Sample records for wip1 phosphatase ppm1d
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Macurek, Libor; Benada, Jan; Müllers, Erik; Halim, Vincentius A.; Krejčíková, Kateřina; Burdová, Kamila; Pecháčková, Sona; Hodný, Zdeněk; Lindqvist, Arne; Medema, René H.; Bartek, Jiri
2013-01-01
Cells are constantly challenged by DNA damage and protect their genome integrity by activation of an evolutionary conserved DNA damage response pathway (DDR). A central core of DDR is composed of a spatiotemporally ordered net of post-translational modifications, among which protein phosphorylation plays a major role. Activation of checkpoint kinases ATM/ATR and Chk1/2 leads to a temporal arrest in cell cycle progression (checkpoint) and allows time for DNA repair. Following DNA repair, cells re-enter the cell cycle by checkpoint recovery. Wip1 phosphatase (also called PPM1D) dephosphorylates multiple proteins involved in DDR and is essential for timely termination of the DDR. Here we have investigated how Wip1 is regulated in the context of the cell cycle. We found that Wip1 activity is downregulated by several mechanisms during mitosis. Wip1 protein abundance increases from G1 phase to G2 and declines in mitosis. Decreased abundance of Wip1 during mitosis is caused by proteasomal degradation. In addition, Wip1 is phosphorylated at multiple residues during mitosis, and this leads to inhibition of its enzymatic activity. Importantly, ectopic expression of Wip1 reduced γH2AX staining in mitotic cells and decreased the number of 53BP1 nuclear bodies in G1 cells. We propose that the combined decrease and inhibition of Wip1 in mitosis decreases the threshold necessary for DDR activation and enables cells to react adequately even to modest levels of DNA damage encountered during unperturbed mitotic progression. PMID:23255129
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Jeong, Ho-Chang; Gil, Na-Yeon; Lee, Ho-Soo; Cho, Seung-Ju; Kim, Kyungtae; Chun, Kwang-Hoon; Cho, Hyeseong; Cha, Hyuk-Jin
2015-08-01
Wip1 belongs to the protein phosphatase C (PP2C) family, of which expression is up-regulated by a number of external stresses, and serves as a stress modulator in normal physiological conditions. When overexpressed, premature dephosphorylation of stress-mediators by Wip1 results in abrogation of tumor surveillance, thus Wip1 acts as an oncogene. Previously, the functional regulation of Wip1 in cell-cycle progression by counteracting cellular G1 and G2/M checkpoint activity in response to DNA damage was reported. However, other than in stress conditions, the function and regulatory mechanism of Wip1 has not been fully determined. Herein, we demonstrated that protein regulation of Wip1 occurs in a cell cycle-dependent manner, which is directly governed by APC/C(Cdh1) at the end of mitosis. In particular, we also showed evidence that Wip1 phosphatase activity is closely associated with its own protein stability, suggesting that reduced phosphatase activity of Wip1 during mitosis could trigger its degradation. Furthermore, to verify the physiological role of its phosphatase activity during mitosis, we established doxycycline-inducible cell models, including a Wip1 wild type (WT) and phosphatase dead mutant (Wip1 DA). When ectopically expressing Wip1 WT, we observed a delay in the transition from metaphase to anaphase. In conclusion, these studies show that mitotic degradation of Wip1 by APC/C(Cdh1) is important for normal mitotic progression. © 2015 Wiley Periodicals, Inc.
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Activation of WIP1 Phosphatase by HTLV-1 Tax Mitigates the Cellular Response to DNA Damage
Dayaram, Tajhal; Lemoine, Francene J.; Donehower, Lawrence A.; Marriott, Susan J.
2013-01-01
Genomic instability stemming from dysregulation of cell cycle checkpoints and DNA damage response (DDR) is a common feature of many cancers. The cancer adult T cell leukemia (ATL) can occur in individuals infected with human T cell leukemia virus type 1 (HTLV-1), and ATL cells contain extensive chromosomal abnormalities, suggesting that they have defects in the recognition or repair of DNA damage. Since Tax is the transforming protein encoded by HTLV-1, we asked whether Tax can affect cell cycle checkpoints and the DDR. Using a combination of flow cytometry and DNA repair assays we showed that Tax-expressing cells exit G1 phase and initiate DNA replication prematurely following damage. Reduced phosphorylation of H2AX (γH2AX) and RPA2, phosphoproteins that are essential to properly initiate the DDR, was also observed in Tax-expressing cells. To determine the cause of decreased DDR protein phosphorylation in Tax-expressing cells, we examined the cellular phosphatase, WIP1, which is known to dephosphorylate γH2AX. We found that Tax can interact with Wip1 in vivo and in vitro, and that Tax-expressing cells display elevated levels of Wip1 mRNA. In vitro phosphatase assays showed that Tax can enhance Wip1 activity on a γH2AX peptide target by 2-fold. Thus, loss of γH2AX in vivo could be due, in part, to increased expression and activity of WIP1 in the presence of Tax. siRNA knockdown of WIP1 in Tax-expressing cells rescued γH2AX in response to damage, confirming the role of WIP1 in the DDR. These studies demonstrate that Tax can disengage the G1/S checkpoint by enhancing WIP1 activity, resulting in reduced DDR. Premature G1 exit of Tax-expressing cells in the presence of DNA lesions creates an environment that tolerates incorporation of random mutations into the host genome. PMID:23405243
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Absence of Wip1 partially rescues Atm deficiency phenotypes in mice
Darlington, Yolanda; Nguyen, Thuy-Ai; Moon, Sung-Hwan; Herron, Alan; Rao, Pulivarthi; Zhu, Chengming; Lu, Xiongbin; Donehower, Lawrence A.
2011-01-01
Wildtype p53-Induced Phosphatase 1 (WIP1) is a serine/threonine phosphatase that dephosphorylates proteins in the ataxia telangiectasia mutated (ATM)-initiated DNA damage response pathway. WIP1 may play a homeostatic role in ATM signaling by returning the cell to a normal pre-stress state following completion of DNA repair. To better understand the effects of WIP1 on ATM signaling, we crossed Atm-deficient mice to Wip1-deficient mice and characterized phenotypes of the double knockout progeny. We hypothesized that the absence of Wip1 might rescue Atm deficiency phenotypes. Atm null mice, like ATM-deficient humans with the inherited syndrome ataxia telangiectasia, exhibit radiation sensitivity, fertility defects, and are T-cell lymphoma prone. Most double knockout mice were largely protected from lymphoma development and had a greatly extended lifespan compared to Atm null mice. Double knockout mice had increased p53 and H2AX phosphorylation and p21 expression compared to their Atm null counterparts, indicating enhanced p53 and DNA damage responses. Additionally, double knockout splenocytes displayed reduced chromosomal instability compared to Atm null mice. Finally, doubly null mice were partially rescued from infertility defects observed in Atm null mice. These results indicate that inhibition of WIP1 may represent a useful strategy for cancer treatment in general and A-T patients in particular. PMID:21765465
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Crescenzi, Elvira; Raia, Zelinda; Pacifico, Francesco; Mellone, Stefano; Moscato, Fortunato; Palumbo, Giuseppe; Leonardi, Antonio
2013-01-01
Premature or drug-induced senescence is a major cellular response to chemotherapy in solid tumors. The senescent phenotype develops slowly and is associated with chronic DNA damage response. We found that expression of wild-type p53-induced phosphatase 1 (Wip1) is markedly down-regulated during persistent DNA damage and after drug release during the acquisition of the senescent phenotype in carcinoma cells. We demonstrate that down-regulation of Wip1 is required for maintenance of permanent G2 arrest. In fact, we show that forced expression of Wip1 in premature senescent tumor cells induces inappropriate re-initiation of mitosis, uncontrolled polyploid progression, and cell death by mitotic failure. Most of the effects of Wip1 may be attributed to its ability to dephosphorylate p53 at Ser15 and to inhibit DNA damage response. However, we also uncover a regulatory pathway whereby suppression of p53 Ser15 phosphorylation is associated with enhanced phosphorylation at Ser46, increased p53 protein levels, and induction of Noxa expression. On the whole, our data indicate that down-regulation of Wip1 expression during premature senescence plays a pivotal role in regulating several p53-dependent aspects of the senescent phenotype. PMID:23612976
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Legionella pneumophila effector WipA, a bacterial PPP protein phosphatase with PTP activity.
Jia, Qian; Lin, Yun; Gou, Xuejing; He, Lei; Shen, Dong; Chen, Dongni; Xie, Wei; Lu, Yongjun
2018-04-26
The gram-negative bacterium Legionella pneumophila invades human's lung and causes Legionnaires' disease. To benefit its survival and replication in cellular milieu, L. pneumophila secrets at least 330 effector proteins into host cells. We found that the effector WipA has the protein tyrosine phosphatase (PTP) activity but does not depend on the classical CX5R motif for activity, suggesting that WipA is an unconventional PTP. Meanwhile, the presence of three other highly conserved motifs typically seen in protein serine/threonine phosphatases and the poor inhibition of WipA activity by okadaic acid led us to propose that WipA is a bacterial protein phosphatase. In addition, the determination of the 2.55-Å crystal structure of WipA revealed that WipA resembles cold-active protein tyrosine phosphatase (CAPTPase), and therefore very likely shares the same catalytic mechanism.
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HDM2 promotes WIP1-mediated medulloblastoma growth
Buss, Meghan C.; Read, Tracy-Ann; Schniederjan, Matthew J.; Gandhi, Khanjan; Castellino, Robert C.
2012-01-01
Medulloblastoma is the most common malignant childhood brain tumor. The protein phosphatase and oncogene WIP1 is over-expressed or amplified in a significant number of primary human medulloblastomas and cell lines. In the present study, we examine an important mechanism by which WIP1 promotes medulloblastoma growth using in vitro and in vivo models. Human cell lines and intracerebellar xenografted animal models were used to study the role of WIP1 and the major TP53 regulator, HDM2, in medulloblastoma growth. Stable expression of WIP1 enhances growth of TP53 wild-type medulloblastoma cells, compared with cells with stable expression of an empty-vector or mutant WIP1. In an animal model, WIP1 enhances proliferation and reduces the survival of immunodeficient mice bearing intracerebellar xenografted human medulloblastoma cells. Cells with increased WIP1 expression also exhibit increased expression of HDM2. HDM2 knockdown or treatment with the HDM2 inhibitor Nutlin-3a, the active enantomer of Nutlin-3, specifically inhibits the growth of medulloblastoma cells with increased WIP1 expression. Nutlin-3a does not affect growth of medulloblastoma cells with stable expression of an empty vector or of mutant WIP1. Knockdown of WIP1 or treatment with the WIP1 inhibitor CCT007093 results in increased phosphorylation of known WIP1 targets, reduced HDM2 expression, and reduced growth specifically in WIP1 wild-type and high-expressing medulloblastoma cells. Combined WIP1 and HDM2 inhibition is more effective than WIP1 inhibition alone in blocking growth of WIP1 high-expressing medulloblastoma cells. Our preclinical study supports a role for therapies that target WIP1 and HDM2 in the treatment of medulloblastoma. PMID:22379189
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WIP1 deficiency inhibits HTLV-1 Tax oncogenesis: novel therapeutic prospects for treatment of ATL?
2012-01-01
Attenuation of p53 activity appears to be a major step in Human T-lymphotropic virus type 1 (HTLV-1) Tax transformation. However, p53 genomic mutations are late and rather infrequent events in HTLV-1 induced Adult T cell leukemia (ATL). The paper by Zane et al. shows that a mediator of p53 activity, Wild-type p53-induced phosphatase 1 (Wip1), contributes to Tax-induced oncogenesis in a mouse model. Wip1 may therefore be a novel target for therapeutic approaches. PMID:23256570
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Tang, Yiting; State Key Laboratory of Animal Nutrition and Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193; Liu, Lan
2015-06-10
Mesenchymal stem cells (MSCs), a unique population of multipotent adult progenitor cells originally found in bone marrow (BM), are extremely useful for multifunctional therapeutic approaches. However, the growth arrest and premature senescence of MSCs in vitro prevent the in-depth characterization of these cells. In addition, the regulatory factors involved in MSCs migration remain largely unknown. Given that protein phosphorylation is associated with the processes of MSCs proliferation and migration, we focused on wild-type p53-inducible phosphatase-1 (Wip1), a well-studied modulator of phosphorylation, in this study. Our results showed that Wip1 knockout significantly inhibited MSCs proliferation and induced G2-phase cell-cycle arrest bymore » reducing cyclinB1 expression. Compared with WT-MSCs, Wip1{sup −/−} MSCs displayed premature growth arrest after six passages in culture. Transwell and scratch assays revealed that Wip1{sup −/−} MSCs migrate more effectively than WT-MSCs. Moreover, the enhanced migratory response of Wip1{sup −/−} MSCs may be attributed to increases in the induction of Rac1-GTP activity, the pAKT/AKT ratio, the rearrangement of filamentous-actin (f-actin), and filopodia formation. Based on these results, we then examined the effect of treatment with a PI3K/AKT and Rac1 inhibitor, both of which impaired the migratory activity of MSCs. Therefore, we propose that the PI3K/AKT/Rac1 signaling axis mediates the Wip1 knockout-induced migration of MSCs. Our findings indicate that the principal function of Wip1 in MSCs transformation is the maintenance of proliferative capacity. Nevertheless, knocking out Wip1 increases the migratory capacity of MSCs. This dual effect of Wip1 provides the potential for purposeful routing of MSCs. - Highlights: • Wip1 knockout inhibited MSCs proliferation through reducing cyclinB1 expression. • Wip1{sup −/−} MSCs displayed premature growth arrest in vitro after six passages. • Knocking out Wip1 increases the migratory capacity of MSCs. • The PI3K/AKT/Rac1 pathway mediates the Wip1-knockout-induced migration of MSCs. • Overexpression of Wip1 reversed premature senescence and migration of Wip1{sup −/−} MSCs.« less
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Tatewaki, Naoto; Konishi, Tetsuya; Nakajima, Yuki; Nishida, Miyako; Saito, Masafumi; Eitsuka, Takahiro; Sakamaki, Toshiyuki; Ikekawa, Nobuo; Nishida, Hiroshi
2016-01-01
Ataxia telangiectasia mutated (ATM) kinase plays a crucial role as a master controller in the cellular DNA damage response. Inhibition of ATM leads to inhibition of the checkpoint signaling pathway. Hence, addition of checkpoint inhibitors to anticancer therapies may be an effective targeting strategy. A recent study reported that Wip1, a protein phosphatase, de-phosphorylates serine 1981 of ATM during the DNA damage response. Squalene has been proposed to complement anticancer therapies such as chemotherapy and radiotherapy; however, there is little mechanistic information supporting this idea. Here, we report the inhibitory effect of squalene on ATM-dependent DNA damage signals. Squalene itself did not affect cell viability and the cell cycle of A549 cells, but it enhanced the cytotoxicity of gamma-irradiation (γIR). The in vitro kinase activity of ATM was not altered by squalene. However, squalene increased Wip1 expression in cells and suppressed ATM activation in γIR-treated cells. Consistent with the potential inhibition of ATM by squalene, IR-induced phosphorylation of ATM effectors such as p53 (Ser15) and Chk1 (Ser317) was inhibited by cell treatment with squalene. Thus, squalene inhibits the ATM-dependent signaling pathway following DNA damage through intracellular induction of Wip1 expression.
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Cadmium is a potent inhibitor of PPM phosphatases and targets the M1 binding site
Pan, Chang; Liu, Hong-Da; Gong, Zheng; Yu, Xiao; Hou, Xu-Ben; Xie, Di-Dong; Zhu, Xi-Bin; Li, Hao-Wen; Tang, Jun-Yi; Xu, Yun-Fei; Yu, Jia-Qi; Zhang, Lian-Ying; Fang, Hao; Xiao, Kun-Hong; Chen, Yu-Guo; Wang, Jiang-Yun; Pang, Qi; Chen, Wei; Sun, Jin-Peng
2013-01-01
The heavy metal cadmium is a non-degradable pollutant. By screening the effects of a panel of metal ions on the phosphatase activity, we unexpectedly identified cadmium as a potent inhibitor of PPM1A and PPM1G. In contrast, low micromolar concentrations of cadmium did not inhibit PP1 or tyrosine phosphatases. Kinetic studies revealed that cadmium inhibits PPM phosphatases through the M1 metal ion binding site. In particular, the negative charged D441 in PPM1G specific recognized cadmium. Our results suggest that cadmium is likely a potent inhibitor of most PPM family members except for PHLPPs. Furthermore, we demonstrated that cadmium inhibits PPM1A-regulated MAPK signaling and PPM1G-regulated AKT signaling potently in vivo. Cadmium reversed PPM1A-induced cell cycle arrest and cadmium insensitive PPM1A mutant rescued cadmium induced cell death. Taken together, these findings provide a better understanding of the effects of the toxicity of cadmium in the contexts of human physiology and pathology. PMID:23903585
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Spinnler, C; Hedström, E; Li, H; de Lange, J; Nikulenkov, F; Teunisse, A F A S; Verlaan-de Vries, M; Grinkevich, V; Jochemsen, A G; Selivanova, G
2011-01-01
Inactivation of the p53 tumour suppressor, either by mutation or by overexpression of its inhibitors Hdm2 and HdmX is the most frequent event in cancer. Reactivation of p53 by targeting Hdm2 and HdmX is therefore a promising strategy for therapy. However, Hdm2 inhibitors do not prevent inhibition of p53 by HdmX, which impedes p53-mediated apoptosis. Here, we show that p53 reactivation by the small molecule RITA leads to efficient HdmX degradation in tumour cell lines of different origin and in xenograft tumours in vivo. Notably, HdmX degradation occurs selectively in cancer cells, but not in non-transformed cells. We identified the inhibition of the wild-type p53-induced phosphatase 1 (Wip1) as the major mechanism important for full engagement of p53 activity accomplished by restoration of the ataxia telangiectasia mutated (ATM) kinase-signalling cascade, which leads to HdmX degradation. In contrast to previously reported transactivation of Wip1 by p53, we observed p53-dependent repression of Wip1 expression, which disrupts the negative feedback loop conferred by Wip1. Our study reveals that the depletion of both HdmX and Wip1 potentiates cell death due to sustained activation of p53. Thus, RITA is an example of a p53-reactivating drug that not only blocks Hdm2, but also inhibits two important negative regulators of p53 – HdmX and Wip1, leading to efficient elimination of tumour cells. PMID:21546907
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Spinnler, C; Hedström, E; Li, H; de Lange, J; Nikulenkov, F; Teunisse, A F A S; Verlaan-de Vries, M; Grinkevich, V; Jochemsen, A G; Selivanova, G
2011-11-01
Inactivation of the p53 tumour suppressor, either by mutation or by overexpression of its inhibitors Hdm2 and HdmX is the most frequent event in cancer. Reactivation of p53 by targeting Hdm2 and HdmX is therefore a promising strategy for therapy. However, Hdm2 inhibitors do not prevent inhibition of p53 by HdmX, which impedes p53-mediated apoptosis. Here, we show that p53 reactivation by the small molecule RITA leads to efficient HdmX degradation in tumour cell lines of different origin and in xenograft tumours in vivo. Notably, HdmX degradation occurs selectively in cancer cells, but not in non-transformed cells. We identified the inhibition of the wild-type p53-induced phosphatase 1 (Wip1) as the major mechanism important for full engagement of p53 activity accomplished by restoration of the ataxia telangiectasia mutated (ATM) kinase-signalling cascade, which leads to HdmX degradation. In contrast to previously reported transactivation of Wip1 by p53, we observed p53-dependent repression of Wip1 expression, which disrupts the negative feedback loop conferred by Wip1. Our study reveals that the depletion of both HdmX and Wip1 potentiates cell death due to sustained activation of p53. Thus, RITA is an example of a p53-reactivating drug that not only blocks Hdm2, but also inhibits two important negative regulators of p53 - HdmX and Wip1, leading to efficient elimination of tumour cells.
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Carlessi, Luigi; Buscemi, Giacomo; Fontanella, Enrico; Delia, Domenico
2010-10-01
The checkpoint kinase Chk2 is an effector component of the ATM-dependent DNA damage response (DDR) pathway. The activation of Chk2 by genotoxic stress involves its phosphorylation on T68 by ATM and additional auto/transphosphorylations. Here we demonstrate that in unperturbed cells, chemical inhibition of Chk2 by VRX0466617 (VRX) enhances the phosphorylation of Chk2-T68 throughout the cell cycle phases. This event, dependent on the presence of ATM and catalytically functional Chk2, is not consequential to DNA damage, as neither gamma-H2AX nuclear foci nor increased ATM activation is detected in VRX-treated cells, suggesting the involvement of other regulatory proteins. As serine/threonine protein phosphatases (PPs) regulate the phosphorylation and deactivation of proteins of the DDR pathway, we analyzed their role in phospho-T68-Chk2 regulation. We found that intracellular inhibition of PP1 and PP2A-like activities by okadaic acid markedly raised the accumulation of Chk2-pT68 without DNA damage induction, and this phenomenon was also seen when PP1-C, PP2A-C, and Wip1/PPM1D were simultaneously knockdown by siRNA. Altogether, these data indicate a novel mechanism in undamaged cells where PPs function to maintain the balance between ATM and its direct substrate Chk2 through a regulatory circuit. Copyright © 2010 Elsevier B.V. All rights reserved.
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Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis
2012-01-01
Background Human T-cell Leukemia Virus type 1 (HTLV-1) infects 20 million individuals world-wide and causes Adult T-cell Leukemia/Lymphoma (ATLL), a highly aggressive T-cell cancer. ATLL is refractory to treatment with conventional chemotherapy and fewer than 10% of afflicted individuals survive more than 5 years after diagnosis. HTLV-1 encodes a viral oncoprotein, Tax, that functions in transforming virus-infected T-cells into leukemic cells. All ATLL cases are believed to have reduced p53 activity although only a minority of ATLLs have genetic mutations in their p53 gene. It has been suggested that p53 function is inactivated by the Tax protein. Results Using genetically altered mice, we report here that Tax expression does not achieve a functional equivalence of p53 inactivation as that seen with genetic mutation of p53 (i.e. a p53−/− genotype). Thus, we find statistically significant differences in tumorigenesis between Tax+p53+/+versus Tax+p53−/− mice. We also find a role contributed by the cellular Wip1 phosphatase protein in tumor formation in Tax transgenic mice. Notably, Tax+Wip1−/− mice show statistically significant reduced prevalence of tumorigenesis compared to Tax+Wip1+/+ counterparts. Conclusions Our findings provide new insights into contributions by p53 and Wip1 in the in vivo oncogenesis of Tax-induced tumors in mice. PMID:23256545
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Pinotsis, Nikos; Waksman, Gabriel
2017-06-02
Legionnaires' disease is a severe form of pneumonia caused by the bacterium Legionella pneumophila. L. pneumophila pathogenicity relies on secretion of more than 300 effector proteins by a type IVb secretion system. Among these Legionella effectors, WipA has been primarily studied because of its dependence on a chaperone complex, IcmSW, for translocation through the secretion system, but its role in pathogenicity has remained unknown. In this study, we present the crystal structure of a large fragment of WipA, WipA435. Surprisingly, this structure revealed a serine/threonine phosphatase fold that unexpectedly targets tyrosine-phosphorylated peptides. The structure also revealed a sequence insertion that folds into an α-helical hairpin, the tip of which adopts a canonical coiled-coil structure. The purified protein was a dimer whose dimer interface involves interactions between the coiled coil of one WipA molecule and the phosphatase domain of another. Given the ubiquity of protein-protein interaction mediated by interactions between coiled-coils, we hypothesize that WipA can thereby transition from a homodimeric state to a heterodimeric state in which the coiled-coil region of WipA is engaged in a protein-protein interaction with a tyrosine-phosphorylated host target. In conclusion, these findings help advance our understanding of the molecular mechanisms of an effector involved in Legionella virulence and may inform approaches to elucidate the function of other effectors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
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Ppm1E is an in cellulo AMP-activated protein kinase phosphatase.
Voss, Martin; Paterson, James; Kelsall, Ian R; Martín-Granados, Cristina; Hastie, C James; Peggie, Mark W; Cohen, Patricia T W
2011-01-01
Activation of 5'-AMP-activated protein kinase (AMPK) is believed to be the mechanism by which the pharmaceuticals, metformin and phenformin, exert their beneficial effects for treatment of type 2 diabetes. These biguanide drugs elevate 5'-AMP, which allosterically activates AMPK and promotes phosphorylation on Thr172 of AMPK catalytic α subunits. Although kinases phosphorylating this site have been identified, phosphatases that dephosphorylate it are unknown. The aim of this study is to identify protein phosphatase(s) that dephosphorylate AMPKα-Thr172 within cells. Our initial data indicated that members of the protein phosphatase Mg/Mn(2+)-dependent [corrected] (PPM) family and not those of the PPP family of protein serine/threonine phosphatases may be directly or indirectly inhibited by phenformin. Using antibodies raised to individual Ppm phosphatases that facilitated the assessment of their activities, phenformin stimulation of cells was found to decrease the Mg(2+)/Mn(2+)-dependent [corrected] protein serine/threonine phosphatase activity of Ppm1E and Ppm1F, but not that attributable to other PPM family members, including Ppm1A/PP2Cα. Depletion of Ppm1E, but not Ppm1A, using lentiviral-mediated stable gene silencing, increased AMPKα-Thr172 phosphorylation approximately three fold in HEK293 cells. In addition, incubation of cells with low concentrations of phenformin and depletion of Ppm1E increased AMPK phosphorylation synergistically. Ppm1E and the closely related Ppm1F interact weakly with AMPK and assays with lysates of cells stably depleted of Ppm1F suggest [corrected] that this phosphatase contributes to dephosphorylation of AMPK. The data indicate that Ppm1E and probably PpM1F are in cellulo AMPK phosphatases and that Ppm1E is a potential anti-diabetic drug target. Copyright © 2010 Elsevier Inc. All rights reserved.
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Liu, Sulai; Jiang, Bo; Li, Hao; He, Zili; Lv, Pin; Peng, Chuang; Wang, Yonggang; Cheng, Wei; Xu, Zhengquan; Chen, Wei; Liu, Zhengkai; Zhang, Bao; Shen, Shengqian; Xiang, Shuanglin
2017-01-01
Wip1 has been shown to correlate with the metastasis/invasion of several tumors. This study was designed to investigate the clinical significance and biological function of Wip1 in intrahepatic cholangiocarcinoma (ICC). The expression of Wip1 was investigated in sixty human ICC biopsy samples by immunohistochemistry. Transient and stable knockdown of Wip1 in two human ICC cells (ICC-9810 and SSP25) were established using short hairpin RNA expression vector. Immunohistochemistry revealed that Wip1 was up-regulated in human ICC tissues (47/60, 78.3%). High levels of Wip1 in human ICC correlated with metastasis to the lymph metastasis (P=0.022). Genetic depletion of Wip1 in ICC cells resulted in significantly inhibited proliferation and invasion compared with controls. Most importantly, Wip1 down-regulation impaired tumor migration capacity of ICC cells in vivo. Subsequent investigations revealed that matrix metalloproteinase-2 (MMP-2) is an important target of Wip1. Consistently, in human ICC tissues, Wip1 level was positively correlated with MMP-2 expression. Taken together, our founding indicates that Wip1 may be a crucial regulator in the tumorigenicity and invasion of human ICC, Wip1 exerts its pro-invasion function at least in part through the MMP-2 signaling pathway, suggesting Wip1 as a potential therapeutic target for ICC. PMID:28915621
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Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
Ruark, Elise; Snape, Katie; Humburg, Peter; Loveday, Chey; Bajrami, Ilirjana; Brough, Rachel; Rodrigues, Daniel Nava; Renwick, Anthony; Seal, Sheila; Ramsay, Emma; Duarte, Silvana Del Vecchio; Rivas, Manuel A.; Warren-Perry, Margaret; Zachariou, Anna; Campion-Flora, Adriana; Hanks, Sandra; Murray, Anne; Pour, Naser Ansari; Douglas, Jenny; Gregory, Lorna; Rimmer, Andrew; Walker, Neil M.; Yang, Tsun-Po; Adlard, Julian W.; Barwell, Julian; Berg, Jonathan; Brady, Angela F.; Brewer, Carole; Brice, Glen; Chapman, Cyril; Cook, Jackie; Davidson, Rosemarie; Donaldson, Alan; Douglas, Fiona; Eccles, Diana; Evans, D. Gareth; Greenhalgh, Lynn; Henderson, Alex; Izatt, Louise; Kumar, Ajith; Lalloo, Fiona; Miedzybrodzka, Zosia; Morrison, Patrick J.; Paterson, Joan; Porteous, Mary; Rogers, Mark T.; Shanley, Susan; Walker, Lisa; Gore, Martin; Houlston, Richard; Brown, Matthew A.; Caufield, Mark J.; Deloukas, Panagiotis; McCarthy, Mark I.; Todd, John A.; Turnbull, Clare; Reis-Filho, Jorge S.; Ashworth, Alan; Antoniou, Antonis C.; Lord, Christopher J.; Donnelly, Peter; Rahman, Nazneen
2013-01-01
Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication1. Here, using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focussed on protein truncating variants (PTVs) and a large-scale sequencing case-control replication experiment in 13,642 individuals, we show that rare PTVs in the p53 inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and to ovarian cancer. PPM1D PTV mutations were present in 25/7781 cases vs 1/5861 controls; P=1.12×10−5, which included 18 mutations in 6,912 individuals with breast cancer; P = 2.42×10−4 and 12 mutations in 1,121 individuals with ovarian cancer; P = 3.10×10−9. Notably, all the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370 bp region in the final exon of the gene, C-terminal to the phosphatase catalytic domain. Functional studies demonstrated that the mutations result in enhanced suppression of p53 in response to ionising radiation exposure, suggesting the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function typically associated with this class of variant, but instead likely have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the utility of sequencing in their identification. PMID:23242139
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Characterization of a Maize Wip1 Promoter in Transgenic Plants
Zhang, Shengxue; Lian, Yun; Liu, Yan; Wang, Xiaoqing; Liu, Yunjun; Wang, Guoying
2013-01-01
The Maize Wip1 gene encodes a wound-induced Bowman-Birk inhibitor (BBI) protein which is a type of serine protease inhibitor, and its expression is induced by wounding or infection, conferring resistance against pathogens and pests. In this study, the maize Wip1 promoter was isolated and its function was analyzed. Different truncated Wip1 promoters were fused upstream of the GUS reporter gene and transformed into Arabidopsis, tobacco and rice plants. We found that (1) several truncated maize Wip1 promoters led to strong GUS activities in both transgenic Arabidopsis and tobacco leaves, whereas low GUS activity was detected in transgenic rice leaves; (2) the Wip1 promoter was not wound-induced in transgenic tobacco leaves, but was induced by wounding in transgenic rice leaves; (3) the truncated Wip1 promoter had different activity in different organs of transgenic tobacco plants; (4) the transgenic plant leaves containing different truncated Wip1 promoters had low GUS transcripts, even though high GUS protein level and GUS activities were observed; (5) there was one transcription start site of Wip1 gene in maize and two transcription start sites of GUS in Wip1::GUS transgenic lines; (6) the adjacent 35S promoter which is present in the transformation vectors enhanced the activity of the truncated Wip1 promoters in transgenic tobacco leaves, but did not influence the disability of truncated Wip1231 promoter to respond to wounding signals. We speculate that an ACAAAA hexamer, several CAA trimers and several elements similar to ACAATTAC octamer in the 5′-untranslated region might contribute to the strong GUS activity in Wip1231 transgenic lines, meanwhile, compared to the 5′-untranslated region from Wip1231 transgenic lines, the additional upstream open reading frames (uORFs) in the 5′-untranslated region from Wip1737 transgenic lines might contribute to the lower level of GUS transcript and GUS activity. PMID:24322445
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Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer.
Ruark, Elise; Snape, Katie; Humburg, Peter; Loveday, Chey; Bajrami, Ilirjana; Brough, Rachel; Rodrigues, Daniel Nava; Renwick, Anthony; Seal, Sheila; Ramsay, Emma; Duarte, Silvana Del Vecchio; Rivas, Manuel A; Warren-Perry, Margaret; Zachariou, Anna; Campion-Flora, Adriana; Hanks, Sandra; Murray, Anne; Ansari Pour, Naser; Douglas, Jenny; Gregory, Lorna; Rimmer, Andrew; Walker, Neil M; Yang, Tsun-Po; Adlard, Julian W; Barwell, Julian; Berg, Jonathan; Brady, Angela F; Brewer, Carole; Brice, Glen; Chapman, Cyril; Cook, Jackie; Davidson, Rosemarie; Donaldson, Alan; Douglas, Fiona; Eccles, Diana; Evans, D Gareth; Greenhalgh, Lynn; Henderson, Alex; Izatt, Louise; Kumar, Ajith; Lalloo, Fiona; Miedzybrodzka, Zosia; Morrison, Patrick J; Paterson, Joan; Porteous, Mary; Rogers, Mark T; Shanley, Susan; Walker, Lisa; Gore, Martin; Houlston, Richard; Brown, Matthew A; Caufield, Mark J; Deloukas, Panagiotis; McCarthy, Mark I; Todd, John A; Turnbull, Clare; Reis-Filho, Jorge S; Ashworth, Alan; Antoniou, Antonis C; Lord, Christopher J; Donnelly, Peter; Rahman, Nazneen
2013-01-17
Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case-control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10(-5)), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10(-4)) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10(-9)). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.
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PPM1D Mosaic Truncating Variants in Ovarian Cancer Cases May Be Treatment-Related Somatic Mutations
Pharoah, Paul D. P.; Song, Honglin; Dicks, Ed; Intermaggio, Maria P.; Harrington, Patricia; Baynes, Caroline; Alsop, Kathryn; Bogdanova, Natalia; Cicek, Mine S.; Cunningham, Julie M.; Fridley, Brooke L.; Gentry-Maharaj, Aleksandra; Hillemanns, Peter; Lele, Shashi; Lester, Jenny; McGuire, Valerie; Moysich, Kirsten B.; Poblete, Samantha; Sieh, Weiva; Sucheston-Campbell, Lara; Widschwendter, Martin; Whittemore, Alice S.; Dörk, Thilo; Menon, Usha; Odunsi, Kunle; Goode, Ellen L.; Karlan, Beth Y.; Bowtell, David D.; Gayther, Simon A.; Ramus, Susan J.
2016-01-01
Mosaic truncating mutations in the protein phosphatase, Mg2+/Mn2+-dependent, 1D (PPM1D) gene have recently been reported with a statistically significantly greater frequency in lymphocyte DNA from ovarian cancer case patients compared with unaffected control patients. Using massively parallel sequencing (MPS) we identified truncating PPM1D mutations in 12 of 3236 epithelial ovarian cancer (EOC) case patients (0.37%) but in only one of 3431 unaffected control patients (0.03%) (P = .001). All statistical tests were two-sided. A combination of Sanger sequencing, pyrosequencing, and MPS data suggested that 12 of the 13 mutations were mosaic. All mutations were identified in post-chemotherapy treatment blood samples from case patients (n = 1827) (average 1234 days post-treatment in carriers) rather than from cases collected pretreatment (less than 14 days after diagnosis, n = 1384) (P = .002). These data suggest that PPM1D variants in EOC cases are primarily somatic mosaic mutations caused by treatment and are not associated with germline predisposition to EOC. PMID:26823519
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PPM1D Mosaic Truncating Variants in Ovarian Cancer Cases May Be Treatment-Related Somatic Mutations.
Pharoah, Paul D P; Song, Honglin; Dicks, Ed; Intermaggio, Maria P; Harrington, Patricia; Baynes, Caroline; Alsop, Kathryn; Bogdanova, Natalia; Cicek, Mine S; Cunningham, Julie M; Fridley, Brooke L; Gentry-Maharaj, Aleksandra; Hillemanns, Peter; Lele, Shashi; Lester, Jenny; McGuire, Valerie; Moysich, Kirsten B; Poblete, Samantha; Sieh, Weiva; Sucheston-Campbell, Lara; Widschwendter, Martin; Whittemore, Alice S; Dörk, Thilo; Menon, Usha; Odunsi, Kunle; Goode, Ellen L; Karlan, Beth Y; Bowtell, David D; Gayther, Simon A; Ramus, Susan J
2016-03-01
Mosaic truncating mutations in the protein phosphatase, Mg(2+)/Mn(2+)-dependent, 1D (PPM1D) gene have recently been reported with a statistically significantly greater frequency in lymphocyte DNA from ovarian cancer case patients compared with unaffected control patients. Using massively parallel sequencing (MPS) we identified truncating PPM1D mutations in 12 of 3236 epithelial ovarian cancer (EOC) case patients (0.37%) but in only one of 3431 unaffected control patients (0.03%) (P = .001). All statistical tests were two-sided. A combination of Sanger sequencing, pyrosequencing, and MPS data suggested that 12 of the 13 mutations were mosaic. All mutations were identified in post-chemotherapy treatment blood samples from case patients (n = 1827) (average 1234 days post-treatment in carriers) rather than from cases collected pretreatment (less than 14 days after diagnosis, n = 1384) (P = .002). These data suggest that PPM1D variants in EOC cases are primarily somatic mosaic mutations caused by treatment and are not associated with germline predisposition to EOC. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Liu, Jianyu; Stevens, Payton D; Eshleman, Nichole E; Gao, Tianyan
2013-08-09
Protein translation initiation is a tightly controlled process responding to nutrient availability and mitogen stimulation. Serving as one of the most important negative regulators of protein translation, 4E binding protein 1 (4E-BP1) binds to translation initiation factor 4E and inhibits cap-dependent translation in a phosphorylation-dependent manner. Although it has been demonstrated previously that the phosphorylation of 4E-BP1 is controlled by mammalian target of rapamycin in the mammalian target of rapamycin complex 1, the mechanism underlying the dephosphorylation of 4E-BP1 remains elusive. Here, we report the identification of PPM1G as the phosphatase of 4E-BP1. A coimmunoprecipitation experiment reveals that PPM1G binds to 4E-BP1 in cells and that purified PPM1G dephosphorylates 4E-BP1 in vitro. Knockdown of PPM1G in 293E and colon cancer HCT116 cells results in an increase in the phosphorylation of 4E-BP1 at both the Thr-37/46 and Ser-65 sites. Furthermore, the time course of 4E-BP1 dephosphorylation induced by amino acid starvation or mammalian target of rapamycin inhibition is slowed down significantly in PPM1G knockdown cells. Functionally, the amount of 4E-BP1 bound to the cap-dependent translation initiation complex is decreased when the expression of PPM1G is depleted. As a result, the rate of cap-dependent translation, cell size, and protein content are increased in PPM1G knockdown cells. Taken together, our study has identified protein phosphatase PPM1G as a novel regulator of cap-dependent protein translation by negatively controlling the phosphorylation of 4E-BP1.
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Demirkıran, Gökhan; Kalaycı Demir, Güleser; Güzeliş, Cüneyt
2018-02-01
This study proposes a two-dimensional (2D) oscillator model of p53 network, which is derived via reducing the multidimensional two-phase dynamics model into a model of ataxia telangiectasia mutated (ATM) and Wip1 variables, and studies the impact of p53-regulators on cell fate decision. First, the authors identify a 6D core oscillator module, then reduce this module into a 2D oscillator model while preserving the qualitative behaviours. The introduced 2D model is shown to be an excitable relaxation oscillator. This oscillator provides a mechanism that leads diverse modes underpinning cell fate, each corresponding to a cell state. To investigate the effects of p53 inhibitors and the intrinsic time delay of Wip1 on the characteristics of oscillations, they introduce also a delay differential equation version of the 2D oscillator. They observe that the suppression of p53 inhibitors decreases the amplitudes of p53 oscillation, though the suppression increases the sustained level of p53. They identify Wip1 and P53DINP1 as possible targets for cancer therapies considering their impact on the oscillator, supported by biological findings. They model some mutations as critical changes of the phase space characteristics. Possible cancer therapeutic strategies are then proposed for preventing these mutations' effects using the phase space approach.
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Jansen, Sandra; Geuer, Sinje; Pfundt, Rolph; Brough, Rachel; Ghongane, Priyanka; Herkert, Johanna C; Marco, Elysa J; Willemsen, Marjolein H; Kleefstra, Tjitske; Hannibal, Mark; Shieh, Joseph T; Lynch, Sally Ann; Flinter, Frances; FitzPatrick, David R; Gardham, Alice; Bernhard, Birgitta; Ragge, Nicola; Newbury-Ecob, Ruth; Bernier, Raphael; Kvarnung, Malin; Magnusson, E A Helena; Wessels, Marja W; van Slegtenhorst, Marjon A; Monaghan, Kristin G; de Vries, Petra; Veltman, Joris A; Lord, Christopher J; Vissers, Lisenka E L M; de Vries, Bert B A
2017-04-06
Intellectual disability (ID) is a highly heterogeneous disorder involving at least 600 genes, yet a genetic diagnosis remains elusive in ∼35%-40% of individuals with moderate to severe ID. Recent meta-analyses statistically analyzing de novo mutations in >7,000 individuals with neurodevelopmental disorders highlighted mutations in PPM1D as a possible cause of ID. PPM1D is a type 2C phosphatase that functions as a negative regulator of cellular stress-response pathways by mediating a feedback loop of p38-p53 signaling, thereby contributing to growth inhibition and suppression of stress-induced apoptosis. We identified 14 individuals with mild to severe ID and/or developmental delay and de novo truncating PPM1D mutations. Additionally, deep phenotyping revealed overlapping behavioral problems (ASD, ADHD, and anxiety disorders), hypotonia, broad-based gait, facial dysmorphisms, and periods of fever and vomiting. PPM1D is expressed during fetal brain development and in the adult brain. All mutations were located in the last or penultimate exon, suggesting escape from nonsense-mediated mRNA decay. Both PPM1D expression analysis and cDNA sequencing in EBV LCLs of individuals support the presence of a stable truncated transcript, consistent with this hypothesis. Exposure of cells derived from individuals with PPM1D truncating mutations to ionizing radiation resulted in normal p53 activation, suggesting that p53 signaling is unaffected. However, a cell-growth disadvantage was observed, suggesting a possible effect on the stress-response pathway. Thus, we show that de novo truncating PPM1D mutations in the last and penultimate exons cause syndromic ID, which provides additional insight into the role of cell-cycle checkpoint genes in neurodevelopmental disorders. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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A Rapid and Simple Integrated Extraction Amplification and Detection Device for Y. pestis
2000-10-01
Yersinia pestis is transmitted by fleas. Three virulence plasmids are characteristic in Y pestis. These vary in different strains by size and...WIP# 330440), dTTP(BD WIP# 330572) and dCsTP(BD WIP# 330546). Additional SDA reagents Additional components: Bovine serum albumin (BSA) (BD WIP# 360653...in a thermocycler, with addition of enzyme following the denaturation step. Efforts to block the effect by prior exposure of the plastic to bovine
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Petri, Sebastian; Grimmler, Matthias; Over, Sabine; Fischer, Utz; Gruss, Oliver J.
