susan Andrea; Sanchez-Corona, Jose; Gonzalez-Lopez, Laura; Davalos-Rodriguez, Ingrid Patricia; Salazar-Paramo, Mario

    2013-01-01

    Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity. PMID:24454473

  19. PADI4 Haplotypes in Association with RA Mexican Patients, a New Prospect for Antigen Modulation

    PubMed Central

    Gonzalez-Montoya, Norma Guadalupe; Gamez-Nava, Jorge I.; Moran-Moguel, Maria Cristina; Rosales-Gomez, Roberto Carlos; Gutierrez-Rubio, Susan Andrea; Sanchez-Corona, Jose; Davalos-Rodriguez, Ingrid Patricia; Salazar-Paramo, Mario

    2013-01-01

    Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity. PMID:24454473

  20. PADI4 haplotypes in association with RA Mexican patients, a new prospect for antigen modulation.

    PubMed

    Zavala-Cerna, Maria Guadalupe; Gonzalez-Montoya, Norma Guadalupe; Nava, Arnulfo; Gamez-Nava, Jorge I; Moran-Moguel, Maria Cristina; Rosales-Gomez, Roberto Carlos; Gutierrez-Rubio, Susan Andrea; Sanchez-Corona, Jose; Gonzalez-Lopez, Laura; Davalos-Rodriguez, Ingrid Patricia; Salazar-Paramo, Mario

    2013-01-01

    Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.

  1. Comparative Analysis Of 226Ra Soil-To-Plant Transfer In Cabbage Grown In Various Regions

    NASA Astrophysics Data System (ADS)

    Madruga, M. J.; Carvalho, F. P.; Silva, L.; Gouveia, J.

    2008-08-01

    The transfer of 226Ra from soil to cabbage was compared amongst regions, namely the surroundings of Urgeiriça uranium milling tailings (GE), regions with past uranium mining activities (GN1), and regions with no uranium mining activities and no uranium deposits (GN2). Results show a slight increase of the concentration ratio values at low radium concentration in soils. Statistical analysis of the mean 226Ra activity concentrations in soil and cabbage for the three regions was carried out. The comparison of 226Ra activity concentrations in soils indicated no difference (p>0.05), between GE and GN2 and significant differences (p<0.05) between GE and GN1 and between GN1 and GN2. Similar statistical results were obtained for 226Ra activity concentrations in cabbage from the same regions. It was concluded that radium Concentration Ratio (CR) for cabbage grown in the region of the main uranium milling site (GE) is of the same order of magnitude of CR in cabagge grown in background regions (GN2). However, 226Ra CR was higher in cabagge from the region with past uranium mining activities (GN1).

  2. Transfer coefficient of 226Ra from vegetation to meadow voles, Microtus pennsylvanicus, on U mill tailings

    SciTech Connect

    Cloutier, N.R.; Clulow, F.V.; Lim, T.P.; Dave, N.K.

    1986-06-01

    The 226Ra level in vegetation growing on U mine tailings in Elliot Lake, Ontario, Canada, was 211 + 22 mBq g-1 (dry weight) compared to less than 7 mBq g-1 (dry weight) in material from a control site. Skeletons of meadow voles (Microtus pennsylvanicus) established on the tailings had concentrations of 226Ra of 6083 +/- 673 mBq per animal in winter; 7163 +/- 1077 mBq per animal in spring; 1506 +/- 625 mBq per animal in summer; and 703 +/- 59 mBq per animal in fall, compared to less than 7 mBq per animal in controls. The /sup 226/Ra transfer coefficient from vegetation to voles (defined as total millibecquerels of /sup 226/Ra in adult vole per total millibecquerels of 226Ra consumed by the vole in its lifetime) was calculated as 4.6 +/- 2.9 X 10(-2) in summer and 2.8 +/- 0.6 X 10(-2) in fall.

  3. Altered retinoic acid signalling underpins dentition evolution.

    PubMed

    Gibert, Yann; Samarut, Eric; Pasco-Viel, Emmanuel; Bernard, Laure; Borday-Birraux, Véronique; Sadier, Alexa; Labbé, Catherine; Viriot, Laurent; Laudet, Vincent

    2015-03-01

    Small variations in signalling pathways have been linked to phenotypic diversity and speciation. In vertebrates, teeth represent a reservoir of adaptive morphological structures that are prone to evolutionary change. Cyprinid fish display an impressive diversity in tooth number, but the signals that generate such diversity are unknown. Here, we show that retinoic acid (RA) availability influences tooth number size in Cyprinids. Heterozygous adult zebrafish heterozygous for the cyp26b1 mutant that encodes an enzyme able to degrade RA possess an extra tooth in the ventral row. Expression analysis of pharyngeal mesenchyme markers such as dlx2a and lhx6 shows lateral, anterior and dorsal expansion of these markers in RA-treated embryos, whereas the expression of the dental epithelium markers dlx2b and dlx3b is unchanged. Our analysis suggests that changes in RA signalling play an important role in the diversification of teeth in Cyprinids. Our work illustrates that through subtle changes in the expression of rate-limiting enzymes, the RA pathway is an active player of tooth evolution in fish.

  4. Retinoic acid receptors: from molecular mechanisms to cancer therapy.

    PubMed

    di Masi, Alessandra; Leboffe, Loris; De Marinis, Elisabetta; Pagano, Francesca; Cicconi, Laura; Rochette-Egly, Cécile; Lo-Coco, Francesco; Ascenzi, Paolo; Nervi, Clara

    2015-02-01

    Retinoic acid (RA), the major bioactive metabolite of retinol or vitamin A, induces a spectrum of pleiotropic effects in cell growth and differentiation that are relevant for embryonic development and adult physiology. The RA activity is mediated primarily by members of the retinoic acid receptor (RAR) subfamily, namely RARα, RARβ and RARγ, which belong to the nuclear receptor (NR) superfamily of transcription factors. RARs form heterodimers with members of the retinoid X receptor (RXR) subfamily and act as ligand-regulated transcription factors through binding specific RA response elements (RAREs) located in target genes promoters. RARs also have non-genomic effects and activate kinase signaling pathways, which fine-tune the transcription of the RA target genes. The disruption of RA signaling pathways is thought to underlie the etiology of a number of hematological and non-hematological malignancies, including leukemias, skin cancer, head/neck cancer, lung cancer, breast cancer, ovarian cancer, prostate cancer, renal cell carcinoma, pancreatic cancer, liver cancer, glioblastoma and neuroblastoma. Of note, RA and its derivatives (retinoids) are employed as potential chemotherapeutic or chemopreventive agents because of their differentiation, anti-proliferative, pro-apoptotic, and anti-oxidant effects. In humans, retinoids reverse premalignant epithelial lesions, induce the differentiation of myeloid normal and leukemic cells, and prevent lung, liver, and breast cancer. Here, we provide an overview of the biochemical and molecular mechanisms that regulate the RA and retinoid signaling pathways. Moreover, mechanisms through which deregulation of RA signaling pathways ultimately impact on cancer are examined. Finally, the therapeutic effects of retinoids are reported. PMID:25543955

  5. Reversible effect of all-trans-retinoic acid on AML12 hepatocyte proliferation and cell cycle progression

    EPA Science Inventory

    The role of all-trans-retinoic acid (atRA) in the regulation of cellular proliferation and differentiation is well documented. Numerous studies have established the cancer preventive propertiesofatRAwhichfunctionstoregulate levels ofcellcycleproteinsessentialfortheGliS transition...

  6. A theoretical model for the production of Ac-225 for cancer therapy by neutron capture transmutation of Ra-226.

    PubMed

    Melville, G; Melville, P

    2013-02-01

    Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation by bombarding Ra-226 with high-energy neutrons from a neutron source to produce Ra-225 and hence Ac-225, which can be used as a generator to produce Bi-213 for use in 'Targeted Alpha Therapy' for cancer. This paper examines the possibility of producing Ac-225 by neutron capture using a theoretical model in which neutron energy is convoluted with the corresponding neutron cross sections of Ra-226. The total integrated yield can then be obtained. This study shows that an intense beam of high-energy neutrons could initiate neutron capture on Ra-226 to produce Ra-225 and hence practical amounts of Ac-225 and a useful reduction of Ra-226.

  7. A Novel Method for the Preparation of Retinoic Acid-Loaded Nanoparticles

    PubMed Central

    Errico, Cesare; Gazzarri, Matteo; Chiellini, Federica

    2009-01-01

    The goal of present work was to investigate the use of bioerodible polymeric nanoparticles as carriers of retinoic acid (RA), which is known to induce differentiation of several cell lines into neurons. A novel method, named “Colloidal-Coating”, has been developed for the preparation of nanoparticles based on a copolymer of maleic anhydride and butyl vinyl ether (VAM41) loaded with RA. Nanoparticles with an average diameter size of 70 nm and good morphology were prepared. The activity of the encapsulated RA was evaluated on SK-N-SH human neuroblastoma cells, which are known to undergo inhibition of proliferation and neuronal differentiation upon treatment with RA. The activity of RA was not affected by the encapsulation and purification processes. PMID:19564952

  8. Production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

    PubMed

    Melville, G; Meriarty, H; Metcalfe, P; Knittel, T; Allen, B J

    2007-09-01

    The increasing application of Ac-225 for cancer therapy indicates the potential need for its increased production and availability. The production of Ac-225 has been achieved using bremsstrahlung photons from an 18 MV medical linear accelerator (linac) to bombard a Ra-226 target. A linac dose of 2800 Gy produced about 64 microCi of Ra-225, which decays to Ac-225. This result, while consistent with the theoretical calculations, is far too low to be of practical use. A more powerful linac is required that runs at a higher current, longer pulse length and higher frequency for practical production. This process could also lead to the reduction of the nuclear waste product Ra-226.

  9. Low-level measurements of Ra-226/Rn-222 by pulse ionization chambers

    NASA Astrophysics Data System (ADS)

    El-Daoushy, Fand; Garcia-Tenorio, Rafael

    1988-10-01

    Characteristics of two ionization chambers have been studied and the chambers utilized for 226Ra/ 222Rn measurements for more than ten years. The results obtained show that coating of internal surfaces with a pure and thin Ag-layer enhances the background of ionization chambers in spite of some improvements at the early stages of operation. In addition to previously known parameters influencing the accuracy in routine measurements, new correction factors are suggested. 226Ra impurities in the body of ionization chambers are found to act not only as a permanent, but also as a temperature-dependent source of background. Earlier accuracies of 226Ra/ 222Rn measurements have been considerably improved by assuring long-term mechanical and thermal stability of the ionization chambers.

  10. Laser spectroscopy of trapped short-lived Ra{sup +} ions

    SciTech Connect

    Versolato, O. O.; Giri, G. S.; Wansbeek, L. W.; Berg, J. E. van den; Hoek, D. J. van der; Jungmann, K.; Kruithof, W. L.; Onderwater, C. J. G.; Sahoo, B. K.; Santra, B.; Shidling, P. D.; Timmermans, R. G. E.; Willmann, L.; Wilschut, H. W.

    2010-07-15

    As an important step toward an atomic parity violation experiment in one single trapped Ra{sup +} ion, laser spectroscopy on short-lived {sup 212,213,214}Ra{sup +} ions was conducted. The isotope shift of the 6 {sup 2}D{sub 3/2}-7 {sup 2}P{sub 1/2} and 6 {sup 2}D{sub 3/2}-7 {sup 2}P{sub 3/2} transitions and the hyperfine structure constants of the 7 {sup 2}P{sub 1/2} and 6 {sup 2}D{sub 3/2} states in {sup 213}Ra{sup +} were measured, which provides a benchmark for the required atomic theory. A lower limit of 232(4) ms for 6 {sup 2}D{sub 5/2} state lifetime was determined.

  11. Ra-226 concentrations in otter, Lutra canadensis, trapped near uranium tailings at Elliot Lake, Ontario

    SciTech Connect

    Wren, C.D.; Cloutier, N.R.; Lim, T.P.; Dave, N.K.

    1987-02-01

    The Elliot Lake area of Ontario, is currently the major uranium producing region of Canada. It is estimated there are 120 million tons of uranium tailings spread over 600 ha in the vicinity of Elliot Lake. The transfer and fate of uranium-series radionuclides from tailing sites remain primary ecological concerns in these areas. It has been demonstrated that the levels of radionuclides, including Ra-226, are elevated in vegetation, small mammals and fish living on or near tailing disposal sites. However, the transfer potential of Ra-226 to predatory species has not been examined in detail. The objective of this study was to measure Ra-226 levels in otters (Lutra canadensis), captured near tailing sites, to provide further information on the fate of radionuclides in the environment.

  12. Optical Performance of Breadboard Amon-Ra Imaging Channel Instrument for Deep Space Albedo Measurement

    NASA Astrophysics Data System (ADS)

    Park, Won Hyun; Kim, Seonghui; Lee, Hanshin; Yi, Hyun-Su; Lee, Jae-Min; Ham, Sun-Jung; Yoon, Jeeyeon; Kim, Sug-Whan; Yang, Ho Soon; Choi, Ki-Hyuk; Kim, Zeen Chul; Lockwood, Mike; Morris, Nigel; Tosh, Ian

    2007-03-01

    The AmonRa instrument, the primary payload of the international EARTHSHINE mission, is designed for measurement of deep space albedo from L1 halo orbit. We report the optical design, tolerance analysis and the optical performance of the breadborad AmonRa imaging channel instrument optimized for the mission science requirements. In particular, an advanced wavefront feedback process control technique was used for the instrumentation process including part fabrication, system alignment and integration. The measured performances for the complete breadboard system are the RMS 0.091 wave(test wavelength: 632.8 nm) in wavefront error, the ensquared energy of 61.7%(in 14 μ m) and the MTF of 35.3%(Nyquist frequency: 35.7 mm^{-1}) at the center field. These resulting optical system performances prove that the breadboard AmonRa instrument, as built, satisfies the science requirements of the EARTHSHINE mission.

  13. A Study of LoRa: Long Range & Low Power Networks for the Internet of Things.

    PubMed

    Augustin, Aloÿs; Yi, Jiazi; Clausen, Thomas; Townsley, William Mark

    2016-09-09

    LoRa is a long-range, low-power, low-bitrate, wireless telecommunications system, promoted as an infrastructure solution for the Internet of Things: end-devices use LoRa across a single wireless hop to communicate to gateway(s), connected to the Internet and which act as transparent bridges and relay messages between these end-devices and a central network server. This paper provides an overview of LoRa and an in-depth analysis of its functional components. The physical and data link layer performance is evaluated by field tests and simulations. Based on the analysis and evaluations, some possible solutions for performance enhancements are proposed.

  14. Applications of 211At and 223Ra in targeted alpha-particle radiotherapy.

    PubMed

    Vaidyanathan, Ganesan; Zalutsky, Michael R

    2011-10-01

    Targeted radiotherapy using agents tagged with α-emitting radionuclides is gaining traction with several clinical trials already undertaken or ongoing, and others in the advanced planning stage. The most commonly used α-emitting radionuclides are 213Bi, 211At, 223Ra and 225Ac. While each one of these has pros and cons, it can be argued that 211At probably is the most versatile based on its half life, decay scheme and chemistry. On the other hand, for targeting bone metastases, 223Ra is the ideal radionuclide because simple cationic radium can be used for this purpose. In this review, we will discuss the recent developments taken place in the application of 211At-labeled radiopharmaceuticals and give an overview of the current status of 223Ra for targeted α-particle radiotherapy. PMID:22202151

  15. Applications of 211At and 223Ra in Targeted Alpha-Particle Radiotherapy

    PubMed Central

    Vaidyanathan, Ganesan; Zalutsky, Michael R.

    2012-01-01

    Targeted radiotherapy using agents tagged with α-emitting radionuclides is gaining traction with several clinical trials already undertaken or ongoing, and others in the advanced planning stage. The most commonly used α-emitting radionuclides are 213Bi, 211At, 223Ra and 225Ac. While each one of these has pros and cons, it can be argued that 211At probably is the most versatile based on its half life, decay scheme and chemistry. On the other hand, for targeting bone metastases, 223Ra is the ideal radionuclide because simple cationic radium can be used for this purpose. In this review, we will discuss the recent developments taken place in the application of 211At-labeled radiopharmaceuticals and give an overview of the current status of 223Ra for targeted α-particle radiotherapy. PMID:22202151

  16. Simulating magnetospheres with numerical relativity: The GiRaFFE code

    NASA Astrophysics Data System (ADS)

    Babiuc-Hamilton, Maria; Etienne, Zach

    2016-01-01

    Numerical Relativity has shown success over the past several years, especially in the simulation of black holes and gravitational waves. In recent years, teams have tackled the problem of the interaction of gravitational and electromagnetic waves. But where there are plasmas, the simulations often have trouble reproducing nature. Neutron stars, black hole accretion disks, astrophysical jets—all of these represent extreme environments both gravitationally and electromagnetically. We are creating the first open-source, dynamical spacetime general relativity force-free electrodynamics code: GiRaFFE.We present here the performance of GiRaFFE in testing. With this code, we will simulate neutron star magnetospheres, collisions between neutron stars and black holes, and particular attention will be paid to the production of jets through the Blandford-Znajek mechanism.GiRaFFE will be made available to the community.

  17. Production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

    PubMed

    Melville, G; Meriarty, H; Metcalfe, P; Knittel, T; Allen, B J

    2007-09-01

    The increasing application of Ac-225 for cancer therapy indicates the potential need for its increased production and availability. The production of Ac-225 has been achieved using bremsstrahlung photons from an 18 MV medical linear accelerator (linac) to bombard a Ra-226 target. A linac dose of 2800 Gy produced about 64 microCi of Ra-225, which decays to Ac-225. This result, while consistent with the theoretical calculations, is far too low to be of practical use. A more powerful linac is required that runs at a higher current, longer pulse length and higher frequency for practical production. This process could also lead to the reduction of the nuclear waste product Ra-226. PMID:17532223

  18. A Study of LoRa: Long Range & Low Power Networks for the Internet of Things

    PubMed Central

    Augustin, Aloÿs; Yi, Jiazi; Clausen, Thomas; Townsley, William Mark

    2016-01-01

    LoRa is a long-range, low-power, low-bitrate, wireless telecommunications system, promoted as an infrastructure solution for the Internet of Things: end-devices use LoRa across a single wireless hop to communicate to gateway(s), connected to the Internet and which act as transparent bridges and relay messages between these end-devices and a central network server. This paper provides an overview of LoRa and an in-depth analysis of its functional components. The physical and data link layer performance is evaluated by field tests and simulations. Based on the analysis and evaluations, some possible solutions for performance enhancements are proposed. PMID:27618064

  19. Applications of 211At and 223Ra in targeted alpha-particle radiotherapy.

    PubMed

    Vaidyanathan, Ganesan; Zalutsky, Michael R

    2011-10-01

    Targeted radiotherapy using agents tagged with α-emitting radionuclides is gaining traction with several clinical trials already undertaken or ongoing, and others in the advanced planning stage. The most commonly used α-emitting radionuclides are 213Bi, 211At, 223Ra and 225Ac. While each one of these has pros and cons, it can be argued that 211At probably is the most versatile based on its half life, decay scheme and chemistry. On the other hand, for targeting bone metastases, 223Ra is the ideal radionuclide because simple cationic radium can be used for this purpose. In this review, we will discuss the recent developments taken place in the application of 211At-labeled radiopharmaceuticals and give an overview of the current status of 223Ra for targeted α-particle radiotherapy.

  20. Criticality safety evaluation for pathfinder fuel elements in model No. RA-3 shipping containers

    SciTech Connect

    Jones, R.R.

    1986-11-01

    Pennsylvania State University presently processes approximately 415 Pathfinder fuel elements which will require shipment from their nuclear facility. Criticality safety calculations have been performed with the Monte Carlo code, KENO-IV, and 16-group Hansen-Roach cross sections for shipment of these fuel elements in Model No. RA-3 shipping containers. Except for a slightly higher U-235 enrichment in the UO/sub 2/ rods of the Pathfinder fuel elements, the parameters for the proposed shipment are within those limits currently approved in Certificate of Compliance No. 4986, Revision No. 17, for shipment of UO/sub 2/ fuel rods in the Model RA-3 shipping containers. The analysis in this report verifies an adequate margin of criticality safety for the Pathfinder fuel elements in Model RA-3 containers for a Fissile Class 1 shipment.

  1. Geology and Topography of Ra Patera, Io, in the Voyager era: Prelude to Eruption

    NASA Technical Reports Server (NTRS)

    Schenk, Paul M.; McEwen, Alfred; Davies, A. G.; Davenport, Trevor; Jones, Kevin; Fessler, Brian

    1997-01-01

    Voyager era stereo images are used to map the geology and topography of Ra Patera (a major active volcanic center and possible site of sulfur eruptions on Io). The summit of Ra Patera reaches only approx.1 km above the surrounding plains. Pre-Voyager-era lava flows occur on slopes of 0.1-0.3 deg, comparable to the lunar mare. These flows were emplaced at either low viscosities, high eruption rates, or both. A 600- km-long ridged mountain unit (rising to approx. 8 km near Carancho Patera) forms a 60 by 90 km wide plateau approx. 0.5 km high 50 km east of Ra Patera. The new lava flows observed by Galileo flowed around the southern edge of this plateau.