2007-01-01
The survival motor neuron (SMN) complex functions in maturation of uridine-rich small nuclear ribonucleoprotein (RNP) particles. SMN mediates the cytoplasmic assembly of Sm proteins onto uridine-rich small RNAs, and then participates in targeting RNPs to nuclear Cajal bodies (CBs). Recent studies have suggested that phosphorylation might control localization and function of the SMN complex. Here, we show that the nuclear phosphatase PPM1G/PP2Cγ interacts with and dephosphorylates the SMN complex. Small interfering RNA knockdown of PPM1G leads to an altered phosphorylation pattern of SMN and Gemin3, loss of SMN from CBs, and reduced stability of SMN. Accumulation in CBs is restored upon overexpression of catalytically active, but not that of inactive, PPM1G. This demonstrates that PPM1G's phosphatase activity is necessary to maintain SMN subcellular distribution. Concomitant knockdown of unr interacting protein (unrip), a component implicated in cytoplasmic retention of the SMN complex, also rescues the localization defects. Our data suggest that an interplay between PPM1G and unrip determine compartment-specific phosphorylation patterns, localization, and function of the SMN complex. PMID:17984321
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Bu, Shizhong; Kapanadze, Bagrat; Hsu, Tien; Trojanowska, Maria
2008-01-01
Transforming growth factor-β (TGF-β) is an important regulator of physiological connective tissue biosynthesis and plays a central role in pathological tissue fibrosis. Previous studies have established that a biologically active lipid mediator, sphingosine 1-phosphate (S1P), mimics some of the profibrotic functions of TGF-β through cross-activation of Smad signaling. Here we report that another product of sphingosine kinase, dihydrosphingosine 1-phosphate (dhS1P), has an opposite role in the regulation of TGF-β signaling. In contrast to S1P, dhS1P inhibits TGF-β-induced Smad2/3 phosphorylation and up-regulation of collagen synthesis. The effects of dhS1P require a lipid phosphatase, PTEN, a key modulator of cell growth and survival. dhS1P stimulates phosphorylation of the C-terminal domain of PTEN and its subsequent translocation into the nucleus. We demonstrate a novel function of nuclear PTEN as a co-factor of the Smad2/3 phosphatase, PPM1A. Complex formation of PTEN with PPM1A does not require the lipid phosphatase activity but depends on phosphorylation of the serine/threonine residues located in the C-terminal domain of PTEN. Upon complex formation with PTEN, PPM1A is protected from degradation induced by the TGF-β signaling. Consequently, overexpression of PTEN abrogates TGF-β-induced Smad2/3 phosphorylation. This study establishes a novel role for nuclear PTEN in the stabilization of PPM1A. PTEN-mediated cross-talk between the sphingolipid and TGF-β signaling pathways may play an important role in physiological and pathological TGF-β signaling. PMID:18482992
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Bu, Shizhong; Kapanadze, Bagrat; Hsu, Tien; Trojanowska, Maria
2008-07-11
Transforming growth factor-beta (TGF-beta) is an important regulator of physiological connective tissue biosynthesis and plays a central role in pathological tissue fibrosis. Previous studies have established that a biologically active lipid mediator, sphingosine 1-phosphate (S1P), mimics some of the profibrotic functions of TGF-beta through cross-activation of Smad signaling. Here we report that another product of sphingosine kinase, dihydrosphingosine 1-phosphate (dhS1P), has an opposite role in the regulation of TGF-beta signaling. In contrast to S1P, dhS1P inhibits TGF-beta-induced Smad2/3 phosphorylation and up-regulation of collagen synthesis. The effects of dhS1P require a lipid phosphatase, PTEN, a key modulator of cell growth and survival. dhS1P stimulates phosphorylation of the C-terminal domain of PTEN and its subsequent translocation into the nucleus. We demonstrate a novel function of nuclear PTEN as a co-factor of the Smad2/3 phosphatase, PPM1A. Complex formation of PTEN with PPM1A does not require the lipid phosphatase activity but depends on phosphorylation of the serine/threonine residues located in the C-terminal domain of PTEN. Upon complex formation with PTEN, PPM1A is protected from degradation induced by the TGF-beta signaling. Consequently, overexpression of PTEN abrogates TGF-beta-induced Smad2/3 phosphorylation. This study establishes a novel role for nuclear PTEN in the stabilization of PPM1A. PTEN-mediated cross-talk between the sphingolipid and TGF-beta signaling pathways may play an important role in physiological and pathological TGF-beta signaling.
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White, Phillip J; McGarrah, Robert W; Grimsrud, Paul A; Tso, Shih-Chia; Yang, Wen-Hsuan; Haldeman, Jonathan M; Grenier-Larouche, Thomas; An, Jie; Lapworth, Amanda L; Astapova, Inna; Hannou, Sarah A; George, Tabitha; Arlotto, Michelle; Olson, Lyra B; Lai, Michelle; Zhang, Guo-Fang; Ilkayeva, Olga; Herman, Mark A; Wynn, R Max; Chuang, David T; Newgard, Christopher B
2018-06-05
Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulates branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis, and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K. Hepatic overexpression of BDK increased ACL phosphorylation and activated de novo lipogenesis. BDK and PPM1K transcript levels were increased and repressed, respectively, in response to fructose feeding or expression of the ChREBP-β transcription factor. These studies identify BDK and PPM1K as a ChREBP-regulated node that integrates BCAA and lipid metabolism. Moreover, manipulation of the BDK:PPM1K ratio relieves key metabolic disease phenotypes in a genetic model of severe obesity. Copyright © 2018 Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ozaki, Hana; Katoh, Tsuyoshi; Nakagawa, Ryoko
2016-09-02
Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) is a Ser/Thr phosphatase that belongs to the PPM family. Growing evidence suggests that PPM phosphatases including CaMKP act as a complex with other proteins to regulate cellular functions. In this study, using the two-dimensional far-western blotting technique with digoxigenin-labeled CaMKP as a probe, in conjunction with peptide mass fingerprinting analysis, we identified neurofilament L (NFL) as a CaMKP-binding protein in a Triton-insoluble fraction of rat brain. We confirmed binding of fluorescein-labeled CaMKP (F-CaMKP) to NFL in solution by fluorescence polarization. The analysis showed that the dissociation constant of F-CaMKP for NFL is 73 ± 17 nMmore » (n = 3). Co-immunoprecipitation assay using a cytosolic fraction of NGF-differentiated PC12 cells showed that endogenous CaMKP and NFL form a complex in cells. Furthermore, the effect of CaMKP on self-assembly of NFL was examined. Electron microscopy revealed that CaMKP markedly prevented NFL from forming large filamentous aggregates, suggesting that CaMKP-binding to NFL inhibits its filament association. These findings may provide new insights into a novel mechanism for regulating network formation of neurofilaments during neuronal differentiation. - Highlights: • NFL was identified as a CaMKP-binding protein in an insoluble fraction of rat brain. • CaMKP bound to NFL in solution with a K{sub d} value of 73 ± 17 nM. • A CaMKP-NFL complex was found in NGF-differentiated PC12 cells. • CaMKP-binding to NFL inhibited its filament association. • CaMKP may regulate network formation of neurofilaments in neurons.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Ruiliang; Potters, M B.; Shi, Liang
2005-09-01
The open reading frames (ORFs) encoding two potential protein-serine/threonine phosphatases from the cyanobacterium Synechocystis sp. strain PCC 6803 were cloned and their protein products expressed in Escherichia coli cells. The product of ORF sll1033, SynPPM3, is a homologue of the PPM family of protein-serine/threonine phosphatases found in all eukaryotes as well as many members of the Bacteria. Surprisingly, the recombinant protein phosphatase dephosphorylated phosphotyrosine- as well as phosphoserine-containing proteins in vitro. While kinetic analyses indicate that the enzyme was more efficient at dephosphorylating the latter, replacement of Asp(608) by asparagine enhanced activity toward a phosphotyrosine-containing protein fourfold. The product ofmore » ORF sll1387, SynPPP1, is the sole homolog of the PPP family of protein phosphatases encoded by the genome of Synechocystis sp. strain PCC 6803. Like many other bacterial PPPs, the enzyme dephosphorylated phosphoserine- and phosphotyrosine-containing proteins with comparable efficiencies. However, while previously described PPPs from prokaryotic organisms required the addition of exogenous metal ion cofactors, such as Mg(2+) or Mn(2+), for activity, recombinantly produced SynPPP1 displayed near-maximal activity in the absence of added metals. Inductively coupled plasma mass spectrometry indicated that recombinant SynPPP1 contained significant quantities, 0.32 to 0.44 mol/mole total, of Mg and Mn. In this respect, the cyanobacterial enzyme resembled eukaryotic members of the PPP family, which are metalloproteins. mRNA encoding SynPPP1 or SynPPM3 could be detected in cells grown under many, but not all, environmental conditions.« less
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Degradation of Chlorpyrifos by an alkaline phosphatase from the cyanobacterium Spirulina platensis.
Thengodkar, Rutwik Ravindra Mandakini; Sivakami, S
2010-07-01
Spirulina is a photosynthetic, filamentous, spiral-shaped, multicellular, blue-green microalga. The two most important species are Spirulina maxima and Spirulina platensis. Spirulina is considered an excellent food, lacking toxicity and having corrective properties against viral attacks, anemia, tumor growth and malnutrition. We have observed that cultures of Spirulina platensis grow in media containing up to 80 ppm of the organophosphorous pesticide, Chlorpyrifos. It was found to be due to an alkaline phosphatase (ALP) activity that was detected in cell free extracts of Spirulina platensis. This activity was purified from the cell free extracts using ammonium sulphate precipitation and gel filtration and shown to belong to the class of EC 3.1.3.1 ALP. The purified enzyme degrades 100 ppm Chlorpyrifos to 20 ppm in 1 h transforming it into its primary metabolite 3, 5, 6-trichloro-2-pyridinol. This is the first report of degradation of Chlorpyrifos by Spirulina platensis whose enzymic mechanism has been clearly identified. These findings have immense potential for harnessing Spirulina platensis in bioremediation of polluted ecosystems.
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New candidate markers of head and neck squamous cell carcinoma progression
NASA Astrophysics Data System (ADS)
Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Kulbakin, D. E.; Choinzonov, E. L.
2017-09-01
The tumor progression in head and neck squamous cell carcinoma (HNSCC) is one of the main causes of high mortality of the patients with HNSCC. The tumor progression, particularly the metastasis, is characterized by the changes in the composition, functions and structure of different proteins. We have previously shown that serum of HNSCC patients contains the proteins which regulate various cellular processes—adenylyl cyclase associated protein 1 (CAP1), protein phosphatase 1 B (PPM1B), etc. The levels of CAP1 and PPM1B were determined using the enzyme immunoassay. The results of this study show that CAP1 and PPM1B take a part in the progression of HNSCC. The levels of CAP1 and PPM1B in the tumor and in morphologically normal tissue depended on the prevalence of the tumor process. The CAP1 and PPM1B levels were significantly higher in tumor tissue of the patients with regional metastasis. Our data allow assuming the potential possibility for predicting the outcome of the HNSCC measuring the level of tissue CAP1.
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Suganuma, Masatoshi; Teh, Aik Hong; Makino, Masatomo; Shimizu, Nobutaka; Kaneko, Tomonori; Hirata, Kunio; Yamamoto, Masaki; Kumasaka, Takashi
2009-01-01
RsbX from Bacillus subtilis is a manganese-dependent PPM phosphatase and negatively regulates the signal transduction of the general stress response by the dephosphorylation of RsbS and RsbR, which are activators of the alternative RNA polymerase σ factor SigB. In order to elucidate the structural–functional relationship of its Ser/Thr protein-phosphorylation mechanism, an X-ray crystallographic diffraction study of RsbX was performed. Recombinant RsbX was expressed in Escherichia coli, purified and crystallized. Crystals were obtained using the sitting-drop vapour-diffusion method and X-ray diffraction data were collected to 1.06 Å resolution with an R merge of 8.1%. The crystals belonged to the triclinic space group P1, with unit-cell parameters a = 33.3, b = 41.7, c = 68.6 Å, α = 98.8, β = 90.0, γ = 108.4°. PMID:19923733
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Suganuma, Masatoshi; Teh, Aik Hong; Makino, Masatomo; Shimizu, Nobutaka; Kaneko, Tomonori; Hirata, Kunio; Yamamoto, Masaki; Kumasaka, Takashi
2009-11-01
RsbX from Bacillus subtilis is a manganese-dependent PPM phosphatase and negatively regulates the signal transduction of the general stress response by the dephosphorylation of RsbS and RsbR, which are activators of the alternative RNA polymerase sigma factor SigB. In order to elucidate the structural-functional relationship of its Ser/Thr protein-phosphorylation mechanism, an X-ray crystallographic diffraction study of RsbX was performed. Recombinant RsbX was expressed in Escherichia coli, purified and crystallized. Crystals were obtained using the sitting-drop vapour-diffusion method and X-ray diffraction data were collected to 1.06 angstrom resolution with an R(merge) of 8.1%. The crystals belonged to the triclinic space group P1, with unit-cell parameters a = 33.3, b = 41.7, c = 68.6 angstrom , alpha = 98.8, beta = 90.0, gamma = 108.4 degrees.
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Wound-Induced Polyploidization: Regulation by Hippo and JNK Signaling and Conservation in Mammals.
Losick, Vicki P; Jun, Albert S; Spradling, Allan C
2016-01-01
Tissue integrity and homeostasis often rely on the proliferation of stem cells or differentiated cells to replace lost, aged, or damaged cells. Recently, we described an alternative source of cell replacement- the expansion of resident, non-dividing diploid cells by wound-induced polyploidization (WIP). Here we show that the magnitude of WIP is proportional to the extent of cell loss using a new semi-automated assay with single cell resolution. Hippo and JNK signaling regulate WIP; unexpectedly however, JNK signaling through AP-1 limits rather than stimulates the level of Yki activation and polyploidization in the Drosophila epidermis. We found that polyploidization also quantitatively compensates for cell loss in a mammalian tissue, mouse corneal endothelium, where increased cell death occurs with age in a mouse model of Fuchs Endothelial Corneal Dystrophy (FECD). Our results suggest that WIP is an evolutionarily conserved homeostatic mechanism that maintains the size and synthetic capacity of adult tissues.
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Wound-Induced Polyploidization: Regulation by Hippo and JNK Signaling and Conservation in Mammals
Losick, Vicki P.; Jun, Albert S.; Spradling, Allan C.
2016-01-01
Tissue integrity and homeostasis often rely on the proliferation of stem cells or differentiated cells to replace lost, aged, or damaged cells. Recently, we described an alternative source of cell replacement- the expansion of resident, non-dividing diploid cells by wound-induced polyploidization (WIP). Here we show that the magnitude of WIP is proportional to the extent of cell loss using a new semi-automated assay with single cell resolution. Hippo and JNK signaling regulate WIP; unexpectedly however, JNK signaling through AP-1 limits rather than stimulates the level of Yki activation and polyploidization in the Drosophila epidermis. We found that polyploidization also quantitatively compensates for cell loss in a mammalian tissue, mouse corneal endothelium, where increased cell death occurs with age in a mouse model of Fuchs Endothelial Corneal Dystrophy (FECD). Our results suggest that WIP is an evolutionarily conserved homeostatic mechanism that maintains the size and synthetic capacity of adult tissues. PMID:26958853
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Gardner, Thomas W; Abcouwer, Steven F; Losiewicz, Mandy K; Fort, Patrice E
2015-09-15
Control of protein synthesis in insulin-responsive tissues has been well characterized, but relatively little is known about how this process is regulated in nervous tissues. The retina exhibits a relatively high protein synthesis rate, coinciding with high basal Akt and metabolic activities, with the majority of retinal ATP being derived from aerobic glycolysis. We examined the dependency of retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but did not affect glycolytic lactate production. Surprisingly, the glycolytic inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG) on retinal protein synthesis correlated with inhibition of lactate production and diminished ATP content, with all these effects reversed by provision of d-mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or eIF2α phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1. 2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce mTORC1 activity, as indicated by unaltered raptor-associated mTOR autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium. Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1. These results demonstrate a novel mechanism regulating protein synthesis in the retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E-BP1. Copyright © 2015 the American Physiological Society.
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Exposure to low levels of hydrogen sulfide elevates circulating glucose in maternal rats
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hayden, L.J.; Goeden, H.; Roth, S.H.
1990-09-01
Although the lethal effect of hydrogen sulfide (H{sub 2}S) has long been known, the results of exposure to low levels of H{sub 2}S have not been well documented. Rat dams and pups were exposed to low levels of H{sub 2}S (less than or equal to 75 ppm) from d 1 of gestation until d 21 postpartum and analyzed for changes in circulating enzymatic activity and metabolites. Blood glucose was significantly elevated in maternal blood on d 21 postpartum at all exposure levels. This increase in glucose was accompanied by a possible decrease in serum triglyceride in the pups and inmore » the dams on d 21 postpartum. There was no evidence of alterations in serum alkaline phosphatase, lactate dehydrogenase, or serum glutamate oxaloacetate transaminase.« less
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Scior, Thomas; Guevara-García, José Antonio; Melendez, F J; Abdallah, Hassan H; Do, Quoc-Tuan; Bernard, Philippe
2010-09-24
Prior to its total synthesis, a new vanadium coordination compound, called TSAG0101, was computationally designed to inhibit the enzyme protein tyrosine phosphatase 1B (PTP1B). The PTP1B acts as a negative regulator of insulin signaling by blocking the active site where phosphate hydrolysis of the insulin receptor takes place. TSAG001, [V(V)O(2)(OH)(picolinamide)], was characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy; IR: ν/cm(-1) 3,570 (NH), 1,627 (C=O, coordinated), 1,417 (C-N), 970/842 (O=V=O), 727 δ̣ (pyridine ring); (13)C NMR: 5 bands between 122 and 151 ppm and carbonyl C shifted to 180 ppm; and (1)H NMR: 4 broad bands from 7.6 to 8.2 ppm and NH(2) shifted to 8.8 ppm. In aqueous solution, in presence or absence of sodium citrate as a biologically relevant and ubiquitous chelator, TSAG0101 undergoes neither ligand exchange nor reduction of its central vanadium atom during 24 hours. TSAG0101 shows blood glucose lowering effects in rats but it produced no alteration of basal- or glucose-induced insulin secretion on β cells during in vitro tests, all of which excludes a direct mechanism evidencing the extrapancreatic nature of its activity. The lethal dose (LD(50)) of TSAG0101 was determined in Wistar mice yielding a value of 412 mg/kg. This value is one of the highest among vanadium compounds and classifies it as a mild toxicity agent when compared with literature data. Due to its nonsubstituted, small-sized scaffold design, its remarkable complex stability, and low toxicity; TSAG0101 should be considered as an innovative insulin-mimetic principle with promising properties and, therefore, could become a new lead compound for potential nonpeptide PTP1B inhibitors in antidiabetic drug research. In view of the present work, the inhibitory concentration (IC(50)) and extended solution stability will be tested.
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Scior, Thomas; Guevara-García, José Antonio; Melendez, FJ; Abdallah, Hassan H; Do, Quoc-Tuan; Bernard, Philippe
2010-01-01
Prior to its total synthesis, a new vanadium coordination compound, called TSAG0101, was computationally designed to inhibit the enzyme protein tyrosine phosphatase 1B (PTP1B). The PTP1B acts as a negative regulator of insulin signaling by blocking the active site where phosphate hydrolysis of the insulin receptor takes place. TSAG001, [VVO2(OH)(picolinamide)], was characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy; IR: ν/cm−1 3,570 (NH), 1,627 (C=O, coordinated), 1,417 (C–N), 970/842 (O=V=O), 727 δ̣ (pyridine ring); 13C NMR: 5 bands between 122 and 151 ppm and carbonyl C shifted to 180 ppm; and 1H NMR: 4 broad bands from 7.6 to 8.2 ppm and NH2 shifted to 8.8 ppm. In aqueous solution, in presence or absence of sodium citrate as a biologically relevant and ubiquitous chelator, TSAG0101 undergoes neither ligand exchange nor reduction of its central vanadium atom during 24 hours. TSAG0101 shows blood glucose lowering effects in rats but it produced no alteration of basal- or glucose-induced insulin secretion on β cells during in vitro tests, all of which excludes a direct mechanism evidencing the extrapancreatic nature of its activity. The lethal dose (LD50) of TSAG0101 was determined in Wistar mice yielding a value of 412 mg/kg. This value is one of the highest among vanadium compounds and classifies it as a mild toxicity agent when compared with literature data. Due to its nonsubstituted, small-sized scaffold design, its remarkable complex stability, and low toxicity; TSAG0101 should be considered as an innovative insulin-mimetic principle with promising properties and, therefore, could become a new lead compound for potential nonpeptide PTP1B inhibitors in antidiabetic drug research. In view of the present work, the inhibitory concentration (IC50) and extended solution stability will be tested. PMID:20957214
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An Analysis of CNO Availability Performance Metrics and Their Relation to Availability Performance
2013-06-01
burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instruction, searching...2. Decide how to exploit the constraint. 3. Subordinate everything else to the above decision. 4 . Restructure the system to exploit the system’s...15 work items. 4 . Significance of WIP Management Along with the production bow wave, WIP is actively managed but not directly controlled like
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Sousa, Magda Catarina; deCastro, Maite; Alvarez, Ines; Gomez-Gesteira, Moncho; Dias, João Miguel
2017-08-15
Former studies about coastal upwelling along the Western Iberian Peninsula (WIP) using historical data indicated contradictory results, showing either its strengthening or reduction, while previous studies using Global Climate Models (GCMs) indicated that global warming is likely to intensify this phenomenon although predicting different rates and not justifying the patterns found. Taking advantage of the recent high spatial resolution Regional Climate Models (RCMs) projections from EURO-CORDEX project (Representative Concentration Pathway, RCP 8.5), detailed higher accuracy estimations of the spatio-temporal trends of Upwelling Index (UI) along the WIP coast were performed in this study, integrating the coastal mesoscale effects within the framework of climate change. Additionally, this research brings new insights about the origin of the WIP coastal upwelling intensification over the next century. These new projections clarified the upwelling strengthening rates predicted along the coast of the WIP from 2006 to 2099 revealing more prominent changes in the northern limit of the region (25-30m 3 s -1 km -1 per decade between 41.5 and 42.5°N). Trends observed at high latitudes of the region were found to be induced by the displacement of the Azores High, which will intensify (0.03hPa per decade) and drift northeastward (10km per decade) during the 21st century. Copyright © 2017 Elsevier B.V. All rights reserved.
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Adak, Totan; Munda, Sushmita; Kumar, Upendra; Berliner, J; Pokhare, Somnath S; Jambhulkar, N N; Jena, M
2016-02-01
Impact of elevated CO2 on chlorpyriphos degradation, microbial biomass carbon, and enzymatic activities in rice soil was investigated. Rice (variety Naveen, Indica type) was grown under four conditions, namely, chambered control, elevated CO2 (550 ppm), elevated CO2 (700 ppm) in open-top chambers and open field. Chlorpyriphos was sprayed at 500 g a.i. ha(-1) at maximum tillering stage. Chlorpyriphos degraded rapidly from rice soils, and 88.4% of initially applied chlorpyriphos was lost from the rice soil maintained under elevated CO2 (700 ppm) by day 5 of spray, whereas the loss was 80.7% from open field rice soil. Half-life values of chlorpyriphos under different conditions ranged from 2.4 to 1.7 days with minimum half-life recorded with two elevated CO2 treatments. Increased CO2 concentration led to increase in temperature (1.2 to 1.8 °C) that played a critical role in chlorpyriphos persistence. Microbial biomass carbon and soil enzymatic activities specifically, dehydrogenase, fluorescien diacetate hydrolase, urease, acid phosphatase, and alkaline phosphatase responded positively to elevated CO2 concentrations. Generally, the enzyme activities were highly correlated with each other. Irrespective of the level of CO2, short-term negative influence of chlorpyriphos was observed on soil enzymes till day 7 of spray. Knowledge obtained from this study highlights that the elevated CO2 may negatively influence persistence of pesticide but will have positive effects on soil enzyme activities.
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Preparative resolution of D,L-threonine catalyzed by immobilized phosphatase.
Scollar, M P; Sigal, G; Klibanov, A M
1985-03-01
Hydrolysis of L- and D-O-phosphothreonines catalyzed by four different phosphatases, alkaline phosphatases from calf intestine and E. coli and acid phosphatases from wheat germ and potato, has been kinetically studied. Alkaline phosphatases were found to have comparable reactivities towards the optical isomers. On the other hand, both acid phosphatases displayed a marked stereoselectivity, hydrolyzing the L-ester much faster than its D counterpart. Wheat germ acid phosphatase was the most stereoselective enzyme: V(L)/V(D) = 24 and K(m,L)/K(m,D) = 0.17. This enzyme was immobilized (in k-carrageenan gel, followed by crosslinking with glutaraldehyde) and used for the preparative resolution of D,L-threonine: the latter was first chemically O-phosphorylated and then asymmetrically hydrolyzed by the immobilized phosphatase. As a result, gram quantities of L-threonine of high optical purity and O-phospho-D-threonine were prepared. Immobilized wheat germ phosphatase has been tested for the resolution of other racemic alcohols: serine, 2-amino-1-butanol, 1-amino-2-propanol, 2-octanol, and menthol. In all those cases, the enzyme was either not sufficiently stereoselective or too slow for preparative resolutions.
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NASA Astrophysics Data System (ADS)
Słomski, Piotr; Mastalerz, Maria; Szczepański, Jacek; Derkowski, Arkadiusz; Topór, Tomasz
2017-04-01
The porosity in the selected Ordovician and Silurian mudstones from the Baltic Basin collected from three wells (W1, M1, B1 and O3) was examined in a suite of 78 samples representing the Kopalino, Sasino, Prabuty, Pasłęk (including Jantar Member) and Pelplin Formations. Organic petrology, mineral composition along with N2 low-pressure adsorption (NLPA), water and kerosene immersion porosimetry (WIP and KIP, respectively) as well as image analysis techniques were used to determine pore volumes, pore sizes and pore-size distributions and to evaluate factors controlling porosity. The majority of the investigated samples represent argillaceous mudstones. Only a few samples from O3 and W1 are different lithologically and represent siliceous-argillaceous, calcareous, or calcareous-argillicaous mudstones. The samples are characterized by total organic carbon (TOC) content ranging from 0.13 to 7.20 wt. % and vitrinite reflectance (Ro) ranging from 1.02 to 1.22%, indicating late mature rocks within condensate - wet gas window. Total porosity measured using WIP is in the range from 4.6 % to 10 %, while KIP gave values from 1.5 % to 8.9 %. NLPA technique on the 75 µm size fraction revealed that mesopores area is in the range from 10.59 to 34.34 m2/g, while mesopores volume ranges from 0.024 to 0.062 cm3/g. Correlation between mesopores surface area and Ro is weak, but in general the surface area of mesopores is the largest in the least mature samples. Moreover, as indicated by gas adsorption data, both pores greater than 30 nm and smaller than 4 nm are important contributors to the total mesoporess surface area. In general, rather weak correlation between different mudstone constituents (including kerogen types) and porosity measured by means of various techniques (WIP, KIP and NLPA) reveal that there is no single factor controlling porosity in the investigated suite of samples. This conclusion is also confirmed by image analysis performed on large-scale high-resolution BSE images for selected representative samples. However, for mesopores, the dominant contribution comes from organic matter for the Jantar, Prabuty and Sasino Formations, as indicated by NLPA technique. Furthermore, importance of clay minerals for macropore volume is indicated by WIP and KIP technique. Acknowledgments: the study was supported from grant SHALESEQ (No PL12-0109) and SHALEMECH (No BG2/ShaleMech/14) funded by the National Centre for Research and Development.
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Wrighton, Katharine H; Willis, Danielle; Long, Jianyin; Liu, Fang; Lin, Xia; Feng, Xin-Hua
2006-12-15
Transforming growth factor-beta (TGF-beta) controls a diverse set of cellular processes, and its canonical signaling is mediated via TGF-beta-induced phosphorylation of receptor-activated Smads (2 and 3) at the C-terminal SXS motif. We recently discovered that PPM1A can dephosphorylate Smad2/3 at the C-terminal SXS motif, implicating a critical role for phosphatases in regulating TGF-beta signaling. Smad2/3 activity is also regulated by phosphorylation in the linker region (and N terminus) by a variety of intracellular kinases, making it a critical platform for cross-talk between TGF-beta and other signaling pathways. Using a functional genomic approach, we identified the small C-terminal domain phosphatase 1 (SCP1) as a specific phosphatase for Smad2/3 dephosphorylation in the linker and N terminus. A catalytically inactive SCP1 mutant (dnSCP1) had no effect on Smad2/3 phosphorylation in vitro or in vivo. Of the other FCP/SCP family members SCP2 and SCP3, but not FCP1, could also dephosphorylate Smad2/3 in the linker/N terminus. Depletion of SCP1/2/3 enhanced Smad2/3 linker phosphorylation. SCP1 increased TGF-beta-induced transcriptional activity in agreement with the idea that phosphorylation in the Smad2/3 linker must be removed for a full transcriptional response. SCP1 overexpression also counteracts the inhibitory effect of epidermal growth factor on TGF-beta-induced p15 expression. Taken together, this work identifies the first example of a Smad2/3 linker phosphatase(s) and reveals an important new substrate for SCPs.
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Effects of aflatoxin and carotenoids on growth performance and immune response in mule ducklings.
Cheng, Y H; Shen, T F; Pang, V F; Chen, B J
2001-01-01
The purpose of this study was to investigate if carotenoids could alleviate the adverse effects caused by aflatoxin with respect to growth performance and immune response. In two experiments, a total of 320 mule ducklings were assigned to 5 treatments, i.e. control, aflatoxin B(1) (AFB(1)) 200 ppb, AFB(1) +beta-carotene (BC) 200 ppm, AFB(1)+BC 400 ppm, and AFB(1)+astaxanthin (AS) 200 ppm. In experiment 1, the addition of beta-carotene or astaxanthin in the diet containing AFB(1) 200 ppb resulted in a significant decrease in average daily gain as compared with the control. AFB(1) 200 ppb alone and the addition of BC or AS on top of AFB(1) resulted in a significantly lower daily feed intake than for the control group. There were no significant differences in relative organ weights among treatment groups. Both treatments of BC 400 ppm and AS 200 ppm had significantly more macrophages harvested per duck than the control and AFB(1) 200 ppb treatments. However, there were no significant differences among treatments in percentages of phagocytotic macrophages and number of Candida albican phagocytized by phagocytotic macrophages. In experiment 2, blood biochemical parameters and antibody titers were evaluated. There were no significant differences among treatments in total bilirubin content and alkaline phosphatase activity in the serum or in antibody titers against fowl cholera. However, AFB(1) treatment had the highest activities of AST and ALT in the serum. The addition of BC 400 ppm on top of AFB(1) significantly reduced ALT activity as compared with the AFB(1) 200 ppb treatment. These results suggest that carotenoids could provide a slightly toxic alleviating effect on growth performance, enhance the chemotaxis ability of macrophages, and reduce ALT activity elevated by AFB(1).
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Reduced expression of CD45 Protein-Tyrosine Phosphatase Pr
2009-05-08
H S /D T R A on A ugust 19, 2009 w w w .jbc.org D ow nloaded from PTP1B , CD45, TCPTP, LMPTP-A, LMPTP-B, MEG1, MEG2, HePTP, PTP), three belong to...the dual specificity phosphatase VHR or the protein-tyrosine phosphatase PTP1B . Given these FIGURE 5. Mice expressing intermediate CD45 levels survive
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Subchronic hepatotoxicity of selenomethionine ingestion in mallard ducks
Hoffman, D.J.; Heinz, G.H.; LeCaptain, L.J.; Bunck, C.M.; Green, D.E.
1991-01-01
Twoyearold male mallards (Anas platyrhynchos) received a control diet (0.2 ppm Se) or diets containing 1, 2, 4, 8, 16, or 32 ppm Se as selenomethionine for 14 wk. Se accumulated readily in the liver in a dosedependent manner, reaching a mean concentration of 29 ppm (wet weight) in the 32 ppm group. Dietary Se of 2 ppm or greater increased plasma glutathione peroxidase activity. Mortality (10%) and histopathological effects, including bile duct hyperplasia and hemosiderin pigmentation of the liver and spleen, occurred in the 32 ppm group. These histopathological effects were accompanied by lower hemoglobin concentrations (16 and 32 ppm groups) and hematocrit (32 ppm group), and elevated plasma alkaline phosphatase activity (32 ppm group) indicative of cholestatic liver inJury. Other manifestations of hepatotoxicity included significant linear dose responses for hepatic oxidized glutathione (GSSG) concentrations and ratio of GSSG to reduced glutathione (GSH). Means for both of these responses differed from controls in groups receiving 832 ppm Se. Mean hepatic GSH and malondialdehyde (a measure of lipid peroxidation) concentrations were significantly elevated in the 16 and 32 ppm groups. Subchronic effects of selenomethionine, which occurs in vegetation, are of particular interest with respect to the health of wild aquatic birds in seleniferous locations.
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Chesapeake Bay Watershed Implementation Plans (WIPs)
This page provides an overview of Watershed Implementation Plans (WIP) and how they play an important role in restoring the Chesapeake Bay. The page also provides links to each jurisdiction's Phase I, II, and III WIP.
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Al-Rashida, Mariya; Ejaz, Syeda Abida; Ali, Sharafat; Shaukat, Aisha; Hamayoun, Mehwish; Ahmed, Maqsood; Iqbal, Jamshed
2015-05-15
The effect of bioisosteric replacement of carboxamide linking group with sulfonamide linking group, on alkaline phosphatase (AP) and carbonic anhydrase (CA) inhibition activity of aromatic benzenesulfonamides was investigated. A series of carboxamide linked aromatic benzenesulfonamides 1a-1c, 2a-2d and their sulfonamide linked bioisosteres 3a-3d, 4a-4d was synthesized and evaluated for inhibitory activity against bovine tissue non-specific alkaline phosphatase (TNAP), intestinal alkaline phosphatase (IAP) and bCA II. A significant increase in CA inhibition activity was observed upon bioisosteric replacement of carboxamide linking group with a sulfonamide group. Some of these compounds were identified as highly potent and selective AP inhibitors. Compounds 1b, 2b, 3d, 4d 5b and 5c were found to be selective bTNAP inhibitors, whereas compounds 1a, 1c, 2a, 2c, 2d, 3a, 3c, 4a, 4b, 4c, 5a were found to be selective bIAP inhibitors. For most active AP inhibitor 3b, detailed kinetic studies indicated a competitive mode of inhibition against tissue non-specific alkaline phosphatase (TNAP) and non-competitive mode of inhibition against intestinal alkaline phosphatase (IAP). Molecular docking studies were carried out to rationalize important binding site interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Cui, Xing; Li, Song; Shraim, Amjad; Kobayashi, Yayoi; Hayakawa, Toru; Kanno, Sanae; Yamamoto, Megumi; Hirano, Seishiro
2004-01-01
Although arsenic exposure causes liver disease and/or hepatoma, little is known about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis. We investigated the effects of arsenic on expression of cancer-related genes in a rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in drinking water), by using real-time quantitative RT-PCR and immunohistochemical analyses. Arsenic accumulated in the rat liver dose-dependently and caused hepatic histopathological changes, such as disruption of hepatic cords, sinusoidal dilation, and fatty infiltration. A 1-month exposure to arsenic significantly increased hepatic mRNA levels of cyclin D1 (10 ppm), ILK (1 ppm), and p27(Kip1) (10 ppm), whereas it reduced mRNA levels of PTEN (1 ppm) and beta-catenin (100 ppm). In contrast, a 4-month arsenic exposure showed increased mRNA expression of cyclin D1 (100 ppm), ILK (1 ppm), and p27(Kip1) (1 and 10 ppm), and decreased expression of both PTEN and beta-catenin at all 3 doses. An immunohistochemical study revealed that each protein expression accords closely with each gene expression of mRNA level. In conclusion, subchronic exposure to inorganic arsenate caused pathological changes and altered expression of cyclin D1, p27(Kip1), ILK, PTEN, and beta-catenin in the liver. This implies that arsenic liver toxicity involves disturbances of some cancer-related molecules.
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Toxicity of trimethyltin and triethyltin to mallard ducklings
Fleming, W.J.; Hill, E.F.; Momot, J.J.; Pang, V.F.
1991-01-01
Trimethyltin chloride (TMTC) and triethyltin chloride (TETC) were fed to mallard (Anas platyrhynchos) ducklings for 73 to 75 d, beginning when ducklings were 3 to 4 d old. Diets were mixed to contain 0,0.5,5 or 50 ppm Sn as either TMTC or TETC. Mortality occurred only in the 5 ppm (2/5 ducklings) and 50 ppm (5/5 ducklings, all dying within 5 d) TMTC groups. Death was preceded by cephalic tremors, lethargy and ataxia; these clinical signs also were observed in surviving ducklings from the 5 ppm TMTC group, but not the 0.5 ppm TMTC group. Ducklings fed 5 and 50 ppm Sn as TMTC exhibited degeneration of the large neurons of the pons, medulla oblongata, gray matter of the spinal cord and pyramidal cells of the cerebral cortex. TETC-fed ducklings showed few signs of clinical toxicosis. Ducklings fed 50 ppm Sn as TETC exhibited mild to severe vacuolization of the white matter of the brain and spinal cord; these lesions were not present in ducklings fed 5 ppm Sn as TETC. Liver, spleen, kidney, thymus, bursa of Fabricius and skeletal muscle presented no abnormal histopathology for either organotin compound. Hematocrit, hemoglobin and plasma aspartate aminotransferase; alanine aminotransferase; lactate dehydrogenase; alkaline phosphatase; and cholinesterase values were determined for the 5- and 50- ppm TMTC and TETC groups, and were not different from those of controls (p < 0.05). Lesions and clinical signs of toxicosis in ducklings were consistent with those described for mammals exposed to TMTC and TETe. The effect threshold for TMTC in ducklings appears to exceed current environmental concentrations. Environmental concentrations of TETC have not been reported.
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Identification of HMX1 target genes: A predictive promoter model approach
Boulling, Arnaud; Wicht, Linda
2013-01-01
Purpose A homozygous mutation in the H6 family homeobox 1 (HMX1) gene is responsible for a new oculoauricular defect leading to eye and auricular developmental abnormalities as well as early retinal degeneration (MIM 612109). However, the HMX1 pathway remains poorly understood, and in the first approach to better understand the pathway’s function, we sought to identify the target genes. Methods We developed a predictive promoter model (PPM) approach using a comparative transcriptomic analysis in the retina at P15 of a mouse model lacking functional Hmx1 (dmbo mouse) and its respective wild-type. This PPM was based on the hypothesis that HMX1 binding site (HMX1-BS) clusters should be more represented in promoters of HMX1 target genes. The most differentially expressed genes in the microarray experiment that contained HMX1-BS clusters were used to generate the PPM, which was then statistically validated. Finally, we developed two genome-wide target prediction methods: one that focused on conserving PPM features in human and mouse and one that was based on the co-occurrence of HMX1-BS pairs fitting the PPM, in human or in mouse, independently. Results The PPM construction revealed that sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein) (Sgcg), teashirt zinc finger homeobox 2 (Tshz2), and solute carrier family 6 (neurotransmitter transporter, glycine) (Slc6a9) genes represented Hmx1 targets in the mouse retina at P15. Moreover, the genome-wide target prediction revealed that mouse genes belonging to the retinal axon guidance pathway were targeted by Hmx1. Expression of these three genes was experimentally validated using a quantitative reverse transcription PCR approach. The inhibitory activity of Hmx1 on Sgcg, as well as protein tyrosine phosphatase, receptor type, O (Ptpro) and Sema3f, two targets identified by the PPM, were validated with luciferase assay. Conclusions Gene expression analysis between wild-type and dmbo mice allowed us to develop a PPM that identified the first target genes of Hmx1. PMID:23946633
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Sueyoshi, Noriyuki; Takao, Toshihiko; Nimura, Takaki
2007-11-23
Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP) and its nuclear isoform CaMKP-N are unique Ser/Thr protein phosphatases that negatively regulate the Ca{sup 2+}/calmodulin-dependent protein kinase (CaMK) cascade by dephosphorylating multifunctional CaMKI, II, and IV. However, the lack of specific inhibitors of these phosphatases has hampered studies on these enzymes in vivo. In an attempt to obtain specific inhibitors, we searched inhibitory compounds and found that Evans Blue and Chicago Sky Blue 6B served as effective inhibitors for CaMKP. These compounds also inhibited CaMKP-N, but inhibited neither protein phosphatase 2C, another member of PPM family phosphatase, nor calcineurin, a typical PPP familymore » phosphatase. The minimum structure required for the inhibition was 1-amino-8-naphthol-4-sulfonic acid. When Neuro2a cells cotransfected with CaMKIV and CaMKP-N were treated with these compounds, the dephosphorylation of CaMKIV was strongly suppressed, suggesting that these compounds could be used as potent inhibitors of CaMKP and CaMKP-N in vivo as well as in vitro.« less
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Jia, Ru; Yang, Dongqing; Xu, Dake; Gu, Tingyue
2017-07-31
Pseudomonas aeruginosa (PA) is a ubiquitous microbe. It can form recalcitrant biofilms in clinical and industrial settings. PA biofilms cause infections in patients. They also cause biocorrosion of medical implants. In this work, D-tyrosine (D-tyr) was investigated as an antimicrobial enhancer for ciprofloxacin (CIP) against a wild-type PA biofilm (strain PAO1) on C1018 carbon steel in a strictly anaerobic condition. Seven-day biofilm prevention test results demonstrated that 2 ppm (w/w) D-tyr enhanced 30 ppm CIP by achieving extra 2-log sessile cell reduction compared with the 30 ppm CIP alone treatment. The cocktail of 30 ppm CIP + 2 ppm D-tyr achieved similar efficacy as the 80 ppm CIP alone treatment in the biofilm prevention test. Results also indicated that the enhanced antimicrobial treatment reduced weight loss and pitting corrosion. In the 3-hour biofilm removal test, the cocktail of 80 ppm CIP + 5 ppm D-tyr achieved extra 1.5-log reduction in sessile cell count compared with the 80 ppm CIP alone treatment. The cocktail of 80 ppm CIP + 5 ppm D-tyr achieved better efficacy than the 150 ppm CIP alone treatment in the biofilm removal test.
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Staudhammer, Christina L; Escobedo, Francisco J; Holt, Nathan; Young, Linda J; Brandeis, Thomas J; Zipperer, Wayne
2015-05-15
We examined the spatial distribution, occurrence, and socioecological predictors of woody invasive plants (WIP) in two subtropical, coastal urban ecosystems: San Juan, Puerto Rico and Miami-Dade, United States. These two cities have similar climates and ecosystems typical of subtropical regions but differ in socioeconomics, topography, and urbanization processes. Using permanent plot data, available forest inventory protocols and statistical analyses of geographic and socioeconomic spatial predictors, we found that landscape level distribution and occurrence of WIPs was not clustered. We also characterized WIP composition and occurrence using logistic models, and found they were strongly related to the proportional area of residential land uses. However, the magnitude and trend of increase depended on median household income and grass cover. In San Juan, WIP occurrence was higher in areas of high residential cover when incomes were low or grass cover was low, whereas the opposite was true in Miami-Dade. Although Miami-Dade had greater invasive shrub cover and numbers of WIP species, San Juan had far greater invasive tree density, basal area and crown cover. This study provides an approach for incorporating field and available census data in geospatial distribution models of WIPs in cities throughout the globe. Findings indicate that identifying spatial predictors of WIPs depends on site-specific factors and the ecological scale of the predictor. Thus, mapping protocols and policies to eradicate urban WIPs should target indicators of a relevant scale specific to the area of interest for their improved and proactive management. Copyright © 2015 Elsevier Ltd. All rights reserved.
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MpWIP regulates air pore complex development in the liverwort Marchantia polymorpha
Jones, Victor A. S.
2017-01-01
The colonisation of the land by plants was accompanied by the evolution of complex tissues and multicellular structures comprising different cell types as morphological adaptations to the terrestrial environment. Here, we show that the single WIP protein in the early-diverging land plant Marchantia polymorpha L. is required for the development of the multicellular gas exchange structure: the air pore complex. This 16-cell barrel-shaped structure surrounds an opening between epidermal cells that facilitates the exchange of gases between the chamber containing the photosynthetic cells inside the plant and the air outside. MpWIP is expressed in cells of the developing air pore complex and the morphogenesis of the complex is defective in plants with reduced MpWIP function. The role of WIP proteins in the control of different multicellular structures in M. polymorpha and the flowering plant Arabidopsis thaliana suggests that these proteins controlled the development of multicellular structures in the common ancestor of land plants. We hypothesise that WIP genes were subsequently co-opted in the control of morphogenesis of novel multicellular structures that evolved during the diversification of land plants. PMID:28174248
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Sun, Meixiu; Chen, Zhuying; Gong, Zhiyong; Zhao, Xiaomeng; Jiang, Chenyu; Yuan, Yuan; Wang, Zhennang; Li, Yingxin; Wang, Chuji
2015-02-01
Over 90% of diabetic patients have Type 2 diabetes. Although an elevated mean breath acetone concentration has been found to exist in Type 1 diabetes (T1D), information on breath acetone in Type 2 diabetes (T2D) has yet to be obtained. In this study, we first used gas chromatography-mass spectrometry (GC-MS) to validate a ringdown breath-acetone analyzer based on the cavity-ringdown-spectroscopy technique, through comparing breath acetone concentrations in the range 0.5-2.5 ppm measured using both methods. The linear fitting of R = 0.99 suggests that the acetone concentrations obtained using both methods are consistent with a largest standard deviation of ±0.4 ppm in the lowest concentration of the range. Next, 620 breath samples from 149 T2D patients and 42 healthy subjects were collected and tested using the breath analyzer. Four breath samples were taken from each subject under each of four different conditions: fasting, 2 h post-breakfast, 2 h post-lunch, and 2 h post-dinner. Simultaneous blood glucose levels were also measured using a standard diabetic-management blood-glucose meter. For the 149 T2D subjects, their exhaled breath acetone concentrations ranged from 0.1 to 19.8 ppm; four different ranges of breath acetone concentration, 0.1-19.8, 0.1-7.1, 0.1-6.3, and 0.1-9.5 ppm, were obtained for the subjects under the four different conditions, respectively. For the 42 healthy subjects, their breath acetone concentration ranged from 0.1 to 2.6 ppm; four different ranges of breath acetone concentration, 0.3-2.6, 0.1-2.6, 0.1-1.7, and 0.3-1.6 ppm, were obtained for the four different conditions. The mean breath acetone concentration of the 149 T2D subjects was determined to be 1.5 ± 1.5 ppm, which was 1.5 times that of 1.0 ± 0.6 ppm for the 42 healthy subjects. No correlation was found between the breath acetone concentration and the blood glucose level of the T2D subjects and the healthy volunteers. This study using a relatively large number of subjects provides new data regarding breath acetone in diabetes (T1D and T2D) and suggests that an elevated mean breath acetone concentration also exists in T2D.