  2. A Study of LoRa: Long Range & Low Power Networks for the Internet of Things.

    PubMed

    Augustin, Aloÿs; Yi, Jiazi; Clausen, Thomas; Townsley, William Mark

    2016-01-01

    LoRa is a long-range, low-power, low-bitrate, wireless telecommunications system, promoted as an infrastructure solution for the Internet of Things: end-devices use LoRa across a single wireless hop to communicate to gateway(s), connected to the Internet and which act as transparent bridges and relay messages between these end-devices and a central network server. This paper provides an overview of LoRa and an in-depth analysis of its functional components. The physical and data link layer performance is evaluated by field tests and simulations. Based on the analysis and evaluations, some possible solutions for performance enhancements are proposed. PMID:27618064

  3. Review of therapeutic drug monitoring of anticancer drugs part 1--cytotoxics.

    PubMed

    Paci, Angelo; Veal, Gareth; Bardin, Christophe; Levêque, Dominique; Widmer, Nicolas; Beijnen, Jos; Astier, Alain; Chatelut, Etienne

    2014-08-01

    Most anticancer drugs are characterised by a steep dose-response relationship and narrow therapeutic window. Inter-individual pharmacokinetic (PK) variability is often substantial. The most relevant PK parameter for cytotoxic drugs is the area under the plasma concentration versus time curve (AUC). Thus it is somewhat surprising that therapeutic drug monitoring (TDM) is still uncommon for the majority of agents. Goals of the review were to assess the rationale for more widely used TDM of cytotoxics in oncology. There are several reasons why TDM has never been fully implemented into daily oncology practice. These include difficulties in establishing appropriate concentration target ranges, common use of combination chemotherapies for many tumour types, analytical challenges with prodrugs, intracellular compounds, the paucity of published data from pharmacological trials and 'Day1 = Day21' administration schedules. There are some specific situations for which these limitations are overcome, including high dose methotrexate, 5-fluorouracil infusion, mitotane and some high dose chemotherapy regimens. TDM in paediatric oncology represents an important challenge. Established TDM approaches includes the widely used anticancer agents carboplatin, busulfan and methotrexate, with 13-cis-retinoic acid also recently of interest. Considerable effort should be made to better define concentration-effect relationships and to utilise tools such as population PK/PD models and comparative randomised trials of classic dosing versus pharmacokinetically guided adaptive dosing. There is an important heterogeneity among clinical practices and a strong need to promote TDM guidelines among the oncological community.

  4. The Role of Isotretinoin Therapy for Cushing's Disease: Results of a Prospective Study.

    PubMed

    Vilar, Lucio; Albuquerque, José Luciano; Lyra, Ruy; Trovão Diniz, Erik; Rangel Filho, Frederico; Gadelha, Patrícia; Thé, Ana Carolina; Ibiapina, George Robson; Gomes, Barbara Sales; Santos, Vera; Melo da Fonseca, Maíra; Frasão Viana, Karoline; Lopes, Isis Gabriella; Araújo, Douglas; Naves, Luciana

    2016-01-01

    Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6-12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6-12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism. PMID:27034666

  5. Autologous stem cell transplantation for the treatment of neuroblastoma in Korea.

    PubMed

    Ryu, Kyung Ha; Ahn, Hyo Seop; Koo, Hong Hoe; Kook, Hoon; Kim, Moon Kyu; Kim, Hack Ki; Ghim, Thad; Moon, Hyung Nam; Seo, Jong Jin; Sung, Ki Woong; Shin, Hee Young; Yoo, Eun Sun; Lyu, Chuhl Joo; Lee, Young Ho; Lee, Hahng; Cho, Bin; Cho, Hyun Sang; Choi, Hyung Soo; Hah, Jeong Ok; Hwang, Tai Ju

    2003-04-01

    Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.

  6. Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system.

    PubMed

    Kushner, B H; Kramer, K; Modak, S; Kernan, N A; Reich, L M; Danis, K; Cheung, N-K V

    2006-02-01

    We report on a three-drug myeloablative regimen designed to consolidate remission and to prevent central nervous system (CNS) relapse of high-risk neuroblastoma (NB). Sixty-six NB patients received topotecan 2 mg/m2/day, x 4 days; thiotepa 300 mg/m2/day, x 3 days; and carboplatin approximately 500 mg/m2/day, x 3 days. Post-SCT treatments included radiotherapy, immunotherapy, 13-cis-retinoic acid, +/-oral etoposide. Significant nonhematologic toxicities were mucositis and skin-related in all patients, convulsions in three patients, and cardiac failure and venocclusive disease of liver in one patient each. Grade 2 hepatotoxicity led to truncating cytoreduction in two patients; both later relapsed in brain. Among 46 patients transplanted in first complete/very good partial remission (CR/VGPR), event-free survival is 54% (s.e.+/-8%) at 36 months post-SCT; notable events were three non-NB-related deaths (adenovirus on day +9, bowel necrosis at 5 months, multiorgan failure at seven months) and four relapses in brain. Of 12 patients transplanted with evidence of NB, two became long-term event-free survivors and two relapsed in the brain. Of eight patients transplanted in second or greater CR/VGPR, one became a long-term event-free survivor and seven relapsed though not in the CNS. This regimen has manageable toxicity but does not prevent CNS relapse.

  7. Regulation of accessory cell function by retinoids in murine immune responses.

    PubMed

    Katz, D R; Drzymala, M; Turton, J A; Hicks, R M; Hunt, R; Palmer, L; Malkovský, M

    1987-06-01

    This study examines the effects of in-vivo immune regulation by vitamin A acetate (VAA) and 13-cis-retinoic acid (13-CRA) on in-vitro accessory cell function. Mice were fed a control diet, or diet containing VAA or 13-CRA, and monitored by body weight gains and diet consumptions at weekly intervals. At 4, 7 and 12 weeks mice were killed, differential blood counts performed and accessory cells isolated from lymphomedullary tissues. Histology confirmed that the chief feature of the lymphomedullary organs of the VAA-fed animals was an expansion of the splenic marginal zone and the paracortical region of the lymph nodes. There was an increase in the number of accessory cells present, and this included both dendritic cells and macrophages. The accessory cell function of these cells was also increased, as evidenced by both alloproliferative and allocytotoxic responses in vitro. In 13-CRA-fed animals the effects were similar to those seen with VAA, but were less pronounced. We suggest that the primary effects of these compounds on in-vivo immunoregulation could be due to their promotion of accessory cell function.

  8. Dinutuximab: first global approval.

    PubMed

    Dhillon, Sohita

    2015-05-01

    United Therapeutics Corporation and the National Cancer Institute are developing dinutuximab (Unituxin™; ch14.18), a monoclonal antibody targeting GD2, for the treatment of neuroblastoma. GD2 is a glycolipid found on the surface of tumour cells, which is overexpressed in neuroblastoma. Dinutuximab, an IgG1 human/mouse chimeric switch variant of murine monoclonal antibody 14G2a, binds to GD2 and induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. The US FDA has recently approved the use of dinutuximab combination therapy for the treatment of high-risk neuroblastoma in paediatric patients. The marketing authorization application for dinutuximab is under regulatory review in the EU, and phase I-III development is underway in several other countries. This article summarizes the milestones in the development of dinutuximab leading to this first approval for use (in combination with granulocyte macrophage colony-stimulating factor, interleukin-2 and 13-cis retinoic acid) in the treatment of paediatric patients with high-risk neuroblastoma who achieve at least partial response to prior first-line multiagent, multimodality therapy. PMID:25940913

  9. The Role of Isotretinoin Therapy for Cushing's Disease: Results of a Prospective Study.

    PubMed

    Vilar, Lucio; Albuquerque, José Luciano; Lyra, Ruy; Trovão Diniz, Erik; Rangel Filho, Frederico; Gadelha, Patrícia; Thé, Ana Carolina; Ibiapina, George Robson; Gomes, Barbara Sales; Santos, Vera; Melo da Fonseca, Maíra; Frasão Viana, Karoline; Lopes, Isis Gabriella; Araújo, Douglas; Naves, Luciana

    2016-01-01

    Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6-12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6-12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism.

  10. Pituitary specific retinoid-X receptor ligand interactions with thyroid hormone receptor signaling revealed by high throughput reporter and endogenous gene responses.

    PubMed

    Mengeling, Brenda J; Furlow, J David

    2015-10-01

    Disruption of thyroid hormone (TH) signaling can compromise vital processes both during development and in the adult. We previously reported on high-throughput screening experiments for man-made TH disruptors using a stably integrated line of rat pituitary cells, GH3.TRE-Luc, in which a thyroid hormone receptor (TR) response element drives luciferase (Luc) expression. In these experiments, several retinoid/rexinoid compounds activated the reporter. Here we show that all-trans and 13-cis retinoic acid appear to function through the heterodimer partners of TRs, retinoid-X receptors (RXRs), as RXR antagonists abrogated retinoid-induced activation. The retinoids also induced known endogenous TR target genes, showing good correlation with Luc activity. Synthetic RXR-specific agonists significantly activated all tested TR target genes, but interestingly, retinoid/rexinoid activation was more consistent between genes than the extent of T3-induced activation. In contrast, the retinoids neither activated the Luc reporter construct in transient transfection assays in the human hepatocarcinoma cell line HuH7, nor two of the same T3-induced genes examined in pituitary cells. These data demonstrate the suitability and sensitivity of GH3.TRE-Luc cells for screening chemical compound libraries for TH disruption and suggest that the extent of disruption can vary on a cell type and gene-specific bases, including an underappreciated contribution by RXRs. PMID:26096596

  11. Induced differentiation inhibits sphere formation in neuroblastoma.

    PubMed

    Craig, Brian T; Rellinger, Eric J; Alvarez, Alexandra L; Dusek, Haley L; Qiao, Jingbo; Chung, Dai H

    2016-08-19

    Neuroblastoma arises from the neural crest, the precursor cells of the sympathoadrenal axis, and differentiation status is a key prognostic factor used for clinical risk group stratification and treatment strategies. Neuroblastoma tumor-initiating cells have been successfully isolated from patient tumor samples and bone marrow using sphere culture, which is well established to promote growth of neural crest stem cells. However, accurate quantification of sphere-forming frequency of commonly used neuroblastoma cell lines has not been reported. Here, we show that MYCN-amplified neuroblastoma cell lines form spheres more frequently than non-MYCN-amplified cell lines. We also show that sphere formation is directly sensitive to cellular differentiation status. 13-cis-retinoic acid is a clinically used differentiating agent that induces a neuronal phenotype in neuroblastoma cells. Induced differentiation nearly completely blocked sphere formation. Furthermore, sphere formation was specifically FGF-responsive and did not respond to increasing doses of EGF. Taken together, these data suggest that sphere formation is an accurate method of quantifying the stemness phenotype in neuroblastoma. PMID:27297102

  12. The Role of Isotretinoin Therapy for Cushing's Disease: Results of a Prospective Study

    PubMed Central

    Vilar, Lucio; Albuquerque, José Luciano; Lyra, Ruy; Trovão Diniz, Erik; Rangel Filho, Frederico; Gadelha, Patrícia; Thé, Ana Carolina; Ibiapina, George Robson; Gomes, Barbara Sales; Santos, Vera; Melo da Fonseca, Maíra; Frasão Viana, Karoline; Lopes, Isis Gabriella; Araújo, Douglas; Naves, Luciana

    2016-01-01

    Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6–12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6–12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism. PMID:27034666

  13. Quantifying seawater recirculation through subtidal estuarine sediments in Elkhorn Slough, California: coupling Ra isotope geochemistry with hydrodynamic modelling.

    NASA Astrophysics Data System (ADS)

    Breier, J. A.; Nidzieko, N. J.; Monismith, S. G.; Paytan, A.

    2006-12-01

    Measurements of short lived ^{224}Ra and ^{223}Ra in concert with hydrodynamic modelling were used to determine the magnitude and spatial extent of sediment/water exchange within Elkhorn Slough a tidally dominated estuary in Monterey Bay, California. Samples for dissolved Ra activity, Ba, U, silicate, nitrate, ammonium, and ortho-phosphate were collected from the estuary and potential endmember streams, sediment porewaters, and groundwater. Hourly precipitation, evaporation, and stream gauge data were used to develop a spatially explicit estimate of stream flow and runoff from the watershed to the estuary and salinity and water depth time series from an in-situ sensor network were used to determine tidal exchange. The sample chemistry indicates the mixing of at least three endmembers within the estuary: streams, seawater from the tidal inlet, and higher Ra activity sediment porewaters. In the case of ^{224}Ra and ^{223}Ra, the most important flux to the estuary is sediment porewater, an input two orders of magnitude greater than any other, which balances the decay of these isotopes in the water column. This large sedimentary source makes ^{224}Ra and ^{223}Ra excellent tracers of sediment/water exchange and differential decay in the water column makes their activity ratio an excellent indicator of water transport within the estuary. The chemical measurements were used in concert with the hydrologic data to develop Ra flux boundary conditions for a coupled three dimensional hydrodynamic and chemical transport model of the estuary which was used as a framework for interpreting the Ra activities and gradients and further refining our estimates of the magnitude and spatial variation in the sediment/water exchange. The results indicate that tidal pumping of intertidal sediments is the principal process by which ^{224}Ra and ^{223}Ra are supplied to Elkhorn Slough.

  14. Biodistribution of 225Ra citrate in mice: retention of daughter radioisotopes in bone.

    PubMed

    Kennel, Stephen J; Lankford, Trish; Garland, Marc; Sundberg, John P; Mirzadeh, Saed

    2005-11-01

    Alpha-particle-emitting radionuclides have potential for therapy of localized disease due to their high linear energy transformation and short pathlengths. Radiometals that home naturally to bone can be exploited for this purpose, and 223Ra (t(1/2)=11.4 days) recently has been studied for therapy of bone tumors in mice and rats. Actinium-225 (t(1/2)=10 days) is also an attractive radioisotope for endoradiotherapy. In a single decay of a 225Ac nucleus and its subsequent decay daughters, over 27 MeV ( approximately 90% of total energy) is released by sequential emission of four alpha particles, ranging in energy from 5.7 to 8.4 MeV. Although Ac3+ does not home naturally to bone, its parent radioisotope 225Ra (beta(-), t(1/2)=15 days) can be used as an in vivo source for 225Ac. Thus, injection of 225Ra takes advantage of the bone-homing properties of radium coupled with the significant amount of energy released from the 225Ac decay chain. Our data confirm that a large fraction of radium citrate injected intravenously into mice localizes rapidly in bone. Injected doses per gram (ID/g) for 225Ra range from 25% in skull to about 10% in sternum. Once deposited, the 225Ra remains in the bone with a biological half life of >40 days. Furthermore, >95% of the daughter radioisotope, 225Ac, is retained in the bone. However, a significant fraction of one of the daughter radioisotopes, 213Bi, is found in kidney. The biodistribution data indicate that 225Ra injection should be a powerful agent for killing cells associated with bone; however, the toxicity of this radioisotope which is similar to that of other alpha emitters limits the dose that can be tolerated. PMID:16253811

  15. Initial Results from the Radiation Dosimetry Experiment (RaD-X) Balloon Flight Mission

    NASA Technical Reports Server (NTRS)

    Mertens, Christopher J.

    2015-01-01

    The NASA Radiation Dosimetry Experiment (RaD-X) high-altitude balloon mission was successfully launched from Fort Sumner, New Mexico USA on 25 September, 2015. Over 15 hours of science data were obtained from four dosimeters at altitudes above about 25 km. The four dosimeters flown on the RaD-X science payload are a Hawk version 3.0 Tissue Equivalent Proportional Counter (TEPC) manufactured by Far West Technologies, a Liulin dosimeter-spectrometer produced by the Solar Research and Technology Institute, Bulgarian Academy of Sciences, a total ionizing dose detector manufactured by Teledyne Microelectronic Technologies, and the RaySure detector provided by the University of Surrey.

  16. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study

    PubMed Central

    Naranjo, Antonio; Sokka, Tuulikki; Descalzo, Miguel A; Calvo-Alén, Jaime; Hørslev-Petersen, Kim; Luukkainen, Reijo K; Combe, Bernard; Burmester, Gerd R; Devlin, Joe; Ferraccioli, Gianfranco; Morelli, Alessia; Hoekstra, Monique; Majdan, Maria; Sadkiewicz, Stefan; Belmonte, Miguel; Holmqvist, Ann-Carin; Choy, Ernest; Tunc, Recep; Dimic, Aleksander; Bergman, Martin; Toloza, Sergio; Pincus, Theodore

    2008-01-01

    Introduction We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. Methods The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. Results Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0

  17. 226Ra as a standard source for efficiency calibration of Ge(Li) detectors

    NASA Astrophysics Data System (ADS)

    Farouk, M. A.; Al-Soraya, A. M.

    1982-09-01

    The relative intensities of gamma-rays resulting from the decay of 226Ra in equilibrium with its short-lived daughters have been measured using two different high resolution Ge(Li) detectors. The accuracy of the measurements does not exceed 2.5%. The most intense components of gamma-rays from thin 226Ra are recommended for use as a calibration standard Ge(Li) detectors in the energy range from 186 keV to 3.050 MeV.

  18. A Novel Bidirectional Interaction between endothelin-3 and Retinoic Acid in Rat Enteric Nervous System Precursors

    PubMed Central

    Gisser, Jonathan M.; Cohen, Ariella R.; Yin, Han; Gariepy, Cheryl E.

    2013-01-01

    Background Signaling through the endothelin receptor B (EDNRB) is critical for the development of the enteric nervous system (ENS) and mutations in endothelin system genes cause Hirschsprung’s aganglionosis in humans. Penetrance of the disease is modulated by other genetic factors. Mutations affecting retinoic acid (RA) signaling also produce aganglionosis in mice. Thus, we hypothesized that RA and endothelin signaling pathways may interact in controlling development of the ENS. Methods Rat immunoselected ENS precursor cells were cultured with the EDNRB ligand endothelin-3, an EDNRB-selective antagonist (BQ-788), and/or RA for 3 or 14 days. mRNA levels of genes related to ENS development, RA- and EDNRB-signaling were measured at 3 days. Proliferating cells and cells expressing neuronal, glial, and myofibroblast markers were quantified. Results Culture of isolated ENS precursors for 3 days with RA decreases expression of the endothelin-3 gene and that of its activation enzyme. These changes are associated with glial proliferation, a higher percentage of glia, and a lower percentage of neurons compared to cultures without RA. These changes are independent of EDNRB signaling. Conversely, EDNRB activation in these cultures decreases expression of RA receptors β and γ mRNA and affects the expression of the RA synthetic and degradative enzymes. These gene expression changes are associated with reduced glial proliferation and a lower percentage of glia in the culture. Over 14 days in the absence of EDNRB signaling, RA induces the formation of a heterocellular plexus replete with ganglia, glia and myofibroblasts. Conclusions A complex endothelin-RA interaction exists that coordinately regulates the development of rat ENS precursors in vitro. These results suggest that environmental RA may modulate the expression of aganglionosis in individuals with endothelin mutations. PMID:24040226

  19. Ameliorative effect of rosmarinic acid on scopolamine-induced memory impairment in rats.

    PubMed

    Hasanein, Parisa; Mahtaj, Azam Kazemian

    2015-01-12

    Rosmarinic acid (RA) is a natural phenol that exerts different biological activities, such as antioxidant activity and neuroprotective effects. In this study, we hypothesized that administration of RA (8, 16, and 32 mg/kg, p.o.) for 7 days would effect on scopolamine-induced cognitive dysfunction as an extensively used model of cognitive impairment. The rats were divided into 10 groups. The acquisition trial was done 1h after the last administration of RA. Animals were divided into control, RA (8, 16, and 32 mg/kg) and donepezil (2 mg/kg) treated controls, scopolamine, RA (8, 16, and 32 mg/kg), and donepezil (2 mg/kg) treated scopolamine groups. Memory impairment was induced by scopolamine treatment (1 mg/kg, i.p.) 30 min after the administration of RA, donepezil, or saline. Scopolamine administration caused cognition deficits in the PAL and memory paradigm. While orally RA administration (16 and 32 mg/kg) improved learning and memory in control rats, it reversed learning and memory deficits of scopolamine received groups. Administration of RA at the dose of 8 mg/kg did not alter cognitive function in control and scopolamine treated groups. The combination of anticholinesterase, neuroprotective, and antioxidant properties of RA may all be responsible for the observed effects. These results indicate the beneficial effects of subchronic RA administration in passive avoidance learning and memory in control rats as well as in a pharmacological model of cholinergic deficit which continue to expand the knowledge base in creating new treatment strategies for cognition deficits and dementia. Of course, further studies are warranted for clinical use of RA in the management of demented subjects.

  20. Molecular cloning and characterization of tyrosine aminotransferase and hydroxyphenylpyruvate reductase, and rosmarinic acid accumulation in Scutellaria baicalensis.