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40 CFR 80.580 - What are the sampling and testing methods for sulfur?
Code of Federal Regulations, 2010 CFR
2010-07-01
...,000 ppm sulfur standard of § 80.510(k), sulfur content may be determined using ASTM D2622... the 500 ppm sulfur standard of § 80.510(a)(1), sulfur content may be determined using ASTM D2622... to the 1,000 ppm sulfur standard of § 80.510(k), sulfur content may be determined using ASTM D4294...
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Hearst, Scoty M; Gilder, Andrew S; Negi, Sandeep S; Davis, Misty D; George, Eric M; Whittom, Angela A; Toyota, Cory G; Husedzinovic, Alma; Gruss, Oliver J; Hebert, Michael D
2009-06-01
Cajal bodies (CBs) are nuclear structures that are thought to have diverse functions, including small nuclear ribonucleoprotein (snRNP) biogenesis. The phosphorylation status of coilin, the CB marker protein, might impact CB formation. We hypothesize that primary cells, which lack CBs, contain different phosphoisoforms of coilin compared with that found in transformed cells, which have CBs. Localization, self-association and fluorescence recovery after photobleaching (FRAP) studies on coilin phosphomutants all suggest this modification impacts the function of coilin and may thus contribute towards CB formation. Two-dimensional gel electrophoresis demonstrates that coilin is hyperphosphorylated in primary cells compared with transformed cells. mRNA levels of the nuclear phosphatase PPM1G are significantly reduced in primary cells and expression of PPM1G in primary cells induces CBs. Additionally, PPM1G can dephosphorylate coilin in vitro. Surprisingly, however, expression of green fluorescent protein alone is sufficient to form CBs in primary cells. Taken together, our data support a model whereby coilin is the target of an uncharacterized signal transduction cascade that responds to the increased transcription and snRNP demands found in transformed cells.
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[Sex determination in cucurbits].
Foucart, Camille; Boualem, Adnane; Lasseur, Bertrand; Eleblu, John; Fahraj, Izhak; Bendahmane, Abdelhafid
2012-01-01
Sex determination in plants leads to the development of unisexual flowers from an originally bisexual floral meristem. Cucurbits are not only species of agronomic interest but they also represent model species for the study of plant sex determination, because of their ability to harbor different sexual types. Such sexual forms are controlled by the identity of the alleles at the following loci: andromonoecious (a) and gynoecious (g) in melon, or androecious (a), Female (F), and Monoecious (M) in cucumber. We firstly showed that the andromonoecious a gene in melon encodes for an ACC synthase (CmACS7) and demonstrated that andromonoecy results from a mutation in the active site of the enzyme. Expression of the active enzyme inhibits the development of the male organs and is not required for carpel development. Because the a gene in melon and M gene in cucumber control the same sexual transition, monoecy to andromonoecy, we isolated the andromonoecy M gene in cucumber using a candidate gene approach in combination with genetic and biochemical analysis. We demonstrated the co-segregation of CsACS2, a close ortholog of CmACS7, with the M locus, and showed that the cucumber andromonoecious phenotype is also due to a loss of ACS enzymatic activity. CsACS2 is expressed specifically in carpel primordia of female flowers and should play a similar role to that of CmACS7 in melon in the inhibition of stamina development. Finally, we also showed that the transition from male to female flowers in the gynoecious lines results from epigenetic changes in the promoter of a C(2)H (2) zinc-finger transcription factor, CmWIP1. This epigenetic change is elicited by the insertion of a DNA transposon, which causes the spreading of DNA methylation to the CmWIP1 promoter. Expression of CmWIP1 leads to carpel abortion, resulting in the development of unisexual male flowers. From all these results, we built a model in which CmACS7 and CmWIP1 interact to control the development of male, female and hermaphrodite flowers in melon. © Société de Biologie, 2012.
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MpWIP regulates air pore complex development in the liverwort Marchantia polymorpha.
Jones, Victor A S; Dolan, Liam
2017-04-15
The colonisation of the land by plants was accompanied by the evolution of complex tissues and multicellular structures comprising different cell types as morphological adaptations to the terrestrial environment. Here, we show that the single WIP protein in the early-diverging land plant Marchantia polymorpha L. is required for the development of the multicellular gas exchange structure: the air pore complex. This 16-cell barrel-shaped structure surrounds an opening between epidermal cells that facilitates the exchange of gases between the chamber containing the photosynthetic cells inside the plant and the air outside. Mp WIP is expressed in cells of the developing air pore complex and the morphogenesis of the complex is defective in plants with reduced Mp WIP function. The role of WIP proteins in the control of different multicellular structures in M. polymorpha and the flowering plant Arabidopsis thaliana suggests that these proteins controlled the development of multicellular structures in the common ancestor of land plants. We hypothesise that WIP genes were subsequently co-opted in the control of morphogenesis of novel multicellular structures that evolved during the diversification of land plants. © 2017. Published by The Company of Biologists Ltd.
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NASA Astrophysics Data System (ADS)
Muslihatin, Wirdhatul; Jadid, Nurul; Puspitasari, Ika D.; Safitri, Chusnul E.
2017-06-01
The spread of Moringa oleifera is also rare for seed germination and viability or survival are low, and the lack of vegetative propagation method. The purpose of this study are to determine the effect of auxin and cytokinin on growth vegetative explants Moringa oleifera and its synthetic seed germination. The explants grown on MS medium with sucrose content of 30% and a range of additional hormone. Addition concentration and different types of hormone made in order to know the sensitivity and response explant growth on a variety of media to get a good callus and embryosomatic. The composition of the hormone given is MS + 2.4 D 3 ppm; MS + 2,4D 2 ppm + BAP 2 ppm; MS + NAA + 0.5 ppm kinetin 1 ppm; MS + NAA 1 ppm + kinetin 1 ppm; MS + NAA 1 ppm + 0.5 ppm kinetin. The explants were incubated at a temperature of 18-20 ° C with a photoperiod 16/8. Explants and MS medium is incubated to form embryonic callus. Seeds synthetic made from embryonic callus growing on medium 1 ppm kinetin + NAA 1 ppm with encapsulation method with sodium alginate 2%. Seed synthetic germinated in some kind of medium that medium ms0 solid (M1), ms0 liquid (M2), MS0 semi-solid (M3), MS solid NAA 1ppm + Kinetin 1 ppm (M4), MS liquid NAA 1 ppm + kinetin (M5), and semi-solid MS + NAA 1 ppm kinetin 1 ppm (M6). Synthetic seed viability was observed with the parameters of the fresh weight of synthetic seed, germination percentage and seedling. Chlorophyll content was measured by spectrophotometric method with solvent asseton. Best callus generated in this study are embryonic callus that grew on media NAA 1 ppm + kinetin 1 ppm. Embryonic callus on M6 + NAA 1 ppm kinetin 1 ppm capable of germination with an average weight of callus and sprouts of 40.38 mg. Of the entire amount of a synthetic seed on M6, just 5 seed germinate, so the percentage of germination of seeds is equal to 41.67%. with an average length of sprouts 1 cm with an average total chlorophyll content of 8.66 mg / g.
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AMPK activation by Tanshinone IIA protects neuronal cells from oxygen-glucose deprivation
Weng, Yingfeng; Lin, Jixian; Liu, Hui; Wu, Hui; Yan, Zhimin; Zhao, Jing
2018-01-01
The current study tested the potential neuroprotective function of Tanshinone IIA (ThIIA) in neuronal cells with oxygen-glucose deprivation (ODG) and re-oxygenation (OGDR). In SH-SY5Y neuronal cells and primary murine cortical neurons, ThIIA pre-treatment attenuated OGDR-induced viability reduction and apoptosis. Further, OGDR-induced mitochondrial depolarization, reactive oxygen species production, lipid peroxidation and DNA damages in neuronal cells were significantly attenuated by ThIIA. ThIIA activated AMP-activated protein kinase (AMPK) signaling, which was essential for neuroprotection against OGDR. AMPKα1 knockdown or complete knockout in SH-SY5Y cells abolished ThIIA-induced AMPK activation and neuroprotection against OGDR. Further studies found that ThIIA up-regulated microRNA-135b to downregulate the AMPK phosphatase Ppm1e. Notably, knockdown of Ppm1e by targeted shRNA or forced microRNA-135b expression also activated AMPK and protected SH-SY5Y cells from OGDR. Together, AMPK activation by ThIIA protects neuronal cells from OGDR. microRNA-135b-mediated silence of Ppm1e could be the key mechanism of AMPK activation by ThIIA. PMID:29435120
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Zhang, J H; Luo, Q; Zhang, H J; Chen, R C
2017-06-12
Objective: To investigate the effect of noninvasive proportional assist ventilation (PAV) on respiratory work in chronic obstructive pulmonary disease(COPD) patients, in comparison to noninvasive pressure support ventilation(PSV). Methods: Ten severe COPD patients with hypercapnia during acute exacerbation were examined. The baseline inspiratory pressure of PSV (PS) and the assistance level of PAV(PA) were titrated by patients' tolerance. In addition to the baseline PS and PA, an additional decrease by 25% (PS-=75% PS, PA-=75% PA) or increase by 25% (PS+ =125% PS, PA+ =125% PA) of the assist level were applied to the patients. After the assessment of unassisted spontaneous breathing (SB), the patient was placed on the 6 levels of noninvasive-PSV and noninvasive-PAV in random sequence. Each level lasted at least 20 minutes. Respiratory rate (RR), tidal volume (Vt), and respiratory work(Wex, Wip and Wv) were measured. Asynchrony index (AI) was calculated. Results: During ventilation, Vt was significantly higher with each assist level than with SB. The Vt was significant increased with PS+ than with PA+ . An increase in expiratory work(Wex) and decrease in inspiratory work(Wip) were observed respectively, with the increasing assist level. The inspiratory muscles assessed by Wip were more unloaded at PS compared with PA [PS: (1.59±1.27) J/min vs PA: (4.99±3.48) J/min P <0.01]. However, the Wex was significantly higher with PS+ than with PA+ [PS+ : (1.17±0.54) J/min vs PA+ : (0.49±0.56)J/min, P <0.01]. The AI was increased with the increasing assist level of PSV [PS-: (0.46±0.57)%, PS: (1.36±1.24)% PS+ : (5.26±4.77)]. No asynchrony events were observed at PA- and PA. "Runaway" (expiratory asynchrony) was observed during PA+ [AI: (2.62±2.72)%]. Conclusions: Noninvasive-PAV can increase the Vt and decrease the Wip of the COPD patients with hypercapnia and avoid the over-assistance. The "Runaway" will occur at assist level higher than that set by tolerance. Physiological data can monitor the patient's responses and the ventilator-patient interaction, which may provide objective criteria for ventilator setting.
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Planning Targets for Phase II Watershed Implementation Plans
On August 1, 2011, EPA provided planning targets for nitrogen, phosphorus and sediment for the Phase II Watershed Implementation Plans (WIPs) of the Chesapeake Bay TMDL. This page provides the letters containing those planning targets.
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Goni, Leticia; Qi, Lu; Cuervo, Marta; Milagro, Fermín I; Saris, Wim H; MacDonald, Ian A; Langin, Dominique; Astrup, Arne; Arner, Peter; Oppert, Jean-Michel; Svendstrup, Mathilde; Blaak, Ellen E; Sørensen, Thorkild Ia; Hansen, Torben; Martínez, J Alfredo
2017-09-01
Background: Circulating branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) have been shown to be associated with insulin resistance and diabetes risk. The common rs1440581 T allele in the protein phosphatase Mg2+/Mn2+ dependent 1K ( PPM1K ) gene has been related to elevated BCAA concentrations and risk of type 2 diabetes. Objective: In the present study, we tested whether dietary fat and carbohydrate intakes influenced the association between the rs1440581 PPM1K genetic variant and glucose-metabolism traits during weight loss. Design: The rs1440581 PPM1K genetic variant was genotyped in a total of 757 nondiabetic individuals who were randomly assigned to 1 of 2 energy-restricted diets that differed in macronutrient composition (low-fat diet: 20-25% fat, 15% protein, and 60-65% carbohydrate; high-fat diet: 40-45% fat, 15% protein, and 40-45% carbohydrate). The changes in fasting glucose, fasting insulin, insulin resistance (homeostasis model assessment of insulin resistance) and homeostasis model assessment of β cell function (HOMA-B) were measured after a mean ± SD weight loss of 6.8 ± 3.4 kg over 10 wk and analyzed according to the presence of the T allele of rs1440581. Results: The rs1440581 T allele was associated with a smaller improvement in glucose concentrations after the 10-wk dietary intervention (β ± SE: 0.05 ± 0.02 mg/dL; P = 0.03). In addition, significant gene-diet interactions were shown for the rs1440581 PPM1K genetic variant in relation to changes in insulin and HOMA-B ( P -interaction = 0.006 and 0.002, respectively). In response to the high-fat diet, the T allele was associated with a higher reduction of insulin (β ± SE: -0.77 ± 0.40 μU/mL; P = 0.04) and HOMA-B (β ± SE: -13.2 ± 3.81; P = 0.003). An opposite effect was observed in the low-fat diet group, although in this group the T allele was marginally ( P = 0.10) and not significantly ( P = 0.24) associated with insulin and HOMA-B, respectively. Conclusion: PPM1K rs1440581 may affect changes in glucose metabolism during weight loss, and this effect is dependent on dietary fat and carbohydrate intakes. This trial was registered at controlled-trials.com as ISRCTN25867281. © 2017 American Society for Nutrition.
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kWIP: The k-mer weighted inner product, a de novo estimator of genetic similarity.
Murray, Kevin D; Webers, Christfried; Ong, Cheng Soon; Borevitz, Justin; Warthmann, Norman
2017-09-01
Modern genomics techniques generate overwhelming quantities of data. Extracting population genetic variation demands computationally efficient methods to determine genetic relatedness between individuals (or "samples") in an unbiased manner, preferably de novo. Rapid estimation of genetic relatedness directly from sequencing data has the potential to overcome reference genome bias, and to verify that individuals belong to the correct genetic lineage before conclusions are drawn using mislabelled, or misidentified samples. We present the k-mer Weighted Inner Product (kWIP), an assembly-, and alignment-free estimator of genetic similarity. kWIP combines a probabilistic data structure with a novel metric, the weighted inner product (WIP), to efficiently calculate pairwise similarity between sequencing runs from their k-mer counts. It produces a distance matrix, which can then be further analysed and visualised. Our method does not require prior knowledge of the underlying genomes and applications include establishing sample identity and detecting mix-up, non-obvious genomic variation, and population structure. We show that kWIP can reconstruct the true relatedness between samples from simulated populations. By re-analysing several published datasets we show that our results are consistent with marker-based analyses. kWIP is written in C++, licensed under the GNU GPL, and is available from https://github.com/kdmurray91/kwip.
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Synthesis of Thymoquinone derivatives and its activity analysis: In-silico approach
NASA Astrophysics Data System (ADS)
Ulfa, Siti Mariyah; Sholikhah, Shoimatus; Utomo, Edi Priyo
2017-03-01
Thymoquinone derivatives which synthesized in this research is bromoalkylquinones with alkyl chain consist of seven carbons (C7) and ten carbons (C10). The synthesis was carried out by oxidation of 2,3-dimethylhydroquinone followed by alkylation using reflux for 1.5 hours. The alkylation products were successfully characterized as 5-(7-bromoheptyl)-2,3-dimethyl-1,4-benzoquinone (C7) and 5-(10-bromodecyl)-2,3-dimethyl-1,4-benzoquinone (C10) in 31.93 and 16.89%, respectively. These compounds were fully characterized using FT-IR, 1H-NMR and 13C-NMR. Thus, the activity of C7 and C10 was analyzed by in silico approach with molecular docking using macromolecule model extracted from Protein Data Bank (PDB). Macromolecules used in this research is mitochondrial translocator protein (TSPO) as an antioxidant receptor, glycogen phosphorylase (GPA) as antidiabetic receptor and phosphatase tensin homolog (PTEN) as an anticancer agent. The result showed that C7 and C10 has a very good activity as antioxidant and antidiabetic agents with IC50 2.03 and 1.02 ppm (TSPO) and 16.98 and 14.88 ppm (GPA) compared with Thymoquinone. While the activity of C7 and C10 against PTEN gave the IC50 23.13 and 18.31 ppm showed a good candidate for an anticancer agent.
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A cucurbit androecy gene reveals how unisexual flowers develop and dioecy emerges.
Boualem, Adnane; Troadec, Christelle; Camps, Céline; Lemhemdi, Afef; Morin, Halima; Sari, Marie-Agnes; Fraenkel-Zagouri, Rina; Kovalski, Irina; Dogimont, Catherine; Perl-Treves, Rafael; Bendahmane, Abdelhafid
2015-11-06
Understanding the evolution of sex determination in plants requires identifying the mechanisms underlying the transition from monoecious plants, where male and female flowers coexist, to unisexual individuals found in dioecious species. We show that in melon and cucumber, the androecy gene controls female flower development and encodes a limiting enzyme of ethylene biosynthesis, ACS11. ACS11 is expressed in phloem cells connected to flowers programmed to become female, and ACS11 loss-of-function mutants lead to male plants (androecy). CmACS11 represses the expression of the male promoting gene CmWIP1 to control the development and the coexistence of male and female flowers in monoecious species. Because monoecy can lead to dioecy, we show how a combination of alleles of CmACS11 and CmWIP1 can create artificial dioecy. Copyright © 2015, American Association for the Advancement of Science.
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Hearst, Scoty M.; Gilder, Andrew S.; Negi, Sandeep S.; Davis, Misty D.; George, Eric M.; Whittom, Angela A.; Toyota, Cory G.; Husedzinovic, Alma; Gruss, Oliver J.; Hebert, Michael D.
2009-01-01
Summary Cajal bodies (CBs) are nuclear structures that are thought to have diverse functions, including small nuclear ribonucleoprotein (snRNP) biogenesis. The phosphorylation status of coilin, the CB marker protein, might impact CB formation. We hypothesize that primary cells, which lack CBs, contain different phosphoisoforms of coilin compared with that found in transformed cells, which have CBs. Localization, self-association and fluorescence recovery after photobleaching (FRAP) studies on coilin phosphomutants all suggest this modification impacts the function of coilin and may thus contribute towards CB formation. Two-dimensional gel electrophoresis demonstrates that coilin is hyperphosphorylated in primary cells compared with transformed cells. mRNA levels of the nuclear phosphatase PPM1G are significantly reduced in primary cells and expression of PPM1G in primary cells induces CBs. Additionally, PPM1G can dephosphorylate coilin in vitro. Surprisingly, however, expression of green fluorescent protein alone is sufficient to form CBs in primary cells. Taken together, our data support a model whereby coilin is the target of an uncharacterized signal transduction cascade that responds to the increased transcription and snRNP demands found in transformed cells. PMID:19435804
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Bastian, Thomas W.; Prohaska, Joseph R.; Georgieff, Michael K.
2014-01-01
Fetal/neonatal iron (Fe) and iodine/TH deficiencies lead to similar brain developmental abnormalities and often coexist in developing countries. We recently demonstrated that fetal/neonatal Fe deficiency results in a mild neonatal thyroidal impairment, suggesting that TH insufficiency contributes to the neurodevelopmental abnormalities associated with Fe deficiency. We hypothesized that combining Fe deficiency with an additional mild thyroidal perturbation (6-propyl-2-thiouracil [PTU]) during development would more severely impair neonatal thyroidal status and brain TH-responsive gene expression than either deficiency alone. Early gestation pregnant rats were assigned to 7 different treatment groups: control, Fe deficient (FeD), mild TH deficient (1 ppm PTU), moderate TH deficient (3 ppm PTU), severe TH deficient (10 ppm PTU), FeD/1 ppm PTU, or FeD/3 ppm PTU. FeD or 1 ppm PTU treatment alone reduced postnatal day 15 serum total T4 concentrations by 64% and 74%, respectively, without significantly altering serum total T3 concentrations. Neither treatment alone significantly altered postnatal day 16 cortical or hippocampal T3 concentrations. FeD combined with 1 ppm PTU treatment produced a more severe effect, reducing serum total T4 by 95%, and lowering hippocampal and cortical T3 concentrations by 24% and 31%, respectively. Combined FeD/PTU had a more severe effect on brain TH-responsive gene expression than either treatment alone, significantly altering Pvalb, Dio2, Mbp, and Hairless hippocampal and/or cortical mRNA levels. FeD/PTU treatment more severely impacted cortical and hippocampal parvalbumin protein expression compared with either individual treatment. These data suggest that combining 2 mild thyroidal insults during development significantly disrupts thyroid function and impairs TH-regulated brain gene expression. PMID:24424046
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Carbon Slurry Fuels for Volume Limited Missiles
1979-11-01
Entwrod) 20. ABSTRACT (CONTINUED) "oomogeneous iron , lead, manganese, ’nd zirconium catalysts at concentrations up to 1000 ppm proved ineffective as...any improvement with manganese, iron , lead or zirconium based homogeneous catalysts at concentrations up to 1000 ppm. We have concluded that...tetrahydrodi 98.5 100 (1) (cyclopentadiene) Other Hydrocarbons - 1.5 Iron , ppm - 10 Flash Point, 0 C (IF) 52 (125) D-93, D-3243 Specific Gravity
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Varying concentrations of nine potential pollutants were tested for effects in vitro against colonies of Wolffia papulifera. Death was observed in...colonies of Wolffia exposed to 100 ppm or above of CS, DDT, Malathion, Diazinon, and indole acetic acid (IAA) and to 1000 ppm of Aldrin, Dieldrin, Sevin...of Aldrin and Malathion; and 0.01 ppm of 2,4-D. Teratogenic effects were observed in Wolffia colonies exposed to Malathion at 1 ppm, of 2,4-D at 0.1
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Witkowska-Sędek, Ewelina; Stelmaszczyk-Emmel, Anna; Majcher, Anna; Demkow, Urszula; Pyrżak, Beata
2018-04-13
The relationships between bone turnover, the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and vitamin D are complex, but still not fully explained. The GH/IGF-1 axis and vitamin D can mutually modulate each other's metabolism and influence the activation of cell proliferation, maturation, and mineralization as well as bone resorption. The aim of this study was to evaluate the reciprocal associations between bone formation markers [alkaline phosphatase (ALP), bone alkaline phosphatase (BALP)], the GH/IGF-1 axis and 25-hydroxyvitamin D [25(OH)D] in children with growth hormone deficiency at baseline and during recombinant human growth hormone (rhGH) therapy. ALP, BALP, 25(OH)D and IGF-1 levels were evaluated in 53 patients included in this prospective three-year study. ALP, BALP and IGF-1 increased during rhGH therapy. Baseline ALP activity correlated positively with baseline height velocity (HV). ALP and BALP activity at 12 months correlated positively with HV in the first year of therapy. We found positive correlations between ALP and IGF-1 at baseline and during the first year of therapy, between BALP activity at 12 months and rhGH dose in the first year of therapy, and between doses of cholecalciferol in the first year of rhGH therapy and early changes in BALP activity during rhGH therapy. Our results indicate that vitamin D supplementation enhances the effect of rhGH on bone formation process, which could improve the effects of rhGH therapy. ALP and BALP activity are useful in the early prediction of the effects of rhGH therapy, but their utility as long-term predictors seemed insufficient.
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Pulmonary biochemical effects of inhaled phosgene in rats.
Franch, S; Hatch, G E
1986-01-01
Three exposure regimens were used to study the time course of indicators of lung damage and recovery response to single or repeated exposures to phosgene (COCl2). Rats were sacrificed immediately or throughout a 38-d recovery period after inhalation of 1 ppm COCl2 for 4 h, at intervals during a 7-h exposure to 1 ppm phosgene, or at several time points throughout a 17-d exposure to 0.125 and 0.25 ppm COCl2 (4 h/d, 5 d/wk) and during a 21-d recovery period. Regimen 1 revealed significantly elevated lung wet weight, lung nonprotein sulfhydryl (NPSH) content, and glucose-6-phosphate dehydrogenase (G6PD) activity that stayed elevated for up to 14 d. A significant decrease in body weight and food intake was observed 1 d after exposure. Regimen 2 caused a slight depression in NPSH content but did not affect G6PD activity. Regimen 3 animals showed sustained elevations in lung wet weight, NPSH content, and G6PD activity after 7 d of exposure. No significant changes in these endpoints were observed for the 0.125 ppm COCl2 group. No consistent elevation in hydroxyproline content was seen at either exposure concentration. Light microscopic examination of lung tissue exposed to 0.25 ppm COCl2 for 17 d revealed moderate multifocal accumulation of mononuclear cells in the centriacinar region. In summary, exposure to COCl2 caused changes similar in most ways to those observed for other lower-respiratory-tract irritants.
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Agricultural costs of the Chesapeake Bay total maximum daily load.
Kaufman, Zach; Abler, David; Shortle, James; Harper, Jayson; Hamlett, James; Feather, Peter
2014-12-16
This study estimates costs to agricultural producers of the Watershed Implementation Plans (WIPs) developed by states in the Chesapeake Bay Watershed to comply with the Chesapeake Bay total maximum daily load (TMDL) and potential cost savings that could be realized by a more efficient selection of agricultural Best Management Practices (BMPs) and spatial targeting of BMP implementation. The cost of implementing the WIPs between 2011 and 2025 is estimated to be about $3.6 billion (in 2010 dollars). The annual cost associated with full implementation of all WIP BMPs from 2025 onward is about $900 million. Significant cost savings can be realized through careful and efficient BMP selection and spatial targeting. If retiring up to 25% of current agricultural land is included as an option, Bay-wide cost savings of about 60% could be realized compared to the WIPs.
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Crystal Structure of the Catalytic Domain of a Serine Threonine Protein Phosphatase
NASA Technical Reports Server (NTRS)
Swinglel, Mark; Honkanel, Richard; Ciszak, Ewa
2003-01-01
Reversible phosphorylation of serine and threonine residues is a well-recognized mechanism in eukaryotic cells for the regulation of cell-cycle progression, cell growth and metabolism. Human serine/threonine phosphatases can be placed into two major families, PPP and PPM. To date the structure on one PPP family member (PPl) has been determined. Here we present the structure of a 323-residue catalytic domain of a second phosphatase belonging to the PPP family of enzyme. catalytic domain of the enzyme has been determined to 1.60Angstrom resolution and refined to R=17.5 and Rfree = 20.8%. The catalytic domain possesses a unique fold consisting of a largely monolithic structure, divisible into closely-associated helical and sheet regions. The catalytic site contains two manganese ions that are involved in substrate binding and catalysis. The enzyme crystallizes as a dimer that completely buries catalytic surfaces of both monomers, Also, the structure shows evidence of some flexibility around the active site cleft that may be related to substrate specificity of this enzyme.
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Korrodi-Gregório, Luís; Vieira, Sandra I.; Esteves, Sara L. C.; Silva, Joana V.; Freitas, Maria João; Brauns, Ann-Kristin; Luers, Georg; Abrantes, Joana; Esteves, Pedro J.; da Cruz e Silva, Odete A. B.; Fardilha, Margarida; da Cruz e Silva, Edgar F.
2013-01-01
Summary Reversible phosphorylation plays an important role as a mechanism of intracellular control in eukaryotes. PPP1, a major eukaryotic Ser/Thr-protein phosphatase, acquires its specificity by interacting with different protein regulators, also known as PPP1 interacting proteins (PIPs). In the present work we characterized a physiologically relevant PIP in testis. Using a yeast two-hybrid screen with a human testis cDNA library, we identified a novel PIP of PPP1CC2 isoform, the T-complex testis expressed protein 1 domain containing 4 (TCTEX1D4) that has recently been described as a Tctex1 dynein light chain family member. The overlay assays confirm that TCTEX1D4 interacts with the different spliced isoforms of PPP1CC. Also, the binding domain occurs in the N-terminus, where a consensus PPP1 binding motif (PPP1BM) RVSF is present. The distribution of TCTEX1D4 in testis suggests its involvement in distinct functions, such as TGFβ signaling at the blood–testis barrier and acrosome cap formation. Immunofluorescence in human ejaculated sperm shows that TCTEX1D4 is present in the flagellum and in the acrosome region of the head. Moreover, TCTEX1D4 and PPP1 co-localize in the microtubule organizing center (MTOC) and microtubules in cell cultures. Importantly, the TCTEX1D4 PPP1BM seems to be relevant for complex formation, for PPP1 retention in the MTOC and movement along microtubules. These novel results open new avenues to possible roles of this dynein, together with PPP1. In essence TCTEX1D4/PPP1C complex appears to be involved in microtubule dynamics, sperm motility, acrosome reaction and in the regulation of the blood–testis barrier. PMID:23789093
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A Lean Approach to Scheduling Systems Engineering Resources
2013-05-01
The CoS that have been identified for the heath care system KSS Network are presented in Table 1. The definition of initial WIP Limits, collaboration...Garry Roedler (Lockheed Martin), Karl Scotland (Rally Software, UK), Alan Shalloway (NetObjectives), Neil Shirk (Lockheed Martin), Neil Siegel
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Jia, Ru; Li, Yingchao; Al-Mahamedh, Hussain H; Gu, Tingyue
2017-01-01
Different species of microbes form mixed-culture biofilms in cooling water systems. They cause microbiologically influenced corrosion (MIC) and biofouling, leading to increased operational and maintenance costs. In this work, two D-amino acid mixtures were found to enhance two non-oxidizing biocides [tetrakis hydroxymethyl phosphonium sulfate (THPS) and NALCO 7330 (isothiazoline derivatives)] and one oxidizing biocide [bleach (NaClO)] against a biofilm consortium from a water cooling tower in lab tests. Fifty ppm (w/w) of an equimass mixture of D-methionine, D-leucine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-phenylalanine, and D-valine (D8) enhanced 15 ppm THPS and 15 ppm NALCO 7330 with similar efficacies achieved by the 30 ppm THPS alone treatment and the 30 ppm NALCO 7330 alone treatment, respectively in the single-batch 3-h biofilm removal test. A sequential treatment method was used to enhance bleach because D-amino acids react with bleach. After a 4-h biofilm removal test, the sequential treatment of 5 ppm bleach followed by 50 ppm D8 achieved extra 1-log reduction in sessile cell counts of acid producing bacteria, sulfate reducing bacteria, and general heterotrophic bacteria compared with the 5 ppm bleach alone treatment. The 10 ppm bleach alone treatment showed a similar efficacy with the sequential treatment of 5 ppm bleach followed by 50 ppm D8. The efficacy of D8 was found better than that of D4 (an equimass mixture of D-methionine, D-leucine, D-tyrosine, and D-tryptophan) in the enhancement of the three individual biocides against the biofilm consortium.
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Jia, Ru; Li, Yingchao; Al-Mahamedh, Hussain H.; Gu, Tingyue
2017-01-01
Different species of microbes form mixed-culture biofilms in cooling water systems. They cause microbiologically influenced corrosion (MIC) and biofouling, leading to increased operational and maintenance costs. In this work, two D-amino acid mixtures were found to enhance two non-oxidizing biocides [tetrakis hydroxymethyl phosphonium sulfate (THPS) and NALCO 7330 (isothiazoline derivatives)] and one oxidizing biocide [bleach (NaClO)] against a biofilm consortium from a water cooling tower in lab tests. Fifty ppm (w/w) of an equimass mixture of D-methionine, D-leucine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-phenylalanine, and D-valine (D8) enhanced 15 ppm THPS and 15 ppm NALCO 7330 with similar efficacies achieved by the 30 ppm THPS alone treatment and the 30 ppm NALCO 7330 alone treatment, respectively in the single-batch 3-h biofilm removal test. A sequential treatment method was used to enhance bleach because D-amino acids react with bleach. After a 4-h biofilm removal test, the sequential treatment of 5 ppm bleach followed by 50 ppm D8 achieved extra 1-log reduction in sessile cell counts of acid producing bacteria, sulfate reducing bacteria, and general heterotrophic bacteria compared with the 5 ppm bleach alone treatment. The 10 ppm bleach alone treatment showed a similar efficacy with the sequential treatment of 5 ppm bleach followed by 50 ppm D8. The efficacy of D8 was found better than that of D4 (an equimass mixture of D-methionine, D-leucine, D-tyrosine, and D-tryptophan) in the enhancement of the three individual biocides against the biofilm consortium. PMID:28861053
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Reduction of Salmonella in skinless chicken breast fillets by lauric arginate surface application.
Sharma, C S; Ates, A; Joseph, P; Nannapaneni, R; Kiess, A
2013-05-01
Lauric arginate (LAE) has been found to be effective against various foodborne pathogens. In this study, the antimicrobial efficacy of LAE against Salmonella and mesophilic organisms was evaluated in fresh, skinless, boneless, uncooked chicken breast fillets. The effect of LAE treatments on pH and color of breast fillets was also assessed. Chicken breast fillets were inoculated with a 4-strain Salmonella cocktail (Salmonella Enteritidis ATCC 4931, Salmonella Heidelberg ATCC 8326, Salmonella Kentucky ATCC 9263, and Salmonella Typhimurium ATCC 14028) and then treated with sterile dionized water (positive control) and 200 ppm and 400 ppm of LAE. The chicken breast fillets were stored at 4 ± 1°C and analyzed on d 0, 1, 3, 5, and 7 for Salmonella, total aerobes, color, and pH. The fillets destined for color analysis were not inoculated with Salmonella cocktail and stored under conditions simulating the retail display. The fillets treated with 400 ppm LAE had lower (P < 0.05) Salmonella counts compared with the positive control from d 0 through d 7 of storage except on d 3, when no effect of LAE was observed. Treating fillets with 200 ppm of LAE caused a significant reduction in Salmonella counts (P < 0.1) on d 0, 1, and 7. Reductions in Salmonella spp. were 0.7 log cfu/g and 0.7 to 1.0 log cfu/g for 200 and 400 ppm treatments, respectively. Lauric arginate did not exhibit any treatment effect on the growth of mesophilic microorganisms, pH, and color of chicken breast fillets (P > 0.05) when applied at 200 and 400 ppm concentrations. These results indicate that surface application of LAE in chicken breast fillets significantly reduces Salmonella during refrigerated aerobic storage without negatively affecting the color of chicken breast fillets.
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Protein phosphatase 2A regulates deoxycytidine kinase activity via Ser-74 dephosphorylation.
Amsailale, Rachid; Beyaert, Maxime; Smal, Caroline; Janssens, Veerle; Van Den Neste, Eric; Bontemps, Françoise
2014-03-03
Deoxycytidine kinase (dCK) is a critical enzyme for activation of anticancer nucleoside analogs. Its activity is controlled via Ser-74 phosphorylation. Here, we investigated which Ser/Thr phosphatase dephosphorylates Ser-74. In cells, the PP1/PP2A inhibitor okadaic acid increased both dCK activity and Ser-74 phosphorylation at concentrations reported to specifically target PP2A. In line with this, purified PP2A, but not PP1, dephosphorylated recombinant pSer-74-dCK. In cell lysates, the Ser-74-dCK phosphatase activity was found to be latent, Mn(2+)-activated, responsive to PP2A inhibitors, and diminished after PP2A-immunodepletion. Use of siRNAs allowed concluding definitively that PP2A constitutively dephosphorylates dCK in cells and negatively regulates its activity. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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Effects of ipriflavone on caged layer bone metabolism in vitro and in vivo.
Yao, J; Zhang, J; Hou, J-F
2007-03-01
The effects of ipriflavone on caged layer bone metabolism were examined in vitro and in vivo. Ipriflavone at 10(-8) M stimulated the activity of osteoblasts cultured from embryonic chick calvariae, and 10(-9) to 10(-7) M inhibited osteoclasts from chick tibias and humeri. Ipriflavone concentrations of 10(-4) and 10(-5) M inhibited osteoblast activity. These results suggest that ipriflavone influences bone metabolism by regulating the functional balance between osteoblasts and osteoclasts. Based on these in vitro experiments, in vivo studies were conducted to further clarify the effects of ipriflavone. Five hundred 58-wk-old ISA caged layers were divided into 5 groups that were fed diets containing 0, 15, 25, 50, and 100 ppm of ipriflavone. The experiment lasted 70 d. Egg production increased in hens fed 25 ppm and decreased in hens fed 50 and 100 ppm when compared with the controls and hens fed 15 ppm (P < 0.05). Egg weight, shell quality, BW, and serum P, Ca, estrogen, and bone mineral content were not affected by inclusion of ipriflavone in the diet. Hens consuming 25 ppm of ipriflavone had greater serum alkaline phosphatase and bone gla-protein levels than controls. Adding 25 ppm of ipriflavone to the feed appears to be close to an ideal level for clinical treatment of osteoporosis because of improved egg production while maintaining bone mineral content.
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Kónya, Zoltán; Bécsi, Bálint; Kiss, Andrea; Tamás, István; Lontay, Beáta; Szilágyi, László; Kövér, Katalin E; Erdődi, Ferenc
2018-05-01
Aralkyl and aryl selenoglycosides as well as glycosyl selenocarboxylate derivatives were assayed on the activity of protein phosphatase-1 (PP1) and -2A (PP2A) catalytic subunits (PP1c and PP2Ac) in search of compounds for PP1c and PP2Ac effectors. The majority of tested selenoglycosides activated both PP1c and PP2Ac by ∼2-4-fold in a phosphatase assay with phosphorylated myosin light chain substrate when the hydroxyl groups of the glycosyl moiety were acetylated, but they were without any effects in the non-acetylated forms. A peptide from the myosin phosphatase target subunit-1 (MYPT1 23-38 ) that included an RVxF PP1c-binding motif attenuated activation of PP1c by 2-Trifluoromethylbenzyl 2,3,4,6-tetra-O-acetyl-1-seleno-β-d-glucopyranoside (TFM-BASG) and 4-Bromobenzyl 2,3,4,6-tetra-O-acetyl-1-seleno-β-d-glucopyranoside (Br-BASG). MYPT1 23-38 stimulated PP2Ac and contributed to PP2Ac activation exerted by either Br-BASG or TFM-BASG. Br-BASG and TFM-BASG suppressed partially binding of PP1c to MYPT1 in surface plasmon resonance based binding experiments. Molecular docking predicted that the hydrophobic binding surfaces in PP1c for interaction with either the RVxF residues of PP1c-interactors or selenoglycosides are partially overlapped. Br-BASG and TFM-BASG caused a moderate increase in the phosphatase activity of HeLa cells in 1 h, and suppressed cell viability in 24 h incubations. In conclusion, our present study identified selenoglycosides as novel activators of PP1 and PP2A as well as provided insights into the structural background of their interactions establishing a molecular model for future design of more efficient phosphatase activator molecules. Copyright © 2018 Elsevier Ltd. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Nguyen, H.; Wang, L; Huang, H
2010-01-01
The haloalkanoic acid dehalogenase (HAD) enzyme superfamily is the largest family of phosphohydrolases. In HAD members, the structural elements that provide the binding interactions that support substrate specificity are separated from those that orchestrate catalysis. For most HAD phosphatases, a cap domain functions in substrate recognition. However, for the HAD phosphatases that lack a cap domain, an alternate strategy for substrate selection must be operative. One such HAD phosphatase, GmhB of the HisB subfamily, was selected for structure-function analysis. Herein, the X-ray crystallographic structures of Escherichia coli GmhB in the apo form (1.6 {angstrom} resolution), in a complex with Mg{supmore » 2+} and orthophosphate (1.8 {angstrom} resolution), and in a complex with Mg{sup 2+} and D-glycero-D-manno-heptose 1{beta},7-bisphosphate (2.2 {angstrom} resolution) were determined, in addition to the structure of Bordetella bronchiseptica GmhB bound to Mg{sup 2+} and orthophosphate (1.7 {angstrom} resolution). The structures show that in place of a cap domain, the GmhB catalytic site is elaborated by three peptide inserts or loops that pack to form a concave, semicircular surface around the substrate leaving group. Structure-guided kinetic analysis of site-directed mutants was conducted in parallel with a bioinformatics study of sequence diversification within the HisB subfamily to identify loop residues that serve as substrate recognition elements and that distinguish GmhB from its subfamily counterpart, the histidinol-phosphate phosphatase domain of HisB. We show that GmhB and the histidinol-phosphate phosphatase domain use the same design of three substrate recognition loops inserted into the cap domain yet, through selective residue usage on the loops, have achieved unique substrate specificity and thus novel biochemical function.« less
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Precision Positioning and Inertial Guidance Sensors. Technology and Operational Aspects
1981-03-01
Ueberlingen, GE EVALUATION D’UN SYSTEME EUROPEEN DE NAVIGATION HYBRIDE A - - GYROLASER POUR HELICOPTERE: "SEXTAN" by D Regnault, Centre d’Essais en Vol de...NAVIGATION SYSTEM AND STANDARD STATE ELEMENT DEVIATIONMEASUREMENT SOURCES( Dead-reckoning with position fxP fy 5000 En ]TAS, heading and wind scale...Reproduction Ltd ilarford House. 7-9 Charlotte St. London. WIP JIHD [i Ii THEME A new class of precision positioning systems , including GPS (Global
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Polito, Marina; Guiot, Elvire; Gangarossa, Giuseppe; Longueville, Sophie; Doulazmi, Mohamed; Valjent, Emmanuel; Hervé, Denis; Girault, Jean-Antoine
2015-01-01
Abstract Type 10A phosphodiesterase (PDE10A) is highly expressed in the striatum, in striatonigral and striatopallidal medium-sized spiny neurons (MSNs), which express D1 and D2 dopamine receptors, respectively. PDE10A inhibitors have pharmacological and behavioral effects suggesting an antipsychotic profile, but the cellular bases of these effects are unclear. We analyzed the effects of PDE10A inhibition in vivo by immunohistochemistry, and imaged cAMP, cAMP-dependent protein kinase A (PKA), and cGMP signals with biosensors in mouse brain slices. PDE10A inhibition in mouse striatal slices produced a steady-state increase in intracellular cAMP concentration in D1 and D2 MSNs, demonstrating that PDE10A regulates basal cAMP levels. Surprisingly, the PKA-dependent AKAR3 phosphorylation signal was strong in D2 MSNs, whereas D1 MSNs remained unresponsive. This effect was also observed in adult mice in vivo since PDE10A inhibition increased phospho-histone H3 immunoreactivity selectively in D2 MSNs in the dorsomedial striatum. The PKA-dependent effects in D2 MSNs were prevented in brain slices and in vivo by mutation of the PKA-regulated phosphorylation site of 32 kDa dopamine- and cAMP-regulated phosphoprotein (DARPP-32), which is required for protein phosphatase-1 inhibition. These data highlight differences in the integration of the cAMP signal in D1 and D2 MSNs, resulting from stronger inhibition of protein phosphatase-1 by DARPP-32 in D2 MSNs than in D1 MSNs. This study shows that PDE10A inhibitors share with antipsychotic medications the property of activating preferentially PKA-dependent signaling in D2 MSNs. PMID:26465004
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Advanced Processing for Biomedical Informatics (APBI)
2009-10-01
phosphatidic acid phosphatase type 2 domain containing 1A PPAPDC1A 1 96051 2.71E-06 4.39E-05 4.55 8.14 12.1 205030_at fatty acid binding protein 7...W81XWH‐06‐2‐0072 Principal Investigator: Craig D. Shriver, COL MC 54 209355_s_at phosphatidic acid phosphatase type 2B PPAP2B 8613 1.62E-06...Investigator: Craig D. Shriver, COL MC 24 209711_at solute carrier family 35 (UDP- glucuronic acid /UDP-N- acetylgalactosamine dual transporter), member
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Fenton, Tanis R; Lyon, Andrew W; Rose, M Sarah
2011-08-31
The objective was to determine the influence of gestational age, maternal, and neonatal variables on reference intervals for cord blood bone minerals (calcium, phosphate, magnesium) and related laboratory tests (alkaline phosphatase, and albumin-adjusted calcium), and to develop gestational age specific reference intervals based on infants without influential pathological conditions. Cross-sectional study. 702 babies were identified as candidates for this study in a regional referral neonatal unit. After exclusions (for anomalies, asphyxia, maternal magnesium sulfate administration, and death), relationships were examined between cord blood serum laboratory analytes (calcium, phosphate, magnesium, alkaline phosphatase, and albumin-adjusted calcium) with gestation age and also with maternal and neonatal variables using multiple linear regression. Infants with influential pathological conditions were omitted from the development of gestational age specific reference intervals for the following categories: 23-27, 28-31, 32-34, 35-36 and > 36 weeks. Among the 506 preterm and 54 terms infants included in the sample. Phosphate, magnesium, and alkaline phosphatase in cord blood serum decreased with gestational age, calcium increased with gestational age. Those who were triplets, small for gestational age, and those whose mother had pregnancy-induced hypertension were influential for most of the analytes. The reference ranges for the preterm infants ≥ 36 weeks were: phosphate 1.5 to 2.6 mmol/L (4.5 to 8.0 mg/dL), calcium: 2.1 to 3.1 mmol/L (8.3 to 12.4 mg/dL); albumin-adjusted calcium: 2.3 to 3.2 mmol/L (9.1 to 12.9 mg/dL); magnesium 0.6 to 1.0 mmol/L (1.4 to 2.3 mg/dL), and alkaline phosphatase 60 to 301 units/L. These data suggest that gestational age, as well as potentially pathogenic maternal and neonatal variables should be considered in the development of reference intervals for preterm infants.
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Leaky Gut and Mycotoxins: Aflatoxin B1 Does Not Increase Gut Permeability in Broiler Chickens.
Galarza-Seeber, Rosario; Latorre, Juan D; Bielke, Lisa R; Kuttappan, Vivek A; Wolfenden, Amanda D; Hernandez-Velasco, Xochitl; Merino-Guzman, Ruben; Vicente, Jose L; Donoghue, Annie; Cross, David; Hargis, Billy M; Tellez, Guillermo
2016-01-01
Previous studies conducted in our laboratory have demonstrated that intestinal barrier function can be adversely affected by diet ingredients or feed restriction, resulting in increased intestinal inflammation-associated permeability. Two experiments were conducted in broilers to evaluate the effect of three concentrations of Aflatoxin B1 (AFB1; 2, 1.5, or 1 ppm) on gastrointestinal leakage and liver bacterial translocation (BT). In experiment 1, 240 day-of-hatch male broilers were allocated in two groups, each group had six replicates of 20 chickens (n = 120/group): Control feed or feed + 2 ppm AFB1. In experiment 2, 240 day-of-hatch male broilers were allocated in three groups, each group had five replicates of 16 chickens (n = 80/group): Control feed; feed + 1 ppm AFB1; or feed + 1.5 ppm AFB1. In both experiments, chickens were fed starter (days 1-7) and grower diets (days 8-21) ad libitum and performance parameters were evaluated every week. At day 21, all chicks received an oral gavage dose of FITC-d (4.16 mg/kg) 2.5 h before collecting blood samples to evaluate gastrointestinal leakage of FITC-d. In experiment 2, a hematologic analysis was also performed. Liver sections were aseptically collected and cultured using TSA plates to determine BT. Cecal contents were collected to determine total colony-forming units per gram of Gram-negative bacteria, lactic acid bacteria (LAB), or anaerobes by plating on selective media. In experiment 2, liver, spleen, and bursa of Fabricius were removed to determine organ weight ratio, and also intestinal samples were obtained for morphometric analysis. Performance parameters, organ weight ratio, and morphometric measurements were significantly different between Control and AFB1 groups in both experiments. Gut leakage of FITC-d was not affected by the three concentrations of AFB1 evaluated (P > 0.05). Interestingly, a significant reduction in BT was observed in chickens that received 2 and 1 ppm AFB1. An increase (P < 0.05) in total aerobic bacteria, total Gram negatives, and total LAB were observed in chickens fed with 2 and 1.5 ppm of AFB1 when compared with Control and 1 ppm chickens. The integrity of gut epithelial barrier was not compromised after exposure to the mycotoxin.
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Fowler, B A; Brown, H W; Lucier, G W; Krigman, M R
1975-03-01
This report describes morphometric and biochemical changes in the renal lysosome system of rats exposed to 3, 5, or 10 p.p.m. concentrations of methyl mercury hydroxide in their drinking water for 4 weeks. Increased numbers of dense, granular lysosomes, previously found to contain mercury, were observed in tubule cells of rats receiving the 3 and 5 p.p.m. dose levels but not those of the 10 p.p.m. group. Tubule cells from animals given the 10 p.p;m. dose level displayed proteinaceous vacuoles with dense crystalloid structures, apical cytoplasmic extrusion, and cellular degeneration; Mitochondrial swelling within tubule cells of treated animals showed a marked dose-response relationship. Renal microsomal activity levels of ss-glucuronidase were strongly inhibited by methyl mercury hydroxide exposure at all dose levels, whereas the activity levels of acid phosphatase were unchanged. Lysosomal beta-glucuronidase was also inhibited by methyl mercury hydroxide exposure, whereas lysosomal acid phosphatase showed approximately a 2-fold increase in activity. The results are discussed in relation to the role of lysosomes in mediating the nephrotoxic effects of methyl mercury and other toxic trace metals.
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NASA Astrophysics Data System (ADS)
Tanjung, WN; Nurhasanah, N.; Suri, QA; Jingga; Aribowo, B.; Mardhika, DA; Gayatri, AM; Safitri, R.; Supriyanto, A.
2017-12-01
The textile industry is one of the 10 commodities of industrial products which are still survives in Indonesia due to the crisis in the year 2009 until 2016. Drawback happened in 2017 by increased the number of demand by approximate 3% compares with previous year. In this case, the research conducted in Small Medium Enterprise (SME) called FBS. SME is a business group that is able to absorb a lot of labor and a source of income for society. SME FBS producing clothing boys and domiciled in Jakarta. To complete FBS product, the WIP products are sent to CMT or depot in Sukabumi. In this study, aims to do the shortest route in the determination of the distribution of WIP product to 10 CMT scattered in the area of Sukabumi. After optimization hapened, the route must be started from the Depot SME FBS Sukabumi-Shell Sand Village - village of Sukamaju Village - Margaluyu Village - Narogong Cicurug, - the village of Parakanlima, Cuguha - Padabeunghar Village - Sagaranten Village - village of Ciherang, Ciguyang, Sagaranten - the village of Bojong Waru, Pasirsalam Village, Purabaya - Students - return to Depot SME FBS Sukabumi with mileage in a single trip of 403.6 kilometers. It spents 10 hours 09 minutes and cost distribution issued amounting to IDR 296,928.52. The route length was optimized 47% from 759.1 become 403.6 kilometers.
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Vogelweid, Catherine M; Zapien, Kathleen A; Honigford, Matthew J; Li, Linghui; Li, Hua; Marshall, Heather
2011-01-01
We measured daily intracage ammonia levels and performed weekly assessments of CD1 male, female, and breeder mice housed within disposable, ventilated cages that remained unchanged for 28 d. We tested housing groups comprising 1, 3, or 5 sex-matched mice per cage and breeder pairs with litters. Mice housed in cages with higher concentrations of ammonia developed degeneration and inflammatory lesions in the nasal passages. Mean ammonia exposure levels that caused rhinitis were 181 ppm for 18 d. Ammonia exposures of 93 ppm for 16 d caused necrosis of the olfactory epithelium, whereas 52 ppm for 13 d caused epithelial degeneration. Observers could not detect visible signs of rhinitis or identify cages with elevated ammonia levels, nor did they identify any sick or distressed mice. Observers consistently assigned poorer welfare scores as cages became dirtier. We conclude that we can extend the cage-change interval to at least 28 d for disposable, ventilated caging housing a single CD1 mouse. Cages containing 3 CD1 mice of either sex should be changed biweekly, and cages containing 5 CD1 mice or breeder pairs should be changed at least once weekly. PMID:22330779
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The Weekend Intervention Program.
ERIC Educational Resources Information Center
Siegal, Harvey A.
The Weekend Intervention Program (WIP) at the Wright State University School of Medicine is described in this report. Designed to address severe health and social problems while supporting the university's academic mission, the program began with the goal of addressing the health and social problems of alcohol abusers. WIP is a 72-hour intensive…
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Tribasic copper chloride and copper sulfate as copper sources for weanling pigs.
Cromwell, G L; Lindemann, M D; Monegue, H J; Hall, D D; Orr, D E
1998-01-01
We conducted three 28-d experiments involving a total of 915 pigs to assess the relative efficacy of tribasic Cu chloride (Cu2[OH]3Cl) and Cu sulfate pentahydrate (CuSO4.5H20) in diets for weanling pigs. Experiments 1 and 2 were conducted at an experiment station (University of Kentucky), and Exp. 3 was conducted at a commercial feed company's swine research facilities (United Feeds, Inc.). The basal diet was a fortified corn-soybean meal-dried whey diet (1.25% lysine) with no antimicrobials in Exp. 1 or with carbadox (55 mg/kg) in Exp. 2 and 3. In Exp. 1, 135 pigs were weaned at 27 to 31 d and fed the basal diet without or with 100 or 200 ppm Cu from Cu chloride, or 100 or 200 ppm Cu from Cu sulfate from 7.9 to 17.7 kg BW. The 200 ppm level of Cu from Cu sulfate improved ADG (P < .10), and both levels of Cu from Cu chloride tended to improve feed:gain. In Exp. 2, 150 pigs were weaned at 27 to 31 d and fed the basal diet without or with 100, 150, or 200 ppm Cu from Cu chloride, or 200 ppm Cu from Cu sulfate from 8.9 to 20.8 kg BW. Addition of 200 ppm Cu improved ADG (P < .08) and ADFI (P < .01), but not feed:gain. Source of Cu did not affect performance. In Exp. 3, 630 pigs were weaned at 16 to 20 d and fed a common diet for 10 to 12 d until the start of the experimental period. The same experimental diets as used in Exp. 2 were fed from 9.1 to 25.5 kg BW. Both Cu sources improved ADG (P < .01), and sources and levels of Cu did not differ. Liver Cu increased in pigs fed 200 ppm Cu, and Cu sulfate tended to increase liver Cu more than did Cu chloride in one experiment, but not in another experiment. The results indicate that tribasic Cu chloride is as effective as Cu sulfate in improving growth in weanling pigs.
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Medical Device Plug-and-Play Interoperability Standards and Technology Leadership
2015-10-01
implemented connectivity to an EHR as an HL7 FHIR gateway from OpenICE. The monitor we used can measure heart rate from EKG, from the pulse oximeter , or... Pulse 2014:5(6):37-39. 2. Wu PL, Raguraman D, Sha L, Berlin RB, Goldman JM. WiP abstract: A treatment coordination protocol for cyber-physical-human
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Characteristics of Flight Simulator Visual Systems
1981-05-01
0 . C,...)l .l.Li J ; I a= c I 0 a= c ~ LEVEL1r AGARD ADVISORY REPORT No.164 Characteristics of Flight Simulator Visual Systems...OT\\g . E L E C l ·: .. ;. . . . . , .. , • I ,t l• • ’f) . JIJL 1 6 \\98\\ .. ~ DISTRIBUTION AND AVAILABILITY ON BACK COVER 1 NORTH ATLANTIC...Printed by Technical Editing and Reproduchton Ltd Harford House, 7-9 Charlotte St. London, WIP )HD I PREFACE The Flight Mechanics Panel (FMP) of the
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Naval War College Review. Volume 60, Number 1, Winter 2007
2007-01-01
hospital system predates World War II, when each service provided for all of its own health care.1 In the sixty years since the conclusion of that conflict...Department of Military and Emergency Medicine at the Uniformed Services University of the Health Sciences in Bethesda, Mary- land. He is also professor...and former president of the Uniformed Services Univer- sity of the Health Sciences. Naval War College Review, Winter 2007, Vol. 60, No. 1 C:\\WIP\\NWCR
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Craciunescu, Oana I.; Blackwell, Kimberly L.; Jones, Ellen L.; MacFall, James R.; Yu, Daohai; Vujaskovic, Zeljko; Wong, Terence Z.; Liotcheva, Vlayka; Rosen, Eric L.; Prosnitz, Leonard R.; Samulski, Thaddeus V.; Dewhirst, Mark W.
2009-01-01
Purpose To use a novel Morpho-Physiological Tumor Score (MPTS) generated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict response to treatment. Materials and Methods A protocol was designed to acquire DCE-MRI images of 20 locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NA ChT) and hyperthermia (HT). Imaging was done over 30 minutes following bolus injection of Gd-based contrast agent. Parametric maps were generated by fitting the signal intensity to a double exponential curve and were used to derive a morphological characterization of the lesions. Enhancement-variance dynamics parameters, washin and washout parameters (WiP, WoP) were extracted. The morphological characterization and the WiP and WoP were combined into a MPTS with the intent of achieving better prognostic efficacy. The MPTS was correlated with response to NA therapy as determined by pathologic residual tumor and MRI imaging. Results The contrast agent in all tumors typically peaked in the first 1–4 minutes. The tumors WiP and WoP varied considerably. The MPTS was highly correlated with whether the patients had a pathologic response. This scoring system has a specificity of 78% and a sensitivity of 91% for predicting response to NA chemotherapy. The kappa was 0.69 with a 95% confidence interval of [0.38, 1.0] and a p-value of 0.002. Conclusions This pilot study shows that the MPTS derived using pre-treatment MRI images has the potential to predict response to NA ChT and HT in LABC patients. Further prospective studies are needed to confirm the validity of these results. PMID:19657852
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NASA Astrophysics Data System (ADS)
Wang, Fangfang; Zhou, Bo
2018-04-01
Protein tyrosine phosphatase 1B (PTP1B) is an intracellular non-receptor phosphatase that is implicated in signal transduction of insulin and leptin pathways, thus PTP1B is considered as potential target for treating type II diabetes and obesity. The present article is an attempt to formulate the three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling of a series of compounds possessing PTP1B inhibitory activities using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. The optimum template ligand-based models are statistically significant with great CoMFA (R2cv = 0.600, R2pred = 0.6760) and CoMSIA (R2cv = 0.624, R2pred = 0.8068) values. Molecular docking was employed to elucidate the inhibitory mechanisms of this series of compounds against PTP1B. In addition, the CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of PTP1B active site. The knowledge of structure-activity relationship and ligand-receptor interactions from 3D-QSAR model and molecular docking will be useful for better understanding the mechanism of ligand-receptor interaction and facilitating development of novel compounds as potent PTP1B inhibitors.
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Niu, Mingshan; Sun, Yan; Liu, Bo
2012-01-01
In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured in vivo phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its in vivo PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions. PMID:22563261
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Enhanced Biocide Mitigation of Field Biofilm Consortia by a Mixture of D-Amino Acids
Li, Yingchao; Jia, Ru; Al-Mahamedh, Hussain H.; Xu, Dake; Gu, Tingyue
2016-01-01
Microbiologically influenced corrosion (MIC) is a major problem in the oil and gas industry as well as in many other industries. Current treatment methods rely mostly on pigging and biocide dosing. Biocide resistance is a growing concern. Thus, it is desirable to use biocide enhancers to improve the efficacy of existing biocides. D-Amino acids are naturally occurring. Our previous work demonstrated that some D-amino acids are biocide enhancers. Under a biocide stress of 50 ppm (w/w) hydroxymethyl phosphonium sulfate (THPS) biocide, 1 ppm D-tyrosine and 100 ppm D-methionine used separately successfully mitigated the Desulfovibrio vulgaris biofilm on carbon steel coupons. The data reported in this work revealed that 50 ppm of an equimolar mixture of D-methionine, D-tyrosine, D-leucine, and D-tryptophan greatly enhanced 50 ppm THPS biocide treatment of two recalcitrant biofilm consortia containing sulfate reducing bacteria (SRB), nitrate reducing bacteria (NRB), and fermentative bacteria, etc., from oil-field operations. The data also indicated that individual D-amino acids were inadequate for the biofilm consortia. PMID:27379039
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Murakami, S; Bacha, E A; Mazmanian, G M; Détruit, H; Chapelier, A; Dartevelle, P; Hervé, P
1997-08-01
Experimental studies reveal that inhaled nitric oxide (NO) can prevent, worsen, or have no effect on lung injury in the setting of ischemia-reperfusion (I-R). We tested the hypothesis that these disparate effects could be related to differences in the timing of administration and/or concentration of inhaled NO during I-R. Isolated rat lungs were subjected to 1-h periods of ischemia followed by 1-h periods of blood reperfusion. We investigated the effects of NO (30 ppm) given during ischemia, NO (30 or 80 ppm) begun immediately at reperfusion, or NO (30 ppm) given 15 min after the beginning of reperfusion, on total pulmonary vascular resistance (PVR), the coefficient of filtration (Kfc), the lung wet/dry weight ratio (W/D) of lung tissue, and lung myeloperoxidase activity (MPO). A control group did not receive NO. NO given during ischemia had no effect on Kfc or MPO, but decreased PVR. NO (30 ppm) during reperfusion (early or delayed) decreased PVR, W/D, Kfc and MPO. NO at 80 ppm decreased PVR and MPO but not W/D or Kfc. In conclusion, NO at 30 ppm, given immediately or in a delayed fashion during reperfusion, attenuates I-R-induced lung injury. NO at 30 ppm given during ischemia or at 80 ppm during reperfusion is not protective.
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Alkaline phosphatase protein increases in response to prednisolone in HeLa cells.
Hanford, W C; Kottel, R H; Fishman, W H
1981-01-01
Quantification of term-placental alkaline phosphatase isoenzyme protein in HeLa TCRC-1 cells grown in the presence and absence of prednisolone indicates that there is a net increase in amount of enzyme-specific protein in prednisolone-stimulated cells. In a similar analysis of HeLa D98AH2 cells, prednisolone treatment causes the appearance of term-placental alkaline phosphatase protein and the loss of the intestinal isoenzyme protein. These results support the interpretation that the response of these cells to corticosteroids is the net accumulation of alkaline phosphatase protein rather than the modification of pre-existing enzyme to a more active state. Images Fig. 1. Fig. 2. PMID:7340849
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El-Nashar, Y I; Asrar, A A
2016-05-06
Chemical mutagenesis is an efficient tool used in mutation-breeding programs to improve the vital characters of the floricultural crops. This study aimed to estimate the effects of different concentrations of two chemical mutagens; sodium azide (SA) and diethyl sulfate (DES). The vegetative growth and flowering characteristics in two generations (M1 and M2) of calendula plants were investigated. Seeds were treated with five different concentrations of SA and DES (at the same rates) of 1000, 2000, 3000, 4000, and 5000 ppm, in addition to a control treatment of 0 ppm. Results showed that lower concentrations of SA mutagen had significant effects on seed germination percentage, plant height, leaf area, plant fresh weight, flowering date, inflorescence diameter, and gas-exchange measurements in plants of both generations. Calendula plants tended to flower earlier under low mutagen concentrations (1000 ppm), whereas higher concentrations delayed flowering significantly. Positive results on seed germination, plant height, number of branches, plant fresh weight, and leaf area were observed in the M2-generation at lower concentrations of SA (1000 ppm), as well as at 4000 ppm DES on number of leaves and inflorescences. The highest total soluble protein was detected at the concentrations of 1000 ppm SA and 2000 ppm DES. DES showed higher average of acid phosphatase activity than SA. Results indicated that lower concentrations of SA and DES mutagens had positive effects on seed germination percentage, plant height, leaf area, plant fresh weight, flowering date, inflorescence diameter, and gas-exchange measurements. Thus, lower mutagen concentrations could be recommended for better floral and physio-chemical performance.
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Mills, Stephen J; Vandeput, Fabrice; Trusselle, Melanie N.; Safrany, Stephen T.; Erneux, Christophe; Potter, Barry V. L.
2009-01-01
Novel benzene polyphosphates were synthesised as inositol polyphosphate mimics and evaluated against both type-I inositol 1,4,5-trisphosphate 5-phosphatase, which only binds soluble inositol polyphosphates, and the PH domain of protein kinase Bα (PKBα), which can bind both soluble inositol polyphosphates and inositol phospholipids. The most potent trisphosphate 5-phosphatase inhibitor is benzene 1,2,4-trisphosphate 2, (IC50 of 14 μm) a potential mimic of d-myo-inositol 1,4,5-trisphosphate, and the most potent tetrakisphosphate Ins(1,4,5)P3 5-phosphatase inhibitor is benzene 1,2,4,5-tetrakisphosphate, with an IC50 of 4 μm. Biphenyl 2,3′,4,5′,6-pentakisphosphate 4 was the most potent inhibitor evaluated against type I Ins(1,4,5)P3 5-phosphatase (IC50 of 1 μm). All new benzene polyphosphates are resistant to dephosphorylation by type I Ins(1,4,5)P3 5-phosphatase. Unexpectedly, all benzene polyphosphates studied bind to the PH domain of PKBα with apparent higher affinity than type 1 Ins(1,4,5)P3 5-phosphatase. The most potent ligand for PKBα PH domain is biphenyl 2,3′,4,5′,6-pentakisphosphate 4 (Ki = 27 nm), measured by inhibition of biotinylated diC8-PtdIns(3,4)P2 binding. The ca 80-fold enhancement of binding relative to parent benzene trisphosphate is rationalised by the involvement of a cation–π interaction. These new molecular tools will be of potential use in structural and cell signalling studies. PMID:18574825
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Chen, Weirong; Wan, Xiaoxiao; Ukah, Tobechukwu K; Miller, Mindy M; Barik, Subhasis; Cattin-Roy, Alexis N; Zaghouani, Habib
2016-11-01
To contain autoimmunity, pathogenic T cells must be eliminated or diverted from reaching the target organ. Recently, we defined a novel form of T cell tolerance whereby treatment with Ag downregulates expression of the chemokine receptor CXCR3 and prevents diabetogenic Th1 cells from reaching the pancreas, leading to suppression of type 1 diabetes (T1D). This report defines the signaling events underlying Ag-induced chemokine receptor-mediated tolerance. Specifically, we show that the mammalian target of rapamycin complex 1 (mTORC1) is a major target for induction of CXCR3 downregulation and crippling of Th1 cells. Indeed, Ag administration induces upregulation of programmed death-ligand 1 on dendritic cells in a T cell-dependent manner. In return, programmed death-ligand 1 interacts with the constitutively expressed programmed death-1 on the target T cells and stimulates docking of Src homology 2 domain-containing tyrosine phosphatase 2 phosphatase to the cytoplasmic tail of programmed death-1. Active Src homology 2 domain-containing tyrosine phosphatase 2 impairs the signaling function of the PI3K/protein kinase B (AKT) pathway, leading to functional defect of mTORC1, downregulation of CXCR3 expression, and suppression of T1D. Thus, mTORC1 component of the metabolic pathway serves as a target for chemokine receptor-mediated T cell tolerance and suppression of T1D. Copyright © 2016 by The American Association of Immunologists, Inc.
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75 FR 12796 - Petitions for Modification
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-17
... to continuously monitor methane, oxygen and carbon monoxide concentrations at the specified... activated for the following initial levels: (1) Oxygen: 19.4%; (2) Methane: 1.5%; (3) Carbon Monoxide: 8 ppm...: 19.0%: (2) Methane: 2.0%; and (3) Carbon Monoxide: 13 ppm; (d) if an AMS sensor indicates an alert...
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Synthesis of carbohydrates in a continuous flow reactor by immobilized phosphatase and aldolase.
Babich, Lara; Hartog, Aloysius F; van Hemert, Lieke J C; Rutjes, Floris P J T; Wever, Ron
2012-12-01
Herein, we report a new flow process with immobilized enzymes to synthesize complex chiral carbohydrate analogues from achiral inexpensive building blocks in a three-step cascade reaction. The first reactor contained immobilized acid phosphatase, which phosphorylated dihydroxyacetone to dihydroxyacetone phosphate using pyrophosphate as the phosphate donor. The second flow reactor contained fructose-1,6-diphosphate aldolase (RAMA, rabbit muscle aldolase) or rhamnulose-1-phosphate aldolase (RhuA from Thermotoga maritima) and acid phosphatase. The immobilized aldolases coupled the formed dihydroxyacetone phosphate to aldehydes, resulting in phosphorylated carbohydrates. A final reactor containing acid phosphatase that dephosphorylated the phosphorylated product yielded the final product. Different aldehydes were used to synthesize carbohydrates on a gram scale. To demonstrate the feasibility of the flow systems, we synthesized 0.6 g of the D-fagomine precursor. By using immobilized aldolase RhuA we were also able to obtain other stereoisomers of the D-fagomine precursor. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
None
One of the Department of Energy’s (DOE) primary forums for helping state and local governments implement costeffective and productive energy systems for American homes, communities, businesses, and industries is the Weatherization and Intergovernmental Programs Office (WIP). WIP is part of DOE’s Office of Energy Efficiency and Renewable Energy’s “all of the above” national energy strategy to create greater energy affordability, security and resiliency.
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Comparative toxicity of acephate in laboratory mice, white-footed mice, and meadow voles
Rattner, B.A.; Hoffman, D.J.
1984-01-01
The LD50 (95% confidence limits) of the organophosphorus insecticide acephate was estimated to be 351, 380, and 321 mg/kg (295?416, 280?516, and 266?388 mg/kg) for CD-1 laboratory mice (Mus musculus), white-footed mice (Peromyscus leucopus noveboracensis), and meadow voles (Microtus pennsylvanicus), respectively. In a second study, these species were provided mash containing 0, 25, 100, and 400 ppm acephate for five days. Brain and plasma cholinesterase activities were reduced in a dose-dependent manner to a similar extent in the three species (inhibition of brain acetyl-cholinesterase averaged for each species ranged from 13 to 22% at 25 ppm, 33 to 42% at 100 ppm, and 56 to 57% at 400 ppm). Mash intake, body or liver weight, plasma enzyme activities (alkaline phosphatase, alanine and aspartate aminotransferase), hepatic enzyme activities (aniline hydroxylase, 7-ethoxycoumarin O-deethylase, and glutathione S-transferase), and cytochrome content (P-450 and b5) were not affected by acephate ingestion, although values differed among species. In a third experiment, mice and voles received 400 ppm acephate for 5 days followed by untreated food for up to 2 weeks. Mean inhibition of brain acetylcholin-esterase for the three species ranged from 47 to 58% on day 5, but by days 12 and 19, activity had recovered to 66 to 76% and 81 to 88% of concurrent control values. These findings indicate that CD-1 laboratory mice, white-footed mice, and meadow voles are equally sensitive to acephate when maintained under uniform laboratory conditions. Several factors (e.g., behavior, food preference, habitat) could affect routes and degree of exposure in the field, thereby rendering some species of wild rodents ecologically more vulnerable to organophosphorus insecticides.
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Comparative toxicity of acephate in laboratory mice, white-footed mice and meadow voles
Rattner, B.A.; Hoffman, D.J.
1983-01-01
The LD50 (95% confidence limits) of the organophosphorus insecticide acephate was estimated to be 351, 380, and 321 mg/kg (295?416, 280?516, and 266?388 mg/kg) for CD-1 laboratory mice (Mus musculus), white-footed mice (Peromyscus leucopus noveboracensis), and meadow voles (Microtus pennsylvanicus), respectively. In a second study, these species were provided mash containing 0, 25, 100, and 400 ppm acephate for five days. Brain and plasma cholinesterase activities were reduced in a dose-dependent manner to a similar extent in the three species (inhibition of brain acetyl-cholinesterase averaged for each species ranged from 13 to 22% at 25 ppm, 33 to 42% at 100 ppm, and 56 to 57% at 400 ppm). Mash intake, body or liver weight, plasma enzyme activities (alkaline phosphatase, alanine and aspartate aminotransferase), hepatic enzyme activities (aniline hydroxylase, 7-ethoxycoumarin O-deethylase, and glutathione S-transferase), and cytochrome content (P-450 and b5) were not affected by acephate ingestion, although values differed among species. In a third experiment, mice and voles received 400 ppm acephate for 5 days followed by untreated food for up to 2 weeks. Mean inhibition of brain acetylcholin-esterase for the three species ranged from 47 to 58% on day 5, but by days 12 and 19, activity had recovered to 66 to 76% and 81 to 88% of concurrent control values. These findings indicate that CD-1 laboratory mice, white-footed mice, and meadow voles are equally sensitive to acephate when maintained under uniform laboratory conditions. Several factors (e.g., behavior, food preference, habitat) could affect routes and degree of exposure in the field, thereby rendering some species of wild rodents ecologically more vulnerable to organophosphorus insecticides.
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Epigallocatechin-3-gallate and penta-O-galloyl-β-D-glucose inhibit protein phosphatase-1.
Kiss, Andrea; Bécsi, Bálint; Kolozsvári, Bernadett; Komáromi, István; Kövér, Katalin E; Erdődi, Ferenc
2013-01-01
Protein phosphatase-1 (PP1) and protein phosphatase-2A (PP2A) are responsible for the dephosphorylation of the majority of phosphoserine/threonine residues in cells. In this study, we show that (-)-epigallocatechin-3-gallate (EGCG) and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), polyphenolic constituents of green tea and tannins, inhibit the activity of the PP1 recombinant δ-isoform of the PP1 catalytic subunit and the native PP1 catalytic subunit (PP1c) with IC(50) values of 0.47-1.35 μm and 0.26-0.4 μm, respectively. EGCG and PGG inhibit PP2Ac less potently, with IC(50) values of 15 and 6.6 μm, respectively. The structure-inhibitory potency relationships of catechin derivatives suggests that the galloyl group may play a major role in phosphatase inhibition. The interaction of EGCG and PGG with PP1c was characterized by NMR and surface plasmon resonance-based binding techniques. Competitive binding assays and molecular modeling suggest that EGCG docks at the hydrophobic groove close to the catalytic center of PP1c, partially overlapping with the binding surface of microcystin-LR or okadaic acid. This hydrophobic interaction is further stabilized by hydrogen bonding via hydroxyl/oxo groups of EGCG to PP1c residues. Comparative docking shows that EGCG binds to PP2Ac in a similar manner, but in a distinct pose. Long-term treatment (24 h) with these compounds and other catechins suppresses the viability of HeLa cells with a relative effectiveness reminiscent of their in vitro PP1c-inhibitory potencies. The above data imply that the phosphatase-inhibitory features of these polyphenols may be implicated in the wide spectrum of their physiological influence. © 2012 The Authors Journal compilation © 2012 FEBS.
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Roy, Souvik; Majumdar, Sumana; Singh, Amit Kumar; Ghosh, Balaram; Ghosh, Nilanjan; Manna, Subhadip; Chakraborty, Tania; Mallick, Sougato
2015-08-01
A new trend was developed for the formation of a complex between vanadium and flavonoid derivatives in order to increase the intestinal absorption and to reduce the toxicity of vanadium compounds. The vanadium-rutin complex was characterized by several spectroscopic techniques like ultraviolet (UV)-visible, Fourier transform infrared (FTIR), NMR, mass spectrometry, and microscopic evaluation by scanning electron microscopy. The mononuclear complex was formed by the interaction between vanadium and rutin with 1:2 metal to ligand stoichiometry. Antioxidant activity of the complex was evaluated by 1,1-diphenyl-2 picrylhydrazyl, ferric-reducing power, and 2,2'-azin-obis 3-ethylbenzothiazoline-6-sulphonic acid methods. It was shown that radical scavenging activity and ferric-reducing potential of free rutin was lower as compared with vanadium-rutin complex. The study was also investigated for oral acute toxicity and 28 days repeated oral subacute toxicity study of vanadium-rutin complex in balb/c mice. The vanadium-rutin complex showed mortality at a dose of 120 mg/kg in the balb/c mice. In 28 days repeated oral toxicity study, vanadium-rutin complex was administered to both sex of balb/c mice at dose levels of 90, 45, and 20 ppm, respectively. In addition, subacute toxicity study of vanadium-rutin complex (at 90 ppm dose level) showed increase levels of white blood cell (WBC), total bilirubin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen and decrease level of total protein (TP) as compared with control group. Histopathological study of vanadium-rutin showed structural alteration in the liver, kidney, and stomach at 90 ppm dose level. No observed toxic level of vanadium-rutin complex at 20 ppm dose level could be good for further study.
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Glucose Regulates the Expression of the Apolipoprotein A5 Gene
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey
2008-04-07
The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter.more » We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.« less
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Lee, M T; Ahmed, T; Friedman, M E
1989-01-01
Purified bovine liver beta-glucuronidase (beta-D-glucuronide glucuronohydrolase, EC 3.2.1.32) and wheat germ acid phosphatase (orthophosphoric monoesterphosphohydrolase, EC 3.1.3.2) were inhibited with freshly dissolved and 24 h aquated tetrahaloaurate (III) compounds. Rate and equilibrium inhibition constants were measured. From this data two acid phosphatases species were observed. Equilibrium inhibition constants ranged from 1 to 12.5 microM for the various gold compounds toward both enzymes. The first order rate constants ranged between 0.005 and 0.04 min.-1 for most reactions with the exception of the fast reacting acid phosphatase which had values as high as 2.6 and 2.8 min.-1. It is observed that the beta-glucuronidase is rapidly inhibited during the equilibrium phase before the more slower reaction covalent bond formation takes place. The acid phosphatases form the covalent bonds more rapidly, especially the faster reacting species suggesting a unique difference in the active site geometry to that of the more slowly reacting species. The tightly bonded gold (III)-enzyme complex is probably the reason for its toxicity and non-anti-inflammatory use as a drug.
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Shekh, Ajam Yakub; Shrivastava, Preeti; Gupta, Ankit; Krishnamurthi, Kannan; Devi, Sivanesan Saravana; Mudliar, Sandeep N
2016-02-01
In this study, the concentrations of MgSO4, salinity and light intensity were optimised for maximum biomass productivity and lipid content in Chlorella sp. Lipid synthesized at varied experimental conditions was also assessed in detail for biodiesel properties through FAME analysis. FAMEs mainly composed of C16:0, C16:1(9), C16:3(7, 10, 13), C18:0, C18:1(11), C18:2(9, 12), C18:3(9, 12, 15). The optimum biomass productivity (372.50mgL(-1)d(-1)) and lipid content (32.57%) was obtained at MgSO4-150ppm; salinity-12.5ppm, and light intensity-25μmolm(-2)s(-1). However, at this condition the cetane number, a major biodiesel property was not complying with worldwide biodiesel standard. Therefore, further optimisations were done to check the suitability of biodiesel fuel. The optimum biomass productivity (348.47mgL(-1)d(-1)) and lipid content (12.43%) with suitable biodiesel fuel properties was obtained at MgSO4-50ppm, salinity-25ppm and light intensity-100μmolm(-2)s(-1). The validation experiments confirmed the closeness of predicted and measured response values. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Oyarzabal, Alfonso; Martínez-Pardo, Mercedes; Merinero, Begoña; Navarrete, Rosa; Desviat, Lourdes R; Ugarte, Magdalena; Rodríguez-Pombo, Pilar
2013-02-01
This article describes a hitherto unreported involvement of the phosphatase PP2Cm, a recently described member of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, in maple syrup urine disease (MSUD). The disease-causing mutation was identified in a patient with a mild variant phenotype, involving a gene not previously associated with MSUD. SNP array-based genotyping showed a copy-neutral homozygous pattern for chromosome 4 compatible with uniparental isodisomy. Mutation analysis of the candidate gene, PPM1K, revealed a homozygous c.417_418delTA change predicted to result in a truncated, unstable protein. No PP2Cm mutant protein was detected in immunocytochemical or Western blot expression analyses. The transient expression of wild-type PPM1K in PP2Cm-deficient fibroblasts recovered 35% of normal BCKDH activity. As PP2Cm has been described essential for cell survival, apoptosis and metabolism, the impact of its deficiency on specific metabolic stress variables was evaluated in PP2Cm-deficient fibroblasts. Increases were seen in ROS levels along with the activation of specific stress-signaling MAP kinases. Similar to that described for the pyruvate dehydrogenase complex, a defect in the regulation of BCKDH caused the aberrant metabolism of its substrate, contributing to the patient's MSUD phenotype--and perhaps others. © 2012 WILEY PERIODICALS, INC.
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Bell, Steven E J; Sirimuthu, Narayana M S
2004-11-01
Rapid, quantitative SERS analysis of nicotine at ppm/ppb levels has been carried out using stable and inexpensive polymer-encapsulated Ag nanoparticles (gel-colls). The strongest nicotine band (1030 cm(-1)) was measured against d(5)-pyridine internal standard (974 cm(-1)) which was introduced during preparation of the stock gel-colls. Calibration plots of I(nic)/I(pyr) against the concentration of nicotine were non-linear but plotting I(nic)/I(pyr) against [nicotine](x)(x = 0.6-0.75, depending on the exact experimental conditions) gave linear calibrations over the range (0.1-10 ppm) with R(2) typically ca. 0.998. The RMS prediction error was found to be 0.10 ppm when the gel-colls were used for quantitative determination of unknown nicotine samples in 1-5 ppm level. The main advantages of the method are that the gel-colls constitute a highly stable and reproducible SERS medium that allows high throughput (50 sample h(-1)) measurements.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, Hengchen; Kogan, M.; Endress, A.G.
The influence of ozone (O{sub 3}) on induced resistance in soybean, Glycine max (L.) Merr., cv. Williams 82, was investigated. Feeding by larval soybean looper, Pseudoplusia includens (Walker), was used to induce resistance, and the feeding preference of the Mexican bean beetle, Epilachna varivetis Mulsant, was used to indicate induced resistance. Greenhouse grown soybean plants at the V9 growth stage (eight open trifoliolates) were used in all experiments. One day following feeding injury by the soybean looper, the injured plants and the uninjured controls were exposed to three concentrations of ozone in transparent mylar chambers; level in ambient air (aboutmore » 0.025 ppm), 0.06 ppm, or 0.1 ppm. Plants were exposed for 5 h a day for a period of 2-4 d. Ozone exposure at the levels used in this study produced no visible injuries to leaves. Low doses (up to 4-d-exposure to 0.06 ppm or 2-d exposure to 0.1 ppm) of ozone overrode the resistance in soybean that had been induced by the feeding of soybean looper larvae. Higher doses (3- or 4-d exposure to 0.1 ppm) of ozone actually resulted in a greater acceptability by the Mexican bean beetle of plants injured by the soybean looper than of uninjured plants. Doses of ozone used in these experiments did not significantly alter the feeding preference of the Mexican bean beetle for the uninjured plants. Because ozone pollution and herbivore injury are commonly experienced by plants in nature, the results of this study add another perspective to insect-plant interactions.« less
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Efficacy of benzocaine as an anaesthetic for Crucian carp (Carassius carassius).
Heo, Gang Joon; Shin, Geewook
2010-03-01
To investigate the anaesthetic induction time and concentrations of stress markers in Crucian carp (Carassius carassius) subjected to different concentrations of benzocaine. Prospective experimental study. Thirty-six Crucian carp [body weight 368.3 +/- 22.7 g and length 28.1 +/- 1.9 cm (mean +/- SD)]. Fish were divided into four groups, initially with nine fish per group. Each group was subjected to one of four final concentrations [0, 25, 50 and 100 parts per million (p.p.m.)] of benzocaine. The times to induction of sedation, to pre-anaesthesia and to anaesthesia were recorded according to the behavioural events observed after exposing the fish to benzocaine. At each stage, blood was collected from the caudal vein of three fish of the group, and these three fish were then euthanized. Plasma cortisol and glucose concentrations in the blood samples were measured as indices of stress response. Induction times for all stages of anaesthesia decreased significantly with increasing concentrations of benzocaine (1678 +/- 103, 475 +/- 73 and 251 +/- 2 seconds for anaesthesia in 25, 50 and 100 p.p.m., respectively). Plasma cortisol and glucose concentrations were significantly lower in the anaesthetized groups than the control group (p < 0.05), and tended to decrease with an increasing dose of benzocaine. The cortisol concentrations (36.1 +/- 5.8 ng dL(-1)) at the anaesthetic stage for the 100 p.p.m. group were significantly decreased compared with the other groups (67.3 +/- 14.9 ng dL(-1) in 25 p.p.m. and 47.6 +/- 2.6 ng dL(-1) in 50 p.p.m.). Differences in glucose concentrations between benzocaine-treated groups were not significant. In this study, the fish group exposed to 100 p.p.m. benzocaine had a fast induction time for all monitored stages, low circulating cortisol and glucose concentrations and no immediate mortality.
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40 CFR Table 1 to Subpart D of... - Concentration for Group Determination
Code of Federal Regulations, 2010 CFR
2010-07-01
... 1 Subpart III of Part 60 NA. Subpart NNN of Part 60 300 ppmv of TOC. Subpart RRR of Part 60 300 ppmv of TOC. Subpart G of Part 63 50 ppmv of HAP 2. 1 The 50 ppm HAP concentration cutoff only applies to... are eligible for the 300 ppm TOC cutoff. There is no concentration cutoff for subpart III sources. The...
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Rirattanapong, Praphasri; Vongsavan, Kadkao; Saengsirinavin, Chavengkiat; Waidee, Sumana
2017-03-01
Fluoride dentifrice is effective in preventive dental caries but may cause fluorosis, especially in young children. Reducing the concentration of fluoride from the regular concentration of 1,000 parts per million (ppm) to 500 ppm can reduce the risk for fluorosis but increases the risk of caries. Adding tricalcium phosphate (TCP) to the dentifrices may improve the efficacy of remineralization possibly allowing for a lower concentration of fluoride to reduce the risk of fluorosis. We studied this to inform future caries prevention efforts in children. We immersed 40 sound primary incisors into demineralizing solution (pH=4.4) for 96 hours at 37°C to create demineralized lesions. The 40 teeth were then divided into 4 groups of 10 teeth each. Group A: control (treated with deionized water only); Group B: treated with fluoride dentifrice at a concentration of 1,000 ppm; Group C: treated with fluoride dentifrice at a concentration of 500 ppm and 500 ppm TCP, and Group D: treated with fluoride dentifrice at a concentration of 1,000 ppm and 500 ppm TCP. The teeth were each subjected to 7 days of pH-cycling and the studied dentifrice was applied for one minute, 3 times daily during the 7 day period. After the 7 day period the teeth were each sectioned and examined with polarized light microscopy. The depths of demineralized areas were measured using Image-Pro plus software. A pair t-test was used to compare lesion depths before and after dentifrice treatment. Differences in mean lesion depths within each group were analyzed using the One-way ANOVA and LSD tests; a 95% confidence intervals were calculated. The mean lesion depths in all the groups before dentifrice treatment were not significantly different (p=0.143). The mean demineralized lesion depths after dentifrice treatment were significantly different by group (p=0.00). The mean demineralized lesion depth in Group A significantly deeper than the other groups (p=0.00). Group D had the shallowest depth, significantly shallower than the other groups (p=0.006). There was no significant difference in the mean demineralized lesion depth between Groups B and C (p=0.478). The mean demineralized lesion depth changed significantly after dentifrice treatment in all the groups (p=0.00). Group A was significantly deeper (p=0.00) and groups B, C and D were all significantly shallow. Group D had the greatest reduction in mean demineralized lesion depth (p<0.05). The 1,000 ppm fluoride plus TCP dentifrice gave superior remineralization than the 500 ppm fluoride plus TCP and the 1,000 ppm fluoride dentifrice. The 500 ppm fluoride plus TCP gave the same remineralizing effect as the 1,000 ppm fluoride dentifrice. TCP enhances remineralization on primary enamel when added to fluoride dentifrice. Our results show if TCP is added to fluoride dentifrice a lower concentration of fluoride is needed to provide the same benefit as fluoride dentifrice with a higher concentration of fluoride, reducing the risk of fluorosis in children.
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Missel, Emilene M C; Cunha, Robson F; Vieira, Ana E M; Cruz, Nathália V S; Castilho, Flavia C N; Delbem, Alberto C B
2016-08-01
This in vitro study investigated the effect of sodium trimetaphosphate (TMP), added to toothpaste containing 250 p.p.m. fluoride, on enamel demineralization. Bovine enamel blocks (n = 96) were subjected to five pH cycles over a 7-d period and treatment with suspensions of toothpastes containing 0, 250, 500, and 1,100 p.p.m. fluoride (as sodium fluoride), as well as with 250 p.p.m. fluoride containing TMP at 0.25, 0.5, 1.0, and 3.0%. Treatment with toothpaste suspensions was performed under agitation twice a day, for 1 min. Surface and cross-sectional hardness, and fluoride firmly bound to enamel, were quantified. Data were subjected to one-way anova, followed by Tukey's test. Low-fluoride toothpastes containing TMP at 0.25-1.0% resulted in enamel mineral loss similar to that seen for the toothpaste containing 1,100 p.p.m. fluoride. Also, the addition of TMP to the toothpaste containing 250 p.p.m. fluoride promoted enamel fluoride concentrations similar to those obtained for the 500 p.p.m. fluoride group. The toothpaste containing 250 p.p.m. fluoride and 0.25% TMP led to the lowest mineral loss among all groups. It was concluded that the addition of as little as 0.25% TMP to a toothpaste containing 250 p.p.m. fluoride can reduce enamel demineralization to levels similar to those seen for a conventional toothpaste containing 1,100 p.p.m. fluoride, in vitro. © 2016 Eur J Oral Sci.