    PubMed

    Kim, Yeon Bok; Uddina, Md Romij; Kim, YeJi; Park, Chun Geon; Park, Sang Un

    2014-09-01

    Rosmarinic acid (a-O-caffeoyl-3,4-dihydroxyphenylacetic acid, RA) is a caffeoyl ester widely distributed in plants. cDNA clones encoding tyrosine aminotransferase (TAT1 and 2) and hydroxyphenylpyruvate reductase (HPPR) have been isolated from Scutellaria baicalensis. The open reading frames (ORFs) of SbTAT1 and 2 were 1230 and 1272 bp long and encoded 409 and 423 amino acid residues, respectively. HPPR corresponded to a 942-bp ORF and 313 amino acid residues of translated protein. To study the molecular mechanisms of TAT and HPPR and investigate RA accumulation in S. baicalensis, we examined the transcript levels of TAT isoforms and HPPR with quantitative real-time PCR and analyzed the RA content in different organs by using high-performance liquid chromatography. The transcript levels of SbTATI SbTAT2, and SbHPPR in the flowers were higher than those in other organs. RA was also highly accumulated in the flowers and with a trace amount in the roots. No RA was detected in the leaves and stems of S. baicalensis. The amount of accumulated RA in the flowers was 28.7 times higher than that in the roots. Our results will be helpful in elucidating the mechanisms of RA biosynthesis in S. baicalensis. PMID:25918800

  1. Roles of retinoic acid signaling in normal and abnormal development of the palate and tongue.

    PubMed

    Okano, Junko; Udagawa, Jun; Shiota, Kohei

    2014-05-01

    Palatogenesis involves various developmental events such as growth, elevation, elongation and fusion of opposing palatal shelves. Extrinsic factors such as mouth opening and subsequent tongue withdrawal are also needed for the horizontal elevation of palate shelves. Failure of any of these steps can lead to cleft palate, one of the most common birth defects in humans. It has been shown that retinoic acid (RA) plays important roles during palate development, but excess RA causes cleft palate in fetuses of both rodents and humans. Thus, the coordinated regulation of retinoid metabolism is essential for normal palatogenesis. The endogenous RA level is determined by the balance of RA-synthesizing (retinaldehyde dehydrogenases: RALDHs) and RA-degrading enzymes (CYP26s). Cyp26b1 is a key player in normal palatogenesis. In this review, we discuss recent progress in the study of the pathogenesis of RA-induced cleft palate, with special reference to the regulation of endogenous RA levels by RA-degrading enzymes.

  2. Interaction of ethanol with retinol and retinoic acid in RAR beta and GAP-43 expression.

    PubMed

    Grummer, M A; Zachman, R D

    2000-01-01

    Fetal ethanol exposure has many detrimental effects on neural development, which possibly occurs through ethanol-induced disruption of the function of vitamin A. In LAN-5 neuroblastoma cells, retinol (10(-6) M) and retinoic acid (RA; 10(-5)-10(-6) M) increased RAR beta mRNA expression. Ethanol downregulated RAR beta levels, even in the presence of retinol. RAR beta mRNA expression was decreased by ethanol in the presence of 10(-6) M RA, but not 10(-5) M RA. With cycloheximide (CX), RA still stimulated RAR beta mRNA, but the effect of ethanol was abolished. The mRNA expression of GAP-43, an important factor in neural development, increased with 10(-6) M retinol and 10(-5)-10(-9) M RA. Ethanol decreased GAP-43 mRNA expression in the presence or absence of retinol. Ethanol was without effect on GAP-43 mRNA at 10(-5) M RA, but did lower the levels at 10(-6) and 10(-7) M RA. CX prevented the effects of both RA and ethanol on GAP-43 mRNA. These studies provide support for the hypothesis that retinoid function is altered by ethanol. PMID:11120388

  3. Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development

    PubMed Central

    Lenti, Elisa; Farinello, Diego; Penkov, Dmitry; Castagnaro, Laura; Lavorgna, Giovanni; Wuputra, Kenly; Tjaden, Naomi E. Butler; Bernassola, Francesca; Caridi, Nicoletta; Wagner, Michael; Kozinc, Katja; Niederreither, Karen; Blasi, Francesco; Pasini, Diego; Trainor, Paul A.

    2016-01-01

    The molecular mechanisms that underlie spleen development and congenital asplenia, a condition linked to increased risk of overwhelming infections, remain largely unknown. The transcription factor TLX1 controls cell fate specification and organ expansion during spleen development, and Tlx1 deletion causes asplenia in mice. Deregulation of TLX1 expression has recently been proposed in the pathogenesis of congenital asplenia in patients carrying mutations of the gene-encoding transcription factor SF-1. Herein, we have shown that TLX1-dependent regulation of retinoic acid (RA) metabolism is critical for spleen organogenesis. In a murine model, loss of Tlx1 during formation of the splenic anlage increased RA signaling by regulating several genes involved in RA metabolism. Uncontrolled RA activity resulted in premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling in Tlx1-deficient animals partially rescued the spleen defect. Finally, spleen growth was impaired in mice lacking either cytochrome P450 26B1 (Cyp26b1), which results in excess RA, or retinol dehydrogenase 10 (Rdh10), which results in RA deficiency. Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insights into the molecular determinants of human congenital asplenia. PMID:27214556

  4. Retinoic acid influences the development of the inferior olivary nucleus in the rodent.

    PubMed

    Yamamoto, Miyuki; Fujinuma, Masahiro; Hirano, Shinji; Hayakawa, Yoshika; Clagett-Dame, Margaret; Zhang, Jinghua; McCaffery, Peter

    2005-04-15

    All-trans retinoic acid (atRA) is an endogenous morphogen that regulates gene transcription. Maternal exposure to atRA results in severe developmental abnormalities by disrupting normal patterns of atRA distribution. Previously, we have shown that the pontine nucleus, which originates from the rhombic lip, is severely atrophied in the mouse on exposure to atRA at gestational days 9 and 10. In this study, we show that this same period of atRA exposure has the contrary effect on the inferior olive and this rhombic lip derivative is expanded in volume and probably contains an increased number of cells. The posterior region of the inferior olive maintains a relatively normal shape but is significantly expanded in size. In contrast, the organization of the anterior inferior olive is severely disrupted. Because endogenous atRA levels are known to be higher in the region of the posterior inferior olive at the time of birth of inferior olivary neurons, these results suggest that endogenous atRA may promote the generation, or select the fate, of posterior neurons of the inferior olive. In support of this concept, a reduction in atRA resulting from vitamin A deficiency results in loss of cells of the posterior inferior olive.

  5. Evidence for the presence of a retinoic acid receptor in rat osteosarcoma cells

    SciTech Connect

    Atkins, K.B.; Beitz, D.C. ); Horst, R.L.; Reinhardt, T.A. )

    1990-02-26

    Research has shown that ROS 17/2.8 cells respond to retinoic acid (RA) and do not express the cellular binding protein (CRABP) for RA. Initial experiments indicated the presence of a cytosolic and nuclear RA-binding activity. Both cytosolic and nuclear extracts were centrifuged (230,000g), and the supernatants labeled with ({sup 3}H)-RA{plus minus}100-fold excess RA. Sucrose gradient analysis of the nuclear extract showed a specific RA-binding activity sedimenting at 3.3S. Scatchard analysis of the nuclear extract showed a single binding component with an apparent K{sub d} of 10{sup {minus}9}M and an estimate of 1,700-3,000 copies/cell. The molecular weight of putative RAR was estimated to be 51KD by gel filtration. The cytosolic RA-binding activity co-sediments (2.0S) on a sucrose gradient with the cytosolic RA-binding activity from rat testis. Scatchard analysis resulted in an apparent Kd of 10{sup {minus}8}M with an estimated 60,000 copies of CRABP/cell. These data indicate ROS 17/2.8 cells express both RAR and CRABP.

  6. Expression and retinoic acid regulation of the zebrafish nr2f orphan nuclear receptor genes

    PubMed Central

    Love, Crystal E.; Prince, Victoria E.

    2012-01-01

    Background The vertebrate nuclear receptor subfamily 2, group f (nr2f) genes encode orphan receptors that have the capacity to act as negative regulators of retinoic acid (RA) signaling. Results We describe embryonic and larval expression of four of the six zebrafish nr2f genes, nr2f1a, nr2f1b, nr2f2 and nr2f5. These genes show highly regulated patterns of expression within the CNS, including in the developing hindbrain, as well as in the mesoderm and endoderm. We also investigated the role of RA and Fgf signaling in regulating early nr2f gene expression. RA is not required for nr2f expression in the hindbrain; however, exogenous RA can repress this expression. Conversely, we find that RA positively regulates nr2f1a expression in trunk endoderm and mesoderm. Fgf signaling is not required for nr2f expression onset in the hindbrain; however, it may play a role in maintaining rhombomere-specific expression. Conclusions We report detailed expression analysis of four nr2f genes in all three germ layers. The onset of nr2f expression in the hindbrain does not require RA or Fgf signals. Our finding that RA positively regulates nr2f1a expression in the trunk supports the possibility that Nr2fs function in a negative feedback loop to modulate RA signaling in this region. PMID:22836912

  7. Retinoic Acid Induced-Autophagic Flux Inhibits ER-Stress Dependent Apoptosis and Prevents Disruption of Blood-Spinal Cord Barrier after Spinal Cord Injury

    PubMed Central

    Zhou, Yulong; Zhang, Hongyu; Zheng, Binbin; Ye, Libing; Zhu, Sipin; Johnson, Noah R; Wang, Zhouguang; Wei, Xiaojie; Chen, Daqing; Cao, Guodong; Fu, Xiaobing; Li, Xiaokun; Xu, Hua-Zi; Xiao, Jian

    2016-01-01

    Spinal cord injury (SCI) induces the disruption of the blood-spinal cord barrier (BSCB) which leads to infiltration of blood cells, an inflammatory response, and neuronal cell death, resulting spinal cord secondary damage. Retinoic acid (RA) has a neuroprotective effect in both ischemic brain injury and SCI, however the relationship between BSCB disruption and RA in SCI is still unclear. In this study, we demonstrated that autophagy and ER stress are involved in the protective effect of RA on the BSCB. RA attenuated BSCB permeability and decreased the loss of tight junction (TJ) molecules such as P120, β-catenin, Occludin and Claudin5 after injury in vivo as well as in Brain Microvascular Endothelial Cells (BMECs). Moreover, RA administration improved functional recovery in the rat model of SCI. RA inhibited the expression of CHOP and caspase-12 by induction of autophagic flux. However, RA had no significant effect on protein expression of GRP78 and PDI. Furthermore, combining RA with the autophagy inhibitor chloroquine (CQ) partially abolished its protective effect on the BSCB via exacerbated ER stress and subsequent loss of tight junctions. Taken together, the neuroprotective role of RA in recovery from SCI is related to prevention of of BSCB disruption via the activation of autophagic flux and the inhibition of ER stress-induced cell apoptosis. These findings lay the groundwork for future translational studies of RA for CNS diseases, especially those related to BSCB disruption. PMID:26722220

  8. Retinoic acid alters the proliferation and survival of the epithelium and mesenchyme and suppresses Wnt/β-catenin signaling in developing cleft palate

    PubMed Central

    Hu, X; Gao, J; Liao, Y; Tang, S; Lu, F

    2013-01-01

    Retinoic acid (RA) contributes to cleft palate; however, the cellular and molecular mechanisms responsible for the deleterious effects on the developing palate are unclear. Wnt signaling is a candidate pathway in the cleft palate and is associated with RA in organ development; thus, we aim to investigate whether RA-induced cleft palate also results from altered Wnt signaling. Administration of RA to mice altered cell proliferation and apoptosis in craniofacial tissues by regulating molecules controlling cell cycle and p38 MAPK signaling, respectively. This altered cell fate by RA is a crucial mechanism contributing to 100% incidence of cleft palate. Moreover, Wnt/β-catenin signaling was completely inhibited by RA in the early developing palate via its binding and activation with RA receptor (RAR) and is responsible for RA-induced cleft palate. Furthermore, PI3K/Akt signaling was also involved in actions of RA. Our findings help in elucidating the mechanisms of RA-induced cleft palate. PMID:24176856

  9. Retinoic acid and dexamethasone affect RAR-beta and surfactant protein C mRNA in the MLE lung cell line.

    PubMed

    Grummer, M A; Zachman, R D

    1998-01-01

    Lung development and surfactant biosynthesis are affected by retinoic acid (RA) and dexamethasone (Dex). Using a mouse lung epithelial cell line, we are exploring RA-Dex interactions through the study of RA and Dex effects on RA receptor (RAR) and surfactant protein (SP) C mRNA expression. RA increased expression of RAR-beta (5.5 times) and SP-C (2 times) mRNA, with maximal effects at 24 h and at 10(-6) M. The RA induction was not inhibited by cycloheximide, suggesting RA affects transcription. With added actinomycin D, RA did not affect the disappearance rate of RAR-beta mRNA, but SP-C mRNA degradation was slowed, indicating an effect on SP-C mRNA stability. Dex decreased RAR-beta and SP-C expression to 75 and 70% of control values, respectively, with greatest effects at 48 h and at 10(-7) M. There was no effect of Dex on either RAR-beta or SP-C mRNA disappearance with actinomycin D. However, cycloheximide prevented the effect of Dex. Despite Dex, RA increased both RAR-beta and SP-C mRNA. This work suggests that RA and Dex affect RAR-beta and SP-C genes by different mechanisms. PMID:9458794

  10. Retinoic Acid Induced-Autophagic Flux Inhibits ER-Stress Dependent Apoptosis and Prevents Disruption of Blood-Spinal Cord Barrier after Spinal Cord Injury.

    PubMed

    Zhou, Yulong; Zhang, Hongyu; Zheng, Binbin; Ye, Libing; Zhu, Sipin; Johnson, Noah R; Wang, Zhouguang; Wei, Xiaojie; Chen, Daqing; Cao, Guodong; Fu, Xiaobing; Li, Xiaokun; Xu, Hua-Zi; Xiao, Jian

    2016-01-01

    Spinal cord injury (SCI) induces the disruption of the blood-spinal cord barrier (BSCB) which leads to infiltration of blood cells, an inflammatory response, and neuronal cell death, resulting spinal cord secondary damage. Retinoic acid (RA) has a neuroprotective effect in both ischemic brain injury and SCI, however the relationship between BSCB disruption and RA in SCI is still unclear. In this study, we demonstrated that autophagy and ER stress are involved in the protective effect of RA on the BSCB. RA attenuated BSCB permeability and decreased the loss of tight junction (TJ) molecules such as P120, β-catenin, Occludin and Claudin5 after injury in vivo as well as in Brain Microvascular Endothelial Cells (BMECs). Moreover, RA administration improved functional recovery in the rat model of SCI. RA inhibited the expression of CHOP and caspase-12 by induction of autophagic flux. However, RA had no significant effect on protein expression of GRP78 and PDI. Furthermore, combining RA with the autophagy inhibitor chloroquine (CQ) partially abolished its protective effect on the BSCB via exacerbated ER stress and subsequent loss of tight junctions. Taken together, the neuroprotective role of RA in recovery from SCI is related to prevention of of BSCB disruption via the activation of autophagic flux and the inhibition of ER stress-induced cell apoptosis. These findings lay the groundwork for future translational studies of RA for CNS diseases, especially those related to BSCB disruption.

  11. Nuclear receptor corepressors Ncor1 and Ncor2 (Smrt) are required for retinoic acid-dependent repression of Fgf8 during somitogenesis.

    PubMed

    Kumar, Sandeep; Cunningham, Thomas J; Duester, Gregg

    2016-10-01

    Retinoic acid (RA) repression of Fgf8 is required for many different aspects of organogenesis, however relatively little is known about how endogenous RA controls gene repression as opposed to gene activation. Here, we show that nuclear receptor corepressors NCOR1 and NCOR2 (SMRT) redundantly mediate the ability of RA to repress Fgf8. Ncor1;Ncor2 double mutants generated by CRISPR/Cas9 gene editing exhibited a small somite and distended heart phenotype similar to that of RA-deficient Raldh2-/- embryos, associated with increased Fgf8 expression and FGF signaling in caudal progenitors and heart progenitors. Embryo chromatin immunoprecipitation studies revealed that NCOR1/2 but not coactivators are recruited to the Fgf8 RA response element (RARE) in an RA-dependent manner, whereas coactivators but not NCOR1/2 are recruited RA-dependently to a RARE near Rarb that is activated by RA. CRISPR/Cas9-mediated genomic deletion of the Fgf8 RARE in mouse embryos often resulted in a small somite defect with Fgf8 derepression caudally, but no defect was observed in heart development or heart Fgf8 expression. This suggests the existence of another DNA element whose function overlaps with the Fgf8 RARE to mediate Fgf8 repression by RA and NCOR1/2. Our studies support a model in which NCOR1/2 mediates direct RA-dependent repression of Fgf8 in caudal progenitors in order to control somitogenesis.

  12. Comparison of the efficacy of three concentrations of retinoic acid for transdifferentiation induction in sheep marrow-derived mesenchymal stem cells into male germ cells.

    PubMed

    Ghasemzadeh-Hasankolaei, M; Eslaminejad, M B; Batavani, R; Sedighi-Gilani, M

    2014-02-01

    Recent studies have shown the unique role of retinoic acid (RA) in the induction of transdifferentiation in mesenchymal stem cells (MSCs) into germ cells (GCs). This study is the first study that compares the efficacy of three different concentrations of RA for the production of male GCs in vitro. Male sheep marrow-derived MSCs (MMSCs) were treated with the following concentrations of RA: 1 μm (RA1), 5 μm (RA2) and 10 μm (RA3) for a period of 21 days. The production of male GCs was evaluated by the assessment of expressions of GC-specific markers (by RT-PCR, qRT-PCR and immunocytochemistry), morphological characteristics and changes in alkaline phosphatase (ALP) activity. All three concentrations created male GC features. RA treatment upregulated the expressions of VASA and beta1 INTEGRIN and downregulated PIWIL2 and OCT4. DAZL was not expressed by RA treatment. Interestingly, immunocytochemistry detected PGP 9.5 expression in all treatment groups, with the highest expression noted in the RA3 group (P < 0.05). GC-like cells along with increased ALP activity were observed in all treated cultures, too. Finally, results showed that 10 μm RA has the most efficiency for transdifferentiation induction in MMSCs and production of male GCs in vitro.

  13. Downregulation of angiotensin II type 1 receptor by all-trans retinoic acid in vascular smooth muscle cells.

    PubMed

    Takeda, K; Ichiki, T; Funakoshi, Y; Ito, K; Takeshita, A

    2000-01-01

    All-trans retinoic acid (atRA) is a biologically active metabolite of vitamin A that plays an important role in cell differentiation and proliferation. Although neointimal formation after balloon injury of rat carotid artery is inhibited by atRA, the mechanisms are not clearly understood. Because the renin-angiotensin system is one of the crucial components of atherosclerosis, we examined the effects of atRA on the expression of angiotensin II type 1 receptor (AT(1)-R) in vascular smooth muscle cells. atRA (1 micromol/L) decreased the AT(1)-R mRNA level by 50% after 24 hours; AT(1)-R number was also reduced to the same extent after 48 hours. atRA markedly suppressed promoter activity of the AT(1)-R promoter-luciferase construct, but AT(1)-R mRNA stability was not affected. Cycloheximide blocked the atRA-induced decrease in AT(1)-R mRNA expression, suggesting that this process requires de novo protein synthesis. Simultaneous treatment with an agonist (Ro40-6055) specific for retinoic acid receptor (RAR) and an agonist (Ro25-7836) specific for retinoid X receptor (RXR) suppressed the AT(1)-R mRNA expression comparable to that with treatment with atRA, suggesting that the RAR/RXR heterodimer mediates the effect of atRA in AT(1)-R downregulation. These results suggest that atRA suppressed AT(1)-R mRNA transcription through new protein synthesis induced by RAR/RXR-dependent transcription. This study provides novel insight into a role of atRA as an important molecule that regulates AT(1)-R gene expression and provides possible mechanisms for the suppression of neointimal formation by atRA.

  14. Nuclear retinoic acid receptors: conductors of the retinoic acid symphony during development.

    PubMed

    Samarut, Eric; Rochette-Egly, Cécile

    2012-01-30

    The vitamin A derivative, retinoic acid (RA), is essential for embryonic development through the activation of cognate nuclear receptors, RARs, which work as ligand dependent regulators of transcription. In vitro studies revealed how RARs control gene expression at the molecular level and now it appears that it is fine-tuned by a phosphorylation code. In addition, several genetic approaches provided valuable insights on the functions of RARs during development and on the influence of other actors such as the enzymes involved in RA synthesis and degradation and other signaling pathways. It appears that RARs are the conductors of the RA signaling symphony through controlling the dynamics and the coordination of the different players and development steps.

  15. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

    PubMed

    Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

    2016-01-01

    Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. PMID:27536103

  16. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

    PubMed Central

    Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

    2016-01-01

    Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. PMID:27536103

  17. Functional Analysis of the Phycomyces carRA Gene Encoding the Enzymes Phytoene Synthase and Lycopene Cyclase

    PubMed Central

    Sanz, Catalina; Velayos, Antonio; Álvarez, María Isabel; Benito, Ernesto P.; Eslava, Arturo P.

    2011-01-01

    Phycomyces carRA gene encodes a protein with two domains. Domain R is characterized by red carR mutants that accumulate lycopene. Domain A is characterized by white carA mutants that do not accumulate significant amounts of carotenoids. The carRA-encoded protein was identified as the lycopene cyclase and phytoene synthase enzyme by sequence homology with other proteins. However, no direct data showing the function of this protein have been reported so far. Different Mucor circinelloides mutants altered at the phytoene synthase, the lycopene cyclase or both activities were transformed with the Phycomyces carRA gene. Fully transcribed carRA mRNA molecules were detected by Northern assays in the transformants and the correct processing of the carRA messenger was verified by RT-PCR. These results showed that Phycomyces carRA gene was correctly expressed in Mucor. Carotenoids analysis in these transformants showed the presence of ß-carotene, absent in the untransformed strains, providing functional evidence that the Phycomyces carRA gene complements the M. circinelloides mutations. Co-transformation of the carRA cDNA in E. coli with different combinations of the carotenoid structural genes from Erwinia uredovora was also performed. Newly formed carotenoids were accumulated showing that the Phycomyces CarRA protein does contain lycopene cyclase and phytoene synthase activities. The heterologous expression of the carRA gene and the functional complementation of the mentioned activities are not very efficient in E. coli. However, the simultaneous presence of both carRA and carB gene products from Phycomyces increases the efficiency of these enzymes, presumably due to an interaction mechanism. PMID:21858003

  18. 224Ra:228Th disequilibrium in coastal sediments: Implications for solute transfer across the sediment-water interface

    NASA Astrophysics Data System (ADS)

    Cai, Pinghe; Shi, Xiangming; Moore, Williard S.; Peng, Shiyun; Wang, Guizhi; Dai, Minhan

    2014-01-01

    We utilized 224Ra/228Th disequilibrium in the sediment to investigate processes that regulate solute transfer across the sediment-water interface. Depth profiles of dissolved and surface-bound 224Ra and 228Th in the upper 0-20 cm sediment column were measured using a delayed coincidence counter during a cruise to the Yangtze estuary from 15 to 24 August 2011. Along with 224Ra and 228Th, depth profiles of 234Th were collected to determine the bioturbation rate in the sediment. At most study sites, a significant deficit of 224Ra relative to 228Th was observed in the upper 0-10 cm. In contrast, 224Ra was in excess with respect to 228Th in the upper 0-5 cm at the river mouth, possibly due to redistribution of 224Ra from the mid-salinity region. By modeling the 224Ra depth profiles in the sediment using the general diagenetic equation, we demonstrated that in most cases molecular diffusion and bioturbation together can account for only ∼20-30% of the measured flux of 224Ra. We concluded that other mechanisms, especially irrigation, must be invoked to explain the remnant 70% of the observed deviation of 224Ra relative to 228Th. On the basis of the 224Ra/228Th disequilibrium in the sediment and a concept of increased surface area for exchange by irrigation as developed by early investigators, we proposed a new approach - the 224Ra/228Th disequilibrium approach to quantify the transfer rate of other dissolved species across the sediment-water interface. We have utilized this new approach to determine the benthic consumption rate of dissolved O2. The result reveals that benthic consumption is an important loss term of dissolved O2 in the Yangtze estuary and must be considered as one of the mechanisms that lead to hypoxia in this area.

  19. RaPAL Bulletin, Numbers 5-13, 1988-1990.

    ERIC Educational Resources Information Center

    RaPAL Bulletin, 1988

    1988-01-01

    This document consists of a 3-year compilation (9 issues) of the RaPAL (Research and Practice in Adult Literacy) Bulletin. Typical articles are: "Student Involvement in Research" (a report of a workshop by Alex Golightly, Nick Nicola, and Marilyn Stone); part of a dialogue between Paolo Freire and Ira Shor, writer/educators of Brazil and the…

  20. Daughter growth in freshly separated Ra-226, Ac-227 and U-232

    NASA Technical Reports Server (NTRS)

    Basile, L. J.; Macias, E. S.; Milstead, J.; Stewart, D. C.

    1969-01-01

    Report provides computer-calculated curves and tables for the daughter buildup of Ra-226, Ac-227 and U-232 chains. Data are presented as a function of time beginning with pure samples of each parent. The information may be of interest to those using decay chains as isotopic alpha sources or neutron sources.

  1. Imaging of Ra-223 with a small-pixel CdTe detector

    NASA Astrophysics Data System (ADS)

    Scuffham, J. W.; Pani, S.; Seller, P.; Sellin, P. J.; Veale, M. C.; Wilson, M. D.; Cernik, R. J.

    2015-01-01

    Ra-223 Dichloride (Xofigo™) is a promising new radiopharmaceutical offering survival benefit and palliation of painful bone metastases in patients with hormone-refractory prostate cancer [1]. The response to radionuclide therapy and toxicity are directly linked to the absorbed radiation doses to the tumour and organs at risk respectively. Accurate dosimetry necessitates quantitative imaging of the biodistribution and kinetics of the radiopharmaceutical. Although primarily an alpha-emitter, Ra-223 also has some low-abundance X-ray and gamma emissions, which enable imaging of the biodistribution in the patient. However, the low spectral resolution of conventional gamma camera detectors makes in-vivo imaging of Ra-223 challenging. In this work, we present spectra and image data of anthropomorphic phantoms containing Ra-223 acquired with a small-pixel CdTe detector (HEXITEC) [2] with a pinhole collimator. Comparison is made with similar data acquired using a clinical gamma camera. The results demonstrate the advantages of the solid state detector in terms of scatter rejection and quantitative accuracy of the images. However, optimised collimation is needed in order for the sensitivity to rival current clinical systems. As different dosage levels and administration regimens for this drug are explored in current clinical trials, there is a clear need to develop improved imaging technologies that will enable personalised treatments to be designed for patients.

  2. Persistence of antibody after subcutaneous vaccination with Wistar RA27/3 rubella vaccine.

    PubMed

    Hillary, I B

    1971-09-01

    After subcutaneous vaccination of rubella sero-negative children with Wistar RA 27/3 rubella vaccine, haemagglutination-inhibiting antibody titres were compared in sera taken 46 days and 2 years after vaccination. Antibody titres were well maintained in the absence of any known exposure to natural infection.

  3. Evolution of the Role of RA and FGF Signals in the Control of Somitogenesis in Chordates.

    PubMed

    Bertrand, Stéphanie; Aldea, Daniel; Oulion, Silvan; Subirana, Lucie; de Lera, Angel R; Somorjai, Ildiko; Escriva, Hector

    2015-01-01

    During vertebrate development, the paraxial mesoderm becomes segmented, forming somites that will give rise to dermis, axial skeleton and skeletal muscles. Although recently challenged, the "clock and wavefront" model for somitogenesis explains how interactions between several cell-cell communication pathways, including the FGF, RA, Wnt and Notch signals, control the formation of these bilateral symmetric blocks. In the cephalochordate amphioxus, which belongs to the chordate phylum together with tunicates and vertebrates, the dorsal paraxial mesendoderm also periodically forms somites, although this process is asymmetric and extends along the whole body. It has been previously shown that the formation of the most anterior somites in amphioxus is dependent upon FGF signalling. However, the signals controlling somitogenesis during posterior elongation in amphioxus are still unknown. Here we show that, contrary to vertebrates, RA and FGF signals act independently during posterior elongation and that they are not mandatory for posterior somites to form. Moreover, we show that RA is not able to buffer the left/right asymmetry machinery that is controlled through the asymmetric expression of Nodal pathway actors. Our results give new insights into the evolution of the somitogenesis process in chordates. They suggest that RA and FGF pathways have acquired specific functions in the control of somitogenesis in vertebrates. We propose that the "clock and wavefront" system was selected specifically in vertebrates in parallel to the development of more complex somite-derived structures but that it was not required for somitogenesis in the ancestor of chordates.

  4. 19. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, 1937 (original print located at Arizona Department of Transportation, Phoenix Az). BRIDGE UNDER CONSTRUCTION. - Cedar Canyon Bridge, Spanning Cedar Canyon at Highway 60, Show Low, Navajo County, AZ

  5. 20. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, 1937 (original print located at Arizona Department of Transportation, Phoenix AZ). BRIDGE UNDER CONSTRUCTION. - Cedar Canyon Bridge, Spanning Cedar Canyon at Highway 60, Show Low, Navajo County, AZ

  6. 21. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, 3 June 1937 (original print located at Arizona Department of Transportation, Phoenix AZ). BRIDGE UNDER CONSTRUCTION. - Cedar Canyon Bridge, Spanning Cedar Canyon at Highway 60, Show Low, Navajo County, AZ

  7. 22. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, 1937 (original print located at Arizona Department of Transportation, Phoenix AZ). BRIDGE SOON AFTER COMPLETION. - Cedar Canyon Bridge, Spanning Cedar Canyon at Highway 60, Show Low, Navajo County, AZ

  8. 21. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, 1937 (original print located at Arizona Department of Transportation, Phoenix AZ). BRIDGE UNDER CONSTRUCTION. - Corduroy Creek Bridge, Spanning Corduroy Creek at Highway 60, Show Low, Navajo County, AZ

  9. 22. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, 1937 (original print located at Arizona Department of Transportation, Phoenix AZ). BRIDGE SOON AFTER COMPLETION. - Corduroy Creek Bridge, Spanning Corduroy Creek at Highway 60, Show Low, Navajo County, AZ

  10. 18. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, 28 May 1937 (original print located at Arizona Department of Transportation, Phoenix AZ). BRIDGE UNDER CONSTRUCTION. - Cedar Canyon Bridge, Spanning Cedar Canyon at Highway 60, Show Low, Navajo County, AZ

  11. 17. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, 1937 (original print located at Arizona Department of Transportation, Phoenix AZ). BRIDGE UNDER CONSTRUCTION. - Cedar Canyon Bridge, Spanning Cedar Canyon at Highway 60, Show Low, Navajo County, AZ

  12. 7 CFR 1940.576 - Rental Assistance (RA) for new construction.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 13 2013-01-01 2013-01-01 false Rental Assistance (RA) for new construction. 1940.576 Section 1940.576 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED)...

  13. 7 CFR 1940.577 - Rental Assistance (RA) for existing projects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 13 2013-01-01 2013-01-01 false Rental Assistance (RA) for existing projects. 1940.577 Section 1940.577 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED)...

  14. 39. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    39. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, ca. July 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). ASSEMBLY OF TRAVELER ON NORTH ARM, SHOWING TEMPORARY TIEBACKS AND ANCHORAGE ARMS. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  15. 34. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    34. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, ca. May 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). CONSTRUCTION ON EIGHT PANEL OF SOUTH ARM. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  16. 41. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, 12 September 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). INSERTION OF CENTER PIN. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  17. 38. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, ca. July 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). VIEW FROM CANYON OF THIRD PANEL OF NORTH ARM UNDER CONSTRUCTION. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  18. 32. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, April 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). CONSTRUCTION OF SOUTH ARM. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  19. 33. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, ca. May 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). CONSTRUCTION OF SOUTH ARM, SHOWING ERECTION TRAVELER. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  20. 31. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    31. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, April 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). INITIAL CONSTRUCTION ON SOUTH ARM. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  1. 36. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    36. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, June 1928 (original print located at Arizona Department of Transportation, Phoenix AZ) COMPLETION OF SOUTH ARM. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  2. 40. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    40. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, ca. July 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). CONSTRUCTION OF NORTH ARM, FROM SOUTH ARM. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  3. 37. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    37. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, ca. July 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). CONSTRUCTION ON THIRD PANEL OF NORTH ARM. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  4. 35. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    35. Photocopy of photograph, R.A. Hoffman, Bridge Engineer, Arizona Highway Department, photographer, June 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). ELEVENTH (LAST) PANEL OF SOUTH ARM UNDER CONSTRUCTION, SHOWING ERECTION TRAVELER. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  5. Ra-Th disequilibria systematics: Timescale of carbonatite magma formation at Oldoinyo Lengai volcano, Tanzania

    NASA Astrophysics Data System (ADS)

    Williams, Ross W.; Gill, James B.; Bruland, Kenneth W.

    1986-06-01

    Carbonatite magma can form and erupt within 7 to 18 years, and the event seems associated with prior volcanic eruptions. This determination of magma age is possible because the carbonatite lava and ash which were erupted in 1960-1966 from Oldoinyo Lengai volcano, Tanzania, have the most extreme disequilibria between U and Th series nuclides yet measured in volcanic rocks. At the time of eruption: ( 228Ra) /( 232Th) ≈ 27 and ( 226Ra) /( 230Th) > 60 ; ( 238U) /( 232Th) > 10 , while ( 232Th) /( 232Th) = 1.0 ; and ( 210Pb) /( 226Ra) ≈ 0.3 . Three end-member models are presented which enable interpretation of these disequilibria. If the disequilibrium formed instantaneously, the event occurred about 7 years before initial eruption, and just before the last preceding but small eruption of Oldoinyo Lengai. If, instead, the disequilibrium formed continuously, the process must have begun 15 to 18 years before initial eruption, just after the last preceding major eruption. The disequilibria data confirm that the carbonatites are not fused trona, but do not distinguish between other genetic options (mantle fusion, selective assimilation, liquid immiscibility). However, the shortness of magma-formation time together with mass-balance considerations suggest formation due to the continuous exsolution of 2 to 20% of carbonatite from nephelinite which was itself Ra-enriched.

  6. 24 CFR 599.505 - Coordinating responsible authority (CoRA).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES RENEWAL COMMUNITIES Post-Designation... 24 Housing and Urban Development 3 2012-04-01 2012-04-01 false Coordinating responsible authority (CoRA). 599.505 Section 599.505 Housing and Urban Development Regulations Relating to Housing...

  7. 24 CFR 599.505 - Coordinating responsible authority (CoRA).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES RENEWAL COMMUNITIES Post-Designation... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Coordinating responsible authority (CoRA). 599.505 Section 599.505 Housing and Urban Development Regulations Relating to Housing...

  8. 24 CFR 599.505 - Coordinating responsible authority (CoRA).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES RENEWAL COMMUNITIES Post-Designation... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Coordinating responsible authority (CoRA). 599.505 Section 599.505 Housing and Urban Development Regulations Relating to Housing...

  9. 24 CFR 599.505 - Coordinating responsible authority (CoRA).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES RENEWAL COMMUNITIES Post-Designation... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Coordinating responsible authority (CoRA). 599.505 Section 599.505 Housing and Urban Development Regulations Relating to Housing...

  10. 24 CFR 599.505 - Coordinating responsible authority (CoRA).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES RENEWAL COMMUNITIES Post-Designation... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Coordinating responsible authority (CoRA). 599.505 Section 599.505 Housing and Urban Development Regulations Relating to Housing...

  11. Active phagocytosis of Mycobacterium tuberculosis (H37Ra) by T lymphocytes (Jurkat cells).

    PubMed

    Zhang, Min; Zhu, Qi; Shi, Ming; Liu, Yang; Ma, Lei; Yang, Yining; Feng, Dongyun; Dai, Wen; Zhang, Lin; Kang, Tao; Chen, Ping; He, Ying; Liu, Tingting; Zhao, Qing; Wang, Wenjing; Zhi, Jin; Feng, Guodong; Zhao, Gang

    2015-08-01

    This study aimed to co-culture Jurkat T lymphocytes with inactivated Mycobacterium tuberculosis (Mtb H37Ra), explore whether T lymphocytes could phagocytose H37Ra cells, and determine the underlying mechanism. Jurkat T lymphocytes were co-cultured with H37Ra cells, and confocal laser scanning microscopy, electron microscopy, and flow cytometry techniques were used to identify phagocytosis and elucidate its mechanism. After Jurkat T lymphocytes phagocytosed H37Ra cells, the cell body became larger, with abundant cytoplasm, the portion of the nucleus closest to the bacterium deformed, long and short pseudopodia were extended, and the folds of the cell membrane formed depressions that created phagocytic vesicles surrounding the bacterium. The macropinocytosis inhibitor amiloride and the cytoskeletal inhibitor cytochalasin D were found to inhibit phagocytic efficacy; serum complements might enhance phagocytosis through opsonization. Jurkat T lymphocytes could actively phagocytose inactivated Mtb via the macropinocytotic mechanism. Actin remodeling played an important role in the macropinocytotic process. Serum complements may regulate phagocytosis.

  12. Evolution of the Role of RA and FGF Signals in the Control of Somitogenesis in Chordates

    PubMed Central

    Bertrand, Stéphanie; Aldea, Daniel; Oulion, Silvan; Subirana, Lucie; de Lera, Angel R.; Somorjai, Ildiko; Escriva, Hector

    2015-01-01

    During vertebrate development, the paraxial mesoderm becomes segmented, forming somites that will give rise to dermis, axial skeleton and skeletal muscles. Although recently challenged, the "clock and wavefront" model for somitogenesis explains how interactions between several cell-cell communication pathways, including the FGF, RA, Wnt and Notch signals, control the formation of these bilateral symmetric blocks. In the cephalochordate amphioxus, which belongs to the chordate phylum together with tunicates and vertebrates, the dorsal paraxial mesendoderm also periodically forms somites, although this process is asymmetric and extends along the whole body. It has been previously shown that the formation of the most anterior somites in amphioxus is dependent upon FGF signalling. However, the signals controlling somitogenesis during posterior elongation in amphioxus are still unknown. Here we show that, contrary to vertebrates, RA and FGF signals act independently during posterior elongation and that they are not mandatory for posterior somites to form. Moreover, we show that RA is not able to buffer the left/right asymmetry machinery that is controlled through the asymmetric expression of Nodal pathway actors. Our results give new insights into the evolution of the somitogenesis process in chordates. They suggest that RA and FGF pathways have acquired specific functions in the control of somitogenesis in vertebrates. We propose that the "clock and wavefront" system was selected specifically in vertebrates in parallel to the development of more complex somite-derived structures but that it was not required for somitogenesis in the ancestor of chordates. PMID:26371756

  13. Self-cleaning in an estuarine area formerly affected by 226Ra anthropogenic enhancements.

    PubMed

    Absi, A; Villa, M; Moreno, H P; Manjón, G; Periañez, R

    2004-08-15

    The estuary of the Odiel River has been affected by both direct discharges of phosphogypsum (radium enriched industrial waste) and dissolution and weathering of the exposed piles where this radium enriched waste was stored. In 1998 the waste management policy for industries changed. The direct discharges stopped and the new phosphogypsum piles were well protected against dissolution processes, avoiding any transference of radium into the environment. This work presents a study of the evolution with time (1999-2002) of the levels of 226Ra in river water and sediment samples with the new waste management policy. A liquid scintillation technique was used to measure the 226Ra activity concentration in sediment samples. A gas-proportional counter was also used to measure the 226Ra activity concentration in river water samples. The main conclusion is that a systematic and continuous decrease of the activity concentration of 226Ra with time in the Odiel River estuary is occurring. Thus, a possible self-cleaning in the estuary, once the direct waste discharges were avoided, can be inferred.

  14. Evolution of the Role of RA and FGF Signals in the Control of Somitogenesis in Chordates.

    PubMed

    Bertrand, Stéphanie; Aldea, Daniel; Oulion, Silvan; Subirana, Lucie; de Lera, Angel R; Somorjai, Ildiko; Escriva, Hector

    2015-01-01

    During vertebrate development, the paraxial mesoderm becomes segmented, forming somites that will give rise to dermis, axial skeleton and skeletal muscles. Although recently challenged, the "clock and wavefront" model for somitogenesis explains how interactions between several cell-cell communication pathways, including the FGF, RA, Wnt and Notch signals, control the formation of these bilateral symmetric blocks. In the cephalochordate amphioxus, which belongs to the chordate phylum together with tunicates and vertebrates, the dorsal paraxial mesendoderm also periodically forms somites, although this process is asymmetric and extends along the whole body. It has been previously shown that the formation of the most anterior somites in amphioxus is dependent upon FGF signalling. However, the signals controlling somitogenesis during posterior elongation in amphioxus are still unknown. Here we show that, contrary to vertebrates, RA and FGF signals act independently during posterior elongation and that they are not mandatory for posterior somites to form. Moreover, we show that RA is not able to buffer the left/right asymmetry machinery that is controlled through the asymmetric expression of Nodal pathway actors. Our results give new insights into the evolution of the somitogenesis process in chordates. They suggest that RA and FGF pathways have acquired specific functions in the control of somitogenesis in vertebrates. We propose that the "clock and wavefront" system was selected specifically in vertebrates in parallel to the development of more complex somite-derived structures but that it was not required for somitogenesis in the ancestor of chordates. PMID:26371756

  15. ETV Report: Siemens Model V-40R-A150 Open Channel UV System

    EPA Science Inventory

    Verification testing of the Siemens Barrier Sunlight V-40R-A150 UV System was completed at the UV Validation and Research Center of New York (UV Center), located in Johnstown, NY. The V-40R System supplied by Siemens utilizes 40 high-output, low-pressure amalgam lamps, oriented ...