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21 CFR 74.2053 - D&C Black No. 3.
Code of Federal Regulations, 2011 CFR
2011-04-01
... may be avoided by current good manufacturing practices: (1) Calcium hydroxyapatite (CaO and P2O5), not... milligrams (mg)/kilogram (kg) (3 parts per million (ppm)); (6) Lead, not more than 10 mg/kg (10 ppm); and (7) Total polycyclic aromatic hydrocarbons (PAHs), not more than 5 mg/kg (5 ppm). (c) Uses and restrictions...
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21 CFR 74.2053 - D&C Black No. 3.
Code of Federal Regulations, 2014 CFR
2014-04-01
... may be avoided by current good manufacturing practices: (1) Calcium hydroxyapatite (CaO and P2O5), not... milligrams (mg)/kilogram (kg) (3 parts per million (ppm)); (6) Lead, not more than 10 mg/kg (10 ppm); and (7) Total polycyclic aromatic hydrocarbons (PAHs), not more than 5 mg/kg (5 ppm). (c) Uses and restrictions...
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21 CFR 74.2053 - D&C Black No. 3.
Code of Federal Regulations, 2013 CFR
2013-04-01
... may be avoided by current good manufacturing practices: (1) Calcium hydroxyapatite (CaO and P2O5), not... milligrams (mg)/kilogram (kg) (3 parts per million (ppm)); (6) Lead, not more than 10 mg/kg (10 ppm); and (7) Total polycyclic aromatic hydrocarbons (PAHs), not more than 5 mg/kg (5 ppm). (c) Uses and restrictions...
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21 CFR 74.2053 - D&C Black No. 3.
Code of Federal Regulations, 2012 CFR
2012-04-01
... may be avoided by current good manufacturing practices: (1) Calcium hydroxyapatite (CaO and P2O5), not... milligrams (mg)/kilogram (kg) (3 parts per million (ppm)); (6) Lead, not more than 10 mg/kg (10 ppm); and (7) Total polycyclic aromatic hydrocarbons (PAHs), not more than 5 mg/kg (5 ppm). (c) Uses and restrictions...
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Hoffman, D.J.; Pattee, O.H.; Wiemeyer, Stanley N.
1985-01-01
The effects on reproduction in screech owls (Otus asio) of chronic dietary sodium fluoride administration at 0, 40, and 200 ppm were examined. Fluoride at 40 ppm resulted in a significantly smaller egg volume, while 200 ppm also resulted in lower egg weights and lengths. Day-one hatchlings in the 200 ppm group weighed almost 10% less than controls and had shorter crown-rump lengths. No gross abnormalities were apparent. Skeletal clearing and staining revealed significantly shorter tibiotarsus lengths in the 40 ppm and 200 ppm groups and a shorter radius-ulna length in the 200 ppm group. By 7 days of age, body weights and lengths did not differ from controls, but the tibiotarsus in the 200 ppm group remained shorter. No significant differences were detected in hematocrit, hemoglobin, plasma calcium or alkaline phosphatase. Plasma phosphorus levels were higher in the 40 ppm group than in controls. These results, in combination with the findings of Pattee et al. [25], revealed significant impairment of overall reproduction, suggesting that sodium fluoride could cause slight to moderate reproduction disorders in owls in fluoride-polluted areas.
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1984-08-17
MODIFICATION-SPECIFIC RELIABILITY SCALAR DERIVATION A 8 C MOD LDZfl 11-R P-1F SI RZLaB.=l sUC NOD # 0g5SXpnflWIP rH SCALAR 1. 42DC 0822 Provide Direct 1964...WSSC Cost x F-16X MSIP Depot Avionics Maint.Mat F-16A Depot Avionics Maint.Materiel - $.028M x $81 297 liT2-2,000 = $. 103M /Squadron/Year C-1O DEPOT
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Pierre, Pascale M; Ryser, Elliot T
2006-03-01
Alfalfa seeds were inoculated with a three-strain cocktail of Escherichia coli O157:H7, Salmonella enterica subsp. enterica serovar Typhimurium DT104, or Listeria monocytogenes by immersion to contain approximately 6 to 8 log CFU/g and then treated with a fatty acid-based sanitizer containing 250 ppm of peroxyacid, 1,000 ppm of caprylic and capric acids (Emery 658), 1,000 ppm of lactic acid, and 500 ppm of glycerol monolaurate at a reference concentration of 1X. Inoculated seeds were immersed at sanitizer concentrations of 5X, 10X, and 15X for 1, 3, 5, and 10 min and then assessed for pathogen survivors by direct plating. The lowest concentration that decreased all three pathogens by >5 log was 15. After a 3-min exposure to the 15X concentration, populations of E. coli O157:H7, Salmonella Typhimurium DT104, and L. monocytogenes decreased by >5.45, >5.62, and >6.92 log, respectively, with no sublethal injury and no significant loss in seed germination rate or final sprout yield. The components of this 15x concentration (treatment A) were assessed independently and in various combinations to optimize antimicrobial activity. With inoculated seeds, treatment C (15,000 ppm of Emery 658, 15,000 ppm of lactic acid, and 7,500 ppm of glycerol monolaurate) decreased Salmonella Typhimurium, E. coli O157:H7, and L. monocytogenes by 6.23 and 5.57 log, 4.77 and 6.29 log, and 3.86 and 4.21 log after 3 and 5 min of exposure, respectively. Treatment D (15,000 ppm of Emery 658 and 15,000 ppm of lactic acid) reduced Salmonella Typhimurium by >6.90 log regardless of exposure time and E. coli )157:H7 and L. monocytogenes by 4.60 and >5.18 log and 3.55 and 3.14 log after 3 and 5 min, respectively. No significant differences (P > 0.05) were found between treatments A, C, and D. Overall, treatment D, which contained Emery 658 and lactic acid as active ingredients, reduced E. coli O157:H7, Salmonella Typhimurium, and L. monocytogenes populations by 3.55 to >6.90 log and may provide a viable alternative to the recommended 20,000 ppm of chlorine for sanitizing alfalfa seeds.
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Memon, Abdul Rehman; Andresen, John; Habib, Muddasar; Jaffar, Muhammad
2014-04-01
The remediation kinetics of simulated sugar factory wastewater (SFW) using an algal-bacterial culture (ABC) of Chlorella vulgaris in association with Pseudomonas putida in a raceway reactor was found to be enhanced by 89% with the addition of 80ppm of copolymer Polyacrylate polyalcohol (PAPA). This was achieved by efficient suspension of the ABC throughout the water body maintaining optimum pH and dissolved oxygen that led to rapid COD removal and improved algal biomass production. The suspension of the ABC using the co-polymer PAPA maintained a DO of 8-10mgl(-1) compared to 2-3mgl(-1) when not suspended. As a result, the non-suspended ABC only achieved a 50% reduction in COD after 96h compared to a 89% COD removal using 80ppm PAPA suspension. In addition, the algae biomass increased from 0.4gl(-1)d(-1) for the non-suspended ABC to 1.1gl(-1)d(-1) when suspended using 80ppm PAPA. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Tangara, M; Chen, W; Xu, J; Huang, F R; Peng, J
2010-10-01
1. The objective of this study was to test the hypothesis that in ovo feeding of carbohydrates and arginine into the duck amnion may improve the glycogen store and perinatal growth. At 23 d of incubation, fertile eggs were injected with 1·2 ml of sodium chloride (NaCl), sucrose + maltose (CHO), arginine (Arg) or sucrose + maltose + arginine (CHO + Arg), with controls not injected. Body weight, liver and muscle glycogen levels, and hepatic glucose-6-phosphatase activity were determined at 25 d of incubation, at hatch, and at 3 and 7 d posthatch. 2. At hatch and 7 d of age, the body weights were greater in the in ovo-feeding treatments than the controls. Arg and CHO + Arg significantly enhanced liver glycogen level at hatch compared with controls. CHO and CHO + Arg significantly increased muscle glycogen level at 25 d of incubation over controls. CHO and Arg decreased glucose-6-phosphatase at 25 d of incubation, whereas NaCl and CHO + Arg increased glucose-6-phosphatase at hatch relative to controls. 3. In ovo feeding of carbohydrates and arginine at 23 d of incubation may improve glycogen reserves, which may, in turn, provide the energy needed for perinatal growth.
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1981-10-01
particularly under conditions of cathodic polarization. Sul- fate ion , while less damaging under free corrosion conditions, is equally aggressive at...Editing and Reproduction Ltd Harford 11ouse, 7-9 Charlotte St, London, WIP 1HD I I - PREFACE Failure by fatigue and degradation by corrosion continue to...of halide ions . In the unstressed state, this degrada- tion may be manifested by localized corrosion such as pitting, crevice corrosion or ex
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Isolation of Lysophosphatidic Acid Phosphatase from Developing Peanut Cotyledons1
Shekar, Sunil; Tumaney, Ajay W.; Rao, T.J.V. Sreenivasa; Rajasekharan, Ram
2002-01-01
The soluble fraction of immature peanut (Arachis hypogaea) was capable of dephosphorylating [3H]lysophosphatidic acid (LPA) to generate monoacylglycerol (MAG). The enzyme responsible for the generation of MAG, LPA phosphatase, has been identified in plants and purified by successive chromatography separations on octyl-Sepharose, Blue Sepharose, Superdex-75, and heparin-agarose to apparent homogeneity from developing peanuts. This enzyme was purified 5,048-fold to a final specific activity of 858 nmol min−1 mg−1. The enzyme has a native molecular mass of approximately 39 kD determined by gel filtration and migrates as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a subunit molecular mass of 39 ± 1.5 kD. The Km values for oleoyl-, stearoyl-, and palmitoyl-sn-glycerol-3-phosphate were determined to be 28.6, 39.3, and 47.9 μm, respectively. The LPA phosphatase was specific to LPA and did not utilize any other substrate such as glycerol-3-phosphate, phosphatidic acid, or p-nitrophenylphosphate. The enzyme activity was stimulated by the low concentrations of detergents such as Triton X-100 and octylglucoside. Cations had no effect on the enzyme activity. Fatty acids, sphingosine, and sphingomyelin at low concentrations stimulated the enzyme activity. The identification of LPA phosphatase in plants demonstrates the existence of MAG biosynthetic machinery in plants. PMID:11891254
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Structural Basis for Rab1 De-AMPylation by the Legionella pneumophila Effector SidD
Neunuebel, M. Ramona; Pallara, Chiara; Brady, Jacqueline; Kinch, Lisa N.; Fernández-Recio, Juan; Rojas, Adriana L.; Machner, Matthias P.; Hierro, Aitor
2013-01-01
The covalent attachment of adenosine monophosphate (AMP) to proteins, a process called AMPylation (adenylylation), has recently emerged as a novel theme in microbial pathogenesis. Although several AMPylating enzymes have been characterized, the only known virulence protein with de-AMPylation activity is SidD from the human pathogen Legionella pneumophila. SidD de-AMPylates mammalian Rab1, a small GTPase involved in secretory vesicle transport, thereby targeting the host protein for inactivation. The molecular mechanisms underlying Rab1 recognition and de-AMPylation by SidD are unclear. Here, we report the crystal structure of the catalytic region of SidD at 1.6 Å resolution. The structure reveals a phosphatase-like fold with additional structural elements not present in generic PP2C-type phosphatases. The catalytic pocket contains a binuclear metal-binding site characteristic of hydrolytic metalloenzymes, with strong dependency on magnesium ions. Subsequent docking and molecular dynamics simulations between SidD and Rab1 revealed the interface contacts and the energetic contribution of key residues to the interaction. In conjunction with an extensive structure-based mutational analysis, we provide in vivo and in vitro evidence for a remarkable adaptation of SidD to its host cell target Rab1 which explains how this effector confers specificity to the reaction it catalyses. PMID:23696742
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NASA Astrophysics Data System (ADS)
Shimizu, Kei; Saal, Alberto E.; Myers, Corinne E.; Nagle, Ashley N.; Hauri, Erik H.; Forsyth, Donald W.; Kamenetsky, Vadim S.; Niu, Yaoling
2016-03-01
We report major, trace, and volatile element (CO2, H2O, F, Cl, S) contents and Sr, Nd, and Pb isotopes of mid-ocean ridge basalt (MORB) glasses from the Northern East Pacific Rise (NEPR) off-axis seamounts, the Quebrada-Discovery-GoFar (QDG) transform fault system, and the Macquarie Island. The incompatible trace element (ITE) contents of the samples range from highly depleted (DMORB, Th/La ⩽ 0.035) to enriched (EMORB, Th/La ⩾ 0.07), and the isotopic composition spans the entire range observed in EPR MORB. Our data suggest that at the time of melt generation, the source that generated the EMORB was essentially peridotitic, and that the composition of NMORB might not represent melting of a single upper mantle source (DMM), but rather mixing of melts from a two-component mantle (depleted and enriched DMM or D-DMM and E-DMM, respectively). After filtering the volatile element data for secondary processes (degassing, sulfide saturation, assimilation of seawater-derived component, and fractional crystallization), we use the volatiles to ITE ratios of our samples and a two-component mantle melting-mixing model to estimate the volatile content of the D-DMM (CO2 = 22 ppm, H2O = 59 ppm, F = 8 ppm, Cl = 0.4 ppm, and S = 100 ppm) and the E-DMM (CO2 = 990 ppm, H2O = 660 ppm, F = 31 ppm, Cl = 22 ppm, and S = 165 ppm). Our two-component mantle melting-mixing model reproduces the kernel density estimates (KDE) of Th/La and 143Nd/144Nd ratios for our samples and for EPR axial MORB compiled from the literature. This model suggests that: (1) 78% of the Pacific upper mantle is highly depleted (D-DMM) while 22% is enriched (E-DMM) in volatile and refractory ITE, (2) the melts produced during variable degrees of melting of the E-DMM controls most of the MORB geochemical variation, and (3) a fraction (∼65% to 80%) of the low degree EMORB melts (produced by ∼1.3% melting) may escape melt aggregation by freezing at the base of the oceanic lithosphere, significantly enriching it in volatile and trace element contents. Our results are consistent with previously proposed geodynamical processes acting at mid-ocean ridges and with the generation of the E-DMM. Our observations indicate that the D-DMM and E-DMM have (1) a relatively constant CO2/Cl ratio of ∼57 ± 8, and (2) volatile and ITE element abundance patterns that can be related by a simple melting event, supporting the hypothesis that the E-DMM is a recycled oceanic lithosphere mantle metasomatized by low degree melts. Our calculation and model give rise to a Pacific upper mantle with volatile content of CO2 = 235 ppm, H2O = 191 ppm, F = 13 ppm, Cl = 5 ppm, and S = 114 ppm.
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Capon; Rooney; Murray; Collins; Sim; Rostas; Butler; Carroll
1998-05-01
A Spongosorites sp. collected during trawling operations off the southern coast of Australia returned the new alkaloid dragmacidin E (3), the structure of which was secured by detailed spectroscopic analysis. Dragmacidin E (3), and its co-metabolite dragmacidin D (1) have been identified as potent inhibitors of serine-threonine protein phosphatases.
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Protein-tyrosine phosphatase Shp2 positively regulates macrophage oxidative burst.
Li, Xing Jun; Goodwin, Charles B; Nabinger, Sarah C; Richine, Briana M; Yang, Zhenyun; Hanenberg, Helmut; Ohnishi, Hiroshi; Matozaki, Takashi; Feng, Gen-Sheng; Chan, Rebecca J
2015-02-13
Macrophages are vital to innate immunity and express pattern recognition receptors and integrins for the rapid detection of invading pathogens. Stimulation of Dectin-1 and complement receptor 3 (CR3) activates Erk- and Akt-dependent production of reactive oxygen species (ROS). Shp2, a protein-tyrosine phosphatase encoded by Ptpn11, promotes activation of Ras-Erk and PI3K-Akt and is crucial for hematopoietic cell function; however, no studies have examined Shp2 function in particulate-stimulated ROS production. Maximal Dectin-1-stimulated ROS production corresponded kinetically to maximal Shp2 and Erk phosphorylation. Bone marrow-derived macrophages (BMMs) from mice with a conditionally deleted allele of Ptpn11 (Shp2(flox/flox);Mx1Cre+) produced significantly lower ROS levels compared with control BMMs. Although YFP-tagged phosphatase dead Shp2-C463A was strongly recruited to the early phagosome, its expression inhibited Dectin-1- and CR3-stimulated phospho-Erk and ROS levels, placing Shp2 phosphatase function and Erk activation upstream of ROS production. Further, BMMs expressing gain of function Shp2-D61Y or Shp2-E76K and peritoneal exudate macrophages from Shp2D61Y/+;Mx1Cre+ mice produced significantly elevated levels of Dectin-1- and CR3-stimulated ROS, which was reduced by pharmacologic inhibition of Erk. SIRPα (signal regulatory protein α) is a myeloid inhibitory immunoreceptor that requires tyrosine phosphorylation to exert its inhibitory effect. YFP-Shp2C463A-expressing cells have elevated phospho-SIRPα levels and an increased Shp2-SIRPα interaction compared with YFP-WT Shp2-expressing cells. Collectively, these findings indicate that Shp2 phosphatase function positively regulates Dectin-1- and CR3-stimulated ROS production in macrophages by dephosphorylating and thus mitigating the inhibitory function of SIRPα and by promoting Erk activation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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Merhi, Zaher; Polotsky, Alex J; Bradford, Andrew P; Buyuk, Erkan; Chosich, Justin; Phang, Tzu; Jindal, Sangita; Santoro, Nanette
2015-10-01
To determine whether obesity alters genes important in cellular growth and inflammation in human cumulus granulosa cells (GCs). Eight reproductive-aged women who underwent controlled ovarian hyperstimulation followed by oocyte retrieval for in vitro fertilization were enrolled. Cumulus GC RNA was extracted and processed for microarray analysis on Affymetrix Human Genome U133 Plus 2.0 chips. Gene expression data were validated on GCs from additional biologically similar samples using quantitative real-time polymerase chain reaction (RT-PCR). Comparison in gene expression was made between women with body mass index (BMI) <25 kg/m(2) (group 1; n = 4) and those with BMI ≥25 kg/m(2) (group 2; n = 4). Groups 1 and 2 had significantly different BMI (21.4 ± 1.4 vs 30.4 ± 2.7 kg/m(2), respectively; P = .02) but did not differ in age (30.5 ± 1.7 vs 32.7 ± 0.3 years, respectively; P = .3). Comparative analysis of gene expression profiles by supervised clustering between group 1 versus group 2 resulted in the selection of 7 differentially expressed genes: fibroblast growth factor 12 (FGF-12), protein phosphatase 1-like (PPM1L), zinc finger protein multitype 2 (ZFPM2), forkhead box M1 (FOXM1), cell division cycle 20 (CDC20), interleukin 1 receptor-like 1 (IL1RL1), and growth arrest-specific protein 7 (GAS7). FOXM1, CDC20, and GAS7 were downregulated while FGF-12 and PPM1L were upregulated in group 2 when compared to group 1. Validation with RT-PCR confirmed the microarray data except for ZFPM2 and IL1RL. As BMI increased, expression of FOXM1 significantly decreased (r = -.60, P = .048). Adiposity is associated with changes in the expression of genes important in cellular growth, cell cycle progression, and inflammation. The upregulation of the metabolic regulator gene PPM1L suggests that adiposity induces an abnormal metabolic follicular environment, potentially altering folliculogenesis and oocyte quality. © The Author(s) 2015.
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Merhi, Zaher; Polotsky, Alex J.; Bradford, Andrew P.; Buyuk, Erkan; Chosich, Justin; Phang, Tzu; Jindal, Sangita; Santoro, Nanette
2015-01-01
Objective: To determine whether obesity alters genes important in cellular growth and inflammation in human cumulus granulosa cells (GCs). Methods: Eight reproductive-aged women who underwent controlled ovarian hyperstimulation followed by oocyte retrieval for in vitro fertilization were enrolled. Cumulus GC RNA was extracted and processed for microarray analysis on Affymetrix Human Genome U133 Plus 2.0 chips. Gene expression data were validated on GCs from additional biologically similar samples using quantitative real-time polymerase chain reaction (RT-PCR). Comparison in gene expression was made between women with body mass index (BMI) <25 kg/m2 (group 1; n = 4) and those with BMI ≥25 kg/m2 (group 2; n = 4). Results: Groups 1 and 2 had significantly different BMI (21.4 ± 1.4 vs 30.4 ± 2.7 kg/m2, respectively; P = .02) but did not differ in age (30.5 ± 1.7 vs 32.7 ± 0.3 years, respectively; P = .3). Comparative analysis of gene expression profiles by supervised clustering between group 1 versus group 2 resulted in the selection of 7 differentially expressed genes: fibroblast growth factor 12 (FGF-12), protein phosphatase 1-like (PPM1L), zinc finger protein multitype 2 (ZFPM2), forkhead box M1 (FOXM1), cell division cycle 20 (CDC20), interleukin 1 receptor-like 1 (IL1RL1), and growth arrest-specific protein 7 (GAS7). FOXM1, CDC20, and GAS7 were downregulated while FGF-12 and PPM1L were upregulated in group 2 when compared to group 1. Validation with RT-PCR confirmed the microarray data except for ZFPM2 and IL1RL. As BMI increased, expression of FOXM1 significantly decreased (r = −.60, P = .048). Conclusions: Adiposity is associated with changes in the expression of genes important in cellular growth, cell cycle progression, and inflammation. The upregulation of the metabolic regulator gene PPM1L suggests that adiposity induces an abnormal metabolic follicular environment, potentially altering folliculogenesis and oocyte quality. PMID:25676576
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Detection of walnut residues in foods using an enzyme-linked immunosorbent assay.
Niemann, Lynn; Taylor, Steve L; Hefle, Susan L
2009-08-01
Tree nuts, including walnuts, can be responsible for allergic reactions. Food manufacturers have the responsibility to declare the presence of walnuts on packaged foods even when trace residues may be present from the use of shared equipment or the adventitious contamination of ingredients. The aim of this study was to develop a rapid, sensitive, and specific enzyme-linked immunosorbent assay (ELISA) method for the detection of walnut protein residues. Mixtures of raw and roasted English walnuts of several varieties were defatted, powdered, and used as separate antigens in sheep and New Zealand white rabbits. An ELISA was developed using the sheep antiroasted walnut serum as the capture reagent and rabbit antiroasted walnut serum as the detector reagent followed by addition of commercial goat anti-rabbit IgG antibody labeled with alkaline phosphatase and subsequent substrate addition. The performance of the ELISA was validated by testing known amounts of walnut (0 to 100 ppm) either spiked into or manufactured into milk chocolate, cookies, muffins, or ice cream. Recoveries of 1 to 100 ppm walnut-in-chocolate ranged from 71.6% to 119%+/- 7% to 16.5%. The walnut ELISA has a detection limit of 1 ppm (1 microg/g) walnut in several food matrices. Substantial cross-reactivity was observed with pecan while minimal cross-reactivity was noted for hazelnut, mustard, mace, and poppy seed among almost 100 foods and food ingredients tested. This walnut ELISA can be used to detect undeclared walnut residues in foods and ingredients and as a tool to validate the effectiveness of allergen control programs for walnuts.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Paine, J.M.; McKee, M.J.; Ryan, M.E.
Laboratory and field studies were used to investigate toxicity and bioaccumulation of PCBs in crickets exposed to contaminated soil. A 14-d laboratory soil bioassay with the house cricket (Acheta domesticus) yielded an LC50 of 1,200 ppm Aroclor 1254. Mean whole-body concentrations of Aroclor 1254 in exposed crickets were 11, 48, 92, 149, and 144 ppm for soil test concentrations of 100, 250, 500, 1,000, and 2,000 ppm, respectively. A whole-body concentration of about 150 ppm appears to be a threshold concentration above which acute mortality will be observed. House crickets placed in cages on a PCB-contaminated landfill accumulated 1.6 andmore » 0.9 ppm of PCBs after 3 and 7 d of exposure, respectively. Although this represents a rapid uptake of PCBs, whole-body concentrations remained considerably below levels expected to cause acute mortality. Abundance of another species, the field cricket (Gryllus pennsylvanicus), was investigated using pitfall traps placed at the PCB-contaminated landfill and a reference site. No adverse effect on abundance was observed at the contaminated site, nor was pitfall trap success correlated to soil PCB concentration. These data indicate that PCBs in soil can rapidly move into epigeic fauna but that the likelihood of acquiring sufficient body burdens to cause acute mortality is low.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Taylor, P.; Sugiman-Marangos, S; Zhang, K
2010-01-01
Lipopolysaccharide is a major component of the outer membrane of Gram-negative bacteria and provides a permeability barrier to many commonly used antibiotics. ADP-heptose residues are an integral part of the LPS inner core, and mutants deficient in heptose biosynthesis demonstrate increased membrane permeability. The heptose biosynthesis pathway involves phosphorylation and dephosphorylation steps not found in other pathways for the synthesis of nucleotide sugar precursors. Consequently, the heptose biosynthetic pathway has been marked as a novel target for antibiotic adjuvants, which are compounds that facilitate and potentiate antibiotic activity. D-{alpha},{beta}-D-Heptose-1,7-bisphosphate phosphatase (GmhB) catalyzes the third essential step of LPS heptose biosynthesis.more » This study describes the first crystal structure of GmhB and enzymatic analysis of the protein. Structure-guided mutations followed by steady state kinetic analysis, together with established precedent for HAD phosphatases, suggest that GmhB functions through a phosphoaspartate intermediate. This study provides insight into the structure-function relationship of GmhB, a new target for combatting Gram-negative bacterial infection.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Cho, Hyeongjin; Ramer, S.E.; Itoh, Michiyasu
1992-01-14
The cytoplasmic domains of two human transmembrane protein tyrosine phosphatases (PTPases), LAR and CD45, have been expressed in Escherichia coli, purified to near-homogeneity, and compared for catalytic efficiency toward several phosphotyrosine-containing peptide substrates. A 615-residue LAR fragment (LAR-D1D2) containing both tandemly repeated PTPase domains shows almost identical specific activity and high catalytic efficiency as the 40-kDa single-domain LAR-D1 fragment, consistent with a single functional active site in the 70-kDa LAR-D1D2 enzyme. A 90-kDa fragment of the human leukocyte CD45 PTPase, containing two similar tandemly repeated PTPase domains, shows parallel specificity to LAR-D1 and LAR-D1D2 with a high k{sub cat}/K{sub M}more » value for a phosphotyrosyl undecapeptide. Sufficient purified LAR-D1 and LAR-D1D2 PTPases were available to demonstrate enzymatic exchange of {sup 18}O from {sup 18}O{sub 4} inorganic phosphate into H{sub 2} {sup 16}O at rates of {approximately}1 {times} 10{sup {minus}2} s{sup {minus}1}. The oxygen-18 exchange probably proceeds via a phosphoenzyme intermediate. Brief incubation of all three PTPase fragments with a ({sup 32}P)phosphotyrosyl peptide substrate prior to quench with SDS sample buffer and gel electrophoresis led to autoradiographic detection of {sup 32}P-labeled enzymes. Pulse/chase studies on the LAR {sup 32}P-enzyme showed turnover of the labeled phosphoryl group.« less
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Park, Shin Young; Ha, Sang-Do
2018-01-01
This study investigated the synergistic effects of sodium hypochlorite (NaClO) and gamma irradiation combination against Vibrio parahaemolyticus in shucked oysters and clams. V. parahaemolyticus decreased to 1.1-5.6 log 10 CFU/g in oysters and 1.1-5.7 log 10 CFU/g in clams by NaClO (20-80 ppm) + γ irradiation (0.1-2.0 kGy) combinations. V. parahaemolyticus was not detected by 60 or 80 ppm NaClO + 2.0 kGy. Synergistic reduction of >1 log was observed by 60 ppm NaClO + 0.3-2 kGy and 80 ppm NaClO + 0.5 or 2 kGy. Specifically, >2 log of the synergistic reduction was obtained by 60 or 80 ppm NaClO + 2 kGy. Furthermore, using the Weibull model, 5D values (5-log reductions) were calculated for 60 or 80 ppm NaClO + 0.5-0.9 kGy. No significant differences were observed for all sensory parameters between samples of 2.0 kGy + 0-80 ppm NaClO. This study suggests that 60 ppm NaClO + 2.0 kGy in reducing 7-log V. parahaemolyticus without any deteriorative changes of sensory qualities could be a potential strategy for post-harvest process in seafood processing and distribution to enhance the microbial safety of molluscan shellfish.
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Yokoyama, V Y; Miller, G T; Hartsell, P L; Leesch, J G
2000-06-01
In total, 30,491 codling moth, Cydia pomonella (L.), 1-d-old eggs on May Grand nectarines in two large-scale tests, and 17,410 eggs on Royal Giant nectarines in four on-site confirmatory tests were controlled with 100% mortality after fumigation with a methyl bromide quarantine treatment (48 g3 for 2 h at > or = 21 degrees C and 50% volume chamber load) on fruit in shipping containers for export to Japan. Ranges (mean +/- SEM) were for percentage sorption 34.7 +/- 6.2 to 46.5 +/- 2.5, and for concentration multiplied by time products 54.3 +/- 0.9 to 74.5 +/- 0.6 g.h/m3 in all tests. In large-scale tests with May Grand nectarines, inorganic bromide residues 48 h after fumigation ranged from 6.8 +/- 0.7 to 6.9 +/- 0.5 ppm, which were below the U.S. Environmental Protection Agency tolerance of 20 ppm; and, organic bromide residues were < 0.01 ppm after 1 d and < 0.001 ppm after 3 d in storage at 0-1 degree C. After completion of larger-scale and on-site confirmatory test requirements, fumigation of 10 nectarine cultivars in shipping containers for export to Japan was approved in 1995. Comparison of LD50s developed for methyl bromide on 1-d-old codling moth eggs on May Grand and Summer Grand nectarines in 1997 versus those developed for nine cultivars in the previous 11 yr showed no significant differences in codling moth response among the cultivars.
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Phosphatidate Phosphatase Plays Role in Zinc-mediated Regulation of Phospholipid Synthesis in Yeast*
Soto-Cardalda, Aníbal; Fakas, Stylianos; Pascual, Florencia; Choi, Hyeon-Son; Carman, George M.
2012-01-01
In the yeast Saccharomyces cerevisiae, the synthesis of phospholipids is coordinately regulated by mechanisms that control the homeostasis of the essential mineral zinc (Carman, G.M., and Han, G. S. (2007) Regulation of phospholipid synthesis in Saccharomyces cerevisiae by zinc depletion. Biochim. Biophys. Acta 1771, 322–330; Eide, D. J. (2009) Homeostatic and adaptive responses to zinc deficiency in Saccharomyces cerevisiae. J. Biol. Chem. 284, 18565–18569). The synthesis of phosphatidylcholine is balanced by the repression of CDP-diacylglycerol pathway enzymes and the induction of Kennedy pathway enzymes. PAH1-encoded phosphatidate phosphatase catalyzes the penultimate step in triacylglycerol synthesis, and the diacylglycerol generated in the reaction may also be used for phosphatidylcholine synthesis via the Kennedy pathway. In this work, we showed that the expression of PAH1-encoded phosphatidate phosphatase was induced by zinc deficiency through a mechanism that involved interaction of the Zap1p zinc-responsive transcription factor with putative upstream activating sequence zinc-responsive elements in the PAH1 promoter. The pah1Δ mutation resulted in the derepression of the CHO1-encoded phosphatidylserine synthase (CDP-diacylglycerol pathway enzyme) and loss of the zinc-mediated regulation of the enzyme. Loss of phosphatidate phosphatase also resulted in the derepression of the CKI1-encoded choline kinase (Kennedy pathway enzyme) but decreased the synthesis of phosphatidylcholine when cells were deficient of zinc. This result confirmed the role phosphatidate phosphatase plays in phosphatidylcholine synthesis via the Kennedy pathway. PMID:22128164
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Wang, Tao; Zou, Hao; Liu, Yun-Xia; Zhang, Xiao-Wen
2018-03-20
Paclitaxel (PTX) could inhibit the growth of fibroblasts, which occurs in proliferative cholangitis and leads to biliary stricture. However, its use has been limited due to poor bioavailability and local administration for short time. This study designed and synthesized a new PTX-conjugated chitosan film (N-succinyl-hydroxyethyl chitosan containing PTX [PTX-SHEC]) and evaluated its safety and efficiency using in vivo and in vitro experiments. The SHEC conjugated with PTX was confirmed by nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FT-IR) measurements. Drug releases in vitro and in vivo were determined using high-performance liquid chromatography. Cell viability in vitro was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Rabbit biliary stricture model was constructed. All rabbits randomly divided into five groups (n = 8 in each group): the sham-operated rabbits were used as control (Group A), Groups B received laparotomies and suture, Group C received laparotomies and covered SHEC suture without the PTX coating, Group D received laparotomies and covered PTX-SHEC suture, and Group E received laparotomies and 1000 μmol/L PTX administration. Liver function tests and residual dosage of PTX from each group were measured by enzyme-linked immunosorbent assay. Histological data and α-smooth muscle actin (SMA) immunohistochemical staining of common bile duct were examined. NMR and FT-IR indicated that PTX was successfully introduced, based on the appearance of signals at 7.41-7.99 ppm, 1.50 ppm, and 1.03 ppm, due to the presence of aromatic protons, methylene protons, and methyl protons of PTX, respectively. No bile leak was observed. The PTX-conjugated film could slowly release PTX for 4 weeks (8.89 ± 0.03 μg at day 30). The in vitro cell viability test revealed significantly different levels of toxicity between films with and without PTX (111.7 ± 4.0% vs. 68.1 ± 6.0%, P < 0.001), whereas no statistically significant difference was observed among the three sets of PTX-contained films (67.7 ± 5.4%, 67.2 ± 3.4%, and 59.1 ± 6.0%, P > 0.05). Histological examinations revealed that after 28 days of implantment, Groups D and E (but not Group C) had less granulation tissue and glandular hyperplasia in the site of biliary duct injury than Group B. The pattern was more obvious in Group D than Group E. Less α-SMA-positive cells were found in tissue from Groups D and E. Comparing with Group E, the liver function was improved significantly in Group D, including total bilirubin (2.69 ± 1.03 μmol/L vs. 0.81 ± 0.54 μmol/L, P = 0.014), alanine aminotransferase (87.13 ± 17.51 U/L vs. 42.12 ± 15.76 U/L, P = 0.012), and alkaline phosphatase (60.61 ± 12.31 U/L vs. 40.59 ± 8.78 U/L, P < 0.001). PTX-SHEC film effectively inhibites the myofibroblast proliferation and extracellular matrix over-deposition during the healing process of biliary reconstruction. This original film might offer a new way for reducing the occurrence of the benign biliary stricture.
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Prieto, Jose M; Mellinas-Gomez, Maria; Zloh, Mire
2016-01-01
The rising trend to consume herbal products for the treatment and/or prevention of minor ailments together with their chemical and pharmacological complexity means there is an urgent need to develop new approaches to their quality and stability. This work looks at the application of one-dimensional diffusion-edited (1)H-NMR spectroscopy (1D DOSY) and (1)H-NMR with suppression of the ethanol and water signals to the characterisation of quality and stability markers in multi-component herbal medicines/food supplements. The experiments were performed with commercial tinctures of Valeriana officinalis L. (valerian), expired and non-expired, as well as its combination with Hummulus lupulus L. (hops), which is one of the most popular blends of relaxant herbs. These techniques did not require purification or evaporation of components for the qualitative analysis of the mixture, but only the addition of D2 O and TSP. The best diagnostic signals were found at δ 7 ppm (H-11, valerenic acid), δ 4.2 ppm (H-1, hydroxyvalerenic acid) and δ 1.5-1.8 ppm (methyl groups in prenylated moieties, α-acids/prenylated flavones). This work concludes on the potential value of 1D DOSY (1)H-NMR to provide additional assurance of quality in complex natural mixtures. Copyright © 2016 John Wiley & Sons, Ltd.
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Ichikawa, Shoji; Austin, Anthony M; Gray, Amie K; Allen, Matthew R; Econs, Michael J
2011-12-01
Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis.
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Austin, Anthony M.; Gray, Amie K.; Allen, Matthew R.; Econs, Michael J.
2011-01-01
Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis. PMID:22009723
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Solution-Based 3D Printing of Polymers of Intrinsic Microporosity.
Zhang, Fengyi; Ma, Yao; Liao, Jianshan; Breedveld, Victor; Lively, Ryan P
2018-05-28
Current additive manufacturing methods have significant limitations in the classes of compatible polymers. Many polymers of significant technological interest cannot currently be 3D printed. Here, a generalizable method for 3D printing of viscous tenary polymer solutions (polymer/solvent/nonsolvent) is applied to both "intrinsically porous" (a polymer of intrinsic microporosity, PIM-1) and "intrinsically nonporous" (cellulose acetate) polymers. Successful ternary ink formulations require balancing of solution thermodynamics (phase separation), mass transfer (solvent evaporation), and rheology. As a demonstration, a microporous polymer (PIM-1) incompatible with current additive manufacturing technologies is 3D printed into a high-efficiency mass transfer contactor exhibiting hierarchical porosity ranging from sub-nanometer to millimeter pores. Short contactors (1.27 cm) can fully purify (<1 ppm) toluene vapor (1000 ppm) in N 2 gas for 1.7 h, which is six times longer than PIM-1 in traditional structures, and more than 4000 times the residence time of gas in the contactor. This solution-based additive manufacturing approach greatly extends the range of 3D-printable materials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Phase locked loop synchronization for direct detection optical PPM communication systems
NASA Technical Reports Server (NTRS)
Chen, C. C.; Gardner, C. S.
1985-01-01
Receiver timing synchronization of an optical pulse position modulation (PPM) communication system can be achieved using a phase locked loop (PLL) if the photodetector output is properly processed. The synchronization performance is shown to improve with increasing signal power and decreasing loop bandwidth. Bit error rate (BER) of the PLL synchronized PPM system is analyzed and compared to that for the perfectly synchronized system. It is shown that the increase in signal power needed to compensate for the imperfect synchronization is small (less than 0.1 dB) for loop bandwidths less than 0.1% of the slot frequency.
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Jiang, Wenhui; Liu, Tianxiang; Nan, Wenzhi; Jeewani, Diddugodage Chamila; Niu, Yanlu; Li, Chunlian; Shi, Xue; Wang, Cong; Wang, Jiahuan; Li, Yang; Wang, Zhonghua
2018-01-01
Abstract Purple pericarps of bread wheat (Triticum aestivum L.) are a useful source of dietary anthocyanins. Previous mapping results indicated that the purple pericarp trait is controlled by two complementary genes located on chromosomes 7D and 2A. However, the identity of the genes and the mechanisms by which they regulate the trait are unknown. In this study, two transcription factors were characterised as anthocyanin activators in purple pericarps: TaPpm1 (purple pericarp-MYB 1) and TaPpb1 (purple pericarp-bHLH 1). Three non-functional variants were detected in the coding sequence of TaPpm1 from non-purple seed lines, in which the function of TaPpm1 was destroyed either by insertion-induced frame shifts or truncated peptides. There were six 261-bp tandem repeats in the promoter region of TaPpb1 in the purple-grained varieties, while there was only one repeat unit present in the non-purple varieties. Furthermore, using yeast two-hybrid, dual luciferase, yeast one-hybrid, and transient assays, we were able to demonstrate that the interaction of TaPpm1 and TaPpb1 co-regulates the synthesis of anthocyanin. Overall, our results provide a better understanding of the molecular basis of anthocyanin synthesis in the wheat pericarp and indicate the existence of an integrated regulatory mechanism that controls production. PMID:29562292
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Goto, A; Tsukamoto, I
2003-08-01
The effect of ascorbic acid deficiency on bone metabolism was evaluated using the ascorbate-requiring Osteogenic Disorder Shionogi (ODS) rat model. Ascorbic acid (Asc)-deficient rats gained body weight in a manner similar to Asc-supplemented rats (control) during 3 weeks, but began to lose weight during the 4th week of Asc deficiency. The tartrate-resistant acid phosphatase (TRAP) activity in serum increased to about 2-fold the control value in the rats fed the Asc-free diet for 2, 3, and 4 weeks (AscD2, AscD3, and AscD4), while a decrease in the alkaline phosphatase (ALP) activity was observed only in AscD4 rats. The serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) level significantly increased to 1.3-, 1.4-, and 1.9-fold of that in the controls in AscD2, D3, and D4, respectively. The ALP activity in the distal femur was unchanged in AscD1, D2, and D3, but decreased to 50% of the control level in AscD4 rats. The TRAP activity in the distal femur increased to about 2-fold of that in the controls in the AscD2 and D3 and decreased to the control level in the AscD4 rats. The amount of hydroxyproline in the distal femur significantly decreased to about 80%, 70%, and 60% of the control in AscD2, D3, and D4 rats, respectively. These decreases were associated with a similar reduction in the calcium content of the distal femur. Histochemical analysis of the distal femur showed an increase in TRAP-positive cells in AscD2 and AscD3 rats and a decrease in the trabecular bone in AscD2, D3, and D4 rats. These results suggested that a deficiency of Asc stimulated bone resorption at an early stage, followed by a decrease in bone formation in mature ODS rats which already had a well-developed collagen matrix and fully differentiated osteoblasts.
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Embryotoxic and teratogenic effects of selenium in the diet of mallards
Hoffman, D.J.; Heinz, G.H.
1988-01-01
Mallards (Anas platyrhynchos) were fed a control diet, diets containing 1, 5, 10, or 25 ppm Se as sodium selenite, or a diet containing 10 ppm Se as seleno-DL-methionine in the first of two experiments. Selenium at 10 ppm as selenomethionine or 25 ppm as sodium selenite caused a 40-44% decrease in the total number of eggs that hatched compared to controls. Selenium at 25 ppm (sodium selenite) resulted in a 19% decrease in mean embryonic weight at 18 d of incubation, accompanied by a 6% decrease in crown-rump length. Ten parts per million Se as selenomethionine was more teratogenic than sodium selenite at 25 ppm. Selenomethionine (10 ppm Se) resulted in an incidence of 13.1% malformations that were often multiple, whereas sodium selenite (10 and 25 ppm Se) resulted in 3.6 and 4.2% malformations. The teratogenicity of selenomethionine was confirmed in a second experiment in which mallards received 1, 2, 4, 8, or 16 ppm Se as selenomethionine, resulting in 0.9, 0.5, 1.4, 6.8, and 67.9% malformations, respectively. These malformations included hydrocephaly, microphthalmia, lower bill defects, and foot defects with ectrodactyly. Both forms of selenium increased the incidence of edema and stunted embryonic growth. Selenomethionine (10 ppm Se) resulted in a significant increase of approximately 40% in plasma glutathione peroxidase activity and a 70% increase in sorbitol dehydrogenase activity (indicative of hepatotoxicity) in hatchlings. Sodium selenite (25 ppm Se) resulted in fourfold elevation in plasma uric acid concentration, indicative of renal alteration. Selenomethionine accumulated much better in eggs than did sodium selenite. These findings indicate that selenomethionine is considerably more teratogenic and generally more embryotoxic than sodium selenite, probably due to higher uptake of selenomethionine.
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MacDonald, Justin A; Sutherland, Cindy; Carlson, David A; Bhaidani, Sabreena; Al-Ghabkari, Abdulhameed; Swärd, Karl; Haystead, Timothy A J; Walsh, Michael P
2016-01-01
A novel inhibitor of zipper-interacting protein kinase (ZIPK) was used to examine the involvement of ZIPK in the regulation of smooth muscle contraction. Pretreatment of de-endothelialized rat caudal arterial smooth muscle strips with the pyrazolo[3,4-d]pyrimidinone inhibitor 2-((1-(3-chlorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo [3,4-d]-pyrimidin-6-yl)thio)propanamide (HS38) decreased the velocity of contraction (time to reach half-maximal force) induced by the phosphatase inhibitor calyculin A in the presence of Ca(2+) without affecting maximal force development. This effect was reversed following washout of HS38 and correlated with a reduction in the rate of phosphorylation of myosin 20-kDa regulatory light chains (LC20) but not of protein kinase C-potentiated inhibitory protein for myosin phosphatase of 17 kDa (CPI-17), prostate apoptosis response-4, or myosin phosphatase-targeting subunit 1 (MYPT1), all of which have been implicated in the regulation of vascular contractility. A structural analog of HS38, with inhibitory activity toward proviral integrations of Moloney (PIM) virus 3 kinase but not ZIPK, had no effect on calyculin A-induced contraction or protein phosphorylations. We conclude that a pool of constitutively active ZIPK is involved in regulation of vascular smooth muscle contraction through direct phosphorylation of LC20 upon inhibition of myosin light chain phosphatase activity. HS38 also significantly attenuated both phasic and tonic contractile responses elicited by phenylephrine, angiotensin II, endothelin-1, U46619, and K(+)-induced membrane depolarization in the presence of Ca(2+), which correlated with inhibition of phosphorylation of LC20, MYPT1, and CPI-17. These effects of HS38 suggest that ZIPK also lies downstream from G protein-coupled receptors that signal through both Gα12/13 and Gαq/11. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.