  16. A new two-phase media method for 226Ra activity measurement in water.

    PubMed

    Sohrabi, M; Khodadadi, F

    2015-06-01

    A new two-phase media method was developed for determination of (226)Ra activity in water. The method was calibrated by applying 7 standard (226)Ra waters with known activities. The method detects alphas in two media; 80 ml of water in a glass bottle with air or a non-polar liquid such as olive oil on top of the water. Alpha particles from (226)Ra, (222)Rn and progeny were detected by two polycarbonate track detectors (PCTDs) which were mounted on a holder inserted in the bottle so that one PCTD is placed in water and the other in air or in the non-polar liquid. The bottles were hermetically sealed and kept for 40 or 48 d. The PCTDs in the bottles shaken every other day enhanced the sensitivity of the measurements. The Calibration Factors for the standard (226)Ra waters, air and olive oil above water are, respectively, (7.85 ± 0.25) × 10(-3), (7.94 ± 0.13) × 10(-3) and 3.02 × 10(-2) tracks.cm(-2) kBq(-1) h(-1) m(3). PMID:25971343

  17. Supply of purified Th228 for Ra224 generators. Final CRADA Report .

    SciTech Connect

    Ehst, D. A.; Nuclear Engineering Division

    2009-10-02

    CRADA was terminated when it was determined that the Russians could not perform the terms of the subcontract. It became apparent that the Russians would not be a reliable source of Th228, as a precursor in the decay chain which leads to Ra224. Their government policies will prohibit the export of Th228 in quantities needed for commercial cancer therapy.

  18. ALTERED RA SIGNALING IN THE GENESIS OF ETHANOL-INDUCED LIMB DEFECTS

    EPA Science Inventory

    Altered RA Signaling in the Genesis of Ethanol-Induced Limb Defects

    Johnson CS(1), Sulik KK(1,2) Hunter, ES III(3)
    (1) Dept of Cell and Developmental Biology, UNC-Chapel Hill (2) Bowles Center for Alcohol Studies, UNC-CH (3) NHEERL, ORD, US EPA, RTP, NC

    Administr...

  19. Retinoic Acid Upregulates Preadipocyte Genes to Block Adipogenesis and Suppress Diet-Induced Obesity

    PubMed Central

    Berry, Daniel C.; DeSantis, David; Soltanian, Hooman; Croniger, Colleen M.; Noy, Noa

    2012-01-01

    Retinoic acid (RA) protects mice from diet-induced obesity. The activity is mediated in part through activation of the nuclear receptors RA receptors (RARs) and peroxisome proliferator–activated receptor β/δ and their associated binding proteins cellular RA binding protein type II (CRABP-II) and fatty acid binding protein type 5 in adipocytes and skeletal muscle, leading to enhanced lipid oxidation and energy dissipation. It was also reported that RA inhibits differentiation of cultured preadipocytes. However, whether the hormone suppresses adipogenesis in vivo and how the activity is propagated remained unknown. In this study, we show that RA inhibits adipocyte differentiation by activating the CRABP-II/RARγ path in preadipose cells, thereby upregulating the expression of the adipogenesis inhibitors Pref-1, Sox9, and Kruppel-like factor 2 (KLF2). In turn, KLF2 induces the expression of CRABP-II and RARγ, further potentiating inhibition of adipocyte differentiation by RA. The data also indicate that RA suppresses adipogenesis in vivo and that the activity significantly contributes to the ability of the hormone to counteract diet-induced obesity. PMID:22396202

  20. Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times.

    PubMed

    Xavier-Neto, José; Sousa Costa, Ângela M; Figueira, Ana Carolina M; Caiaffa, Carlo Donato; Amaral, Fabio Neves do; Peres, Lara Maldanis Cerqueira; da Silva, Bárbara Santos Pires; Santos, Luana Nunes; Moise, Alexander R; Castillo, Hozana Andrade

    2015-02-01

    Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested evidence for the pleiotropic roles of RA signaling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signaling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signaling is exquisitely regulated according to specific phases of cardiac development and that RA signaling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signaling by RA receptors (RARs) in early phases of heart development. This article is part of a Special Issue entitled: Nuclear receptors in animal development.

  1. SIGNALLING THROUGH RETINOIC ACID RECEPTORS IN CARDIAC DEVELOPMENT: DOING THE RIGHT THINGS AT THE RIGHT TIMES

    PubMed Central

    Xavier-Neto, José; Costa, Ângela M. Sousa; Figueira, Ana Carolina M.; Caiaffa, Carlo Donato; do Amaral, Fabio Neves; Peres, Lara Maldanis Cerqueira; da Silva, Bárbara Santos Pires; Santos, Luana Nunes; Moise, Alexander R.; Castillo, Hozana Andrade

    2015-01-01

    Retinoic acid (RA) is a terpenoid that is synthesized from Vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinic and experimental data provide uncontested evidence for the pleiotropic roles of RA signalling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signalling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signalling is exquisitely regulated according to specific phases of cardiac development and that RA signalling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signalling by RA receptors (RARs) in early phases of heart development. PMID:25134739

  2. Ψ-RA: a parallel sparse index for genomic read alignment

    PubMed Central

    2011-01-01

    Background Genomic read alignment involves mapping (exactly or approximately) short reads from a particular individual onto a pre-sequenced reference genome of the same species. Because all individuals of the same species share the majority of their genomes, short reads alignment provides an alternative and much more efficient way to sequence the genome of a particular individual than does direct sequencing. Among many strategies proposed for this alignment process, indexing the reference genome and short read searching over the index is a dominant technique. Our goal is to design a space-efficient indexing structure with fast searching capability to catch the massive short reads produced by the next generation high-throughput DNA sequencing technology. Results We concentrate on indexing DNA sequences via sparse suffix arrays (SSAs) and propose a new short read aligner named Ψ-RA (PSI-RA: parallel sparse index read aligner). The motivation in using SSAs is the ability to trade memory against time. It is possible to fine tune the space consumption of the index based on the available memory of the machine and the minimum length of the arriving pattern queries. Although SSAs have been studied before for exact matching of short reads, an elegant way of approximate matching capability was missing. We provide this by defining the rightmost mismatch criteria that prioritize the errors towards the end of the reads, where errors are more probable. Ψ-RA supports any number of mismatches in aligning reads. We give comparisons with some of the well-known short read aligners, and show that indexing a genome with SSA is a good alternative to the Burrows-Wheeler transform or seed-based solutions. Conclusions Ψ-RA is expected to serve as a valuable tool in the alignment of short reads generated by the next generation high-throughput sequencing technology. Ψ-RA is very fast in exact matching and also supports rightmost approximate matching. The SSA structure that Ψ-RA is built

  3. RaInCube: a proposed constellation of precipitation profiling Radars In Cubesat

    NASA Astrophysics Data System (ADS)

    Peral, E.; Tanelli, S.; Haddad, Z. S.; Stephens, G. L.; Im, E.

    2014-12-01

    Precipitation radars in Low-Earth-Orbit provide vertically resolved profiles of rain and snow on a global scale. With the recent advances in miniaturized radar and CubeSat/SmallSat technologies, it would now be feasible to launch multiple copies of the same radar instrument in desirable formations to allow measurements of short time scale evolution of atmospheric processes. One such concept is the novel radar architecture compatible with the 6U CubeSat class that is being developed at JPL by exploiting simplification and miniaturization of the radar subsystems. The RaInCube architecture would significantly reduce the number of components, power consumption and mass with respect to existing spaceborne radars. The baseline RaInCube instrument configuration would be a fixed nadir-pointing profiler at Ka-band with a minimum detectable reflectivity better than +10 dBZ at 250m range resolution and 5 km horizontal resolution. The low cost nature of the RaInCube platform would enable deployment of a constellation of identical copies of the same instrument in various relative positions in LEO to address specific observational gaps left open by the current missions that require high-resolution vertical profiling capability. A constellation of only four RaInCubes would populate the precipitation statistics in a distributed fashion across the globe and across the times of day, and therefore, would enable substantially better sampling of the diurnal cycle statistics. One could extend this scheme by adding more RaInCubes in each of the orbital planes, and phase them once in orbit so that they would be separated by an arbitrary amount of time among them. Wide separations (say 20-30 min) would further extend the sampling of the diurnal cycle to sub-hourly scales. Narrower time separations between RaInCubes would allow studying the evolution of convective systems at the convective time scale in each region of interest and would reveal the dominant modes of evolution of each

  4. Association of the IL2RA/CD25 Gene With Juvenile Idiopathic Arthritis

    PubMed Central

    Hinks, Anne; Ke, Xiayi; Barton, Anne; Eyre, Steve; Bowes, John; Worthington, Jane; Thompson, Susan D; Langefeld, Carl D; Glass, David N; Thomson, Wendy

    2009-01-01

    Objective IL2RA/CD25, the gene for interleukin-2 receptor α, is emerging as a general susceptibility gene for autoimmune diseases because of its role in the development and function of regulatory T cells and the association of single-nucleotide polymorphisms (SNPs) within this gene with type 1 diabetes mellitus (DM), Graves' disease, rheumatoid arthritis (RA), and multiple sclerosis (MS). The aim of this study was to determine whether SNPs within the IL2RA/CD25 gene are associated with juvenile idiopathic arthritis (JIA). Methods Three SNPs within the IL2RA/CD25 gene, that previously showed evidence of an association with either RA, MS, or type 1 DM, were selected for genotyping in UK JIA cases (n = 654) and controls (n = 3,849). Data for 1 SNP (rs2104286) were also available from North American JIA cases (n = 747) and controls (n = 1,161). Association analyses were performed using Plink software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results SNP rs2104286 within the IL2RA/CD25 gene was significantly associated with UK JIA cases (OR for the allele 0.76 [95% CI 0.66–0.88], P for trend = 0.0002). A second SNP (rs41295061) also showed modest evidence for association with JIA (OR 0.80 [95% CI 0.63–1.0], P = 0.05). Association with rs2104286 was convincingly replicated in the North American JIA cohort (OR 0.84 [95% CI 0.65–0.99], P for trend = 0.05). Meta-analysis of the 2 cohorts yielded highly significant evidence of association with JIA (OR 0.76 [95% CI 0.62–0.88], P = 4.9 × 10−5). Conclusion These results provide strong evidence that the IL2RA/CD25 gene represents a JIA susceptibility locus. Further investigation of the gene using both genetic and functional approaches is now required. PMID:19116909

  5. Evolution of rosmarinic acid biosynthesis.

    PubMed

    Petersen, Maike; Abdullah, Yana; Benner, Johannes; Eberle, David; Gehlen, Katja; Hücherig, Stephanie; Janiak, Verena; Kim, Kyung Hee; Sander, Marion; Weitzel, Corinna; Wolters, Stefan

    2009-01-01

    Rosmarinic acid and chlorogenic acid are caffeic acid esters widely found in the plant kingdom and presumably accumulated as defense compounds. In a survey, more than 240 plant species have been screened for the presence of rosmarinic and chlorogenic acids. Several rosmarinic acid-containing species have been detected. The rosmarinic acid accumulation in species of the Marantaceae has not been known before. Rosmarinic acid is found in hornworts, in the fern family Blechnaceae and in species of several orders of mono- and dicotyledonous angiosperms. The biosyntheses of caffeoylshikimate, chlorogenic acid and rosmarinic acid use 4-coumaroyl-CoA from the general phenylpropanoid pathway as hydroxycinnamoyl donor. The hydroxycinnamoyl acceptor substrate comes from the shikimate pathway: shikimic acid, quinic acid and hydroxyphenyllactic acid derived from l-tyrosine. Similar steps are involved in the biosyntheses of rosmarinic, chlorogenic and caffeoylshikimic acids: the transfer of the 4-coumaroyl moiety to an acceptor molecule by a hydroxycinnamoyltransferase from the BAHD acyltransferase family and the meta-hydroxylation of the 4-coumaroyl moiety in the ester by a cytochrome P450 monooxygenase from the CYP98A family. The hydroxycinnamoyltransferases as well as the meta-hydroxylases show high sequence similarities and thus seem to be closely related. The hydroxycinnamoyltransferase and CYP98A14 from Coleus blumei (Lamiaceae) are nevertheless specific for substrates involved in RA biosynthesis showing an evolutionary diversification in phenolic ester metabolism. Our current view is that only a few enzymes had to be "invented" for rosmarinic acid biosynthesis probably on the basis of genes needed for the formation of chlorogenic and caffeoylshikimic acid while further biosynthetic steps might have been recruited from phenylpropanoid metabolism, tocopherol/plastoquinone biosynthesis and photorespiration. PMID:19560175

  6. Evolution of rosmarinic acid biosynthesis.

    PubMed

    Petersen, Maike; Abdullah, Yana; Benner, Johannes; Eberle, David; Gehlen, Katja; Hücherig, Stephanie; Janiak, Verena; Kim, Kyung Hee; Sander, Marion; Weitzel, Corinna; Wolters, Stefan

    2009-01-01

    Rosmarinic acid and chlorogenic acid are caffeic acid esters widely found in the plant kingdom and presumably accumulated as defense compounds. In a survey, more than 240 plant species have been screened for the presence of rosmarinic and chlorogenic acids. Several rosmarinic acid-containing species have been detected. The rosmarinic acid accumulation in species of the Marantaceae has not been known before. Rosmarinic acid is found in hornworts, in the fern family Blechnaceae and in species of several orders of mono- and dicotyledonous angiosperms. The biosyntheses of caffeoylshikimate, chlorogenic acid and rosmarinic acid use 4-coumaroyl-CoA from the general phenylpropanoid pathway as hydroxycinnamoyl donor. The hydroxycinnamoyl acceptor substrate comes from the shikimate pathway: shikimic acid, quinic acid and hydroxyphenyllactic acid derived from l-tyrosine. Similar steps are involved in the biosyntheses of rosmarinic, chlorogenic and caffeoylshikimic acids: the transfer of the 4-coumaroyl moiety to an acceptor molecule by a hydroxycinnamoyltransferase from the BAHD acyltransferase family and the meta-hydroxylation of the 4-coumaroyl moiety in the ester by a cytochrome P450 monooxygenase from the CYP98A family. The hydroxycinnamoyltransferases as well as the meta-hydroxylases show high sequence similarities and thus seem to be closely related. The hydroxycinnamoyltransferase and CYP98A14 from Coleus blumei (Lamiaceae) are nevertheless specific for substrates involved in RA biosynthesis showing an evolutionary diversification in phenolic ester metabolism. Our current view is that only a few enzymes had to be "invented" for rosmarinic acid biosynthesis probably on the basis of genes needed for the formation of chlorogenic and caffeoylshikimic acid while further biosynthetic steps might have been recruited from phenylpropanoid metabolism, tocopherol/plastoquinone biosynthesis and photorespiration.

  7. Retinoic acid signaling in cancer: The parable of acute promyelocytic leukemia.

    PubMed

    Ablain, Julien; de Thé, Hugues

    2014-11-15

    Inevitably fatal some 40 years, acute promyelocytic leukemia (APL) can now be cured in more than 95% of cases. This clinical success story is tightly linked to tremendous progress in our understanding of retinoic acid (RA) signaling. The discovery of retinoic acid receptor alpha (RARA) was followed by the cloning of the chromosomal translocations driving APL, all of which involve RARA. Since then, new findings on the biology of nuclear receptors have progressively enlightened the basis for the clinical efficacy of RA in APL. Reciprocally, the disease offered a range of angles to approach the cellular and molecular mechanisms of RA action. This virtuous circle contributed to make APL one of the best-understood cancers from both clinical and biological standpoints. Yet, some important questions remain unanswered including how lessons learnt from RA-triggered APL cure can help design new therapies for other malignancies. PMID:25130873

  8. Retinoic acid signaling in cancer: The parable of acute promyelocytic leukemia.

    PubMed

    Ablain, Julien; de Thé, Hugues

    2014-11-15

    Inevitably fatal some 40 years, acute promyelocytic leukemia (APL) can now be cured in more than 95% of cases. This clinical success story is tightly linked to tremendous progress in our understanding of retinoic acid (RA) signaling. The discovery of retinoic acid receptor alpha (RARA) was followed by the cloning of the chromosomal translocations driving APL, all of which involve RARA. Since then, new findings on the biology of nuclear receptors have progressively enlightened the basis for the clinical efficacy of RA in APL. Reciprocally, the disease offered a range of angles to approach the cellular and molecular mechanisms of RA action. This virtuous circle contributed to make APL one of the best-understood cancers from both clinical and biological standpoints. Yet, some important questions remain unanswered including how lessons learnt from RA-triggered APL cure can help design new therapies for other malignancies.

  9. Inhibition of ultraviolet-induced carcinogenesis by all-trans retinoic acid

    SciTech Connect

    Epstein, J.H.; Grekin, D.A.

    1981-03-01

    The effects of all-trans retinoic acid (RA) in 0.05%, 0.025% and 0.005% concentrations on ultraviolet (UV) induced carcinogenesis was investigated in the skin of Uscd strain hairless mice. A carcinogenic amount of UV energy was delivered over the 12-mo period of the study. The 0.025% and 0.005% RA solutions did not alter the development of cutaneous cancers. However, the 0.05% RA concentration significantly inhibited the tumor formation in this study.

  10. A comparison of the natural survival of beagle dogs injected intravenously with low levels of 239Pu, 226Ra, 228Ra, 228Th, or 90Sr.

    PubMed

    Bruenger, F W; Miller, S C; Lloyd, R D

    1991-06-01

    The natural survival, relative to properly chosen controls, of 26 beagle dogs injected once intravenously with an average of 0.58 +/- 0.04 kBq 239Pu/kg, 23 dogs injected with 2.31 +/- 0.43 kBq 226Ra/kg, 13 dogs injected with 1.84 +/- 0.26 kBq 228Ra/kg, 12 dogs injected with 0.56 +/- 0.030 kBq 228Th/kg, and 12 dogs injected with 21.13 +/- 1.74 kBq 90Sr/kg was evaluated statistically. The amounts of these radionuclides are related directly to the estimated maximum permissible body burdens for humans suggested in ICRP II (1959). They constitute a level of exposure that initially was assumed to cause no deleterious effects in dogs. This study had two objectives: (1) identification of homogeneous control groups against which to evaluate the survival of the irradiated groups and (2) comparison of the survival characteristics and estimation of mortality or hazard rate ratios for control dogs vs dogs injected with the baseline dosages given above. It was shown, by goodness-of-fit plots, that the Cox proportional hazards model was an appropriate method of analysis. Therefore, covariates that possibly could influence survival were tested for significance. Only the effects of grand mal seizure, which is caused in epileptic dogs by an external stimulus and can be fatal if untreated, were significant (P less than 0.0001). Consequently, in the final model, death from grand mal seizure was considered as accidental. After censoring the dogs dying from grand mal seizure, it was established that the data for the control groups from previous and contemporary experiments could be pooled. The change in hazard rates relative to controls resulting from exposure to the baseline radionuclide level was modest, 1.6 times for 239Pu (P = 0.033), 1.0(4) for 226Ra (P = 0.86), 1.9 for 228Ra (P = 0.035), 2.5 for 228Th (P less than 0.001), and 0.52 for 90Sr (P = 0.041). Bone tumor induction was clearly elevated in dogs injected with 239Pu and 228Th. When the effect of these bone tumors on survival

  11. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity

    PubMed Central

    Kane, Maureen A.; Folias, Alexandra E.; Wang, Chao; Napoli, Joseph L.

    2010-01-01

    All-trans-retinoic acid (atRA) supports embryonic development, central nervous system function, and the immune response. atRA initiates neurogenesis and dendritic growth in the hippocampus and is required for spatial memory; superphysiological atRA inhibits neurogenesis, causes teratology and/or embryo toxicity, and alters cognitive function and behavior. Because abnormal atRA shares pathological conditions with alcoholism, inhibition of retinol (vitamin A) activation into atRA has been credited widely as a mechanism of ethanol toxicity. Here, we analyze the effects of ethanol on retinoid concentrations in vivo during normal vitamin A nutriture, using sensitive and analytically robust assays. Ethanol either increased or had no effect on atRA, regardless of changes in retinol and retinyl esters. Acute ethanol (3.5 g/kg) increased atRA in adult hippocampus (1.6-fold), liver (2.4-fold), and testis (1.5-fold). Feeding dams a liquid diet with 6.5% ethanol from embryonic day 13 (e13) to e19 increased atRA in fetal hippocampus (up to 20-fold) and cortex (up to 50-fold), depending on blood alcohol content. One-month feeding of the 6.5% ethanol diet increased atRA in adult hippocampus (20-fold), cortex (2-fold), testis (2-fold), and serum (10-fold). Tissue-specific increases in retinoid dehydrogenase mRNAs and activities, extrahepatic retinol concentrations, and atRA catabolism combined to produce site-specific effects. Because a sustained increase in atRA has deleterious effects on the central nervous system and embryo development, these data suggest that superphysiological atRA contributes to ethanol pathological conditions, including cognitive dysfunction and fetal alcohol syndrome.—Kane, M. A., Folias, A. E., Wang, C., Napoli, J. L. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity. PMID:19890016

  12. Human Alveolar Macrophage Gene Responses to Mycobacterium tuberculosis Strains H37Ra and H37Rv

    PubMed Central

    Silver, Richard F.; Walrath, Jessica; Lee, Hung; Jacobson, Bruce A.; Horton, Heidi; Bowman, Michael R.; Nocka, Karl; Sypek, Joseph P.

    2009-01-01

    H37Rv and H37Ra have been widely used as models of virulent and avirulent strains, respectively, of Mycobacterium tuberculosis. Since the sequencing of H37Rv, microarrays have been used to investigate gene expression of M. tuberculosis strains under various conditions, and to compare gene expression of specific isolates of the organism. Because differences in the virulence of these organisms could also be manifest via their differential induction of host genes, we used Affymetrix Human Genome Arrays U133A and U133B to evaluate human alveolar macrophage (AM) responses to infection with H37Rv and H37Ra. H37Rv altered expression of far more genes than did H37Ra. Moreover, the genes induced by H37Rv to a greater extent than by H37Ra were predominantly associated with the development of effective immunity. H37Rv markedly increased expression of IL-23 p19, whereas neither organism significantly induced IL-12 p35 expression. Quantitative PCR confirmed that H37Rv induced significantly more AM p19 expression than did H37Ra. After low-level infection of both AM and peripheral blood monocytes (MN) with H37Rv, neither cell type produced IL-12 (by ELISA). In contrast, AM displayed significant IL-23 production in response to H37Rv, whereas MN did not. Our findings thus suggest an important role for IL-23 in human host responses to pulmonary infection with M. tuberculosis, and are consistent with epidemiologic and genetic studies that imply that H37Rv may not have unusual capacity to cause human disease. PMID:18787177

  13. Possible cluster preformation in the sup 14 C decay of sup 223 Ra

    SciTech Connect

    Hussonnois, M.; Le Du, J.F.; Brillard, L.; Ardisson, G. )

    1990-08-01

    A recent experiment on the {sup 14}C fine structure has shown that the branching ratio to {sup 209}Pb ground state is quite different from the one predicted by the various models of cluster emission. Assuming that the {sup 14}C is preformed in the {sup 223}Ra nucleus, we have calculated the hindrance factor {ital F}{sup 14}C of the three {sup 14}C branches to {sup 209}Pb states with a barrier penetrability approximated by a square-well Coulomb potential. The {ital F}{sup 14}C=3.9 and 4.6 values found for the {sup 14}C transitions to the two excited states at 779 keV ({ital I}{sup {pi}}=11/2{sup +}) and 1423 keV ({ital I}{sup {pi}}=15/2{sup {minus}}), respectively, reveal that the cluster formation amplitudes in both transitions are close to those of the {sup 222}Ra and {sup 224}Ra {sup 14}C decays. Such values could be the result of {vert bar}{ital nlj}{r angle} shell-model components common to both the wave functions of the octupole deformed {sup 223}Ra nucleus and of the two first excited states of {sup 209}Pb spherical nucleus. The high hindrance factor {ital F}{sup 14}C=583 of the {sup 14}C branch to the {sup 209}Pb ground state ({ital I}{sup {pi}}=9/2{sup +}) could reveal the absence of {vert bar}1{ital g}{sub 9/2}{r angle} shell-model component in the {sup 223}Ra wave function.

  14. Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA study

    PubMed Central

    Jawaheer, Damini; Olsen, Jørn; Lahiff, Maureen; Forsberg, Sinikka; Lähteenmäki, Jukka; Silveira, Ines Guimaraes da; Rocha, Francisco Airton; Laurindo, Ieda Maria Magalhães; Mota, Licia Maria Henrique da; Drosos, Alexandros A.; Murphy, Eithne; Sheehy, Claire; Quirke, Edel; Cutolo, Maurizio; Rexhepi, Sylejman; Dadoniene, Jolanta; Verstappen, Suzan M.M.; Sokka, Tuulikki

    2010-01-01

    Objective To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Methods Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student’s t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. Results A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. Conclusion BMI appears to be associated with RA disease activity in women, but not in men. PMID:20810033

  15. 226Ra-in marine barite: relationship with carbonate dissolution and sediment focusing in the equatorial pacific

    NASA Astrophysics Data System (ADS)

    van Beek, P.; Reyss, J.-L.; DeMaster, D.; Paterne, M.

    2004-02-01

    Sedimentation rates were determined from the 226Ra ( T 1/2=1602 a) decay in barite in seven cores collected from the western, central and eastern equatorial Pacific. Timing of the last carbonate dissolution increase was investigated with this new chronometer. However, an unconformity in the 226Ra-in-barite profiles was observed at some sites, which could be related to this carbonate dissolution event. We discuss different mechanisms that may have generated these unconformities, including (1) bioturbation, (2) possible bias in the estimate of the correction for supported 226Ra activities, (3) changes in the 226Ra/Ba ratio within surface waters and (4) processes that may have affected the 226Ra/Ba ratio recorded in barite, either within the water column or at the sediment-water interface. Among the processes invoked, an increase in the sediment focusing during the Holocene constitutes the mechanism that can most likely explain the observed unconformities. An increase in the sediment redistribution by bottom currents would enhance the lateral transport of old resuspended barite crystals (with a low 226Ra/Ba ratio). The 226Ra/Ba ratio of barite that accumulates in the sediments, therefore, may have decreased, leading to the unconventional 226Ra-profile shape observed in several cores. A change in the chemistry of the bottom waters that transport the resuspended sediment may have also affected the sediment carbonate contents.

  16. Disequilibrium between [sup 226]Ra and supported [sup 210]Pb in a sediment core from a shallow Florida lake

    SciTech Connect

    Brenner, M.; Peplov, A.J.; Schelske, C.L. )

    1994-07-01

    [sup 210]Pb dating can be used to assign ages in lake sediment cores, calculate rates of sediment accumulation, and determine the timing of recent changes in lake-watershed ecosystems. We used low-background gamma counting to measure [sup 226]Ra and total [sup 210]Pb activity in a core from Lake Rowell, Florida. [sup 226]Ra activity was high and strongly variable throughout the core, even exceeding total [sup 210]Pb activity in recently deposited sediments. We traced one source of Ra-rich sediments to the only inflow, Alligator Creek, where stream-bottom deposits display disequilibrium between [sup 226]Ra and supported [sup 210]Pb. High and variable [sup 226]Ra activity in the Lake Rowell profile argues for direct estimates of in situ Ra in lake sediment cores from disturbed watersheds that have Ra-bearing bedrock. Isotopic disequilibrium between [sup 226]Ra and supported [sup 210]Pb makes it difficult to distinguish between supported and unsupported [sup 210]Pb activity throughout the Lake Rowell core and would require special assumptions and nonconventional dating models to establish age-depth relationships. 78 refs., 3 figs., 1 tab.

  17. Critical function of RA-GEF-2/Rapgef6, a guanine nucleotide exchange factor for Rap1, in mouse spermatogenesis.

    PubMed

    Okada, Keisuke; Miyake, Hideaki; Yamaguchi, Kohei; Chiba, Koji; Maeta, Kazuhiro; Bilasy, Shymaa E; Edamatsu, Hironori; Kataoka, Tohru; Fujisawa, Masato

    2014-02-28

    Small GTPase Rap1 has been implicated in the proper differentiation of testicular germ cells. In the present study, we investigated the functional significance of RA-GEF-2/Rapgef6, a guanine nucleotide exchange factor for Rap1, in testicular differentiation using mice lacking RA-GEF-2. RA-GEF-2 was expressed predominantly on the luminal side of the seminiferous tubules in wild-type mice. No significant differences were observed in the body weights or hormonal parameters of RA-GEF-2(-)(/)(-) and wild-type mice. However, the testes of RA-GEF-2(-)(/)(-) male mice were significantly smaller than those of wild-type mice and were markedly atrophied as well as hypospermatogenic. The concentration and motility of epididymal sperm were also markedly reduced and frequently had an abnormal shape. The pregnancy rate and number of fetuses were markedly lower in wild-type females after they mated with RA-GEF-2(-)(/)(-) males than with wild-type males, which demonstrated the male infertility phenotype of RA-GEF-2(-)(/)(-) mice. Furthermore, a significant reduction and alteration were observed in the expression level and cell junctional localization of N-cadherin, respectively, in RA-GEF-2(-)(/)(-) testes, which may, at least in part, account for the defects in testicular differentiation and spermatogenesis in these mice. PMID:24491570

  18. [sup 226]Ra-[sup 230]Th disequilibrium in axial and off-axis mid-ocean ridge basalts

    SciTech Connect

    Volpe, A.M.; Goldstein, S.J. Los Alamos National Lab., NM )

    1993-03-01

    The authors describe [sup 226]Ra-[sup 230]Th disequilibrium in mid-ocean ridge basalt (MORB) glasses from the Juan de Fuca, Gorda, and East Pacific ridges. These first mass spectrometric measurements of [sup 226]Ra in MORB glasses at sub-picogram abundance levels confirm the large excesses over [sup 230]Th determined by radon-emanation techniques and alpha spectrometry. All off-axis MORB glasses have [sup 226]Ra-[sup 230]Th and [sup 234]U-[sup 238]U in secular equilibrium. This suggests that magmatic processes, not secondary post-eruption alteration, generate [sup 238]U-series disequilibrium in these MORB. Least evolved, N-MORB from axial valleys have ([sup 226]Ra/[sup 230]Th) between 2.2-2.3. Differentiated and enriched E-type MORB have consistently low ([sup 226]Ra/[sup 230]Th) ratios compared with N-MORB from the same ridge sections. Ra-Th fractionation may be less pronounced, or magma residence-transit periods may be long for differentiated MORB. Also, E-MORB may be generated by different melt extraction volumes and rates. Estimated [sup 226]Ra-[sup 230]Th ages for N-MORB agree with location on and off ridge segments, and with Th-U model ages. These preliminary results show that [sup 226]Ra-[sup 230]Th disequilibrium could be used to quantify volcanic episodicity at ocean ridges. 39 refs., 6 figs., 4 tabs.

  19. Essential role for retinoic acid in the promotion of CD4+ T cell effector responses via retinoic acid receptor alpha

    PubMed Central

    Hall, J.A.; Cannons, J.L.; Grainger, J.R.; Santos, L.M. Dos; Hand, T.W.; Naik, S.; Wohlfert, E.A.; Chou, D.B.; Oldenhove, G.; Robinson, M.; Grigg, M.E.; Kastenmayer, R.; Schwartzberg, P.L.; Belkaid, Y.

    2012-01-01

    SUMMARY Vitamin A and its metabolite, retinoic acid (RA), have recently been implicated in the regulation of immune homeostasis via the peripheral induction of regulatory T cells. Here we show that RA is also required to elicit proinflammatory CD4+ helper T cell responses to infection and mucosal vaccination. Retinoic acid receptor alpha (RARα) is the critical mediator of these effects. Strikingly, antagonism of RAR signaling and deficiency in RARα(Rara−/−) results in a cell autonomous CD4+ T cell activation defect. Altogether, these findings reveal a fundamental role for the RA/RARα axis in the development of both regulatory and inflammatory arms of adaptive immunity and establish nutritional status as a broad regulator of adaptive T cell responses. PMID:21419664

  20. Studies of transport pathways of Th, U, rare earths, Ra-228, and Ra-226 from soil to plants and farm animals: Final progress report, 1983-1988

    SciTech Connect

    Linsalata, P

    1988-07-01

    This report consists of three parts. Part 1 discusses a field study conducted in an area of enhanced, natural radioactivity to assess the soil to edible vegetable concentration ratios (CR = concentration in dry vegetable/concentration in dry soil) of Th-232, Th-230, Ra-226, Ra-228, and the light rare earth elements (REE's), La, Ce, and Nd. Twenty-eight soil, and approximately 42 vegetable samples consisting of relatively equal numbers of seven varieties, were obtained from 11 farms on the Pocos de Caldas Plateau in the state of Minas Gerais, Brazil. This region is the site of a major natural analogue study to assess the mobilization and retardation processes affecting thorium and the REE's at the Morro do Ferro ore body, and uranium series radionuclides at the Osamu Utsumi open pit uranium mine. Thorium (IV) serves as a chemical analogue for quadrivalent plutonium, the light REE's (III) as chemical analogues for trivalent americium and curium, and uranium (VI) as an analogue for transuranics with stable oxidation states above IV, e.g., Pu(VI). Part 2 includes our final measurement results for naturally occurring light rare earth elements (REE's include La, Ce, Nd, and SM), U-series and Th-series radionuclides in adult farm animal tissues, feeds and soils. Our findings on soil-to-tissue concentration ratios (CR's) and the comparative behavior of these elements in farm animals raised under natural conditions by local farmers are presented. Part 3 summarizes our findings to date on the distribution and mobilization of Th-232, light rare earth elements (LREE), U-238 and Ra-228 in the MF basin. Estimates of first order, present day, mobilization rate constants resulting from ground water solubilization and seepage/stream transport are calculated using revised inventory estimates for the occurrence of these elements in the ore body and annual flux estimates for the transport of these elements away from the ore body. 151 refs., 20 figs., 40 tabs.

  1. Retinoic acid deficiency alters second heart field formation.

    PubMed

    Ryckebusch, Lucile; Wang, Zengxin; Bertrand, Nicolas; Lin, Song-Chang; Chi, Xuan; Schwartz, Robert; Zaffran, Stéphane; Niederreither, Karen

    2008-02-26

    Retinoic acid (RA), the active derivative of vitamin A, has been implicated in various steps of cardiovascular development. The retinaldehyde dehydrogenase 2 (RALDH2) enzyme catalyzes the second oxidative step in RA biosynthesis and its loss of function creates a severe embryonic RA deficiency. Raldh2(-/-) knockout embryos fail to undergo heart looping and have impaired atrial and sinus venosus development. To understand the mechanism(s) producing these changes, we examined the contribution of the second heart field (SHF) to pharyngeal mesoderm, atria, and outflow tract in Raldh2(-/-) embryos. RA deficiency alters SHF gene expression in two ways. First, Raldh2(-/-) embryos exhibited a posterior expansion of anterior markers of the SHF, including Tbx1, Fgf8, and the Mlc1v-nlacZ-24/Fgf10 reporter transgene as well as of Islet1. This occurred at early somite stages, when cardiac defects became irreversible in an avian vitamin A-deficiency model, indicating that endogenous RA is required to restrict the SHF posteriorly. Explant studies showed that this expanded progenitor population cannot differentiate properly. Second, RA up-regulated cardiac Bmp expression levels at the looping stage. The contribution of the SHF to both inflow and outflow poles was perturbed under RA deficiency, creating a disorganization of the heart tube. We also investigated genetic cross-talk between Nkx2.5 and RA signaling by generating double mutant mice. Strikingly, Nkx2.5 deficiency was able to rescue molecular defects in the posterior region of the Raldh2(-/-) mutant heart, in a gene dosage-dependent manner. PMID:18287057

  2. The association between lipid levels and major adverse cardiovascular events in rheumatoid arthritis compared to non-RA

    PubMed Central

    Liao, Katherine P.; Liu, Jun; Lu, Bing; Solomon, Daniel H.; Kim, Seoyoung C.

    2015-01-01

    Objectives Lower levels of low density lipoprotein (LDL-C) may be associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). We studied whether the complex relationship between LDL-C and high density lipoprotein cholesterol (HDL-C) levels with CV risk is different in RA compared to non-RA. Methods Using data from a US health insurance plan (2003–2012), we conducted a cohort study that included RA and non-RA patients matched on age, sex and index date. Non-linearity between lipid levels and major adverse CV events (MACE) was tested. We used multivariable Cox proportional hazards regression models to examine for an interaction between lipids and RA on the risk of MACE, adjusting for CV risk factors. Results We studied 16,085 RA and 48,499 non-RA subjects with mean age 52.6 years and 78.6% women. The relationship between LDL-C and MACE was non-linear and similar between RA and non-RA (p for interaction=0.72). We observed no significant increase in CV risk between the lowest LDL-C quintile (<91.g/dL) and successive quintiles until the highest quintile (>190.0mg/dL) was compared; hazard ratio (HR) 1.40,95%CI 1.17,1.68). The relationship between HDL and MACE was also non-linear and similar in RA and non-RA (p for interaction=0.39). Compared to the lowest HDL-C quintile, each successive quintile was associated with reduced risk of MACE [lowest (<43.0mg/dL) vs highest quintile (>71.0mg/dL), HR 0.45,95%CI 0.48,0.72]. Conclusions The complex relationship between LDL-C, HDL-C and MACE was non-linear in RA and also not statistically different from an age- and sex-matched non-RA cohort. PMID:25917955

  3. High IgE in rheumatoid arthritis (RA) patients is complexed with anti-IgE autoantibodies

    PubMed Central

    Millauer, N; Zuercher, A W; Miescher, S M; Gerber, H A; Seitz, M; Stadler, B M

    1999-01-01

    This study presents data on more than 300 RA and allergic patients analysed for their serum levels of anti-immunoglobulin isotype autoantibodies and IgE. We observed high levels of IgE in sera of RA and allergic patients. Interestingly, we measured significantly higher specific IgE levels against Alternaria but not against nine other allergens in the RA compared with the allergic group. As expected, anti-IgG autoantibodies (rheumatoid factors (RF)) of different isotypes were detected in sera from RA patients only. However, we found increased titres of complexed anti-IgE autoantibodies in all RF+ groups and in the allergic group. These findings may explain why despite elevated IgE levels a decreased prevalence of allergic diseases in RA patients has been observed. PMID:9933440

  4. Comparative effects of retinoic acid or glycolic acid vehiculated in different topical formulations.

    PubMed

    Maia Campos, Patrícia Maria Berardo Gonçalves; Gaspar, Lorena Rigo; Gonçalves, Gisele Mara Silva; Pereira, Lúcia Helena Terenciane Rodrigues; Semprini, Marisa; Lopes, Ruberval Armando

    2015-01-01

    Retinoids and hydroxy acids have been widely used due to their effects in the regulation of growth and in the differentiation of epithelial cells. However, besides their similar indication, they have different mechanisms of action and thus they may have different effects on the skin; in addition, since the topical formulation efficiency depends on vehicle characteristics, the ingredients of the formulation could alter their effects. Thus the objective of this study was to compare the effects of retinoic acid (RA) and glycolic acid (GA) treatment on the hairless mouse epidermis thickness and horny layer renewal when added in gel, gel cream, or cream formulations. For this, gel, gel cream, and cream formulations (with or without 6% GA or 0.05% RA) were applied in the dorsum of hairless mice, once a day for seven days. After that, the skin was analyzed by histopathologic, morphometric, and stereologic techniques. It was observed that the effects of RA occurred independently from the vehicle, while GA had better results when added in the gel cream and cream. Retinoic acid was more effective when compared to glycolic acid, mainly in the cell renewal and the exfoliation process because it decreased the horny layer thickness.

  5. Simulated acid rain alters litter decomposition and enhances the allelopathic potential of the invasive plant Wedelia trilobata (Creeping Daisy)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Invasive species and acid rain cause global environmental problems. Limited information exists, however, concerning the effects of acid rain on the invasiveness of these plants. For example, creeping daisy, an invasive exotic allelopathic weed, has caused great damage in southern China where acid ra...

  6. Effects of ruminant trans fatty acids on cardiovascular disease and cancer: a comprehensive review of epidemiological, clinical, and mechanistic studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are two predominant sources of dietary trans fatty acids in the food supply, those formed during the industrial partial hydrogenation of vegetable oils (iTFA) and those formed by biohydrogenation in ruminants (rTFA), including vaccenic acid and (VA) and rumenic acid [RA, a conjugated linoleic ...

  7. Early retinoic acid deprivation in developing zebrafish results in microphthalmia.

    PubMed

    Le, Hong-Gam T; Dowling, John E; Cameron, D Joshua

    2012-09-01

    Vitamin A deficiency causes impaired vision and blindness in millions of children around the world. Previous studies in zebrafish have demonstrated that retinoic acid (RA), the acid form of vitamin A, plays a vital role in early eye development. The objective of this study was to describe the effects of early RA deficiency by treating zebrafish with diethylaminobenzaldehyde (DEAB), a potent inhibitor of the enzyme retinaldehyde dehydrogenase (RALDH) that converts retinal to RA. Zebrafish embryos were treated for 2 h beginning at 9 h postfertilization. Gross morphology and retinal development were examined at regular intervals for 5 days after treatment. The optokinetic reflex (OKR) test, visual background adaptation (VBA) test, and the electroretinogram (ERG) were performed to assess visual function and behavior. Early treatment of zebrafish embryos with 100 μM DEAB (9 h) resulted in reduced eye size, and this microphthalmia persisted through larval development. Retinal histology revealed that DEAB eyes had significant developmental abnormalities but had relatively normal retinal lamination by 5.5 days postfertilization. However, the fish showed neither an OKR nor a VBA response. Further, the retina did not respond to light as measured by the ERG. We conclude that early deficiency of RA during eye development causes microphthalmia as well as other visual defects, and that timing of the RA deficiency is critical to the developmental outcome.