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García-Pérez, A; Irigoyen-Camacho, M E; Borges-Yáñez, A
2013-01-01
To explore the association between fluoride in drinking water and the prevalence and severity of fluorosis and dental caries in children living in communities receiving fluoridated salt. Participants were schoolchildren (n = 457) living in two rural areas of the State of Morelos, Mexico, where the water fluoride concentration was 0.70 or 1.50 ppm. Dental caries status was assessed using Pitts' criteria. Lesions that were classified as D3 (decayed) were identified to determine the decayed, missing, and filled teeth index (D3MFT). Fluorosis was assessed using the Thylstrup-Fejerskov Index (TFI). Information regarding drinking water source and oral hygiene practices (tooth brushing frequency, dentifrice use, and oral hygiene index) was obtained. The prevalence of fluorosis (TFI ≥1) in communities with 0.70 and 1.50 ppm water fluoride was 39.4 and 60.5% (p = 0.014), respectively, while the prevalence of more severe forms (TFI ≥4) was 7.9 and 25.5% (p < 0.001), respectively. The mean D3MFT was 0.49 (±1.01) in the 0.70 ppm community and 0.61 (±1.47) in the 1.50 ppm community (p = 0.349). A logistic regression model for caries (D3 >1) showed that higher fluorosis categories (TFI 5-6 OR = 6.81, p = 0.001) were associated with higher caries experience, adjusted by age, number of teeth present, tooth brushing frequency, bottled water use, and natural water fluoride concentration. The prevalence of fluorosis was associated with the water fluoride concentration. Fluorosis at moderate and severe levels was associated with a higher prevalence of dental caries, compared with lesser degrees of fluorosis. The impact of dental fluorosis should be considered in dental public health programs. Copyright © 2013 S. Karger AG, Basel.
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Noda, Seiko; Yamada, Asako; Nakaoka, Kanae; Goseki-Sone, Masae
2017-10-01
Vitamin D insufficiency is associated with a greater risk of osteoporosis and also influences skeletal muscle functions, differentiation, and development. The principal function of vitamin D in calcium homeostasis is to increase the absorption of calcium from the intestine, and the level of alkaline phosphatase (ALP) activity, a differentiation marker for intestinal epithelial cells, is regulated by vitamin D. Intestinal-type ALP is expressed at a high concentration in the brush border membrane of intestinal epithelial cells, and is known to be affected by several kinds of nutrients. Recent reviews have highlighted the importance of intestinal-type ALP in gut homeostasis. Intestinal-type ALP controls bacterial endotoxin-induced inflammation by dephosphorylating lipopolysaccharide and is a gut mucosal defense factor. In this study, we investigated the influence of vitamin D on the expression of 2 types of alternative mRNA variants encoding the human alkaline phosphatase, intestinal (ALPI) gene in human Caco-2 cells as an in vitro model of the small intestinal epithelium. After treatment with 1-alpha,25-dihydroxyvitamin D 3 , the biologically active form of vitamin D 3 , there were significant increases in the ALP activities of Caco-2 cells. Inhibitor and thermal inactivation experiments showed that the increased ALP had properties of intestinal-type ALP. Reverse transcription-polymerase chain reaction analysis revealed that expression of the 2 types of alternative mRNA variants from the ALPI gene was markedly enhanced by vitamin D in Caco-2 cells. In conclusion, these findings agree with the hypothesis: vitamin D up-regulated the expression of 2 types of human intestinal alkaline phosphatase alternative splicing variants in Caco-2 cells; vitamin D may be an important regulator of ALPI gene expression in gut homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.
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Subchronic organophosphorus ester-induced delayed neurotoxicity in mallards
Hoffman, D.J.; Sileo, L.; Murray, H.C.
1984-01-01
Eighteen-week-old mallard hens received 0, 10, 30, 90, or 270 ppm technical grade EPN (phenylphosphonothioic acid O-ethyl-O-4-nitrophenyl ester) in the diet for 90 days. Ataxia was first observed in the 270-ppm group after 16 days, in the 90-ppm group after 20 days, in the 30-ppm group after 38 days; 10 ppm failed to produce ataxia. By the end of 90 days all 6 birds in the 270-ppm group exhibited ataxia or paralysis whereas 5 of 6 birds in the 90-ppm group and 2 of 6 birds in the 30-ppm group were visibly affected. Treatment with 30 ppm or more resulted in a significant reduction in body weight. Brain neurotoxic esterase activity was inhibited by averages of 16, 69, 73, and 74% in the 10-, 30-, 90-, and 270-ppm groups, respectively. Brain acetylcholinesterase, plasma cholinesterase, and plasma alkaline phosphatase were significantly inhibited as well. Distinct histopathological effects were seen in the 30-, 90-, and 270-ppm groups which included demyelination and degeneration of axons of the spinal cord. Additional ducks were exposed in a similar manner to 60-, 270-, or 540-ppm leptophos (phosphonothioic acid O-4-bromo-2,5-dichlorophenyl-O-methylphenyl ester) which resulted in similar behavioral, biochemical, and histopathological alterations. These findings indicate that adult mallards are probably somewhat less sensitive than chickens to subchronic dietary exposure to organophosphorus insecticides that induce delayed neurotoxicity.
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Hua, Marti Z; Feng, Shaolong; Wang, Shuo; Lu, Xiaonan
2018-08-30
We report the development of a molecularly imprinted polymers-surface-enhanced Raman spectroscopy (MIPs-SERS) method for rapid detection and quantification of a herbicide residue 2,4-dichlorophenoxyacetic acid (2,4-D) in milk. MIPs were synthesized via bulk polymerization and utilized as solid phase extraction sorbent to selectively extract and enrich 2,4-D from milk. Silver nanoparticles were synthesized to facilitate the collection of SERS spectra of the extracts. Based on the characteristic band intensity of 2,4-D (391 cm -1 ), the limit of detection was 0.006 ppm and the limit of quantification was 0.008 ppm. A simple logarithmic working range (0.01-1 ppm) was established, satisfying the sensitivity requirement referring to the maximum residue level of 2,4-D in milk in both Europe and North America. The overall test of 2,4-D for each milk sample required only 20 min including sample preparation. This MIPs-SERS method has potential for practical applications in detecting 2,4-D in agri-foods. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Paleogeographic Control on Climate Sensitivity of the Cretaceous-Palaeogene-Eocene.
NASA Astrophysics Data System (ADS)
Farnsworth, A.; Lunt, D. J.; Robinson, S.; O'Brien, C. L.; Pancost, R.
2016-12-01
Just how sensitive are warm climates of the past (Cretaceous-Eocene-Palaeogene (CPE)) to atmospheric carbon dioxide (pCO2) concentrations. We present an ensemble [1] of 21 climate model simulations spanning the CPE at both 560ppm and 1120ppm using state of the art paleogeographies (GETECH Plc. [1]), to ascertain how sensitive warm climates of the past are to pCO2. We find depending on the time period in the CPE, a doubling of pCO2results in a 2-3°C increase in SST and a 3-5°C increase in surface air temperature. We analyse the reasons behind the varying climate sensitivity, and the geographical distribution of warming, including some of the periods with regions of cooling (figure 1) and how this may help inform future climate change. Further to this we construct a model derived CO2 curve through the CPE based on avaliable proxy-data. Figure 1 - Mean surface annual surface temperature (°C) anomaly (4 x Pre-Industrial pCO2 (1120ppm) minus 2 x Pre-Industrial pCO2(560ppm)) in the Ypresian ( 52 Myr). [1] Lunt, D. J., Farnsworth, A., Loptson, C., Foster, G. L., Markwick, P., O'Brien, C. L., Pancost, R. D., Robinson, S. A., and Wrobel, N.: Palaeogeographic controls on climate and proxy interpretation, Clim. Past Discuss., 11, 5683-5725, doi:10.5194/cpd-11-5683-2015, 2015.
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Cemin, H S; Vieira, S L; Stefanello, C; Kindlein, L; Ferreira, T Z; Fireman, A K
2018-05-01
A study was conducted to evaluate growth performance, carcass and breast yields, and the occurrence and severity of white striping (WS) and wooden breast (WB) myopathies of broilers fed diets supplemented with increasing dietary levels of an organic source of selenium (Zn-L-SeMet). Broilers were fed 6 treatments with 12 replications of 26 birds in a 4-phase feeding program from 1 to 42 days. Corn-soy-based diets were supplemented with 0, 0.2, 0.4, 0.6, 0.8, and 1.0 ppm of Zn-L-SeMet. At 42 d, 6 birds were randomly selected from each pen (n = 72) and processed for carcass and breast yields. Breast fillets were scored for WS and WB at 42 days. Increasing Zn-L-SeMet led to quadratic responses (P < 0.05) for FCR from 1 to 7 d, BWG from 22 to 35 d, and for both responses from 8 to 21 d and 36 to 42 d, as well as in the overall period of 42 days. Carcass and breast yields presented a quadratic improvement (P < 0.01) with increasing Zn-L-SeMet supplementation and Se requirements were estimated at 0.85 and 0.86 ppm, respectively. In the overall period, estimates of Se requirements were 0.64 ppm for BWG and 0.67 ppm for FCR. White striping and WB scores presented quadratic increases (P < 0.01), and maximum scores were observed at 0.68 and 0.67 ppm, respectively. Broilers fed diets formulated without Se supplementation had a higher percentage of normal fillets compared to other Se supplementation levels (quadratic, P < 0.05). In conclusion, increasing Se supplementation to reach maximum growth performance led to higher degrees of severity of WS and WB. Selenium requirements determined in the present study were significantly higher than the present commercial recommendations.
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Dietary oregano essential oil alleviates experimentally induced coccidiosis in broilers.
Mohiti-Asli, M; Ghanaatparast-Rashti, M
2015-06-15
An experiment was conducted to determine the effects of oregano essential oil on growth performance and coccidiosis prevention in mild challenged broilers. A total of 250 1-d-old chicks were used in a completely randomized design with 5 treatments and 5 replicates with 10 birds in each replication. Experimental treatments included: (1) negative control (NC; unchallenged), (2) positive control (PC; challenged with sporulated oocysts of Eimeria), (3) PC fed 200 ppm Diclazuril in diet, (4) PC fed 300 ppm oregano oil in diet, and (5) PC fed 500 ppm oregano oil in diet. At 22 d of age, all the experimental groups except for NC were challenged with 50-fold dose of Livacox T as a trivalent live attenuated coccidiosis vaccine. On d 28, two birds were slaughtered and intestinal coccidiosis lesions were scored 0-4. Moreover, dropping was scored in the scale of 0-3, and oocysts per gram feces (OPG) were measured. Oregano oil at either supplementation rate increased body weight gain (P=0.039) and improved feed conversion ratio (P=0.010) from d 22 to 28, when compared with PC group. Using 500 ppm oregano oil in challenged broilers diet increased European efficiency factor than PC group (P=0.020). Moreover, challenged broilers fed 500 ppm oregano oil or Diclazuril in diets displayed lower coccidiosis lesions scores in upper (P=0.003) and middle (P=0.018) regions of intestine than PC group, with the effect being similar to unchallenged birds. In general, challenged birds fed 500 ppm oregano oil or Diclazuril in diets had lower OPG (P=0.001), dropping scores (P=0.001), litter scores (P=0.001), and pH of litter (P=0.001) than PC group. It could be concluded that supplementation of oregano oil at the dose of 500 ppm in diet may have beneficial effect on prevention of coccidiosis in broilers. Copyright © 2015 Elsevier B.V. All rights reserved.
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Back-arc with frontal-arc component origin of Triassic Karmutsen basalt, British Columbia, Canada
Barker, F.; Sutherland, Brown A.; Budahn, J.R.; Plafker, G.
1989-01-01
The largely basaltic, ???4.5-6.2-km-thick, Middle to Upper Triassic Karmutsen Formation is a prominent part of the Wrangellian sequence. Twelve analyses of major and minor elements of representative samples of pillowed and massive basalt flows and sills from Queen Charlotte and Vancouver Islands are ferrotholeiites that show a range of 10.2-3.8% MgO (as normalized, H2O- and CO2-free) and related increases in TiO2 (1.0-2.5%), Zr (43-147 ppm) and Nb (5-16 ppm). Other elemental abundances are not related simply to MgO: distinct groupings are evident in Al2O3, Na2O and Cr, but considerable scatter is present in FeO* (FeO + 0.9Fe2O3) and CaO. Some of the variation is attributed to alteration during low-rank metamorphism or by seawater - including variation of Ba, Rb, Sr and Cu, but high-field-strength elements (Sc, Ti, Y, Zr and Nb) as well as Cr, Ni, Cu and rare-earth elements (REE's) were relatively immobile. REE's show chondrite-normalized patterns ranging from light-REE depleted to moderately light-REE enriched. On eleven discriminant plots these analyses fall largely into or across fields of within-plate basalt (WIP), normal or enriched mid-ocean-ridge tholeiite (MORB) and island-arc tholeiite (IAT). Karmutsen basalts are chemically identical to the stratigraphically equivalent Nikolai Greenstone of southern Alaska and Yukon Territory. These data and the fact that the Karmutsen rests on Sicker Group island-arc rocks of Paleozoic age suggest to us that: 1. (1) the basal arc, after minor carbonate-shale deposition, underwent near-axial back-arc rifting (as, e.g., the Mariana arc rifted at different times); 2. (2) the Karmutsen basalts were erupted along this rift or basin as "arc-rift" tholeiitite; and 3. (3) after subsequent deposition of carbonates and other rocks, and Jurassic magmatism, a large fragment of this basalt-sediment-covered island arc was accreted to North America as Wrangellia. The major- and minor-elemental abundances of Karmutsen basalt is modeled by first mixing primitive arc magma with enriched basaltic liquid derived either from garnet peridotite or metasomatized mantle, followed by fractionation of olivine, pyroxenes, plagioclase and spinel. ?? 1989.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Clewell, H.J., E-mail: hclewell@thehamner.org; Efremenko, A.; Campbell, J.L.
Male and female Fischer 344 rats were exposed to naphthalene vapors at 0 (controls), 0.1, 1, 10, and 30 ppm for 6 h/d, 5 d/wk, over a 90-day period. Following exposure, the respiratory epithelium and olfactory epithelium from the nasal cavity were dissected separately, RNA was isolated, and gene expression microarray analysis was conducted. Only a few significant gene expression changes were observed in the olfactory or respiratory epithelium of either gender at the lowest concentration (0.1 ppm). At the 1.0 ppm concentration there was limited evidence of an oxidative stress response in the respiratory epithelium, but not in themore » olfactory epithelium. In contrast, a large number of significantly enriched cellular pathway responses were observed in both tissues at the two highest concentrations (10 and 30 ppm, which correspond to tumorigenic concentrations in the NTP bioassay). The nature of these responses supports a mode of action involving oxidative stress, inflammation and proliferation. These results are consistent with a dose-dependent transition in the mode of action for naphthalene toxicity/carcinogenicity between 1.0 and 10 ppm in the rat. In the female olfactory epithelium (the gender/site with the highest incidences of neuroblastomas in the NTP bioassay), the lowest concentration at which any signaling pathway was significantly affected, as characterized by the median pathway benchmark dose (BMD) or its 95% lower bound (BMDL) was 6.0 or 3.7 ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4 ppm, respectively. In the male respiratory epithelium (the gender/site with the highest incidences of adenomas in the NTP bioassay), the lowest pathway BMD and BMDL were 0.4 and 0.3 ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9 ppm, respectively. Using a published physiologically based pharmacokinetic (PBPK) model to estimate target tissue dose relevant to the proposed mode of action (total naphthalene metabolism per gram nasal tissue), the lowest transcriptional BMDLs from this analysis equate to human continuous naphthalene exposure at approximately 0.3 ppm. It is unlikely that significant effects of naphthalene or its metabolites will occur at exposures below this concentration. - Highlights: • We investigated mode of action for carcinogenicity of inhaled naphthalene in rats. • Gene expression changes were measured in rat nasal tissues after 90 day exposures. • Support a non-linear mode of action (oxidative stress, inflammation, and proliferation) • Suggest a dose-dependent transition in the mode of action between 1.0 and 10 ppm • Transcriptional benchmark doses could inform point of departure for risk assessment.« less
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Evidence for a latent form of protein phosphatase 1 associated with cardiac myofibrils.
Schlender, K K; Wang, W; Wilson, S E
1989-02-28
Detergent-purified myofibrils from bovine heart contained very little spontaneously active protein phosphatase 1 activity. Phosphatase 1, extracted from the myofibrils by freeze-thawing in the presence of 500 mM KCl, was markedly activated by cobalt/trypsin treatment. Myofibril phosphatase 1 was separated from phosphatase 2A by chromatography on heparin-Sepharose. The phosphatase 1 was isolated in a latent form. Pretreatment with trypsin released free catalytic subunit and increased activity about 25-fold. Addition of cobalt with the trypsin increased activity another 2-fold. The latent myofibril phosphatase 1 did not appear to be the same as previously characterized forms of protein phosphatase 1. We suggest that cardiac myofibril phosphatase 1 contains a unique inhibitory subunit which directs the enzyme to the myofibril and regulates the dephosphorylation of myofibril phosphoproteins.
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Reproduction in mallards fed selenium
Heinz, G.H.; Hoffman, D.J.; Krynitsky, A.J.; Weller, D.M.G.
1987-01-01
Mallards (Anas platyrhynchos) were fed diets containing 1, 5, 10, 25 or 100 ppm selenium as sodium selenite, a diet containing 10 ppm selenium as seleno-DL-methionine or a control diet. There were no effects of 1, 5 or 10 ppm selenium as sodium selenite on either weight or survival of adults or on reproductive success, and there did not appear to be a dose-response relationship at these lower levels. The 100 ppm selenium diet killed 11 of 12 adults; one adult male fed 25 ppm selenium died. Selenium at 25 and 100 ppm caused weight loss in adults. Females fed 25 ppm selenium took longer to begin laying eggs and intervals between eggs were longer than in females in other treatment groups. Hatching success appeared to be reduced in birds fed 10 ppm selenium at selenomethionine, but the reduction was not statistically significant. The survival of ducklings and the mean number of 21-d-old ducklings produced per female were reduced in the 25 ppm selenium as sodium selenite group and the 10 ppm selenium as selenomethionine group. Egg weights were not affected by any selenium treatment, but 25 ppm selenium lowered the Ratcliffe Index. Duckling weights at hatching and at 21 d of age were reduced 28 and 36%, respectively, in birds fed 25 ppm selenium, as compared with controls. Body weights measured on day 21 were lower for ducklings fed 10 ppm selenium as selenomethionine than in some other groups. Selenium in concentrations of 10 and 25 ppm as sodium selenite caused mainly embryotoxic effects, whereas 10 ppm as selenomethionine was more teratogenic, causing hydrocephaly, bill defects, eye defects (microphthalmia and anophthalmia) and foot and toe defects, including ectrodactyly. Selenomethionine was much more readily taken up by mallards and passed into their eggs than was sodium selenite, and a greater proportion of the selenium in the eggs ended up in the white when selenomethionine was fed. Adult males accumulated more selenium than did females, probably because of the females' ability to eliminate selenium in their eggs.
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Shi, Y; Nikulenkov, F; Zawacka-Pankau, J; Li, H; Gabdoulline, R; Xu, J; Eriksson, S; Hedström, E; Issaeva, N; Kel, A; Arnér, E S J; Selivanova, G
2014-01-01
Rescue of the p53 tumor suppressor is an attractive cancer therapy approach. However, pharmacologically activated p53 can induce diverse responses ranging from cell death to growth arrest and DNA repair, which limits the efficient application of p53-reactivating drugs in clinic. Elucidation of the molecular mechanisms defining the biological outcome upon p53 activation remains a grand challenge in the p53 field. Here, we report that concurrent pharmacological activation of p53 and inhibition of thioredoxin reductase followed by generation of reactive oxygen species (ROS), result in the synthetic lethality in cancer cells. ROS promote the activation of c-Jun N-terminal kinase (JNK) and DNA damage response, which establishes a positive feedback loop with p53. This converts the p53-induced growth arrest/senescence to apoptosis. We identified several survival oncogenes inhibited by p53 in JNK-dependent manner, including Mcl1, PI3K, eIF4E, as well as p53 inhibitors Wip1 and MdmX. Further, we show that Wip1 is one of the crucial executors downstream of JNK whose ablation confers the enhanced and sustained p53 transcriptional response contributing to cell death. Our study provides novel insights for manipulating p53 response in a controlled way. Further, our results may enable new pharmacological strategy to exploit abnormally high ROS level, often linked with higher aggressiveness in cancer, to selectively kill cancer cells upon pharmacological reactivation of p53. PMID:24413150
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Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B
Verma, Neelam; Mittal, Minakshi; Verma, Raman kumar
2008-01-01
Protein Tyrosine Phosphatases (PTPs) that function as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing Protein Tyrosine Phosphatase1B (PTP1B) abundance not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high fat feeding. PTP1B inhibitors such as Formylchromone derivatives, 1, 2-Naphthoquinone derivatives and Oxalyl aryl amino benzoic derivatives may eventually find an important clinical role as insulin sensitizers in the management of Type-II Diabetes and metabolic syndrome. We have carried out docking of modified oxalyl aryl amino benzoic acid derivatives into three dimensional structure of PTP1B using BioMed CAChe 6.1. These compounds exhibit good selectivity for PTP1B over most of phosphatases in selectivity panel such as SHP-2, LAR, CD45 and TCPTP found in literature. This series of compounds identified the amino acid residues such as Gly220 and Arg221 are important for achieving specificity via H-bonding interactions. Lipophilic side chain of methionine in modified oxalyl aryl amino benzoic acid derivative [1b (a2, b2, c1, d)] lies in closer vicinity of hydrophobic region of protein consisted of Meth258 and Phe52 in comparison to active ligand. Docking Score in [1b (a2, b2, c1, d)] is -131.740Kcal/mol much better than active ligand score -98.584Kcal/mol. This information can be exploited to design PTP1B specific inhibitors. PMID:19238234
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Stable structural color patterns displayed on transparent insect wings.
Shevtsova, Ekaterina; Hansson, Christer; Janzen, Daniel H; Kjærandsen, Jostein
2011-01-11
Color patterns play central roles in the behavior of insects, and are important traits for taxonomic studies. Here we report striking and stable structural color patterns--wing interference patterns (WIPs)--in the transparent wings of small Hymenoptera and Diptera, patterns that have been largely overlooked by biologists. These extremely thin wings reflect vivid color patterns caused by thin film interference. The visibility of these patterns is affected by the way the insects display their wings against various backgrounds with different light properties. The specific color sequence displayed lacks pure red and matches the color vision of most insects, strongly suggesting that the biological significance of WIPs lies in visual signaling. Taxon-specific color patterns are formed by uneven membrane thickness, pigmentation, venation, and hair placement. The optically refracted pattern is also stabilized by microstructures of the wing such as membrane corrugations and spherical cell structures that reinforce the pattern and make it essentially noniridescent over a large range of light incidences. WIPs can be applied to map the micromorphology of wings through direct observation and are useful in several fields of biology. We demonstrate their usefulness as identification patterns to solve cases of cryptic species complexes in tiny parasitic wasps, and indicate their potentials for research on the genetic control of wing development through direct links between the transregulatory wing landscape and interference patterns we observe in Drosophila model species. Some species display sexually dimorphic WIPs, suggesting sexual selection as one of the driving forces for their evolution.
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Stable structural color patterns displayed on transparent insect wings
Shevtsova, Ekaterina; Hansson, Christer; Janzen, Daniel H.; Kjærandsen, Jostein
2011-01-01
Color patterns play central roles in the behavior of insects, and are important traits for taxonomic studies. Here we report striking and stable structural color patterns—wing interference patterns (WIPs)—in the transparent wings of small Hymenoptera and Diptera, patterns that have been largely overlooked by biologists. These extremely thin wings reflect vivid color patterns caused by thin film interference. The visibility of these patterns is affected by the way the insects display their wings against various backgrounds with different light properties. The specific color sequence displayed lacks pure red and matches the color vision of most insects, strongly suggesting that the biological significance of WIPs lies in visual signaling. Taxon-specific color patterns are formed by uneven membrane thickness, pigmentation, venation, and hair placement. The optically refracted pattern is also stabilized by microstructures of the wing such as membrane corrugations and spherical cell structures that reinforce the pattern and make it essentially noniridescent over a large range of light incidences. WIPs can be applied to map the micromorphology of wings through direct observation and are useful in several fields of biology. We demonstrate their usefulness as identification patterns to solve cases of cryptic species complexes in tiny parasitic wasps, and indicate their potentials for research on the genetic control of wing development through direct links between the transregulatory wing landscape and interference patterns we observe in Drosophila model species. Some species display sexually dimorphic WIPs, suggesting sexual selection as one of the driving forces for their evolution. PMID:21199954
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hefferan, T.E.; Sherman, S.S.; Sinha, R.
Eighty female Sprague-Dawley 8 week old rats were pair-fed for 2 months a semi-purified egg white diet containing 0.2% Ca and Zn at 4.5, 10, 100 or 200ppm. The vitamin D source was D/sub 3/ or 1,25(OH)/sub 2/D. Serum 1,25(OH)/sub 2/D, Ca and femur densities were determined. Femur densities were shown to regress significantly (p<0.01) with increasing dietary Zn when D/sub 3/ was in the diet. In addition, feeding D/sub 3/ resulted in a significant negative correlation of serum Ca with increased dietary Zn (p<0.05). There was a trend for 1,25(OH)/sub 2/D to increase with increasing Zn intake. However, serummore » values in rats consuming 1,25(OH)/sub 2/D were lower compared to rats consuming D/sub 3/ (25.9+/-3.6 vs 53.0+/-5.9 pg/ml). A second study was conducted to determine if non-fasted rats had elevated 1,25(OH)/sub 2/D serum levels. The rats were fed a similar semi-purified diet containing 0.2% Ca, 10ppm Zn and D/sub 3/ or 1,25(OH)/sub 2/D. No significant difference in 1,25(OH)/sub 2/D values was found between D/sub 3/ and 1,25(OH)/sub 2/D fed groups in the full fed state (80.8+/-11.4 vs 81.0+/-14.3 pg/ml). These results indicate high Zn intakes antagonize normal calcification and may interfere with normal function of the vitamin D endocrine system.« less
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Saran, Raj K; Ziegler, Melissa; Kudlie, Sara; Harrison, Danielle; Leva, David M; Scherer, Clay; Coffelt, Mark A
2014-10-01
Intrinsic toxicities of chlorantraniliprole, fipronil, and imidacloprid were evaluated with topical applications on worker termites. Worker termites were exposed to substrates treated with formulated chlorantraniliprole to study contact toxicity, tunneling, and postexposure behaviors. The intrinsic toxicities (LD50, ng/termite) of chlorantraniliprole (1.25, 0.96, and 0.44) and fipronil (0.12, 0.11, and 0.13) at 11 d were similar for workers from three termite colonies. Imidacloprid toxicity (LD50) values were highly variable among the workers from three different colonies, values at 11 d ranging from 0.7 to 75 ng/termite. Termite workers exposed to sand and soils treated with chlorantraniliprole at 50 ppm exhibited delayed mortality and, for most of the exposure times, it took >5 d to observe 90-100% mortality in termite workers. Exposure to chlorantraniliprole-treated sand (50 ppm) for as little as 1 min stopped feeding and killed 90-100% of the workers. Tunneling (≈ 2 h) in different soil types treated with chlorantraniliprole at 50 ppm, even those with high organic matter (6.3%) and clay content (30%), caused immediate feeding cessation in worker termites and mortality in the next 7-14 d. Worker termites exposed for 1 and 60 min to sand treated with chlorantraniliprole (50 ppm) were able to walk normally for 4 h after exposure in most cases. Delayed toxicity, increased aggregation, and grooming were observed in exposed termites and discussed in the context of horizontal transfer effects within termite colonies. © 2014 Entomological Society of America.
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Liu, Gang; Szczepankiewicz, Bruce G; Pei, Zhonghua; Janowick, David A; Xin, Zhili; Hajduk, Philip J; Abad-Zapatero, Cele; Liang, Heng; Hutchins, Charles W; Fesik, Stephen W; Ballaron, Steve J; Stashko, Mike A; Lubben, Tom; Mika, Amanda K; Zinker, Bradley A; Trevillyan, James M; Jirousek, Michael R
2003-05-22
Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.
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NASA Astrophysics Data System (ADS)
Ghavami, Raouf; Sadeghi, Faridoon; Rasouli, Zolikha; Djannati, Farhad
2012-12-01
Experimental values for the 13C NMR chemical shifts (ppm, TMS = 0) at 300 K ranging from 96.28 ppm (C4' of indole derivative 17) to 159.93 ppm (C4' of indole derivative 23) relative to deuteride chloroform (CDCl3, 77.0 ppm) or dimethylsulfoxide (DMSO, 39.50 ppm) as internal reference in CDCl3 or DMSO-d6 solutions have been collected from literature for thirty 2-functionalized 5-(methylsulfonyl)-1-phenyl-1H-indole derivatives containing different substituted groups. An effective quantitative structure-property relationship (QSPR) models were built using hybrid method combining genetic algorithm (GA) based on stepwise selection multiple linear regression (SWS-MLR) as feature-selection tools and correlation models between each carbon atom of indole derivative and calculated descriptors. Each compound was depicted by molecular structural descriptors that encode constitutional, topological, geometrical, electrostatic, and quantum chemical features. The accuracy of all developed models were confirmed using different types of internal and external procedures and various statistical tests. Furthermore, the domain of applicability for each model which indicates the area of reliable predictions was defined.
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NASA Astrophysics Data System (ADS)
Son, In-Hyuk; Shin, Woo-Cheol; Lee, Yong-Kul; Lee, Sung-Chul; Ahn, Jin-Gu; Han, Sang-Il; kweon, Ho-Jin; Kim, Ju-Yong; Kim, Moon-Chan; Park, Jun-Yong
A polymer electrolyte membrane fuel cell (PEMFC) system is developed to power a notebook computer. The system consists of a compact methanol-reforming system with a CO preferential oxidation unit, a 16-cell PEMFC stack, and a control unit for the management of the system with a d.c.-d.c. converter. The compact fuel-processor system (260 cm 3) generates about 1.2 L min -1 of reformate, which corresponds to 35 We, with a low CO concentration (<30 ppm, typically 0 ppm), and is thus proven to be capable of being targetted at notebook computers.
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Dixit, Saurabh; Sahu, Rajnish; Verma, Richa; Duncan, Skyla; Giambartolomei, Guillermo H; Singh, Shree R; Dennis, Vida A
2018-03-01
We previously developed a Chlamydia trachomatis nanovaccine (PPM) by encapsulating a chlamydial M278 peptide within poly(lactic acid)-poly(ethylene glycol) biodegradable nanoparticles that immunopotentiated Chlamydia-specific immune effector responses in mice. Herein, we investigated the mechanistic interactions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its uptake, trafficking, and T cell activation. Our results reveal that PPM triggered enhanced expression of effector cytokines and chemokines, surface activation markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2, Nod1), co-stimulatory (CD40, CD80, CD86) and MHC class I and II molecules. Co-culturing of PPM-primed DCs with T cells from C. muridarum vaccinated mice yielded an increase in Chlamydia-specific immune effector responses including CD3 + lymphoproliferation, CD3 + CD4 + IFN-γ-secreting cells along with CD3 + CD4 + memory (CD44 high and CD62L high ) and effector (CD44 high and CD62L low ) phenotypes. Intracellular trafficking analyses revealed an intense expression and colocalization of PPM predominantly in endosomes. PPM also upregulated the transcriptional and protein expression of the endocytic mediator, caveolin-1 in DCs. More importantly, the specific inhibition of caveolin-1 led to decreased expression of PPM-induced cytokines and co-stimulatory molecules. Our investigation shows that PPM provided enhancement of uptake, probably by exploiting the caveolin-mediated endocytosis pathway, endosomal processing, and MHC II presentation to immunopotentiate Chlamydia-specific immune effector responses mediated by CD4 + T cells. Copyright © 2017 Elsevier Ltd. All rights reserved.
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1996-01-01
Cadherins are a family of cell-cell adhesion molecules which play a central role in controlling morphogenetic movements during development. Cadherin function is regulated by its association with the actin containing cytoskeleton, an association mediated by a complex of cytoplasmic proteins, the catenins: alpha, beta, and gamma. Phosphorylated tyrosine residues on beta-catenin are correlated with loss of cadherin function. Consistent with this, we find that only nontyrosine phosphorylated beta-catenin is associated with N-cadherin in E10 chick retina tissue. Moreover, we demonstrate that a PTP1B-like tyrosine phosphatase associates with N-cadherin and may function as a regulatory switch controlling cadherin function by dephosphorylating beta-catenin, thereby maintaining cells in an adhesion-competent state. The PTP1B-like phosphatase is itself tyrosine phosphorylated. Moreover, both direct binding experiments performed with phosphorylated and dephosphorylated molecules, and treatment of cells with tyrosine kinase inhibitors indicate that the interaction of the PTP1B-like phosphatase with N-cadherin depends on its tyrosine phosphorylation. Concomitant with the tyrosine kinase inhibitor-induced loss of the PTP1B-like phosphatase from its association with N-cadherin, phosphorylated tyrosine residues are retained on beta-catenin, the association of N- cadherin with the actin containing cytoskeleton is lost and N-cadherin- mediated cell adhesion is prevented. Tyrosine phosphatase inhibitors also result in the accumulation of phosphorylated tyrosine residues on beta-catenin, loss of the association of N-cadherin with the actin- containing cytoskeleton, and prevent N-cadherin mediated adhesion, presumably by directly blocking the function of the PTP1B-like phosphatase. We previously showed that the binding of two ligands to the cell surface N-acetylgalactosaminylphosphotransferase (GalNAcPTase), the monoclonal antibody 1B11 and a proteoglycan with a 250-kD core protein, results in the accumulation of phosphorylated tyrosine residues on beta-catenin, uncoupling of N-cadherin from its association with the actin containing cytoskeleton, and loss of N- cadherin function. We now report that binding of these ligands to the GalNAcPTase results in the absence of the PTP1B-like phosphatase from its association with N-cadherin as well as the loss of the tyrosine kinase and tyrosine phosphatase activities that otherwise co- precipitate with N-cadherin. Control antibodies and proteoglycans have no such effect. This effect is similar to that observed with tyrosine kinase inhibitors, suggesting that the GalNAcPTase/proteoglycan interaction inhibits a tyrosine kinase, thereby preventing the phosphorylation of the PTP1B-like phosphatase, and its association with N-cadherin. Taken together these data indicate that a PTP1B-like tyrosine phosphatase can regulate N-cadherin function through its ability to dephosphorylate beta-catenin and that the association of the phosphatase with N-cadherin is regulated via the interaction of the GalNAcPTase with its proteoglycan ligand. In this manner the GalNAcPTase-proteoglycan interaction may play a major role in morphogenetic cell and tissue interactions during development. PMID:8707857
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2008-09-01
Code of Federal Regulations CO carbon monoxide CSAF Chief of Staff of the Air Force dB decibels DNL day-night average sound level DNLmr onset rate...the health and welfare of the general public. These seven pollutants (the “criteria pollutants”) include ozone, carbon monoxide (CO), nitrogen... Monoxide 9 ppm (10 mg/m3) 8-hour (1) None 35 ppm (40 mg/m3) 1-hour (1) None Lead 1.5 µg/m3 Quarterly Average Same as Primary Nitrogen Dioxide 0.053
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Bobeck, Elizabeth A; Hellestad, Erica M; Helvig, Christian F; Petkovich, P Martin; Cook, Mark E
2016-03-01
While it is well established that active vitamin D treatment increases dietary phytate phosphate utilization, the mechanism by which intestinal alkaline phosphatase (IAP) participates in phytate phosphate use is less clear. The ability of human IAP (hIAP) oral antibodies to prevent dietary phytate phosphate utilization in the presence of 1α-hydroxycholecalciferol (1α-(OH) D3) in a chick model was investigated. hIAP specific chicken immunoglobulin Y (IgY) antibodies were generated by inoculating laying hens with 17 synthetic peptides derived from the human IAP amino acid sequence and harvesting egg yolk. Western blot analysis showed all antibodies recognized hIAP and 6 of the 8 antibodies selected showed modest inhibition of hIAP activity in vitro (6 to 33% inhibition). In chicks where dietary phosphate was primarily in the form of phytate, 4 selected hIAP antibodies inhibited 1α-(OH) D3-induced increases in blood phosphate, one of which, generated against selected peptide (MFPMGTPD), was as effective as sevelamer hydrochloride in preventing the 1α-(OH) D3-induced increase in blood phosphate, but ineffective in preventing an increase in body weight gain and bone ash induced by 1α-(OH) D3. These studies demonstrated that orally-delivered antibodies to IAP limit dietary phytate-phosphate utilization in chicks treated with 1α-(OH) D3, and implicate IAP as an important host enzyme in increasing phytate phosphate bioavailability in 1α-(OH) D3 fed chicks. © 2015 Poultry Science Association Inc.
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Hair methylmercury levels of mummies of the Aleutian Islands, Alaska
DOE Office of Scientific and Technical Information (OSTI.GOV)
Egeland, G.M.; Ponce, Rafael; Bloom, Nicolas S.
2009-04-15
Ancient human hair specimens can shed light on the extent of pre-historic exposures to methylmercury and provide valuable comparison data with current-day exposures, particularly for Indigenous Peoples who continue to rely upon local traditional food resources. Human hair from ancient Aleutian Island Native remains were tested for total and methylmercury (Hg, MeHg) and were radiocarbon dated. The remains were approximately 500 years old (1450 A.D.). For four adults, the mean and median total hair mercury concentration was 5.8 ppm (SD=0.9). In contrast, MeHg concentrations were lower with a mean of 1.2 ppm (SD=1.8) and a median of 0.54 ppm (0.12-3.86).more » For the five infants, the mean and median MeHg level was 1.2 ppm (SD=1.8) and 0.20 ppm (0.007-4.61), respectively. Segmental analyses showed variations in MeHg concentrations in 1-cm segments, consistent with fluctuations in naturally occurring exposure to mercury through dietary sources. The levels are comparable to or lower than those found in fish and marine mammal-eating populations today who rely far less on subsistence food than pre-historic humans. The findings are, therefore, compatible with increased anthropogenic release of trace metals during the past several centuries.« less
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Borges, L G; Seifert, R A; Grant, F J; Hart, C E; Disteche, C M; Edelhoff, S; Solca, F F; Lieberman, M A; Lindner, V; Fischer, E H; Lok, S; Bowen-Pope, D F
1996-09-01
We have cloned from cultured vascular smooth muscle cells a protein tyrosine phosphatase, rat density-enhanced phosphatase-1 (rDEP-1), which is a probable rat homologue of DEP-1/HPTP eta. rDEP-1 is encoded by an 8.7-kb transcript and is expressed as a 180- to 220-kD protein. The rDEP-1 gene is located on human chromosome 11 (region p11.2) and on mouse chromosome 2 (region 2E). The cDNA sequence predicts a transmembrane protein consisting of a single phosphatase catalytic domain in the intracellular region, a single transmembrane domain, and eight fibronectin type III repeats in the extracellular region (GenBank accession number U40790). In situ hybridization analysis demonstrates that rDEP-1 is widely expressed in vivo but that expression is highest in cells that form epithelioid monolayers. In cultured cells with epitheliod morphology, including endothelial cells and newborn smooth muscle cells, but not in fibroblast-like cells, rDEP-1 transcript levels are dramatically upregulated as population density increases. In vivo, quiescent endothelial cells in normal arteries express relatively high levels of rDEP-1. During repair of vascular injury, expression of rDEP-1 is downregulated in migrating and proliferating endothelial cells. In vivo, rDEP-1 transcript levels are present in very high levels in megakaryocytes, and circulating plates have high levels of the rDEP-1 protein. In vitro, initiation of differentiation of the human megakaryoblastic cell line CHRF-288-11 with phorbol 12-myristate 13-acetate leads to a very strong upregulation of rDEP-1 transcripts. The deduced structure and the regulation of expression of rDEP-1 suggest that it may play a role in adhesion and/or signaling events involving cell-cell and cell-matrix contact.
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Abarikwu, Sunny O; Adebayo, Olusegun L; Otuechere, Chiagoziem A; Iserhienrhien, Blessing O; Badejo, Temitope A
2016-01-01
Selenium (Se) and rutin (RUT) are antioxidants that protect against tissue damage. In this study, the separate and combine protective effects of RUT and Se against cadmium (Cd)-induced renal damage were evaluated in rats. Wistar rats were treated by gavage to RUT (30 mg/kg) or Se (0.15 ppm) or Cd (200 ppm) in drinking water alone or in combination (30 mg/kg RUT +0.15 ppm Se + 200 ppm Cd). Corn oil was used as vehicle (2 mL/kg). After a 5-week treatment period, rat kidneys were removed for biochemical assays and histopathological examination. Se and Cd levels were evaluated by flame atomic absorption spectrophotometry. The malondialdehyde and glutathione levels as well as superoxide dismutase and catalase activities in the Cd-treated animals were increased compared with control values (0.056 ± 0.0003 versus 0.011 ± 0.0005 μmol/mg; 0.005 ± 0.0006 versus 0.00085 ± 0.0002 μg/mg; 1.62 ± 0.09 versus 0.48 ± 0.12 units/mg; 650 ± 25 versus 361.89 ± 31 μmol H2O2/mg, respectively). Cd treatment was also associated with decreased renal Se concentration (4.19 ± 0.92 versus 7.73 ± 0.7 μg/g dry weight), increased alkaline phosphatase (0.07 ± 0.0015 versus 0.033 ± 0.0019 unit/mg), acid phosphatase (0.029 ± 0.0021 versus 0.015 ± 0.0016 unit/mg), and lactate dehydrogenase (0.032 ± 0.004 versus 0.014 ± 0.0027 unit/mg) activities, respectively, and with evidence of severe renal damage. The combination of RUT and Se or their separate effects prevented the Cd-induced oxidative renal damage. However, their combine effects do not have stronger effects than their separate effect against Cd-induced renal damage. RUT and Se function as potent antioxidant in the protection of renal damage induced by Cd.
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NASA Astrophysics Data System (ADS)
Alt, Jeffrey C.; Garrido, Carlos J.; Shanks, W. C.; Turchyn, Alexandra; Padrón-Navarta, José Alberto; López Sánchez-Vizcaíno, Vicente; Gómez Pugnaire, María Teresa; Marchesi, Claudio
2012-04-01
We use the concentrations and isotope compositions of water, carbon, and sulfur in serpentinites and their dehydration products to trace the cycling of volatiles during subduction. Antigorite serpentinites from the Cerro del Almirez complex, Spain, contain 9-12 wt.% H2O and 910 ± 730 ppm sulfur, and have bulk δ18O values of 8.6 ± 0.4‰, δD = - 54 ± 5‰, and δ34S = 5.0‰, consistent with serpentinization at temperatures of ~ 200 °C by seawater hydrothermal fluids in a seafloor setting. The serpentinites were dehydrated to chlorite-harzburgite (olivine + orthopyroxene + chlorite) at 700 °C and 1.6-1.9 GPa during subduction metamorphism, resulting in loss of water, and sulfur. The chlorite-harzburgites contain 5.7 ± 1.9 wt.% H2O, and have bulk δ18O = 8.0 ± 0.9‰, and δD = - 77 ± 11‰. The rocks contain 650 ± 620 ppm sulfur having δ34S = 1.2‰. Dehydration of serpentinite resulted in loss of 5 wt.% H2O having δ18O = 8-10‰ and δD = - 27 to - 65‰, and loss of 260 ppm sulfur as sulfate, having δ34S = 14.5‰. The contents and δ13C of total carbon in the two rock types overlap, with a broad trend of decreasing carbon contents and δ13C from ~ 1300 to 200 ppm and - 9.6 to - 20.2‰. This reflects mixing between reduced carbon in the rocks (210 ppm, δ13C ≈ - 26‰) and seawater-derived carbonate (δ13C ≈ - 1‰). Our results indicate: 1) Serpentinized oceanic peridotites carry significant amounts of isotopically fractionated water, carbon and sulfur into subduction zones; 2) Subduction of serpentinites to high P and T results in loss of water, and sulfur, which can induce melting and contribute to 18O, D, and 34S enrichments and oxidation of the sub-arc mantle wedge; and 3) Isotopically fractionated water, carbon, and sulfur in serpentinite dehydration products are recycled deeper into the mantle where they can contribute to isotope heterogeneities and may be significant for volatile budgets of the deep Earth.
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Alt, Jeffrey C.; Garrido, Carlos J.; Shanks, Wayne C.; Turchyn, Alexandra; Padrón-Navarta, José Alberto; López Sánchez-Vizcaíno, Vicente; Gómez Pugnaire, María Teresa; Marchesi, Claudio
2012-01-01
We use the concentrations and isotope compositions of water, carbon, and sulfur in serpentinites and their dehydration products to trace the cycling of volatiles during subduction. Antigorite serpentinites from the Cerro del Almirez complex, Spain, contain 9–12 wt.% H2O and 910 ± 730 ppm sulfur, and have bulk δ18O values of 8.6 ± 0.4‰, δD = − 54 ± 5‰, and δ34S = 5.0‰, consistent with serpentinization at temperatures of ~ 200 °C by seawater hydrothermal fluids in a seafloor setting. The serpentinites were dehydrated to chlorite–harzburgite (olivine + orthopyroxene + chlorite) at 700 °C and 1.6–1.9 GPa during subduction metamorphism, resulting in loss of water, and sulfur. The chlorite–harzburgites contain 5.7 ± 1.9 wt.% H2O, and have bulk δ18O = 8.0 ± 0.9‰, and δD = − 77 ± 11‰. The rocks contain 650 ± 620 ppm sulfur having δ34S = 1.2‰. Dehydration of serpentinite resulted in loss of 5 wt.% H2O having δ18O = 8–10‰ and δD = − 27 to − 65‰, and loss of 260 ppm sulfur as sulfate, having δ34S = 14.5‰. The contents and δ13C of total carbon in the two rock types overlap, with a broad trend of decreasing carbon contents and δ13C from ~ 1300 to 200 ppm and − 9.6 to − 20.2‰. This reflects mixing between reduced carbon in the rocks (210 ppm, δ13C ≈ − 26‰) and seawater-derived carbonate (δ13C ≈ − 1‰). Our results indicate: 1) Serpentinized oceanic peridotites carry significant amounts of isotopically fractionated water, carbon and sulfur into subduction zones; 2) Subduction of serpentinites to high P and T results in loss of water, and sulfur, which can induce melting and contribute to 18O, D, and 34S enrichments and oxidation of the sub-arc mantle wedge; and 3) Isotopically fractionated water, carbon, and sulfur in serpentinite dehydration products are recycled deeper into the mantle where they can contribute to isotope heterogeneities and may be significant for volatile budgets of the deep Earth.
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NASA Technical Reports Server (NTRS)
Narayanan, R.; Smith, C. L.; Weigel, N. L.
2002-01-01
Skeletal unloading in an animal hindlimb suspension model and microgravity experienced by astronauts or as a result of prolonged bed rest causes site-specific losses in bone mineral density of 1%-2% per month. This is accompanied by reductions in circulating levels of 1,25-(OH)(2)D(3), the active metabolite of vitamin D. 1,25-(OH)(2)D(3), the ligand for the vitamin D receptor (VDR), is important for calcium absorption and plays a role in differentiation of osteoblasts and osteoclasts. To examine the responses of cells to activators of the VDR in a simulated microgravity environment, we used slow-turning lateral vessels (STLVs) in a rotating cell culture system. We found that, similar to cells grown in microgravity, MG-63 cells grown in the STLVs produce less osteocalcin, alkaline phosphatase, and collagen Ialpha1 mRNA and are less responsive to 1,25-(OH)(2)D(3). In addition, expression of VDR was reduced. Moreover, growth in the STLV caused activation of the stress-activated protein kinase pathway (SAPK), a kinase that inhibits VDR activity. In contrast, the 1,25-(OH)(2)D(3) analog, EB1089, was able to compensate for some of the STLV-associated responses by reducing SAPK activity, elevating VDR levels, and increasing expression of osteocalcin and alkaline phosphatase. These studies suggest that, not only does simulated microgravity reduce differentiation of MG-63 cells, but the activity of the VDR, an important regulator of bone metabolism, is reduced. Use of potent, less calcemic analogs of 1,25-(OH)(2)D(3) may aid in overcoming this defect. Copyright 2002 Elsevier Science Inc.
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Relationship between Escherichia coli virulence factors and postpartum metritis in dairy cows.
Kassé, F N; Fairbrother, J M; Dubuc, J
2016-06-01
The objectives of this study were to report the prevalence of Escherichia coli and Trueperella pyogenes in the uterus of postpartum dairy cows before the onset of postpartum metritis (PPM) and to quantify their association with subsequent occurrence of PPM, to quantify the association between the presence of genes encoding E. coli virulence factors (VF) and PPM, and to determine the accuracy of using early postpartum uterine bacteriology results (bacteria and VF) to identify cows at risk of PPM. A prospective cohort study was conducted on 3 commercial dairy farms. Uterine swabs were collected from 371 Holstein dairy cows (3 commercial herds) at 1 to 7d in milk and submitted to the laboratory for identification of E. coli, T. pyogenes, and E. coli VF. A total of 40 VF were tested using the radioactive probe hybridization method. Postpartum metritis was defined as the presence of a fetid watery red-brown uterine discharge, associated with fever (rectal temperature >39.5°C), and systemic signs of illness (dullness, reduced appetite, and milk production). Surveillance of PPM was done by trained farmers blinded to laboratory results and cows were followed until 21d in milk. Statistical analyses were conducted using 2×2 tables and mixed logistical regression models. Prevalences of E. coli, T. pyogenes, and PPM were 42, 34, and 15%, respectively. A total of 32 VF were found in E. coli isolates. Most prevalent VF were extraintestinal pathogenic genes such as fimH (89%), hlyE (87%), and iss (70%). Cows positive for intrauterine E. coli were 3.2 times more likely to have subsequent PPM compared with bacteriologically negative cows. Cows with VF hra1 in their uterus were 2.7 times more likely to have PPM than cows positive for E. coli and negative for hra1 and 5.9 times more likely than bacteriologically negative cows. Cows with VF kpsMTII in their uterus were 3.2 times more likely to have PPM than cows positive for E. coli and negative for kpsMTII and 6.2 times more likely than bacteriologically negative cows. Using E. coli, hra1, and kpsMTII as predictors for subsequent PPM, positive predictive values were 23, 31, and 42%, respectively, whereas the negative predictive values were 91, 80, and 78%, respectively. Overall, these results showed that E. coli and some VF were associated with PPM. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
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Yamada, Kazuki; Endo, Hirosuke; Tetsunaga, Tomonori; Miyake, Takamasa; Sanki, Tomoaki; Ozaki, Toshifumi
2018-01-01
The accuracy of various navigation systems used for total hip arthroplasty has been described, but no publications reported the accuracy of cup orientation in computed tomography (CT)-based 2D-3D (two-dimensional to three-dimensional) matched navigation. In a prospective, randomized controlled study, 80 hips including 44 with developmental dysplasia of the hips were divided into a CT-based 2D-3D matched navigation group (2D-3D group) and a paired-point matched navigation group (PPM group). The accuracy of cup orientation (absolute difference between the intraoperative record and the postoperative measurement) was compared between groups. Additionally, multiple logistic regression analysis was performed to evaluate patient factors affecting the accuracy of cup orientation in each navigation. The accuracy of cup inclination was 2.5° ± 2.2° in the 2D-3D group and 4.6° ± 3.3° in the PPM group (P = .0016). The accuracy of cup anteversion was 2.3° ± 1.7° in the 2D-3D group and 4.4° ± 3.3° in the PPM group (P = .0009). In the PPM group, the presence of roof osteophytes decreased the accuracy of cup inclination (odds ratio 8.27, P = .0140) and the absolute value of pelvic tilt had a negative influence on the accuracy of cup anteversion (odds ratio 1.27, P = .0222). In the 2D-3D group, patient factors had no effect on the accuracy of cup orientation. The accuracy of cup positioning in CT-based 2D-3D matched navigation was better than in paired-point matched navigation, and was not affected by patient factors. It is a useful system for even severely deformed pelvises such as developmental dysplasia of the hips. Copyright © 2017 Elsevier Inc. All rights reserved.
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Sánchez-Lombardo, Irma; Alvarez, Santiago; McLauchlan, Craig C; Crans, Debbie C
2015-06-01
Shape analysis of coordination complexes is well-suited to evaluate the subtle distortions in the trigonal bipyramidal (TBPY-5) geometry of vanadium coordinated in the active site of phosphatases and characterized by X-ray crystallography. Recent studies using the tau (τ) analysis support the assertion that vanadium is best described as a trigonal bipyramid, because this geometry is the ideal transition state geometry of the phosphate ester substrate hydrolysis (C.C. McLauchlan, B.J. Peters, G.R. Willsky, D.C. Crans, Coord. Chem. Rev. http://dx.doi.org/10.1016/j.ccr.2014.12.012 ; D.C. Crans, M.L. Tarlton, C.C. McLauchlan, Eur. J. Inorg. Chem. 2014, 4450-4468). Here we use continuous shape measures (CShM) analysis to investigate the structural space of the five-coordinate vanadium-phosphatase complexes associated with mechanistic transformations between the tetrahedral geometry and the five-coordinate high energy TBPY-5 geometry was discussed focusing on the protein tyrosine phosphatase 1B (PTP1B) enzyme. No evidence for square pyramidal geometries was observed in any vanadium-protein complexes. The shape analysis positioned the metal ion and the ligands in the active site reflecting the mechanism of the cleavage of the organic phosphate in a phosphatase. We identified the umbrella distortions to be directly on the reaction path between tetrahedral phosphate and the TBPY-5-types of high-energy species. The umbrella distortions of the trigonal bipyramid are therefore identified as being the most relevant types of transition state structures for the phosphoryl group transfer reactions for phosphatases and this may be related to the possibility that vanadium is an inhibitor for enzymes that support both exploded and five-coordinate transition states. Copyright © 2015 Elsevier Inc. All rights reserved.
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Energetic Polyoxetane Thermoplastic Elastomers: Synthesis and Characterization
1988-12-01
Stockmayer, L. D. Moore, M. Fixman, and B. N. Epstein, Copolymers in Dilute Solution. I. Preliminary Results for Styrene- Methyl Methacrylate , J. Polym. Sci... methyl groups of p-dicumyl chloride showed a singlet peak at about 2.0 ppm. The integration ratio of the peak at 2.0 ppm and 7.6 ppm is about 3 within...were prepared by Aerojet. 1H and 13C NMR spectra of polymer solutions in deuteriochloro- form (CDCl3), MSD Isotopes, Montreal, Quebec, Canada, were
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Kinetic behaviour of calf intestinal alkaline phosphatase with pNPP.
Chaudhuri, Gouri; Chatterjee, Saswata; Venu-Babu, P; Ramasamy, K; Thilagaraj, W Richard
2013-02-01
The hydrolysis of p-nitrophenyl phosphate (pNPP) by calf intestinal alkaline phosphatase (CIAP) was investigated with respect to kinetic parameters such as V(max), K(m) and K(cat) under varying pH, buffers, substrate concentration, temperature and period of incubation. Highest activity was obtained with Tris-HCl at pH 11, while in the case of glycine-NaOH buffer the peak activity was recorded at pH 9.5. The enzyme showed the following kinetic characteristics with pNPP in 50 mM Tris-HCl at pH 11 and 100 mM glycine-NaOH at pH 9.5 at an incubation temperature of 37 degrees C: V(max), 3.12 and 1.6 micromoles min(-1) unit(-1); K(m), 7.6 x 10(-4) M and 4 x 10(-4) M; and K(cat), 82.98 s(-1) and 42.55 s(-1), respectively. CIAP displayed a high temperature optimum of 45 degrees C at pH 11. The kinetic behaviour of the enzyme under different parameters suggested that the enzyme might undergo subtle conformational changes in response to the buffers displaying unique characteristics. Bioprecipitation of Cu2+ from 50 ppm of CuCl2 solution was studied where 64.3% of precipitation was obtained. P(i) generated from CIAP-mediated hydrolysis of pNPP was found to bind with copper and precipitated as copper-phosphate. Thus, CIAP could be used as a test candidate in bioremediation of heavy metals from industrial wastes through generation of metal-phosphate complexes.
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Inhibition of AMP Kinase by the Protein Phosphatase 2A Heterotrimer, PP2APpp2r2d*
Joseph, Biny K.; Liu, Hsing-Yin; Francisco, Jamie; Pandya, Devanshi; Donigan, Melissa; Gallo-Ebert, Christina; Giordano, Caroline; Bata, Adam; Nickels, Joseph T.
2015-01-01
AMP kinase is a heterotrimeric serine/threonine protein kinase that regulates a number of metabolic processes, including lipid biosynthesis and metabolism. AMP kinase activity is regulated by phosphorylation, and the kinases involved have been uncovered. The particular phosphatases counteracting these kinases remain elusive. Here we discovered that the protein phosphatase 2A heterotrimer, PP2APpp2r2d, regulates the phosphorylation state of AMP kinase by dephosphorylating Thr-172, a residue that activates kinase activity when phosphorylated. Co-immunoprecipitation and co-localization studies indicated that PP2APpp2r2d directly interacted with AMP kinase. PP2APpp2r2d dephosphorylated Thr-172 in rat aortic and human vascular smooth muscle cells. A positive correlation existed between decreased phosphorylation, decreased acetyl-CoA carboxylase Acc1 phosphorylation, and sterol response element-binding protein 1c-dependent gene expression. PP2APpp2r2d protein expression was up-regulated in the aortas of mice fed a high fat diet, and the increased expression correlated with increased blood lipid levels. Finally, we found that the aortas of mice fed a high fat diet had decreased AMP kinase Thr-172 phosphorylation, and contained an Ampk-PP2APpp2r2d complex. Thus, PP2APpp2r2d may antagonize the aortic AMP kinase activity necessary for maintaining normal aortic lipid metabolism. Inhibiting PP2APpp2r2d or activating AMP kinase represents a potential pharmacological treatment for many lipid-related diseases. PMID:25694423
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Changes in mineral composition of eggshells from black ducks and mallards fed DDE in the diet
Longcore, J.R.; Samson, F.B.; Kreitzer, J.F.; Spann, J.W.
1971-01-01
Diets containing 10 and 30 ppm (dry weight) DDE were fed to black ducks, and diets containing 1, 5, and 10 ppm (dry weight) DDE were fed to mallards. Among the results were the following changes in black duck eggshell composition: (a) significant increase in the percentage of Mg, (b) significant decreases in Ba and Sr, (c) increases (which approached significance) in average percentage of eggshell Na and Cu, (d) a decrease in shell Ca which approached significance, (e) patterns of mineral correlations which in some instances were distinct to dosage groups, and (f) inverse correlations in the control group between eggshell thickness Mg and Na. Changes in mallard eggshells were: (a) significant increase in percentage of magnesium at 5 and 10 ppm DDE, (b) significant decrease in Al at 5 and 10 ppm DDE, (c) a significant decrease in Ca from eggshells from the 10 ppm DDE group, and (d) an increase in average percentage of Na in eggshells from DDE dosed ducks which approached significance.
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NASA Astrophysics Data System (ADS)
Dunfield, K. E.; Gaiero, J. R.; Condron, L.
2017-12-01
Healthy and diverse communities of soil organisms influence key soil ecosystem services such as carbon sequestration, water quality protection, climate regulation and nutrient cycling. Microbially driven mineralization of organic phosphorus is an important contributor to plant available inorganic orthophosphates. In acidic soils, microbes produce non-specific acid phosphatases (NSAPs) which act on common forms of organic phosphorus (P). Our current understanding of P turnover in soils has been limited by lack of research tools capable of targeting these genes. Thus, we developed a set of oligonucleotide PCR primers that targeted bacteria with the genetic potential for acid phosphatase production. A long term randomized-block pasture trial was sampled following 22 years of continued aerial biomass removal and retention. Primers were used to target genes encoding alkaline phosphatase (phoD) and the three classes (CAAP, CBAP, CCAP) of non-specific acid phosphatases. PCR amplicons targeting total genes and gene transcripts were sequenced using Illumina MiSeq to understand the diversity of the bacterial phosphatase producing communities. In general, the majority of operational taxonomic units (OTUs) were shared across both treatments and across metagenomes and transcriptomes. However, analysis of DNA OTUs revealed significantly different communities driven by treatment differences (P < 0.05). Transcript expression was highest in the removed biomass treatment which corresponded the reduced Olsen P levels (15 vs. 36 mg kg-1 in retained treatment). Acid phosphatase activity was measured in all samples, and found to be highest in the biomass retained treatment (16.8 vs. 11.4 µmol g-1 dry soil h-1), likely elevated due to plant-derived enzymes; however, was still correlated to bacterial gene abundances. Overall, the phosphatase producing microbial communities responded to the effect of consistent P limitation as expected, through alteration in the composition of the community structure and through increased levels of gene expression of the phosphatase genes.
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Szumańska, G; Gadamski, R
1992-01-01
Some lectins were used to study the localization of sugar residues on the endothelial cell surface in the pia mater blood vessels of control (WKY) and hypertensive rats (SHR). The lectins tested recognized the following residues: beta-D-galactosyl (Ricinus communis agglutinin 120, RCA-1), alpha-L-fucosyl (Ulex europaeus agglutinin, UEA-1), N-acetylglucosaminyl and sialyl (Wheat germ agglutinin, WGA), N-glycolyl-neuraminic acid (Limax flavus agglutinin, LFA), and N-acetyl-D-galactosaminyl (Helix pomatia agglutinin, HPA). Several differences were revealed in the presence of sugar receptors on the surface of endothelial cells between the control and the hypertensive rats. Our studies showed also differences in the localization of the tested glycoconjugates between pial capillaries, small, medium-size and large pial arteries. The histochemical evaluation of alkaline phosphatase revealed an increased activity of the enzyme in the pial vessels of SHRs as compared with control rats with a similar localization of the enzyme activity. Some differences in the distribution of lectin binding sites and alkaline phosphatase activity could be associated with the different functions of particular segments of the pial vascular network.
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Rozentur-Shkop, Eva; Goobes, Gil; Chill, Jordan H
2016-12-01
Intrinsically disordered proteins (IDPs) are multi-conformational polypeptides that lack a single stable three-dimensional structure. It has become increasingly clear that the versatile IDPs play key roles in a multitude of biological processes, and, given their flexible nature, NMR is a leading method to investigate IDP behavior on the molecular level. Here we present an IDP-tailored J-modulated experiment designed to monitor changes in the conformational ensemble characteristic of IDPs by accurately measuring backbone one- and two-bond J( 15 N, 13 Cα) couplings. This concept was realized using a unidirectional (H)NCO 13 C-detected experiment suitable for poor spectral dispersion and optimized for maximum coverage of amino acid types. To demonstrate the utility of this approach we applied it to the disordered actin-binding N-terminal domain of WASp interacting protein (WIP), a ubiquitous key modulator of cytoskeletal changes in a range of biological systems. One- and two-bond J( 15 N, 13 Cα) couplings were acquired for WIP residues 2-65 at various temperatures, and in denaturing and crowding environments. Under native conditions fitted J-couplings identified in the WIP conformational ensemble a propensity for extended conformation at residues 16-23 and 45-60, and a helical tendency at residues 28-42. These findings are consistent with a previous study of the based upon chemical shift and RDC data and confirm that the WIP 2-65 conformational ensemble is biased towards the structure assumed by this fragment in its actin-bound form. The effects of environmental changes upon this ensemble were readily apparent in the J-coupling data, which reflected a significant decrease in structural propensity at higher temperatures, in the presence of 8 M urea, and under the influence of a bacterial cell lysate. The latter suggests that crowding can cause protein unfolding through protein-protein interactions that stabilize the unfolded state. We conclude that J-couplings are a useful measureable in characterizing structural ensembles in IDPs, and that the proposed experiment provides a practical method for accurately performing such measurements, once again emphasizing the power of NMR in studying IDP behavior.
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13C NMR investigation of nonenzymatic glucosylation of protein. Model studies using RNase A.
Neglia, C I; Cohen, H J; Garber, A R; Ellis, P D; Thorpe, S R; Baynes, J W
1983-12-10
Nonenzymatic glucosylation of protein is initiated by the reversible condensation of glucose in its open chain form with the amino groups on the protein. The initial product is an aldimine (Schiff base) which cyclizes to the glycosylamine derivative. The aldimine can undergo a slow Amadori rearrangement to yield the relatively stable ketoamine adduct which is structurally analogous to fructose. 13C NMR has been used to characterize these early products of nonenzymatic glucosylation, using RNase A as a model protein. C-1 of the beta-pyranose anomer of the glycosylamine was identified at 88.8 ppm in the spectrum of RNase glucosylated approximately 1:1 with D-[1-13C]glucose. C-1 of the Amadori product was also apparent in this spectrum, resonating as a pair of intense peaks at 52.7 and 53.1 ppm. The anomeric (C-2) resonances of the Amadori adduct were seen in the spectrum of RNase glucosylated approximately 1:1 with [U-13C]glucose. This spectrum was interpreted by comparison to the spectra of reference compounds: D-fructose, fructose-glycine, N alpha-formyl-N epsilon-fructose-lysine, and glucosylated poly-L-lysine. In the protein spectrum, the most intense of the C-2 resonances was that of the beta-fructopyranose anomer at 95.8 ppm. The alpha- and beta-fructofuranose anomers were also observed at 101.7 and 99.2 ppm, respectively. One unidentified signal in the anomeric region was observed in the spectra of poly-L-lysine and RNase, both glucosylated with [U-13C]glucose; no comparable resonances were observed in the spectra of the model compounds.
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A high-resolution (13)C 3D CSA-CSA-CSA correlation experiment by means of magic angle turning.
Hu, J Z; Ye, C; Pugmire, R J; Grant, D M
2000-08-01
It is shown in this paper that a previously reported 90 degrees sample flipping (13)C 2D CSA-CSA correlation experiment may be carried out alternatively by employing constant slow sample rotation about the magic angle axis and by synchronizing the read pulse to 13 of the rotor cycle. A high-resolution 3D CSA-CSA-CSA correlation experiment based on the magic angle turning technique is reported in which the conventional 90 degrees 2D CSA-CSA powder pattern for each carbon in a system containing a number of inequivalent carbons may be separated according to the isotropic chemical shift value. The technique is demonstrated on 1,2,3-trimethoxybenzene in which all of the overlapping powder patterns that cannot be segregated by the 2D CSA-CSA experiment are resolved successfully by the 3D CSA-CSA-CSA experiment, including even the two methoxy groups (M(1) and M(3)) whose isotropic shifts, confirmed by high-speed MAS, are separated by only 1 ppm. A difference of 4 ppm in the principal value component (delta(33)) between M(1) and M(3) is readily obtained. Copyright 2000 Academic Press.
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Martin, T W
1988-10-14
The conversion of phosphatidylcholine (PC) to diacylglycerol (DAG) was studied in sonicated endothelial cells and in subcellular fractions in the presence of 0.05% Triton X-100 and 2 mM EDTA. DAG formation occurred predominantly in an organelle fraction that sedimented at 15,000 x g. In parallel reactions with exogenous 1-oleoyl-2-[3H]oleoyl-PC (sn-2-[3H]DOPC) and phosphatidyl[3H]choline ([choline-3H]PC), [3H]DAG was formed by a reaction pathway in which [3H]choline was the only product derived from [choline-3H]PC. [3H]Choline was not formed secondarily from [3H]glycerophosphocholine or [3H]phosphocholine. Small amounts of [3H]phosphatidate ([3H]PA) were isolated from reactions with sn-2-[3H]DOPC at short incubation times, and substantial PA phosphatase activity was demonstrated. These data, taken together, supported a phospholipase D-PA phosphatase pathway of DAG formation. Kinetic data established that the low ratio of [3H]PA/[3H]DAG formed in reactions with sn-2-[3H]DOPC was due to a 15-fold higher Vmax and 7-fold lower apparent Km of the PA phosphatase. The [3H]PA/[3H]DAG product ratio was increased by addition of unlabeled PA or by selective extraction of phospholipase D with Triton X-100. The characteristics of the phospholipase D indicated a unique enzyme. Activity was optimal in the presence of EDTA and was almost totally dependent upon Triton X-100. The pH profile displayed a peak at 7.0. Of particular significance was the stringent substrate specificity. Phosphatidylinositol was not hydrolyzed, and activities towards phosphatidylethanolamine and sphingomyelin were at most 30- to 50-fold lower than those towards PC. Phospholipase D and PA phosphatase were identified in a number of rat tissues and other cells. The highest activities of phospholipase D were present in lung and endothelial cells. Phospholipase D was partially purified from rat lung by Triton X-100 extraction and anion exchange chromatography. When linked with PA phosphatase, the phospholipase D could initiate a pathway of DAG formation that is highly specific for PC.
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1998-05-01
Mission Research Corporation MRC/WDC-R-424 COMPARISON OF HELIX TWT SIMULATION USING 2-D PIC ( MAGIC ), 2-D MODAL (GATOR), AND 1-D MODAL (CHRISTINE...BRILLOUIN RUN 9 3.4 OUTLIER ELECTRON EFFECT IN GATOR 12 3.5 EMISSION CONDITION AND NONLAMINAR FLOW IN MAGIC 12 3.6 RADIAL SHEAR 13 SECTION 4. PPM B...Simulation using 2-D PIC ( MAGIC ), 2-D Modal (GATOR) and 1-D Modal (CHRISTINE) methods * D.N. Smithe(a), H. Freund(b), T. M. Antonsen Jr.,(b)’(c), E
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Combination effect of fluoride dentifrices and varnish on deciduous enamel demineralization.
Gatti, Alessandra; Camargo, Lucila Basto; Imparato, José Carlos Pettorossi; Mendes, Fausto Medeiros; Raggio, Daniela Prócida
2011-01-01
The aim of this study was to evaluate the anticaries potential of 500 or 1100 ppm F dentifrices combined with fluoride varnish using a pH-cycling regimen. Seventy primary canines were covered with nail polish, leaving a 4×4 mm window on their buccal surface, and randomly assigned into 7 groups (n = 10): S: sound enamel not submitted to the pH-cycling regimen or treatment; N: negative control, submitted to the pH-cycling regimen without any treatment; D1 and D2: subjected to the pH-cycling regimen and treated twice daily with 1100 or 500 ppm F dentifrice, respectively; VF: fluoride varnish (subjected to F-varnish before and in the middle of the pH-cycling regimen); and VF+D1 and VF+D2. After 10 days, the teeth were sectioned, and enamel demineralization was assessed by cross-sectional hardness at different distances from the dental surface. Data were analyzed using a two-way ANOVA followed by Tukey's test. Dentifrice with 1100 ppm F and the combination of F-varnish with the dentifrices significantly reduced enamel demineralization compared with the negative control (p < 0.05), but the isolated effects of F-varnish and dentifrice with low concentration were not significant (p > 0.05). The effect of combining F-varnish with the dentifrices was not greater than the effect of the dentifrices alone (p < 0.05). The data suggest that the combination of F-varnish with dentifrices containing 500 and 1100 ppm F is not more effective in reducing demineralization in primary teeth than the isolated effect of dentifrice containing 1100 ppm F.
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[Substrate specifity in Amoeba proteus].
Sopina, V A
2006-01-01
Three different phosphatases ("slow", "middle" and "fast") were found in Amoeba proteus (strain B) after PAGE and a subsequent gel staining in 1-naphthyl phosphate containing incubation mixture (pH 9.0). Substrate specificity of these phosphatases was determined in supernatants of homogenates using inhibitors of phosphatase activity. All phosphatases showed a broad substrate specificity. Of 10 tested compounds, p-nitrophenyl phosphate was a preferable substrate for all 3 phosphatases. All phosphatases were able to hydrolyse bis-p-nitrophenyl phosphate and, hence, displayed phosphodiesterase activity. All phosphatases hydrolysed O-phospho-L-tyrosine to a greater or lesser degree. Only little differences in substrate specificity of phosphatases were noticed: 1) "fast" and "middle" phosphatases hydrolysed naphthyl phosphates and O-phospho-L-tyrosine less efficiently than did "slow" phosphatase; 2) "fast" and "middle" phosphatases hydrolysed 2- naphthyl phosphate to a lesser degree than 1-naphthyl phosphate 3) "fast" and "middle" phosphatases hydrolysed O-phospho-L-serine and O-phospho-L-threonine with lower intensity as compared with "slow" phosphatase; 4) as distinct from "middle" and "slow" phosphatases, the "fast" phosphatase hydrolysed glucose-6-phosphate very poorly. The revealed broad substrate specificity of "slow" phosphatase together with data of inhibitory analysis and results of experiments with reactivation of this phosphatase by Zn2+-ions after its inactivation by EDTA strongly suggest that only the "slow" phosphatase is a true alkaline phosphatase (EC 3.1.3.1). The alkaline phosphatase of A. proteus is secreted into culture medium where its activity is low. The enzyme displays both phosphomono- and phosphodiesterase activities, in addition to supposed protein phosphatase activity. It still remains unknown, to which particular phosphatase class the amoeban "middle" and "fast" phosphatases (pH 9.0) may be assigned.
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Sun, Yidi; Leong, Nicole T; Jiang, Tommy; Tangara, Astou; Darzacq, Xavier; Drubin, David G
2017-08-16
Actin-related protein 2/3 (Arp2/3) complex activation by nucleation promoting factors (NPFs) such as WASP, plays an important role in many actin-mediated cellular processes. In yeast, Arp2/3-mediated actin filament assembly drives endocytic membrane invagination and vesicle scission. Here we used genetics and quantitative live-cell imaging to probe the mechanisms that concentrate NPFs at endocytic sites, and to investigate how NPFs regulate actin assembly onset. Our results demonstrate that SH3 (Src homology 3) domain-PRM (proline-rich motif) interactions involving multivalent linker proteins play central roles in concentrating NPFs at endocytic sites. Quantitative imaging suggested that productive actin assembly initiation is tightly coupled to accumulation of threshold levels of WASP and WIP, but not to recruitment kinetics or release of autoinhibition. These studies provide evidence that WASP and WIP play central roles in establishment of a robust multivalent SH3 domain-PRM network in vivo, giving actin assembly onset at endocytic sites a switch-like behavior.
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Phosphatidic acid (PA) binds PP2AA1 to regulate PP2A activity and PIN1 polar localization.
Gao, Hong-Bo; Chu, Yu-Jia; Xue, Hong-Wei
2013-09-01
Phospholipase D (PLD) exerts broad biological functions in eukaryotes through regulating downstream effectors by its product, phosphatidic acid (PA). Protein kinases and phosphatases, such as mammalian target of rapamycin (mTOR), Protein Phosphatase 1 (PP1) and Protein Phosphatase 2C (PP2C), are PA-binding proteins that execute crucial regulatory functions in both animals and plants. PA participates in many signaling pathways by modulating the enzymatic activity and/or subcellular localization of bound proteins. In this study, we demonstrated that PLD-derived PA interacts with the scaffolding A1 subunit of Protein Phosphatase 2A (PP2A) and regulates PP2A-mediated PIN1 dephosphorylation in Arabidopsis. Genetic and pharmacological studies showed that both PA and PP2A participate in the regulation of auxin distribution. In addition, both the phosphorylation status and polar localization of PIN1 protein were affected by PLD inhibitors. Exogenous PA triggered the membrane accumulation of PP2AA1 and enhanced the PP2A activity at membrane, while PLD inhibition resulted in the reduced endosomal localization and perinuclear aggregation of PP2AA1. These results demonstrate the important role of PLD-derived PA in normal PP2A-mediated PIN dephosphorylation and reveal a novel mechanism, in which PA recruits PP2AA1 to the membrane system and regulates PP2A function on membrane-targeted proteins. As PA and PP2A are conserved among eukaryotes, other organisms might use similar mechanisms to mediate multiple biological processes.
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Alkaline phosphatase from the hyperthermophilic bacterium T. maritima requires cobalt for activity
Wojciechowski, Cheryl L.; Cardia, James P.; Kantrowitz, Evan R.
2002-01-01
The hyperthermophilic bacterium Thermotoga maritima encodes a gene sharing sequence similarities with several known genes for alkaline phosphatase (AP). The putative gene was isolated and the corresponding protein expressed in Escherichia coli, with and without a predicted signal sequence. The recombinant protein showed phosphatase activity toward the substrate p-nitrophenyl-phosphate with a kcat of 16 s−1 and a Km of 175 μM at a pH optimum of 8.0 when assayed at 25°C. T. maritima phosphatase activity increased at high temperatures, reaching a maximum kcat of 100 s−1, with a Km of 93 μM at 65°C. Activity was stable at 65°C for >24 h and at 90°C for 5 h. Phosphatase activity was dependent on divalent metal ions, specifically Co(II) and Mg(II). Circular dichroism spectra showed that the enzyme gains secondary structure on addition of these metals. Zinc, the most common divalent metal ion required for activity in known APs, was shown to inhibit the T. maritima phosphatase enzyme at concentrations above 0.3 moles Zn: 1 mole monomer. All activity was abolished in the presence of 0.1 mM EDTA. The T. maritima AP primary sequence is 28% identical when compared with E. coli AP. Based on a structural model, the active sites are superimposable except for two residues near the E. coli AP Mg binding site, D153 and K328 (E. coli numbering) corresponding to histidine and tryptophan in T. maritima AP, respectively. Sucrose-density gradient sedimentation experiments showed that the protein exists in several quaternary forms predominated by an octamer. PMID:11910033
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Proteomic analysis of protein phosphatase Z1 from Candida albicans
Pfliegler, Walter P.; Petrényi, Katalin; Boros, Enikő; Pócsi, István; Tőzsér, József; Dombrádi, Viktor
2017-01-01
Protein phosphatase Z is a “novel type” fungus specific serine/threonine protein phosphatase. Previously our research group identified the CaPPZ1 gene in the opportunistic pathogen Candida albicans and reported that the gene deletion had several important physiological consequences. In order to reveal the protein targets and the associated mechanisms behind the functions of the phosphatase a proteomic method was adopted for the comparison of the cappz1 deletion mutant and the genetically matching QMY23 control strain. Proteins extracted from the control and deletion mutant strains were separated by two-dimensional gel electrophoresis and the protein spots were stained with RuBPS and Pro-Q Diamond in order to visualize the total proteome and the phosphoproteome, respectively. The alterations in spot intensities were determined by densitometry and were analysed with the Delta2D (Decodon) software. Spots showing significantly different intensities between the mutant and control strains were excised from the gels and were digested with trypsin. The resulting peptides were identified by LC-MS/MS mass spectrometry. As many as 15 protein spots were found that exhibited significant changes in their intensity upon the deletion of the phosphatase and 20 phosphoproteins were identified in which the level of phosphorylation was modified significantly in the mutant. In agreement with previous findings we found that the affected proteins function in protein synthesis, oxidative stress response, regulation of morphology and metabolism. Among these proteins we identified two potential CaPpz1 substrates (Eft2 and Rpp0) that may regulate the elongation step of translation. RT-qPCR experiments revealed that the expression of the genes coding for the affected proteins was not altered significantly. Thus, the absence of CaPpz1 exerted its effects via protein synthesis/degradation and phosphorylation/dephosphorylation. In addition, our proteomics data strongly suggested a role for CaPpz1 in biofilm formation, was confirmed experimentally. Thus our unbiased proteomic approach lead to the discovery of a novel function for this phosphatase in C. albicans. PMID:28837603
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Sasaki, Tatsunori; Li, Wei; Higai, Koji; Quang, Tran Hong; Kim, Young Ho; Koike, Kazuo
2014-05-01
Protein tyrosine phosphatase 1B is a non-transmembrane protein tyrosine phosphatase and major negative regulator in insulin signaling cascades, and much attention has been paid to protein tyrosine phosphatase 1B inhibitors as potential therapies for diabetes. The screening of a natural compound library led to the discovery of five lavandulyl flavonoids, which were isolated from the roots of Sophora flavescens, as novel PTP1B inhibitors: kuraridin (1), norkurarinone (2), kurarinone (3), 2'-methoxykurarinone (4), and kushenol T (5). The three most potent compounds, 1, 2, and 4 (IC50 < 30 µM), were demonstrated to be noncompetitive inhibitors of protein tyrosine phosphatase 1B based on a kinetic analysis, and they exhibited different inhibitory selectivities against four homologous protein tyrosine phosphatases (T cell protein tyrosine phosphatase, vaccinia H1-related phosphatase, and Src homology domain 2-containing protein tyrosine phosphatases 1 and 2). Compounds 1, 2, and 4 also exhibited cellular activity in the insulin signaling pathway by increasing the insulin-stimulated Akt phosphorylation level in human hepatocellular liver carcinoma HepG2 cells, suggesting their potential for new anti-insulin-resistant drug developments. Georg Thieme Verlag KG Stuttgart · New York.
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Comprehensive Logic Based Analyses of Toll-Like Receptor 4 Signal Transduction Pathway
Padwal, Mahesh Kumar; Sarma, Uddipan; Saha, Bhaskar
2014-01-01
Among the 13 TLRs in the vertebrate systems, only TLR4 utilizes both Myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adapter interferon-β-inducing Factor (TRIF) adaptors to transduce signals triggering host-protective immune responses. Earlier studies on the pathway combined various experimental data in the form of one comprehensive map of TLR signaling. But in the absence of adequate kinetic parameters quantitative mathematical models that reveal emerging systems level properties and dynamic inter-regulation among the kinases/phosphatases of the TLR4 network are not yet available. So, here we used reaction stoichiometry-based and parameter independent logical modeling formalism to build the TLR4 signaling network model that captured the feedback regulations, interdependencies between signaling kinases and phosphatases and the outcome of simulated infections. The analyses of the TLR4 signaling network revealed 360 feedback loops, 157 negative and 203 positive; of which, 334 loops had the phosphatase PP1 as an essential component. The network elements' interdependency (positive or negative dependencies) in perturbation conditions such as the phosphatase knockout conditions revealed interdependencies between the dual-specific phosphatases MKP-1 and MKP-3 and the kinases in MAPK modules and the role of PP2A in the auto-regulation of Calmodulin kinase-II. Our simulations under the specific kinase or phosphatase gene-deficiency or inhibition conditions corroborated with several previously reported experimental data. The simulations to mimic Yersinia pestis and E. coli infections identified the key perturbation in the network and potential drug targets. Thus, our analyses of TLR4 signaling highlights the role of phosphatases as key regulatory factors in determining the global interdependencies among the network elements; uncovers novel signaling connections; identifies potential drug targets for infections. PMID:24699232
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21 CFR 558.555 - Semduramicin.
Code of Federal Regulations, 2010 CFR
2010-04-01
... tolerances. See § 556.597 of this chapter. (d) Conditions of use in chickens. It is used in chicken feed as... Sponsor (1) 22.7 (25 ppm) Broiler chickens: For the prevention of coccidiosis caused by Eimeria acervulina.... 066104 (2) 22.7 Bacitracin methylene disalicylate 10 to 50 Broiler chickens: As in paragraph (d)(1) of...
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de Sá Rodrigues, L. C.; Holmes, K. E.; Thompson, V.; Piskun, C. M.; Lana, S. E.; Newton, M. A.; Stein, T. J.
2016-01-01
Serum alkaline phosphatase (ALP) concentration is a prognostic factor for osteosarcoma in multiple studies, although its biological significance remains incompletely understood. To determine whether gene expression patterns differed in osteosarcoma from patients with differing serum ALP concentrations, microarray analysis was performed on 18 primary osteosarcoma samples and six osteosarcoma cell lines from dogs with normal and increased serum ALP concentration. No differences in gene expression patterns were noted between tumours or cell lines with differing serum ALP concentration using a gene-specific two-sample t-test. Using a more sensitive empirical Bayes procedure, defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was increased in both the tissue and cell lines of the normal ALP group. Using quantitative PCR (qPCR), differences in DCUN1D1 expression between the two groups failed to reach significance. The homogeneity of gene expression patterns of osteosarcoma associated differing serum ALP concentrations are consistent with previous studies suggesting serum ALP concentration is not associated with intrinsic differences of osteosarcoma cells. PMID:25643733
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Restoration algorithms for imaging through atmospheric turbulence
2017-02-18
the Fourier spectrum of each frame. The reconstructed image is then obtained by taking the inverse Fourier transform of the average of all processed...with wipξq “ Gσp|Fpviqpξq|pq řM j“1Gσp|Fpvjqpξq|pq , where F denotes the Fourier transform (ξ are the frequencies) and Gσ is a Gaussian filter of...a combination of SIFT [26] and ORSA [14] algorithms) in order to remove affine transformations (translations, rotations and homothety). The authors
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NASA Astrophysics Data System (ADS)
Richey, Jon D.; Upchurch, Garland R.; Montañez, Isabel P.; Lomax, Barry H.; Suarez, Marina B.; Crout, Neil M. J.; Joeckel, R. M.; Ludvigson, Greg A.; Smith, Jon J.
2018-06-01
Past greenhouse intervals of the Mesozoic were repeatedly punctuated by Ocean Anoxic Events (OAEs), major perturbations to the global carbon cycle and abrupt climate changes that may serve as relevant analogs for Earth's greenhouse gas-forced climate future. The key to better understanding these transient climate disruptions and possible CO2-forced tipping-points resides in high-resolution, precise, and accurate estimates of atmospheric CO2 for individual OAEs. Here we present a high-temporal resolution, multi-proxy pCO2 reconstruction for the onset of mid-Cretaceous (Albian-Cenomanian Boundary) OAE1d. Coupling of pCO2 estimates with carbon isotopic compositions (δ13C) of charcoal, vitrain, and cuticle from the Rose Creek Pit (RCP), Nebraska, reveals complex phasing, including a lag between the well-documented negative δ13C excursion defining the onset of OAE1d and the CO2 increase. This lag indicates that increased CO2 or other C-based greenhouse gases may not have been the primary cause of the negative excursion. Our study reveals a pCO2 increase within the interval of the negative δ13C excursion, reaching a maximum of up to ∼840 ppm (95% confidence interval -307 ppm/+167 ppm) toward its end. The reconstructed magnitude of CO2 increase (∼357 ppm) is similar to that of Late Cretaceous OAE2 but of smaller magnitude than that of other major carbon cycle perturbations of the Mesozoic assessed via stomatal methods (e.g., the Toarcian OAE [TOAE], Triassic-Jurassic boundary event, Cretaceous-Paleogene Boundary event). Furthermore, our results indicate a possible shared causal or developmental mechanism with OAE1a and the TOAE.
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Kim, Ji-Eun; Takanche, Jyoti Shrestha; Kim, Jeong-Seok; Lee, Min-Ho; Jeon, Jae-Gyu; Park, Il-Song; Yi, Ho-Keun
2018-04-12
Poor bone quality and osteolysis are the major causes of implant failure in dentistry. Here, this study tested the effect of phelligridin D-loaded nanotubes titanium (Ti) for bone formation around the dental implants. The purpose of this study was to enhance osseointegration of phelligridin D-loaded implant into the bone for bone formation and prevention of osteolysis. Cell viability, crystal violet staining, Western blot, alizarin red S staining, alkaline phosphatase activity, tartrate-resistant acid phosphatase staining, micro-computed tromography (μ-CT), hematoxylin and eosin (H&E) and immunohistochemical staining were used in vitro and in vivo to test the biocompatibility of phelligridin D. Phelligridin D enhanced osteoblast differentiation and mineralization by increasing bone morphogenic protein-2/7 (BMP-2/7), Osterix, Runx-2, osteoprotegerin (OPG), alkaline phosphatase and inhibited osteoclast differentiation by decreasing receptor activator of nuclear factor kappa-B ligand (RANKL) in MC-3T3 E1 cells. Further, phelligridin D promoted bone regeneration around nanotube Ti implant surface by increasing the levels of BMP-2/7 and OPG in a rat model. Phelligridin D also inhibited osteolysis by suppressing the expression of RANKL. These findings strongly suggest that phelligridin D is a new compound representing a potential therapeutic candidate for implant failure caused by osteolysis and poor bone quality of teeth.
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Experimental oral lead toxicity in young dogs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stowe, H.D.; Goyer, R.A.; Krigman, M.M.
1973-02-01
Litter-mate male pups were fed a calcium-and-phosphorus-low purified diet with and without 100 ppm of lead as lead acetate from age 6 to 18 weeks. Lead-toxic dogs exhibited cyclic but terminally severe anorexia and cachexia, significant anemia, normoblastocytosis and leukopenia within six weeks, hypoproteinemia, decreased serum albumin, ..cap alpha../sub 1/-globulin, ..beta../sub 2/-globulin, alkaline phosphatase and lactic dehydrogenase 1, elevated serum glutamic oxaloacetic and pyruvic transaminases, delayed closure of the thoracic vertebral epiphyses, lead lines in the distal radii and thoracic spinous processes, enlargement of liver, kidney, and brain, hepatic fatty metamorphosis, focal proximal renal tubular necrosis, hydropic degeneration of spermatognia,more » and lead inclusion body formation. Approximately 97% of the tissue lead was estimated to be skeletal; the greatest concentration of lead in the brain was found in the occipital gray matter.« less
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The amoebal MAP kinase response to Legionella pneumophila is regulated by DupA.