  8. Rosmarinic Acid and Melissa officinalis Extracts Differently Affect Glioblastoma Cells

    PubMed Central

    Ramanauskiene, Kristina; Raudonis, Raimondas

    2016-01-01

    Lemon balm (Melissa officinalis L.) has many biological effects but especially important is its neuroprotective activity. The aim of the study is to produce different extracts of Melissa officinalis and analyse their chemical composition and biological properties on rat glioblastoma C6 cells. Results revealed that rosmarinic acid (RA) is the predominant compound of lemon balm extracts. RA has cytotoxic effect on glioblastoma cells (LC50 290.5 μM after the incubation of 24 h and LC50 171.3 μM after 48 h). RA at concentration 80–130 μM suppresses the cell proliferation and has an antioxidant effect. 200 μM and higher concentrations of RA have a prooxidant effect and initiate cell death through necrosis. The aqueous extract of lemon balm is also enriched in phenolic compounds: protocatechuic, caftaric, caffeic, ferulic, and cichoric acids and flavonoid luteolin-7-glucoside. This extract at concentrations 50 μM–200 μM RA has cytotoxic activity and initiates cell death through apoptosis. Extracts prepared with 70% ethanol contain the biggest amount of active compounds. These extracts have the highest cytotoxic activity on glioblastoma cells. They initiate generation of intracellular ROS and cell death through apoptosis and necrosis. Our data suggest that differently prepared lemon balm extracts differently affect glioblastoma cells and can be used as neuroprotective agents in several therapeutic strategies.

  9. Rosmarinic Acid and Melissa officinalis Extracts Differently Affect Glioblastoma Cells

    PubMed Central

    Ramanauskiene, Kristina; Raudonis, Raimondas

    2016-01-01

    Lemon balm (Melissa officinalis L.) has many biological effects but especially important is its neuroprotective activity. The aim of the study is to produce different extracts of Melissa officinalis and analyse their chemical composition and biological properties on rat glioblastoma C6 cells. Results revealed that rosmarinic acid (RA) is the predominant compound of lemon balm extracts. RA has cytotoxic effect on glioblastoma cells (LC50 290.5 μM after the incubation of 24 h and LC50 171.3 μM after 48 h). RA at concentration 80–130 μM suppresses the cell proliferation and has an antioxidant effect. 200 μM and higher concentrations of RA have a prooxidant effect and initiate cell death through necrosis. The aqueous extract of lemon balm is also enriched in phenolic compounds: protocatechuic, caftaric, caffeic, ferulic, and cichoric acids and flavonoid luteolin-7-glucoside. This extract at concentrations 50 μM–200 μM RA has cytotoxic activity and initiates cell death through apoptosis. Extracts prepared with 70% ethanol contain the biggest amount of active compounds. These extracts have the highest cytotoxic activity on glioblastoma cells. They initiate generation of intracellular ROS and cell death through apoptosis and necrosis. Our data suggest that differently prepared lemon balm extracts differently affect glioblastoma cells and can be used as neuroprotective agents in several therapeutic strategies. PMID:27688825

  10. Current (1984) status of the study of /sup 226/Ra and /sup 228/Ra in humans at the Center for Human Radiobiology

    SciTech Connect

    Rundo, J.; Keane, A.T.; Lucas, H.F.; Schlenker, R.A.; Stebbings, J.H.; Stehney, A.F.

    1984-01-01

    The Center for Human Radiobiology has identified 5784 persons by name and type of exposure to /sup 226/Ra and /sup 228/Ra. Included are 4863 dial painters (mostly women) and non-laboratory employees of the radium dial industry, 410 laboratory workers, 399 persons who received radium for supposed therapeutic effects, and 112 in other categories. Body contents of radium have been measured in 1916 of the dial workers and about one-half of the subjects in the other groups. Bone sarcomas, carcinomas of the paranasal sinuses and mastoids, and deterioration of skeletal tissue are still the only effects unequivocally attributable to internal radium. Excess leukemias have not been observed and other malignancies, if in excess, appear more likely to be related to external gamma radiation or radon than to internal radium. Positive correlations with radium burdens have been found for the incidence of benign exostoses among subjects exposed to radium before age 18 and for shortened latency of ocular cataracts. 26 references, 3 figures, 5 tables.

  11. Studies of transport pathways of Th, rare earths, Ra-228, and Ra-226 from soil to plants and farm animals. Progress report, April 1, 1985-February 28, 1986

    SciTech Connect

    Linsalata, P.

    1986-02-01

    The field study is to assess the soil-to-plant and soil-to-animal concentration factors of the naturally occurring radionuclides /sup 226/Ra, /sup 228/Ra, /sup 232/Th, /sup 230/Th, and /sup 228/Th, as well as of the light rare earth elements (REE), La, Ce and Nd. Farms situated near the center of a deeply weathered alkalic intrusive known as the Pocos de Caldas (PC) plateau were selected for study because of their proximity (i.e., within a few kilometers) to what may be the largest single near-surface deposit of Th (approx.30,000 tonnes) and REE's (>100,000 tonnes) situated near the summit of a hill (the Morro do Ferro (MF)). An ancillary field study is being conducted in Orange County, New York, where a local cattleman has permitted sampling members of the herd as well as soil and feeds which are all grown on the premises. Vegetable samples and soil have also been analyzed from five additional farms in Orange County, NY. 64 refs., 25 figs., 45 tabs.

  12. NEA 2100 Ra-Shalom: K-class and Source of CV3 Chondrite Grosnaja?

    NASA Astrophysics Data System (ADS)

    Shepard, M. K.; Clark, B. E.; Swetra, S.; Vilas, F.; Jarvis, K.; Lederer, S. M.

    2004-11-01

    We obtained rotationally resolved spectra of the near-Earth asteroid 2100 Ra-Shalom in Aug 2003 in the visible (0.5-0.9 micron) at McDonald Observatory and infrared (0.8-2.5 micron) at the Infrared Telescope Facility (IRTF). Ra-Shalom is one of the larger members of the Aten family. Its effective diameter is 2.5 km (Harris et al. Icarus 135, 441-450, 1998; Shepard et al. Icarus 147, 520-529, 2000) and its rotation period is 19.8 h (Pravec et al. Icarus 136, 124-153, 1998). Ra-Shalom has been classified as C- (Binzel et al., Icarus 170, 259-294, 2004), S- (Harris et al. 1998), and Xc- class (Bus and Binzel, Icarus 158, 146-177, 2002). Our observations show significant spectral variations with rotation phase, however their proximity to the Milky Way makes interpretation difficult. Our hemispheric-averaged spectrum is an excellent match to the CV3 chondrite Grosnaja, suggesting Ra-Shalom to be its source (RELAB sample MR-MJG-119-P1; Gaffey, JGR 81, 905-920, 1976). Given the purported link between K-class asteroids and CV3 and CO3 chondrites (Bell, Meteoritics 23, 256-257, 1988; Doressoundiram, et al. Icarus 131, 15-31, 1998; Burbine et al. Meteoritics Planet. Sci 36, 245-253, 2001), we suggest that Ra-Shalom is K-class, making it the second known Aten of that class after 1999 JD6 (Binzel et al. Icarus 151, 139-149, 2001). This raises difficult dynamical questions. The major reservoir of K-class asteroids is the Eos family in the outer main-belt ( 3 AU). Dynamical simulations by Bottke et al. (Icarus 156, 399-433, 2002) suggest that Atens originate from the 3:1 mean motion resonance with Jupiter (2.5 AU), the nu6 secular resonance (2.1-2.3 AU), or the Mars crossing population (2.1-2.8 AU). Specific computations for Ra-Shalom mirror this (Bottke, personal comm.). Either there is an unknown dynamical path or another K-class source to populate the Atens.

  13. Retinoic acid and arsenic trioxide trigger degradation of mutated NPM1, resulting in apoptosis of AML cells.

    PubMed

    El Hajj, Hiba; Dassouki, Zeina; Berthier, Caroline; Raffoux, Emmanuel; Ades, Lionel; Legrand, Olivier; Hleihel, Rita; Sahin, Umut; Tawil, Nadim; Salameh, Ala; Zibara, Kazem; Darwiche, Nadine; Mohty, Mohamad; Dombret, Hervé; Fenaux, Pierre; de Thé, Hugues; Bazarbachi, Ali

    2015-05-28

    Nucleophosmin-1 (NPM1) is the most frequently mutated gene in acute myeloid leukemia (AML). Addition of retinoic acid (RA) to chemotherapy was proposed to improve survival of some of these patients. Here, we found that RA or arsenic trioxide synergistically induce proteasomal degradation of mutant NPM1 in AML cell lines or primary samples, leading to differentiation and apoptosis. NPM1 mutation not only delocalizes NPM1 from the nucleolus, but it also disorganizes promyelocytic leukemia (PML) nuclear bodies. Combined RA/arsenic treatment significantly reduced bone marrow blasts in 3 patients and restored the subnuclear localization of both NPM1 and PML. These findings could explain the proposed benefit of adding RA to chemotherapy in NPM1 mutant AMLs, and warrant a broader clinical evaluation of regimen comprising a RA/arsenic combination.

  14. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    SciTech Connect

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  15. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo.

    PubMed

    Chen, Pei-Jen; Padgett, William T; Moore, Tanya; Winnik, Witold; Lambert, Guy R; Thai, Sheau-Fung; Hester, Susan D; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  16. The SCFA butyrate stimulates the epithelial production of retinoic acid via inhibition of epithelial HDAC.

    PubMed

    Schilderink, Ronald; Verseijden, Caroline; Seppen, Jurgen; Muncan, Vanesa; van den Brink, Gijs R; Lambers, Tim T; van Tol, Eric A; de Jonge, Wouter J

    2016-06-01

    In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory disease, and allergy. We hypothesized that SCFAs contribute to mucosal homeostasis by enhancing RA production in intestinal epithelia. With the use of human and mouse epithelial cell lines and primary enteroids, we studied the effect of SCFAs on the production of RA. Functional RA conversion was analyzed by Adlefluor activity assays. Butyrate (0-20 mM), in contrast to other SCFAs, dose dependently induced aldh1a1 or aldh1a3 transcript expression and increased RA conversion in human and mouse epithelial cells. Epithelial cell line data were replicated in intestinal organoids. In these organoids, butyrate (2-5 mM) upregulated aldh1a3 expression (36-fold over control), whereas aldh1a1 was not significantly affected. Butyrate enhanced maturation markers (Mucin-2 and villin) but did not consistently affect stemness markers or other Wnt target genes (lgr5, olfm4, ascl2, cdkn1). In enteroids, the stimulation of RA production by SCFA was mimicked by inhibitors of histone deacetylase 3 (HDAC3) but not by HDAC1/2 inhibitors nor by agonists of butyrate receptors G-protein-coupled receptor (GPR)43 or GPR109A, indicating that butyrate stimulates RA production via HDAC3 inhibition. We conclude that the SCFA butyrate inhibits HDAC3 and thereby supports epithelial RA production. PMID:27151945

  17. Targeting of Osseous Sites with Alpha-emitting Ra-223: Comparison with the Beta-emitter Sr-89 in Mice

    SciTech Connect

    Henriksen, Gjermund; Fisher, Darrell R.; Roeske, John C.; Bruland, Oyvind S.; Larsen, Roy H.

    2003-05-16

    The bone-seeking property of and the potential to irradiate red marrow by the alpha-particle emitter Ra-223 (t1/2 = 11.43 d) were compared to those of the beta-emitter Sr-89 (t1/2 = 50.53 d). Methods: The biodistributions of Ra-223 and Sr-89 were studied in mice. Tissue uptakes were determined at 1 h, 6 h, 1 d, 3 d, and 14 d after intravenous administration. The potential redistribution of progeny from Ra-223 located in bone was investigated. Radiation absorbed doses were calculated for soft tissues and bone. Doses were also estimated for marrow-containing cavities assuming spheric geometries. Results: We found that both Sr-89 and Ra-223 selectively concentrated on bone surfaces relative to soft tissues. The measured bone uptake of Ra-223 was slightly higher than that of Sr-89. At the 24 h time-point, the femur uptake of Ra-223 was 40.1% of the administered activity per gram tissue. The uptake in spleen and most other soft tissues was higher for Ra-223 than for Sr-89. We observed rapid clearance of Ra-223 from soft tissues within the first 24 hours, but the bone surface uptake of Ra-223 increased with time up to 24 h. Among the soft tissues, the spleen had the greatest accumulation and retention of Ra-223. The femur-to-spleen ratio increased with time, from 6.4 at 6 h to 23.7 at 3 days after injections. We found little redistribution of Ra-223 daughter products away from bone (about 2% at 6 h and less than 1% detectable at 3 d). Estimates of dose to marrow-containing cavities showed that the Ra-223 alpha-emitter might have a marrow-sparing advantage compared to beta-emitters due to high linear-energy-transfer and short alpha range targeting osteoid surfaces. The alpha-emitters irradiate a smaller fraction of the marrow-containing volumes--sparing marrow and enhancing survival of marrow cells. At the same time, the bone surfaces receives a therapeutically effective radiation dose. Conclusion: The results of this study indicate that Ra-223 is a promising candidate

  18. Retinoic acid inhibits angiogenesis and tumor growth of thyroid cancer cells.

    PubMed

    Hoffmann, Sebastian; Rockenstein, Andreas; Ramaswamy, Anette; Celik, Ilhan; Wunderlich, Anette; Lingelbach, Susanne; Hofbauer, Lorenz C; Zielke, Andreas

    2007-01-29

    The anti-proliferative effect of retinoic acid (RA) has been documented for various tumors. Some 40% of patients with advanced and poorly differentiated thyroid cancer have been shown to respond to RA with increased uptake of radioiodine. It has been suggested that these effects may be caused by redifferentiation. Presently, little is known about the effects of RA on tumor angiogenesis, a prerequisite for growth and metastatic spread. The aim of the current study was to determine, whether tumor-induced angiogenesis of thyroid cancer is affected by RA. In vitro, the effect of 0.1/10 microM 13-cis RA on tumor cell number (MTT assay) and secretion of VEGF (ELISA) was analyzed in three thyroid cancer cell lines (FTC 236, C634 and XTC), as well as in endothelial cells (HUVEC) over several passages. In vivo, tumor growth, VEGF-expression and microvessel density (VSD) of RA treated thyroid cancer cells after xenotransplantation to nude mice was evaluated by morphometric analysis. In vitro, thyroid cancer cell lines responded to RA with reduced proliferation, ranging from 26 to 34% after 2 weeks of treatment and with up to 80% reduced secretion of VEGF. In vivo, tumor volumes of animals receiving RA were reduced by 33% (FTC 236), 27% (C643) and 6% (XTC), respectively. VSD of experimental tumors was diminished in the FTC 236 (25%) and the C643 cell line (15%), and almost unchanged in XTC tumors (7%). In vivo, VEGF-expression and apoptosis were not significantly affected by RA. In vitro, proliferation of HUVEC was inhibited by conditioned medium of C643 cells pretreated with RA (0.1/10 microM), as well as by administration of RA (0.1/10 microM). This study confirms thyroid tumor cell growth to be inhibited by RA. It demonstrates a decrease of in vitro VEGF accumulation and reduction of VSD in experimental undifferentiated thyroid carcinoma, suggesting that reduced angiogenesis may be an important mechanism responsible for the therapeutic effect of RA in thyroid cancer

  19. Characterization, anticancer drug susceptibility and atRA-induced growth inhibition of a novel cell line (HUMEMS) established from pleural effusion of alveolar rhabdomyosarcoma of breast tissue.

    PubMed

    Ohi, Satoshi

    2007-05-01

    We recently established a cell line derived from pleural effusion from a 13-year-old girl with primary alveolar rhabdomyosarcoma (RMS with a chromosomal translocation t[2;13]) in the breast tissue. The cell line was designated as HUMEMS. Cases of primary alveolar RMS swelling in the breast are extremely rare (about 0.2% of all RMSs). Therefore, the HUMEMS cell line is an important material for studying therapeutics for malignant tumors in children. The HUMEMS cell line we isolated consisted of two morphological subtypes. One type (SSN cells) is small in size and has a single nucleus. Another (LMN cells) is large in size and has two or more nuclei. Both SSN cells and LMN cells were immunohistochemically positive for desmin and slightly positive for myoglobin. Our data suggested LMN cells are well-differentiated SSN cells. Moreover, in some of the LMN cells, rapid cell contractions (1-5 times/10 sec) were observed. We investigated the anticancer drug susceptibility of the HUMEMS cell line with an oxygen electrode apparatus (Daikin, DOX-10, JPN) and effect of all-trans-retinoic acid (atRA) to the cell line. The atRA-treatment inhibited proliferation of the HUMEMS cells.

  20. Identification of moderately halophilic bacteria from Thai fermented fish ( pla-ra ) and proposal of Virgibacillus siamensis sp. nov.

    PubMed

    Tanasupawat, Somboon; Chamroensaksri, Nitcha; Kudo, Takuji; Itoh, Takashi

    2010-10-01

    Forty-one isolates of moderately halophilic bacteria were isolated from fermented fish (pla-ra) in Thailand. On the basis of their phenotypic and chemotaxonomic characteristics, DNA-DNA relatedness and 16S rRNA gene sequences analyses, they were divided into six groups. The isolates in Group I to V were Gram-positive rod-shaped bacteria. They contained meso-diaminopimelic acid in the cell-wall peptidoglycan and menaquinone with seven isoprene units (MK-7). An isolate in Group VI was a Gram-negative rod-shaped bacterium. The DNA G+C contents of tested strains ranged from 36.5-63 mol%. Ten strains (Group I) were identified as Virgibacillus dokdonensis, 13 isolates (Group II) as V. halodenitrificans, 14 isolates (Group III) as V. marismortui, 1 isolate (Group IV) as Virgibacillus sp., 2 isolates (Group V) as Bacillus vietnamnensis, and 1 isolate (Group VI) as Chromohalobacter salexigens. Isolate MS3-4 in Group IV was closely related to V. carmonensis KCTC 3819(T) (95.9%). This strain contained anteiso-C(15:0) (55.8%) and anteiso-C(17:0) (17.7%) as major cellular fatty acids and had phosphatidylglycerol, diphosphatidylglycerol and an unidentified glycolipid as polar lipids. The DNA G+C content of MS3-4 was 38.0 mol%. The strain from Group IV is proposed as Virgibacillus siamensis sp. nov. and MS3-4(T) is the type strain (JCM 15395(T) =PCU 312(T) =TISTR 1957(T)). PMID:21099133

  1. Three Conazoles Increase Hepatic Microsomal Retinoic Acid Metabolism and Decrease Mouse Hepatic Retinoic Acid Levels In Vivo

    EPA Science Inventory

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with...

  2. Retinoic acid-mediated gene expression in transgenic reporter zebrafish.

    PubMed

    Perz-Edwards, A; Hardison, N L; Linney, E

    2001-01-01

    Retinoic acid-mediated gene activation is important for normal vertebrate development. The size and nature of retinoic acid make it difficult to identify the precise cellular location of this signaling molecule throughout an embryo. Additionally, retinoic acid (RA) signaling is regulated by a complex combination of receptors, coactivators, and antagonizing proteins. Thus, in order to integrate these signals and identify regions within a whole developing embryo where cells can respond transcriptionally to retinoic acid, we have used a reporter transgenic approach. We have generated several stable lines of transgenic zebrafish which use retinoic acid response elements to drive fluorescent protein expression. In these zebrafish lines, transgene expression is localized to regions of the neural tube, retina, notochord, somites, heart, pronephric ducts, branchial arches, and jaw muscles in embryos and larvae. Transgene expression can be induced in additional regions of the neural tube and retina as well as the immature notochord, hatching gland, enveloping cell layer, and fin by exposing embryos to retinoic acid. Treatment with retinoic acid synthase inhibitors, citral and diethylaminobenzaldehyde (DEAB), during neurulation, greatly reduces transgene expression. DEAB treatment of embryos at gastrulation phenocopies the embryonic effects of vitamin A deprivation or targeted disruption of the RA synthase retinaldehyde dehydrogenase-2 in other vertebrates. Together these data suggest that the reporter expression we see in zebrafish is dependent upon conserved vertebrate pathways of RA synthesis.

  3. Expression Analysis of Phenylalanine Ammonia Lyase Gene and Rosmarinic Acid Production in Salvia officinalis and Salvia virgata Shoots Under Salicylic Acid Elicitation.

    PubMed

    Ejtahed, Roghayeh Sadat; Radjabian, Tayebeh; Hoseini Tafreshi, Sayed Ali

    2015-08-01

    Partial fragments of phenylalanine ammonia lyase (PAL) genes were cloned and characterized from Salvia officinalis (SoPAL) and Salvia virgata (SvPAL). Different concentrations (250 and 500 μM) of exogenous salicylic acid (SA) were used when correlation between PAL expression and rosmarinic acid (RA) accumulation was compared. The results showed that the deduced cDNA sequences of the partial genes had high similarities with those of known PAL gene from other plant species. Semi-quantitative reverse transcription PCR (RT-PCR) analysis revealed that exogenous application of SA led to up-regulating of the PAL expression. Further analysis showed that in S. virgata, at higher concentration of SA, higher accumulation of RA was achieved, while in S. officinalis, the higher RA accumulation was observed at lower concentration of SA. It was concluded that there was no positive correlation between the intensity of PAL transcription and the RA accumulation in the studied species. Therefore, despite of the increase in transcription rate of the PAL at the higher concentration of SA, the lower amounts of RA were accumulated in the case of S. officinalis. Consequently, the hypothesis that PAL is the rate-determining step in RA biosynthesis is not always valid and probably some other unknown factors participate in the synthesis of phenolics.

  4. Rosmarinic acid content in antidiabetic aqueous extract of Ocimum canum Sims grown in Ghana

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rosmarinic acid (RA) is an important polyphenol that is found in a variety of herbs including Ocimum canum sims (locally called eme or akokobesa in Ghana). Aqueous extracts from the leaves of O.canum are used as an antidiabetic herbal medicine in Ghana. Interestingly, rosmarinic acid content and p...

  5. A COMPARISON OF THE ROSE-WAALER, LATEX FIXATION, "RA-TEST," AND BENTONITE FLOCCULATION TESTS.

    PubMed

    Greenbury, C L; Keningale, J

    1960-07-01

    The bentonite flocculation test of Bozicevich, Bunim, Freund, and Ward (1958), the latex fixation test of Singer and Plotz (1956), and the "RA-test" (a latex reagent for use as a slide test) of Hyland Laboratories have been compared with each other and with a modified Rose-Waaler test, the behaviour of which has been previously extensively investigated. In these tests sera from 2,250 patients were tested by two or more methods on 3,000 occasions. The findings of this trial are set out and the merits of the tests and reasons for disagreement among them are discussed. It is concluded that the most satisfactory means of testing rheumatoid sera is by the Rose-Waaler test and the "RA-test," or a satisfactory modification of it, in parallel.

  6. TheRadio Science Experiment VeRa onboard ESA's Venus Express (VEX) Spacecraft

    NASA Astrophysics Data System (ADS)

    Haeusler, Bernd; Paetzold, M.; Bird, M. K.; Simpson, R. A.; Tyler, L. G.; Dehant, V.; Imamura, T.; Tellmann, S.; Mattei, R.

    2006-09-01

    The VEX spacecraft was successfully injected into the Venus orbit on April 11, 2006. VeRa is an active radio sounding instrument which will measure atmospheric/ionospheric temperature and density profiles, sound with bistatic radar experiments the surface of the planet, will measure its gravity anomalies and investigate also the structure of the corona by analyzing radio carrier signals received on ground in the S- and X-frequency bands. The radio science instrument VeRa is equipped with an ultrastable oscillator (USO) which will be used especially for atmospheric sounding and bistatic radar experiments as frequency reference in the OneWay transmission mode. We will present the current status of the experiment, the results of the commissioning tests and first scientific results.

  7. Electric dipole moments of actinide atoms and RaO molecule

    SciTech Connect

    Flambaum, V. V.

    2008-02-15

    We have calculated the atomic electric dipole moments (EDMs) induced in {sup 229}Pa and {sup 225}Ac by their respective nuclear Schiff moments S. The results are d({sup 229}Pa)=-9.5x10{sup -17} [S/(e fm)]e cm=-1.1x10{sup -20}{eta} e cm and d({sup 225}Ac)=-8.6x10{sup -17} [S/(e fm)]e cm=-0.8x10{sup -21}{eta} e cm. EDM of {sup 229}Pa is 3x10{sup 4} times larger than {sup 199}Hg EDM and 40 times larger than {sup 225}Ra EDM. Possible use of actinides in solid state experiments is also discussed. The (T,P)-odd spin-axis interaction in RaO molecule is 500 times larger than in TlF.

  8. Investigations of Ra{sup +} properties to test possibilities for new optical-frequency standards

    SciTech Connect

    Sahoo, B. K.; Das, B. P.; Chaudhuri, R. K.; Mukherjee, D.; Timmermans, R. G. E.; Jungmann, K.

    2007-10-15

    The present work tests the suitability of the narrow transitions 7s {sup 2}S{sub 1/2}{yields}6d {sup 2}D{sub 3/2} and 7s {sup 2}S{sub 1/2}{yields}6d {sup 2}D{sub 5/2} in Ra{sup +} for optical frequency standard studies. Our calculations of the lifetimes of the metastable 6d states using the relativistic coupled-cluster theory suggest that they are sufficiently long for Ra{sup +} to be considered as a potential candidate for an atomic clock. This is further corroborated by our studies of the hyperfine interactions, dipole and quadrupole polarizabilities, and quadrupole moments of the appropriate states of this system.

  9. Exotic nuclear decay of /sup 223/Ra by emission of /sup 14/C nuclei

    SciTech Connect

    Gales, S.; Hourani, E.; Hussonnois, M.; Schapira, J.P.; Stab, L.; Vergnes, M.

    1984-08-20

    The exotic nuclear decay of /sup 223/Ra by emission of /sup 14/C nuclei has been investigated by use of an intense radioactive /sup 227/Ac source and a magnetic spectrometer with a large solid angle. After a run of 5 d, a group of eleven events was observed at the expected location of /sup 14/C in a ..delta..E-E telescope calibrated with a /sup 14/C beam. A branching ratio of (5.5 +- 2.0) x 10/sup -10/ was measured for the emission of /sup 14/C nuclei relative to ..cap alpha.. particles from /sup 223/Ra in agreement with the previously reported ratio of (8.5 +- 2.5) x 10/sup -10/. .AE

  10. Interpretation of the fine structure in the sup 14 C radioactive decay of sup 223 Ra

    SciTech Connect

    Sheline, R.K. ); Ragnarsson, I. )

    1991-03-01

    The experimental hindrance factors determined from the fine structure in the {sup 14}C decay of {sup 223}Ra are strikingly similar to the hindrance factors observed in the alpha decay of odd-{ital A} reflection-asymmetric deformed nuclei in spite of the deformed to spherical shape which occurs in the {sup 14}C decay. Calculations of the overlap between the reflection-asymmetric ground state of {sup 223}Ra and the spherical shell-model orbitals of {sup 209}Pb involved in the {sup 14}C decay are consistent with the experimental hindrance factors from the {sup 14}C fine structure except that the {ital j}{sub 15/2} orbital is more strongly populated experimentally than the calculations suggest.

  11. Retinoic acid modulates intrahippocampal levels of corticosterone in middle-aged mice: consequences on hippocampal plasticity and contextual memory.

    PubMed

    Bonhomme, Damien; Pallet, Véronique; Dominguez, Gaelle; Servant, Laure; Henkous, Nadia; Lafenêtre, Pauline; Higueret, Paul; Béracochéa, Daniel; Touyarot, Katia

    2014-01-01

    It is now established that vitamin A and its derivatives, retinoic acid (RA), are required for cognitive functions in adulthood. RA hyposignaling and hyperactivity of glucocorticoid (GC) pathway appear concomitantly during aging and would contribute to the deterioration of hippocampal synaptic plasticity and functions. Furthermore, recent data have evidenced counteracting effects of retinoids on GC signaling pathway. In the present study, we addressed the following issue: whether the stimulation of RA pathway could modulate intrahippocampal corticosterone (CORT) levels in middle-aged mice and thereby impact on hippocampal plasticity and cognitive functions. We firstly investigated the effects of vitamin A supplementation and RA treatment in middle-aged mice, on contextual serial discrimination task, a paradigm which allows the detection of early signs of age-related hippocampal-dependent memory dysfunction. We then measured intrahippocampal CORT concentrations by microdialysis before and after a novelty-induced stress. Our results show that both RA treatment and vitamin A supplementation improve "episodic-like" memory in middle-aged mice but RA treatment appears to be more efficient. Moreover, we show that the beneficial effect of RA on memory is associated to an increase in hippocampal PSD-95 expression. In addition, intrahippocampal CORT levels are reduced after novelty-induced stress in RA-treated animals. This effect cannot be related to a modulation of hippocampal 11β-HSD1 expression. Interestingly, RA treatment induces a modulation of RA receptors RARα and RARβ expression in middle-aged mice, a finding which has been correlated with the amplitude of intrahippocampal CORT levels after novelty-induced stress. Taken together, our results suggest that the preventive action of RA treatment on age-related memory deficits in middle-aged mice could be, at least in part, due to an inhibitory effect of retinoids on GC activity. PMID:24570662

  12. Retinoic acid modulates intrahippocampal levels of corticosterone in middle-aged mice: consequences on hippocampal plasticity and contextual memory

    PubMed Central

    Bonhomme, Damien; Pallet, Véronique; Dominguez, Gaelle; Servant, Laure; Henkous, Nadia; Lafenêtre, Pauline; Higueret, Paul; Béracochéa, Daniel; Touyarot, Katia

    2014-01-01

    It is now established that vitamin A and its derivatives, retinoic acid (RA), are required for cognitive functions in adulthood. RA hyposignaling and hyperactivity of glucocorticoid (GC) pathway appear concomitantly during aging and would contribute to the deterioration of hippocampal synaptic plasticity and functions. Furthermore, recent data have evidenced counteracting effects of retinoids on GC signaling pathway. In the present study, we addressed the following issue: whether the stimulation of RA pathway could modulate intrahippocampal corticosterone (CORT) levels in middle-aged mice and thereby impact on hippocampal plasticity and cognitive functions. We firstly investigated the effects of vitamin A supplementation and RA treatment in middle-aged mice, on contextual serial discrimination task, a paradigm which allows the detection of early signs of age-related hippocampal-dependent memory dysfunction. We then measured intrahippocampal CORT concentrations by microdialysis before and after a novelty-induced stress. Our results show that both RA treatment and vitamin A supplementation improve “episodic-like” memory in middle-aged mice but RA treatment appears to be more efficient. Moreover, we show that the beneficial effect of RA on memory is associated to an increase in hippocampal PSD-95 expression. In addition, intrahippocampal CORT levels are reduced after novelty-induced stress in RA-treated animals. This effect cannot be related to a modulation of hippocampal 11β-HSD1 expression. Interestingly, RA treatment induces a modulation of RA receptors RARα and RARβ expression in middle-aged mice, a finding which has been correlated with the amplitude of intrahippocampal CORT levels after novelty-induced stress. Taken together, our results suggest that the preventive action of RA treatment on age-related memory deficits in middle-aged mice could be, at least in part, due to an inhibitory effect of retinoids on GC activity. PMID:24570662

  13. Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish

    PubMed Central

    Frey, Ruth A.; Hunter, Samuel S.; Ashino, Ryuichi; Kawamura, Shoji; Stenkamp, Deborah L.

    2015-01-01

    The signaling molecule retinoic acid (RA) regulates rod and cone photoreceptor fate, differentiation, and survival. Here we elucidate the role of RA in differential regulation of the tandemly-duplicated long wavelength-sensitive (LWS) cone opsin genes. Zebrafish embryos were treated with RA from 48 hours post-fertilization (hpf) to 75 hpf, and RNA was isolated from eyes for microarray analysis. ~170 genes showed significantly altered expression, including several transcription factors and components of cellular signaling pathways. Of interest, the LWS1 opsin gene was strongly upregulated by RA. LWS1 is the upstream member of the tandemly duplicated LWS opsin array and is normally not expressed embryonically. Embryos treated with RA 48 hpf to 100 hpf or beyond showed significant reductions in LWS2-expressing cones in favor of LWS1-expressing cones. The LWS reporter line, LWS-PAC(H) provided evidence that individual LWS cones switched from LWS2 to LWS1 expression in response to RA. The RA signaling reporter line, RARE:YFP indicated that increased RA signaling in cones was associated with this opsin switch, and experimental reduction of RA signaling in larvae at the normal time of onset of LWS1 expression significantly inhibited LWS1 expression. A role for endogenous RA signaling in regulating differential expression of the LWS genes in postmitotic cones was further supported by the presence of an RA signaling domain in ventral retina of juvenile zebrafish that coincided with a ventral zone of LWS1 expression. This is the first evidence that an extracellular signal may regulate differential expression of opsin genes in a tandemly duplicated array. PMID:26296154

  14. Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish.

    PubMed

    Mitchell, Diana M; Stevens, Craig B; Frey, Ruth A; Hunter, Samuel S; Ashino, Ryuichi; Kawamura, Shoji; Stenkamp, Deborah L

    2015-08-01

    The signaling molecule retinoic acid (RA) regulates rod and cone photoreceptor fate, differentiation, and survival. Here we elucidate the role of RA in differential regulation of the tandemly-duplicated long wavelength-sensitive (LWS) cone opsin genes. Zebrafish embryos were treated with RA from 48 hours post-fertilization (hpf) to 75 hpf, and RNA was isolated from eyes for microarray analysis. ~170 genes showed significantly altered expression, including several transcription factors and components of cellular signaling pathways. Of interest, the LWS1 opsin gene was strongly upregulated by RA. LWS1 is the upstream member of the tandemly duplicated LWS opsin array and is normally not expressed embryonically. Embryos treated with RA 48 hpf to 100 hpf or beyond showed significant reductions in LWS2-expressing cones in favor of LWS1-expressing cones. The LWS reporter line, LWS-PAC(H) provided evidence that individual LWS cones switched from LWS2 to LWS1 expression in response to RA. The RA signaling reporter line, RARE:YFP indicated that increased RA signaling in cones was associated with this opsin switch, and experimental reduction of RA signaling in larvae at the normal time of onset of LWS1 expression significantly inhibited LWS1 expression. A role for endogenous RA signaling in regulating differential expression of the LWS genes in postmitotic cones was further supported by the presence of an RA signaling domain in ventral retina of juvenile zebrafish that coincided with a ventral zone of LWS1 expression. This is the first evidence that an extracellular signal may regulate differential expression of opsin genes in a tandemly duplicated array.

  15. Geochemistry of Ca, Sr, Ba and Ra sulfates in some deep brines from the Palo Duro basin, Texas

    SciTech Connect

    Langmuir, D.; Melchior, D.

    1985-11-01

    The geochemistry of Ca, Sr, Ba and Ra sulfates in some deep brines from the Palo Duro Basin of north Texas, was studied to define geochemical controls on radionuclides such as /sup 90/Sr and /sup 226/Ra. Published solubility data for gypsum, anhydrite, celestite, barite and RaSO/sub 4/ were first reevaluated, in most cases using the ion interaction approach of Pitzer, to determine solubility products of the sulfates as a function of temperature and pressure. Ionic strengths of the brines were from 2.9 to 4.8 m, their temperatures and pressures up to 40/sup 0/C and 130 bars. Saturation indices of the sulfates were computed with the ion-interaction approach in one brine from the arkosic granite wash facies and four from the carbonate Wolfcamp Formation. All five brines are saturated with respect to gypsum, anhydrite and celestite, and three of the five with respect to barite. All are undersaturated by from 5 to 6 orders of magnitude with respect to pure RaSO/sub 4/. /sup 226/Ra concentrations in the brines, which ranged from 10/sup -11.3/ to 10/sup -12.7/ m, are not controlled by RaSO/sub 4/ solubility or adsorption, but possibly by the solubility of trace Ra solid solutions in sulfates including celestite and barite.

  16. The geochemistry of Ca, Sr, Ba and Ra sulfates in some deep brines from the Palo Duro Basin, Texas

    NASA Astrophysics Data System (ADS)

    Langmuir, Donald; Melchior, Daniel

    1985-11-01

    The geochemistry of Ca, Sr, Ba and Ra sulfates in some deep brines from the Palo Duro Basin of north Texas, was studied to define geochemical controls on radionuclides such as 90Sr and 226Ra. Published solubility data for gypsum, anhydrite, celestite, barite and RaSO 4 were first reevaluated, in most cases using the ion interaction approach of Pitzer, to determine solubility products of the sulfates as a function of temperature and pressure. Ionic strengths of the brines were from 2.9 to 4.8 m, their temperatures and pressures up to 40°C and 130 bars. Saturation indices of the sulfates were computed with the ion-interaction approach in one brine from the arkosic granite wash fades and four from the carbonate Wolfcamp Formation. All five brines are saturated with respect to gypsum, anhydrite and celestite, and three of the five with respect to barite. All are undersaturated by from 5 to 6 orders of magnitude with respect to pure RaSO 4. 226Ra concentrations in the brines, which ranged from 10 -11.3 to 10 -12.7 m, are not controlled by RaSO 4 solubility or adsorption, but possibly by the solubility of trace Ra solid solutions in sulfates including celestite and barite.

  17. Study of the distribution of ²²⁶Ra in ground water near the uranium industry of Jharkhand, India.

    PubMed

    Tripathi, R M; Jha, V N; Sahoo, S K; Sethy, N K; Shukla, A K; Puranik, V D; Kushwaha, H S

    2012-01-01

    Ground water is the principal source of drinking water in the rural areas of India. With the aim of determining, the contribution of (226)Ra to natural background radiation through drinking water exposure pathway near an operating uranium mining industry at Jaduguda, Jharkhand state of eastern India, the (226)Ra activity concentrations were measured in potable ground water. The water analysed, both tube well and well water, was collected in areas near the uranium industry and away. The (226)Ra concentration was measured by emanometric technique. The (226)Ra level in ground water was ranging between minimum detection limit of 3.5 mBq l(-1) and a maximum of 208 mBq l(-1). The analysis of variance reveals that there is insignificant statistical variation in the median (226)Ra concentration up to a distance of >10 km from the mining complex. Variation in concentration of (226)Ra in sources is attributed to the local geochemistry and environmental factors. The (226)Ra concentration was significantly elevated in natural artesian wells in the vicinity of uranium mineralised hill and it varies from 53.4 to 754 mBq l(-1). The WHO [Guidelines for Drinking Water Quality. Third Edition, Vol. 1, Recommendation (2004)] guideline value of 1000 mBq l(-1) has not been exceeded in any of the sources investigated.

  18. Spontaneous secretion of interleukin 1 receptor antagonist (IL-1ra) by cells isolated from herniated lumbar discal tissue after discectomy.

    PubMed

    Koch, H; Reinecke, J A; Meijer, H; Wehling, P

    1998-09-01

    In the study presented, cells of a herniated lumbar disc were cultivated in vitro and analysed for interleukin 1beta (IL-1beta) and interleukin 1 receptor antagonist (IL-1Ra) production. The objective of this study was the detection of IL-1beta and IL-1Ra secreted by herniated lumbar discal cells after discectomy. The involvement of cytokines in the degeneration of intervertebral discs and in the pathophysiology of radiculopathy is established. Antagonizing proteins, e.g. IL-1Ra are thought to have considerable therapeutic potential. In the present study, a 51-year-old male with massive sequestrated lumbar disc herniation at L5/S1 was treated by microsurgical discectomy. Discal cells were isolated, cultures and culture supernatants immunochemically analysed for IL-1beta and IL-1Ra secretion. Spontaneous secretion of IL-1Ra was found. IL-1beta was not detected. Our findings might contradict recent studies on the role of IL-1beta and IL-1Ra. A possible therapeutic role of exogenous IL-1Ra in disc degeneration needs further research. PMID:9770331

  19. Quantifying bone weathering stages using the average roughness parameter Ra measured from 3D data

    NASA Astrophysics Data System (ADS)

    Vietti, Laura A.

    2016-09-01

    Bone surface texture is known to degrade in a predictable fashion due to subaerial exposure, and can thus act as a relative proxy for estimating temporal information from modern and ancient bone assemblages. To date, the majority of bone weathering data is collected on a categorical scale based on descriptive terms. While this qualitative classification of weathering data is well established, textural analyses of bone surfaces may provide means to quantify weathering stages but have yet to be tested. Here, I examined the suitability of textural analyses for bone weathering studies by first establishing bone surface regions most appropriate for weathering analyses. I then measured and compared the roughness texture of weathered bones at different stages. To establish regions of bone most suitable for textural analyses, Ra was measured from 3D scans of dorsal ribs of four adult ungulate taxa. Results indicate that the rib-shafts from unweathered ungulate skeletons were similar and are likely good candidates because differences in surface texture will not be due to differences in initial bone texture. To test if textural measurements could reliably characterize weathering stages, the average roughness values (Ra) were measured from weathered ungulate rib-shafts assigned to four descriptive weathering stages. Results from analyses indicate that the Ra was statistically distinct for each weathering stage and that roughness positively correlates with the degree of weathering. As such, results suggest that textural analyses may provide the means for quantifying bone-weathering stages. Using Ra and other quantifiable texture parameters may enable more reliable and comparative taphonomic analyses by reducing inter-observer variations and by providing numerical data more compatible for multivariate statistics.