Li, Zhiru; Dugan, Aisling S; Bloomfield, Gareth; Skelton, Jason; Ivens, Alasdair; Losick, Vicki; Isberg, Ralph R
2009-09-17
The amoeba Dictyostelium discoideum can support replication of Legionella pneumophila. Here we identify the dupA gene, encoding a putative tyrosine kinase/dual-specificity phosphatase, in a screen for D. discoideum mutants altered in allowing L. pneumophila intracellular replication. Inactivation of dupA resulted in depressed L. pneumophila growth and sustained hyperphosphorylation of the amoebal MAP kinase ERK1, consistent with loss of a phosphatase activity. Bacterial challenge of wild-type amoebae induced dupA expression and resulted in transiently increased ERK1 phosphorylation, suggesting that dupA and ERK1 are part of a response to bacteria. Indeed, over 500 of the genes misregulated in the dupA(-) mutant were regulated in response to L. pneumophila infection, including some thought to have immune-like functions. MAP kinase phosphatases are known to be highly upregulated in macrophages challenged with L. pneumophila. Thus, DupA may regulate a MAP kinase response to bacteria that is conserved from amoebae to mammals.
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NASA Astrophysics Data System (ADS)
Widowati, Ita; Zainuri, Muhammad; Pancasakti Kusumaningrum, Hermien; Susilowati, Ragil; Hardivillier, Yann; Leignel, Vincent; Bourgougnon, Nathalie; Mouget, Jean-Luc
2017-02-01
Natural alternatives antioxidant source has become a trending topic in the past decades to replace synthetic antioxidant. Microalgae have been mentioned to show interesting bioactive properties and one of them is its antioxidant activity. This study aims to evaluate the potential of three microalgae Dunaliella salina, Tetraselmis chuii and Isochrysis galbanaas new source of natural antioxidant. Proximate analysis and total phenolic content of D. salina, T. chuii and I. galbanas were determined. Antioxidant activity of methanolic extracts of these three species prepared in different concentration (50, 100, 250, 500, and 1000 ppm) was performed through DPPH assay. I. galbana clone Tahiti demonstrated a highest antioxidant potential with 61.64 of inhibition at 50 ppm followed by D. salina with 58.45 % of inhibition and T. chuii with 52.58 % of inhibition. I. galbana clone Tahiti was the best antioxidant with total phenol content of 17.798 mg GAE g-1 extract at 50 ppm; followed by T. chuii 16.868 mg GAE g-1 extract and the lowest was D. salina with 4.672 mg GAE g-1 extract. Results suggest that these microalgae posses antioxidant potential which could be considered for future applications in medicine, dietary supplements, cosmetics or food industries.
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Lycopene intake facilitates the increase of bone mineral density in growing female rats.
Iimura, Yuki; Agata, Umon; Takeda, Satoko; Kobayashi, Yuki; Yoshida, Shigeki; Ezawa, Ikuko; Omi, Naomi
2014-01-01
Intake of the antioxidant lycopene has been reported to decrease oxidative stress and have beneficial effects on bone health. However, few in vivo studies have addressed these beneficial effects in growing female rodents or young women. The aim of this study was to investigate the effect of lycopene intake on bone metabolism through circulating oxidative stress in growing female rats. Six-week-old Sprague-Dawley female rats were randomly divided into 3 groups according to the lycopene content in their diet: 0, 50, and 100 ppm. The bone mineral density (BMD) of the lumbar spine and the tibial proximal metaphysis increased with lycopene content in a dose-dependent manner; the BMD in 100 ppm group was significantly higher than in the 0 ppm group. The urine deoxypyridinoline concentrations were significantly lower in the 50 and 100 ppm groups than in the 0 ppm group, and the serum bone-type alkaline phosphatase activity was significantly higher in 100 ppm group than in the 0 ppm group. No difference in systemic oxidative stress level was observed; however, the oxidative stress level inversely correlated with the tibial BMD. Our findings suggested that lycopene intake facilitates bone formation and inhibits bone resorption, leading to an increase of BMD in growing female rats.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Stone, W.E.; Crocket, J.H.; Fleet, M.E.
1990-08-01
Iron-nickel monosulfide and basalt glass containing trace amounts of PGE equilibrated at 1,200{degree}C, and f{sub o{sub 2}} = 10{sup {minus}9.2} (close to the wustite-magnetite buffer) and f{sub s{sub 2}} = 10{sup {minus}0.9}, have been analyzed for noble metals by radiochemical and instrumental neutron activation analysis. The average contents of PGE in coexisting Fe-Ni sulfide and basalt glass, respectively, are Pd, 50 ppm and 0.5 ppb; Ir, 50 ppm and 0.5 ppb; Pt, 100 ppm and 10 ppb; and Au, 0.7 ppm and 0.8 ppb. The sulfide liquid-silicate melt partition coefficients (D values) for the noble metals are (9 {plus minus}more » 7) {times} 10{sup 4} for Pd, (1 {plus minus} 0.7) {times} 10{sup 5} for Ir, (9 {plus minus} 6) {times} 10{sup 3} Pt, and (1 {plus minus} 0.9) {times} 10{sup 3} for Au. The noble metals are strongly partitioned into sulfide liquid, but the affinity of Pd and Ir for sulfide liquid is about 50 times greater than that of Pt and about 500 times greater than that of Au. The D values indicate that equilibrium partitioning between immiscible sulfide liquid and basalt magma would result in fractionation of the noble metals, which differs significantly from that generally observed in nature.« less
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An evaluation of liquid ammonia (ammonium hydroxide) as a candidate piscicide
Ward, David L.; Morton-Starner, R.; Hedwall, Shaula J.
2013-01-01
Eradication of populations of nonnative aquatic species for the purpose of reintroducing native fish is often difficult because very few effective tools are available for removing aquatic organisms. This creates the need to evaluate new chemicals that could be used as management tools for native fish conservation. Ammonia is a natural product of fish metabolism and is naturally present in the environment at low levels, yet is known to be toxic to most aquatic species. Our objective was to determine the feasibility of using liquid ammonia as a fisheries management tool by evaluating its effectiveness at killing undesirable aquatic species and its persistence in a pond environment. A suite of invasive aquatic species commonly found in the southwestern USA were introduced into two experimental outdoor ponds located at the Rocky Mountain Research Station in Flagstaff, Arizona. Each pond was treated with ammonium hydroxide (29%) at 38 ppm. This target concentration was chosen because previous studies using anhydrous ammonia reported incomplete fish kills in ponds at concentrations less than 30 ppm. Water quality was monitored for 49 d to determine how quickly the natural bacteria in the environment converted the ammonia to nitrate. Ammonia levels remained above 8 ppm for 24 and 18 d, respectively, in ponds 1 and 2. Nitrite levels in each pond began to rise approximately 14 d after dosing with ammonia and stayed above 5 ppm for an additional 21 d in pond 1 and 18 d in pond 2. After 49 d all water in both ponds was drained and no fish, crayfish, or tadpoles were found to have survived the treatment, but aquatic turtles remained alive and appeared unaffected. Liquid ammonia appears to be an effective tool for removing many problematic invasive aquatic species and may warrant further investigation as a piscicide.
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2006-12-01
7 Figure 3.1-3. Net Heat of Combustion ...No. 1 Aromatic Carbon, max ASTM D-5292 Mol % < 0.5 Sulfur, Total, Max ASTM D-5453 ppm 1 Cetane Index ASTM D-976 Report Net Heat of Combustion , min ASTM...12 /2 00 6 8/ 19 /2 00 6 8/ 26 /2 00 6 9/ 2/ 20 06 8 Figure 3.1-3. Net Heat of Combustion Trend Figure 3.1-4. Freezing Point Trend Net
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Ono, Yuji; Futamura, Ryusuke; Hattori, Yoshiyuki; Sakai, Toshio; Kaneko, Katsumi
2017-12-15
The adsorption and desorption of D 2 O on hydrophobic activated carbon fiber (ACF) occurs at a smaller pressure than the adsorption and desorption of H 2 O. The behavior of the critical desorption pressure difference between D 2 O and H 2 O in the pressure range of 1.25-1.80kPa is applied to separate low concentrated D 2 O from water using the hydrophobic ACF, because the desorption branches of D 2 O and H 2 O drop almost vertically. The deuterium concentration of all desorbed water in the above pressure range is lower than that of water without adsorption-treatment on ACF. The single adsorption-desorption procedure on ACF at 1.66kPa corresponding to the maximum difference of adsorption amount between D 2 O and H 2 O reduced the deuterium concentration of desorbed water to 130.6ppm from 143.0ppm. Thus, the adsorption-desorption procedure of water on ACF is a promising separation and concentration method of low concentrated D 2 O from water. Copyright © 2017 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Cody, G.; Fogel, M. L.; Jin, K.; Griffen, P.; Steele, A.; Wang, Y.
2011-12-01
Approximately 6 years ago, while at the Geophysical Laboratory, James Scott became interested in the application of Solid State Nuclear Magnetic Resonance Spectroscopy to study bacterial metabolism. As often happens, other experiments intervened and the NMR experiments were not pursued. We have revisited Jame's question and find that using a multi-nuclear approach (1H, 2H, and 13C Solid State NMR) on laboratory cell culture has some distinct advantages. Our experiments involved batch cultures of E. coli (MG1655) harvested at stationary phase. In all experiments the growth medium consisted of MOPS medium for enterobacteria, where the substrate is glucose. In one set of experiments, 10 % of the water was D2O; in another 10 % of the glucose was per-deuterated. The control experiment used both water and glucose at natural isotopic abundance. A kill control of dead E. coli immersed in pure D2O for an extended period exhibited no deuterium incorporation. In both deuterium enriched experiments, considerable incorporation of deuterium into E. coli's biomolecular constituents was detected via 2H Solid State NMR. In the case of the D2O enriched experiment, 58 % of the incorporated deuterium is observed in a sharp peak at a frequency of 0.31 ppm, consistent with D incorporation in the cell membrane lipids, the remainder is observed in a broad peak at a higher frequency (centered at 5.4 ppm, but spanning out to beyond 10 ppm) that is consistent with D incorporation into predominantly DNA and RNA. In the case of the D-glucose experiments, 61 % of the deuterium is observed in a sharp resonance peak at 0.34 ppm, also consistent with D incorporation into membrane lipids, the remainder of the D is observed at a broad resonance peak centered at 4.3 ppm, consistent with D enrichment in glycogen. Deuterium abundance in the E. coli cells grown in 10 % D2O is nearly 2X greater than that grown with 10 % D-glucose. Very subtle differences are observed in both the 1H and 13C solid-state NMR experiments, most notably in the spectral region corresponding to glycogen H and C, respectively. Interestingly, whereas in both experiments the predominant site of incorporation was in the membrane lipids, the line width of the aliphatic-D resonance in the D2O enriched experiment is 67 % wider than that observed in the D-glucose enriched experiment. This difference could be due to greater residual 1H-2H dipolar coupling in membrane lipids synthesized with 10 % D2O due to D being incorporated during NADP(D) reduction of the fatty acid precursor during synthesis and the H-glucose being the source of carbon and hydrogen starting with acetyl-CoA. In the case of the D-glucose experiment, the narrower absorption line may be consistent with individual FA's being more homogeneously deuterated. Analysis of the membrane lipids is currently being performed via GCMS in order to gain potentially more insight to guide interpretation of the 2H solid state NMR spectra.
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Prevalence of lead exposure among age and sex cohorts of Canada geese
DeStefano, S.; Brand, C.J.; Rusch, D.H.
1992-01-01
We examined the prevalence of lead exposure from ingestion of waste lead shot among age and sex cohorts of Canada geese (Branta canadensis) on the breeding, migration, and wintering grounds of the Eastern Prairie Population. Blood samples from 6963 geese were assayed for lead concentration by atomic absorption spectrophotometry. On the breeding grounds, no goslings and < 1 % of adults showed evidence of recent exposure to lead shot (i.e., concentrations in the blood elevated above the threshold value of 0. 18 ppm lead). However, median background blood lead concentrations (i.e., blood samples with < 0.18 ppm lead) were higher in adults than goslings, indicating that exposure of adults to lead had occurred during previous seasons. Waste lead shot was available on the migration and wintering grounds, where a larger proportion of the blood samples from immatures (< 1 year old) than adults (> 1 year old) had lead concentrations greater-than-or-equal-to 0.18 ppm. Median background lead levels remained higher in adults than in immatures throughout fall and winter. We also found that more immature males than immature females had elevated lead concentrations. Higher rates of intake of food and grit (including shot) probably partially account for the higher prevalence of elevated lead concentrations in immature Canada geese.//Nous avons ??tudi?? l'importance des expositions au plomb par ingestion de plombs de chasse chez les diff??rentes cohortes (??ge et sexe) de Bernaches du Canada (Branta canadensis) dans les zones de reproduction et de migration et dans les territoires d'hiver chez la population de la Prairie de l'Est. Des ??chantillons de sang ont ??t?? pr??lev??s chez 6963 bernaches et analys??s au sphectrophotom??tre ? absorption atomique pour en d??terminer le contenu en plomb. Dans les zones de reproduction, les traces d'exposition r??cente ? des plombs (i.e. concentrations de plomb dans le sang au-dessus de la valeur seuil de 0,18 ppm) ??taient apparentes chez moins de 1% des adultes et aucun oison n'en portait. Cependant, les concentrations sanguines m??dianes de base (??chantillons de sang contenant moins de 0,18 ppm de plomb) ??taient plus ??lev??es chez les adultes que chez les oisons, ce qui signifie probablement que les adultes avaient ??t?? expos??s au plomb au cours de saisons pr??c??dentes. Les plombs perdus ??taient abondants dans les territoires de migration et les territoires d'hiver et la proportion d'??chantillons de sang contenant des concentrations a?Y 0,18 ppm ??tait plus ??lev??e chez les oiseaux immatures (< 1 an) que chez les oiseaux adultes (> 1 an). Les concentrations m??dianes de base sont demeur??es plus ??lev??es chez les adultes que chez les immatures durant tout l'automne et tout l'hiver. Nous avons ??galement constat?? que plus de m??les immatures que de femelles immatures avaient des concentrations ??lev??es de plomb. Les taux plus ??lev??s d'ingestion de nourriture et de mati??res min??rales (y compris des plombs de chasse) expliquent probablement en partie la pr??sence de concentrations ??lev??es de plomb chez les Bernaches du Canada immatures.
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Jarrahy, Reza; Huang, Weibiao; Rudkin, George H; Lee, Jane M; Ishida, Kenji; Berry, Micah D; Sukkarieh, Modar; Wu, Benjamin M; Yamaguchi, Dean T; Miller, Timothy A
2005-08-01
Osteogenic differentiation of osteoprogenitor cells in three-dimensional (3D) in vitro culture remains poorly understood. Using quantitative real-time RT-PCR techniques, we examined mRNA expression of alkaline phosphatase, osteocalcin, and vascular endothelial growth factor (VEGF) in murine preosteoblastic MC3T3-E1 cells cultured for 48 h and 14 days on conventional two-dimensional (2D) poly(l-lactide-co-glycolide) (PLGA) films and 3D PLGA scaffolds. Differences in VEGF secretion and function between 2D and 3D culture systems were examined using Western blots and an in vitro Matrigel-based angiogenesis assay. Expression of both alkaline phosphatase and osteocalcin in cells cultured on 3D scaffolds was significantly downregulated relative to 2D controls in 48 h and 14 day cultures. In contrast, elevated levels of VEGF expression in 3D culture were noted at every time point in short- and long-term culture. VEGF protein secretion in 3D cultures was triple the amount of secretion observed in 2D controls. Conditioned medium from 3D cultures induced an enhanced level of angiogenic activity, as evidenced by increases in branch points observed in in vitro angiogenesis assays. These results collectively indicate that MC3T3-E1 cells commit to osteogenic differentiation at a slower rate when cultured on 3D PLGA scaffolds and that VEGF is preferentially expressed by these cells when they are cultured in three dimensions.
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Adaptive Optics Communications Performance Analysis
NASA Technical Reports Server (NTRS)
Srinivasan, M.; Vilnrotter, V.; Troy, M.; Wilson, K.
2004-01-01
The performance improvement obtained through the use of adaptive optics for deep-space communications in the presence of atmospheric turbulence is analyzed. Using simulated focal-plane signal-intensity distributions, uncoded pulse-position modulation (PPM) bit-error probabilities are calculated assuming the use of an adaptive focal-plane detector array as well as an adaptively sized single detector. It is demonstrated that current practical adaptive optics systems can yield performance gains over an uncompensated system ranging from approximately 1 dB to 6 dB depending upon the PPM order and background radiation level.
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78 FR 70864 - Metaldehyde; Pesticide Tolerances
Federal Register 2010, 2011, 2012, 2013, 2014
2013-11-27
... plus cob with husks removed at 0.05 ppm; grass, forage at 1.5 ppm; grass, hay at 1.8 ppm; leaf petioles...: ``Metaldehyde; Human Health Risk Assessment for Proposed Uses on Grass Grown for Seed, Leaf Petioles [Crop....10 ppm; grass, forage from 1.5 ppm to 2.0 ppm; grass, hay from 1.8 ppm to 2.0 ppm; leaf petioles...
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A Novel Association and Therapeutic Targeting of Neuropilin-1 and MUC1 in Pancreatic Cancer
2015-12-01
be potentially translated to human clinical trials. Other Achievements References 1. Besmer DM, Curry JM, Roy LD, Tinder TL, Sahraei M, Schettini J...containing protein tyrosine phosphatase 2. J Cell Sci 2009, 122(Pt 18):3385-3392. 4. Roy LD, Sahraei M, Subramani DB, Besmer D, Nath S, Tinder TL, Bajaj E
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NASA Astrophysics Data System (ADS)
Lipovsky, Bradley Paul; Dunham, Eric M.
2017-04-01
The Whillans Ice Plain (WIP), Antarctica, experiences twice daily tidally modulated stick-slip cycles. Slip events last about 30 min, have sliding velocities as high as ˜0.5 mm/s (15 km/yr), and have total slip ˜0.5 m. Slip events tend to occur during falling ocean tide: just after high tide and just before low tide. To reproduce these characteristics, we use rate-and-state friction, which is commonly used to simulate tectonic faulting, as an ice stream sliding law. This framework describes the evolving strength of the ice-bed interface throughout stick-slip cycles. We present simulations that resolve the cross-stream dimension using a depth-integrated treatment of an elastic ice layer loaded by tides and steady ice inflow. Steady sliding with rate-weakening friction is conditionally stable with steady sliding occurring for sufficiently narrow ice streams relative to a nucleation length. Stick-slip cycles occur when the ice stream is wider than the nucleation length or, equivalently, when effective pressures exceed a critical value. Ice streams barely wider than the nucleation length experience slow-slip events, and our simulations suggest that the WIP is in this slow-slip regime. Slip events on the WIP show a sense of propagation, and we reproduce this behavior by introducing a rate-strengthening region in the center of the otherwise rate-weakening ice stream. If pore pressures are raised above a critical value, our simulations predict that the WIP would exhibit quasi-steady tidally modulated sliding as observed on other ice streams. This study validates rate-and-state friction as a sliding law to describe ice stream sliding styles.
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Togao, Osamu; Keupp, Jochen; Hiwatashi, Akio; Yamashita, Koji; Kikuchi, Kazufumi; Yoneyama, Masami; Honda, Hiroshi
2017-06-01
To assess the quantitative performance of three-dimensional (3D) fast spin-echo (FSE) Dixon amide proton transfer (APT) imaging of brain tumors compared with B 0 correction with separate mapping methods. Twenty-two patients with brain tumors (54.2 ± 18.7 years old, 12 males and 10 females) were scanned at 3 Tesla (T). Z-spectra were obtained at seven different frequency offsets at ±3.1 ppm, ± 3.5 ppm, ± 3.9 ppm, and -1560 ppm. The scan was repeated three times at +3.5 ppm with echo shifts for Dixon B 0 mapping. The APT image corrected by a three-point Dixon-type B 0 map from the same scan (3D-Dixon) or a separate B 0 map (2D-separate and 3D-separate), and an uncorrected APT image (3D-uncorrected) were generated. We compared the APT-weighted signals within a tumor obtained with each 3D method with those obtained with 2D-separate as a reference standard. Excellent agreements and correlations with the 2D-separate were obtained by the 3D-Dixon method for both mean (ICC = 0.964, r = 0.93, P < 0.0001) and 90th-percentile (ICC = 0.972, r = 0.95, P < 0.0001) APT-weighted signals. These agreements and correlations for 3D-Dixon were better than those obtained by the 3D-uncorrected and 3D-separate methods. The 3D FSE Dixon APT method with intrinsic B 0 correction offers a quantitative performance that is similar to that of established two-dimensional (2D) methods. Magn Reson Med 77:2272-2279, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.
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Airborne detection of diffuse carbon dioxide emissions at Mammoth Mountain, California
Gerlach, T.M.; Doukas, M.P.; McGee, K.A.; Kessler, R.
1999-01-01
We report the first airborne detection of CO2 degassing from diffuse volcanic sources. Airborne measurement of diffuse CO2 degassing offers a rapid alternative for monitoring CO2 emission rates at Mammoth Mountain. CO2 concentrations, temperatures, and barometric pressures were measured at ~2,500 GPS-referenced locations during a one-hour, eleven-orbit survey of air around Mammoth Mountain at ~3 km from the summit and altitudes of 2,895-3,657 m. A volcanic CO2 anomaly 4-5 km across with CO2 levels ~1 ppm above background was revealed downwind of tree-kill areas. It contained a 1-km core with concentrations exceeding background by >3 ppm. Emission rates of ~250 t d-1 are indicated. Orographic winds may play a key role in transporting the diffusely degassed CO2 upslope to elevations where it is lofted into the regional wind system.We report the first airborne detection of CO2 degassing from diffuse volcanic sources. Airborne measurement of diffuse CO2 degassing offers a rapid alternative for monitoring CO2 emission rates at Mammoth Mountain. CO2 concentrations, temperatures, and barometric pressures were measured at approximately 2,500 GPS-referenced locations during a one-hour, eleven-orbit survey of air around Mammoth Mountain at approximately 3 km from the summit and altitudes of 2,895-3,657 m. A volcanic CO2 anomaly 4-5 km across with CO2 levels approximately 1 ppm above background was revealed downwind of tree-kill areas. It contained a 1-km core with concentrations exceeding background by >3 ppm. Emission rates of approximately 250 t d-1 are indicated. Orographic winds may play a key role in transporting the diffusely degassed CO2 upslope to elevations where it is lofted into the regional wind system.
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Effects of concanavalin A on chondrocyte hypertrophy and matrix calcification.
Yan, W; Pan, H; Ishida, H; Nakashima, K; Suzuki, F; Nishimura, M; Jikko, A; Oda, R; Kato, Y
1997-03-21
Resting chondrocytes do not usually undergo differentiation to the hypertrophic stage and calcification. However, incubating these cells with concanavalin A resulted in 10-100-fold increases in alkaline phosphatase activity, binding of 1,25(OH)2-vitamin D3, type X collagen synthesis, 45Ca incorporation into insoluble material, and calcium content. On the other hand, other lectins tested (including wheat germ agglutinin, lentil lectin, pea lectin, phytohemagglutinin-L, and phytohemagglutinin-E) marginally affected alkaline phosphatase activity, although they activate lymphocytes. Methylmannoside reversed the effect of concanavalin A on alkaline phosphatase within 48 h. Concanavalin A did not increase alkaline phosphatase activity in articular chondrocyte cultures. In resting chondrocyte cultures, succinyl concanavalin A was as potent as concanavalin A in increasing alkaline phosphatase activity, the incorporation of [35S]sulfate, D-[3H]glucosamine, and [3H]serine into proteoglycans, and the incorporation of [3H]serine into protein, although concanavalin A, but not succinyl concanavalin A, induced a rapid change in the shape of the cells from flat to spherical. These findings suggest that concanavalin A induces a switch from the resting, to the growth-plate stage, and that this action of concanavalin A is not secondary to changes in the cytoskeleton. Chondrocytes exposed to concanavalin A may be useful as a novel model of endochondral bone formation.
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Tokpohozin, Sedjro Emile; Fischer, Susann; Sacher, Bertram; Becker, Thomas
2016-11-01
Sorghum malt used during African beer processing contains a high level of cyanogenic glucoside (dhurrin), up to 1375 ppm. In traditional sorghum malting and mashing, dhurrin is not sufficiently hydrolyzed due to uncontrolled germination and a high gelatinization temperature. The cyanide content of traditional African beers (11 ppm) is higher than the minimum dose (1 ppm) required to form carcinogenic ethyl carbamate during alcoholic fermentation. In the detoxification process, aryl-β-d-glucosidase (dhurrinase) is the "key component". For significant dhurrin hydrolysis during mashing, optimizing dhurrinase synthesis during malting is a good solution to reduce dhurrin completely to below the harmful dose in the sorghum wort. Lactic acid bacteria which exhibit aryl-β-d-glucosidase prior to alcoholic fermentation may help to reduce ethyl carbamate content in alcoholic beverages. Moreover, some specific β-d-glucosidases have a dual property, being able to cleave and synthesize glucosides bonds and thereby generating good precursors for beer bioflavouring. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Kikkas, Ingrid; Mallone, Roberto; Larger, Etienne; Volland, Hervé; Morel, Nathalie
2014-01-01
Type 1 diabetes (T1D) results from the destruction of pancreatic insulin-producing beta cells and is strongly associated with the presence of islet autoantibodies. Autoantibodies to tyrosine phosphatase-like protein IA-2 (IA-2As) are considered to be highly predictive markers of T1D. We developed a novel lateral flow immunoassay (LFIA) based on a bridging format for the rapid detection of IA-2As in human serum samples. In this assay, one site of the IA-2As is bound to HA-tagged-IA-2, which is subsequently captured on the anti-HA-Tag antibody-coated test line on the strip. The other site of the IA-2As is bound to biotinylated IA-2, allowing the complex to be visualized using colloidal gold nanoparticle-conjugated streptavidin. For this study, 35 serum samples from T1D patients and 44 control sera from non-diabetic individuals were analyzed with our novel assay and the results were correlated with two IA-2A ELISAs. Among the 35 serum samples from T1D patients, the IA-2A LFIA, the in-house IA-2A ELISA and the commercial IA-2A ELISA identified as positive 21, 29 and 30 IA-2A-positive sera, respectively. The major advantages of the IA-2A LFIA are its rapidity and simplicity.
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Saghir, Shakil A; Marty, Mary S; Zablotny, Carol L; Passage, Julie K; Perala, Adam W; Neal, Barbara H; Hammond, Larry; Bus, James S
2013-12-01
Life-stage-dependent toxicity and dose-dependent toxicokinetics (TK) were evaluated in Sprague Dawley rats following dietary exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D renal clearance is impacted by dose-dependent saturation of the renal organic anion transporter; thus, this study focused on identifying inflection points of onset of dietary nonlinear TK to inform dose selection decisions for toxicity studies. Male and female rats were fed 2,4-D-fortified diets at doses to 1600 ppm for 4-weeks premating, <2 weeks during mating, and to test day (TD) 71 to parental (P1) males and to P1 females through gestation/lactation to TD 96. F1 offspring were exposed via milk with continuing diet exposure until postnatal day (PND) 35. As assessed by plasma area under the curve for the time-course plasma concentration, nonlinear TK was observed ≥ 1200 ppm (63 mg/kg/day) for P1 males and between 200 and 400 ppm (14-27 mg/kg/day) for P1 females. Dam milk and pup plasma levels were higher on lactation day (LD) 14 than LD 4. Relative to P1 adults, 2,4-D levels were higher in dams during late gestation/lactation and postweaning pups (PND 21-35) and coincided with elevated intake of diet/kg body weight. Using conventional maximum tolerated dose (MTD) criteria based on body weight changes for dose selection would have resulted in excessive top doses approximately 2-fold higher than those identified incorporating critical TK data. These data indicate that demonstration of nonlinear TK, if present at dose levels substantially above real-world human exposures, is a key dose selection consideration for improving the human relevance of toxicity studies compared with studies employing conventional MTD dose selection strategies.
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Marty, Mary S.
2013-01-01
Life-stage-dependent toxicity and dose-dependent toxicokinetics (TK) were evaluated in Sprague Dawley rats following dietary exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D renal clearance is impacted by dose-dependent saturation of the renal organic anion transporter; thus, this study focused on identifying inflection points of onset of dietary nonlinear TK to inform dose selection decisions for toxicity studies. Male and female rats were fed 2,4-D-fortified diets at doses to 1600 ppm for 4-weeks premating, <2 weeks during mating, and to test day (TD) 71 to parental (P1) males and to P1 females through gestation/lactation to TD 96. F1 offspring were exposed via milk with continuing diet exposure until postnatal day (PND) 35. As assessed by plasma area under the curve for the time-course plasma concentration, nonlinear TK was observed ≥1200 ppm (63mg/kg/day) for P1 males and between 200 and 400 ppm (14–27mg/kg/day) for P1 females. Dam milk and pup plasma levels were higher on lactation day (LD) 14 than LD 4. Relative to P1 adults, 2,4-D levels were higher in dams during late gestation/lactation and postweaning pups (PND 21–35) and coincided with elevated intake of diet/kg body weight. Using conventional maximum tolerated dose (MTD) criteria based on body weight changes for dose selection would have resulted in excessive top doses approximately 2-fold higher than those identified incorporating critical TK data. These data indicate that demonstration of nonlinear TK, if present at dose levels substantially above real-world human exposures, is a key dose selection consideration for improving the human relevance of toxicity studies compared with studies employing conventional MTD dose selection strategies. PMID:24105888
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1980-04-01
subambient temperature capability of our design . The aerosol fluorination system designed to produce a controlled , con- tinuous stream of aerosol...F3 H8 , 117 (68.9) C6F2H7 CN: D I Mixture CO: D I’’ Difluorocyclohexane Isomer (two nonequivalent CFR groups ) 1 H NMR no integration given 1 9F NMR: d...two nonequivalent CFH groups ) 1H NMR no integration given 19F NMR d? at 193.5 ppm (J = 106.8 Rz ?) 32 TABLE 7 (CONTINUED) MS: CI: 119 (1.4) C6F2
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[Phosphatase activity in Amoeba proteus at pH 9.0].
Sopina, V A
2007-01-01
In the free-living amoeba Amoeba proteus (strain B), after PAAG disk-electrophoresis of the homogenate supernatant, at using 1-naphthyl phosphate as a substrate and pH 9.0, three forms of phosphatase activity were revealed; they were arbitrarily called "fast", "intermediate", and "slow" phosphatases. The fast phosphatase has been established to be a fraction of lysosomal acid phosphatase that preserves some low activity at alkaline pH. The question as to which particular class the intermediate phosphatase belongs to has remained unanswered: it can be both acid phosphatase and protein tyrosine phosphatase (PTP). Based on data of inhibitor analysis, large substrate specificity, results of experiments with reactivation by Zn ions after inactivation with EDTA, other than in the fast and intermediate phosphatases localization in the amoeba cell, it is concluded that only slow phosphatase can be classified as alkaline phosphatase (EC 3.1.3.1).
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[Alkaline phosphatase in Amoeba proteus].
Sopina, V A
2005-01-01
In free-living Amoeba proteus (strain B), 3 phosphatase were found after disc-electrophoresis of 10 microg of protein in PAGE and using 1-naphthyl phosphate as a substrate a pH 9.0. These phosphatases differed in their electrophoretic mobilities - "slow" (1-3 bands), "middle" (one band) and "fast" (one band). In addition to 1-naphthyl phosphate, "slow" phosphatases were able to hydrolyse 2-naphthyl phosphate and p-nitrophenyl phosphate. They were slightly activated by Mg2+, completely inhibited by 3 chelators (EDTA, EGTA and 1,10-phenanthroline), L-cysteine, sodium dodecyl sulfate and Fe2+, Zn2+ and Mn2+ (50 mM), considerably inactivated by orthovanadate, molybdate, phosphatase inhibitor cocktail 1, p-nitrophenyl phosphate, Na2HPO4, DL-dithiothreitol and urea and partly inhibited by H2O2, DL-phenylalanine, 2-mercaptoethanol, phosphatase inhibitor cocktail 2 and Ca2+. Imidazole, L-(+)-tartrate, okadaic acid, NaF and sulfhydryl reagents -p-(hydroxy-mercuri)benzoate and N-ethylmaleimide - had no influence on the activity of "slow" phosphatases. "Middle" and "fast" phosphatases, in contrast to "slow" ones, were not inactivated by 3 chelators. The "middle" phosphatase differed from the "fast" one by smaller resistance to urea, Ca2+, Mn2+, phosphates and H2O2 and greater resistance to dithiothreitol and L-(+)-tartrate. In addition, the "fast" phosphatase was inhibited by L-cysteine but the "middle" one was activated by it. Of 5 tested ions (Mg2+, Cu2+, Mn2+, Ca2+ and Zn2+), only Zn2+ reactivated "slow" phosphatases after their inactivation by EDTA treatment. The reactivation of apoenzyme was only partial (about 35 %). Thus, among phosphatases found in amoebae at pH 9.0, only "slow" ones are Zn-metalloenzymes and may be considered as alkaline phosphatases (EC 3.1.3.1). It still remains uncertain, to which particular phosphatase class "middle" and "fast" phosphatases (pH 9.0) may belong.
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Rapid analysis of 2,4-D in soil samples by modified Soxhlet apparatus using HPLC with UV detection.
Kashyap, Sanjay M; Pandya, Girish H; Kondawar, Vivek K; Gabhane, Sanjay S
2005-02-01
The 2,4-dichlorophenoxy acetic acid (2,4-D) is used as a systemic herbicide to control broadleaf weeds in wheat, corn, range land/pasture land, sorghum, and barley. In this study, a fast and efficient method is developed by selection of modified extraction apparatus and high-performance liquid chromatography (HPLC)-UV conditions for the determination of 2,4-D in soil samples. The method is applied to the study of soil samples collected from the agricultural field. The herbicide is extracted from soil samples by acetonitrile in a modified Soxhlet apparatus. The advantages of the apparatus are that it uses small volume of organic solvent, reduced time of extraction, and better recovery of the analyte. The extract is filtered using a very fine microfiber paper. The total extract is concentrated in a rotatory evaporator, dried under ultrahigh pure N2, and finally reconstituted in 1 mL of acetonitrile. HPLC-UV at 228 nm is used for analysis. The herbicide is identified and quantitated using the HPLC system. The method is validated by the analysis of spiked soil samples. Recoveries obtained varied from 85% to 100% for spiked soil samples. The limit of quantitation (LOQ) and the limit of detection (LOD) are 0.010 and 0.005 parts per million (ppm), respectively, for spiked soil samples. The LOQ and LOD are 0.006 and 0.003 ppm for unspiked soil samples. The measured concentrations of 2,4-D in spiked soil samples are between 0.010 and 0.020 ppm with an average of 0.016 +/- 0.003 ppm. For unspiked soil samples it is between 0.006 ppm and 0.012 ppm with an average of 0.009 +/- 0.002 ppm. The measured concentrations of 2,4-D in soil samples are generally low and do not exceed the regulatory agencies guidelines.
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Panda, Sandeep; Akcil, Ata; Mishra, Srabani; Erust, Ceren
2017-03-05
Pyrite ash, a waste by-product formed during roasting of pyrite ores, is a good source of valuable metals. The waste is associated with several environmental issues due to its dumping in sea and/or land filling. Although several other management practices are available for its utilization, the waste still awaits and calls for an eco-friendly biotechnological application for metal recovery. In the present study, chemolithotrophic meso-acidophilic iron and sulphur oxidisers were evaluated for the first time towards simultaneous mutli-metal recovery from pyrite ash. XRD and XRF analysis indicated higher amount of Hematite (Fe 2 O 3 ) in the sample. ICP-OES analysis indicated concentrations of Cu>Zn>Co>As that were considered for bioleaching. Optimization studies indicated Cu - 95%, Co - 97%, Zn - 78% and As - 60% recovery within 8days at 10% pulp density, pH - 1.75, 10% (v/v) inoculum and 9g/L Fe 2+ . The productivity of the bioleaching system was found to be Cu - 1696ppm/d (12% dissolution/d), Co - 338ppm/d (12.2% dissolution/d), Zn k 576ppm/d (9.8% dissolution/d) and As - 75ppm/d (7.5% dissolution/d). Synergistic actions for Fe 2+ - S° oxidation by iron and sulphur oxidisers were identified as the key drivers for enhanced metal dissolution from pyrite ash sample. Copyright © 2016 Elsevier B.V. All rights reserved.
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Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.
Yapo, Cedric; Nair, Anu G; Clement, Lorna; Castro, Liliana R; Hellgren Kotaleski, Jeanette; Vincent, Pierre
2017-12-15
Brief dopamine events are critical actors of reward-mediated learning in the striatum; the intracellular cAMP-protein kinase A (PKA) response of striatal medium spiny neurons to such events was studied dynamically using a combination of biosensor imaging in mouse brain slices and in silico simulations. Both D1 and D2 medium spiny neurons can sense brief dopamine transients in the sub-micromolar range. While dopamine transients profoundly change cAMP levels in both types of medium spiny neurons, the PKA-dependent phosphorylation level remains unaffected in D2 neurons. At the level of PKA-dependent phosphorylation, D2 unresponsiveness depends on protein phosphatase-1 (PP1) inhibition by DARPP-32. Simulations suggest that D2 medium spiny neurons could detect transient dips in dopamine level. The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of the dopamine effect on intracellular signalling remains poorly understood. We used genetically encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation levels, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D 1 or D 2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy is much higher on D 2 than on D 1 receptors. However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate to a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of protein phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a 'tone-sensing' mode, allowing them to detect transient dips in basal dopamine. Overall, our results show that D2 MSNs may sense much more complex patterns of dopamine than previously thought. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.
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Greenhouse gas emissions from naturally ventilated freestall dairy barns
NASA Astrophysics Data System (ADS)
Joo, H. S.; Ndegwa, P. M.; Heber, A. J.; Ni, J.-Q.; Bogan, B. W.; Ramirez-Dorronsoro, J. C.; Cortus, E.
2015-02-01
Greenhouse gas (GHG) emissions from two naturally-ventilated dairy freestall barns measured for a total of 21 d, one week each in May, July, and September 2009, are presented in this article. The holding capacity of Barn 1 (B1) was 400 Holstein cows, while that for Barn 2 (B2) was 850 cows. Air samples were taken from inlets and outlets of the barns via a custom made multiplexer gas sampling system for measurement of gas concentrations using a photoacoustic infrared multigas analyzer. Barn ventilation rates were based on air velocity measured with arrays of 3-D ultrasonic anemometers at inlets and outlets. Gas concentrations (10 min means) in the barns ranged from: 443-789 ppm for CO2, 0.0-39.4 ppm for CH4, and 0.25-0.39 ppm for N2O; with mean concentrations ranging from 6 to 20%, 0 to 4%, and 26 to 180% above the average background concentrations for CO2, N2O, and CH4, respectively. The correlations between CO2 and CH4 enhanced concentrations were relatively stronger (R of 0.67-0.74) than between CO2 and N2O enhanced concentrations (R of 0.10-0.20). Environmental conditions did not significantly (p = 0.46) impact the enhanced concentrations of N2O in the barns. All three parameters (T, RH, and v) had significant (p < 0.01) influences on CO2 enhanced concentrations; while only T (p < 0.01) and v (p < 0.01) had significant influences on CH4 enhanced concentrations. Enhanced concentrations of CO2 and CH4 correlated negatively with all three parameters. The influence of the temperature-humidity index (THI) on CO2 enhanced concentrations was higher than that of v; while the effect v had on CH4 enhanced concentrations was slightly higher than that of the temperature-humidity index. The average emissions, based on hourly means, ranged from 5.3 to 10.7 kg d-1 AU-1 for CO2; 0.3 to 2.5 g d-1 AU-1 for N2O; and between 67 and 252 g d-1 AU-1 for CH4. Nitrous oxide emissions from the smaller barn, B1 (0.4-2.5 g d-1 AU-1), were significantly higher than from the larger barn, B2 (0.3-0.5 g d-1 AU-1) most probably because 50% of B1 was open (no stalls) loose dirt floor.
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NASA Astrophysics Data System (ADS)
Newcombe, M. E.; Beckett, J. R.; Baker, M. B.; Newman, S.; Guan, Y.; Eiler, J. M.; Stolper, E. M.
2016-12-01
We have conducted water diffusion experiments in synthetic Apollo 15 "yellow glass" (LG) and an iron-free basaltic analog melt (AD) at 1 atm and 1350 °C over a range of fO2 conditions from IW-2.2 to IW+6.7 and over a range of pH2/pH2O from nominally zero to 10. The water concentrations measured in our quenched experimental glasses by SIMS and FTIR vary from a few ppm to 430 ppm. Many studies of water diffusion at higher water concentrations indicate that the apparent diffusivity of total water (D*water; see [1]) in silicate melts is highly concentration dependent at water contents >0.1 wt% (e.g., [1]). However, water concentration gradients in each of our AD and LG experiments are well described by models in which D*water is assumed to be constant. Best-fit values of D*water obtained for our AD and LG experiments are consistent with a modified speciation model [2] in which both molecular water and hydroxyl are allowed to diffuse, and in which hydroxyl is the dominant diffusing species at the low total water concentrations of our experiments. Water concentration gradients generated during hydration and dehydration experiments conducted simultaneously propagate approximately equal distances into the melt and have the same concentration of water dissolved in the melt at the melt-vapor interface, suggesting that hydration and dehydration are symmetric under the conditions of our experiments. Best-fit values of D*water for our LG experiments vary within a factor of 2 over a range of pH2/pH2O from 0.007 to 9.7 (a range of ƒO2 from IW-2.2 to IW+4.9) and a water concentration range from 80 ppm to 280 ppm. The relative insensitivity of D*water to variations in pH2 suggests that loss of H during the degassing of the lunar melts described by [3] was not primarily by loss of dissolved H2. The value of D*water chosen by [3] for modeling diffusive degassing of lunar volcanic glasses is within a factor of three of our measured value in LG melt at 1350 °C. [1] Zhang et al. (1991) GCA 55, 441-456; [2] Ni et al. (2013) GCA 103, 36-48; [3] Saal et al. (2008) Nature 454, 192-195.
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Clinical Phenotype in a Toddler with a Novel Heterozygous Mutation of the Vitamin D Receptor.
Brar, Preneet Cheema; Dingle, Elena; Pappas, John; Raisingani, Manish
2017-01-01
We present the clinical phenotype of a toddler who presented with vitamin D-resistant rickets, with one of the highest initial levels of alkaline phosphatase and parathyroid hormone (PTH) levels reported in the literature. The toddler had novel compound heterozygous mutations in the ligand-binding site of the vitamin D receptor and had an excellent response to calcitriol (1,25(OH)2D).
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Zheng, Jie; Pritts, Wayne A; Zhang, Shuhong; Wittenberger, Steve
2009-12-05
Dimethyl sulfate (DMS) is an alkylating reagent commonly used in organic syntheses and pharmaceutical manufacturing processes. Due to its potential carcinogenicity, the level of DMS in the API process needs to be carefully monitored. However, in-process testing for DMS is challenging because of its reactivity and polarity as well as complex matrix effects. In this short communication, we report a GC-MS method for determination of DMS in an API intermediate that is a methyl sulfate salt. To overcome the complex matrix interference, DMS and an internal standard, d6-DMS, were extracted from the matrix with methyl tert-butyl ether. GC separation was conducted on a DB-624 column (30 m long, 0.32 mm ID, 1.8 microm film thickness). MS detection was performed on a single-quad Agilent MSD equipped with an electron impact source while the MSD signal was acquired in selected ion monitoring mode. This GC/MS method showed a linear response for DMS equivalent from 1.0 to 60 ppm. The practical quantitation limit for DMS was 1.0 ppm and the practical detection limit was 0.3 ppm. The relative standard derivation for analyte response was found as 0.1% for six injections of a working standard equivalent to 18.6 ppm of DMS. The spike recovery was ranged from 102.1 to 108.5% for a sample of API intermediate spiked with 8.0 ppm of DMS. In summary, the GC/MS method showed adequate specificity, linearity, sensitivity, repeatability and accuracy for determination of DMS in the API intermediate. This method has been successfully applied to study the efficiency of removing DMS from the process.
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Suh, Nanjoo; Reddy, Bandaru S.; DeCastro, Andrew; Paul, Shiby; Lee, Hong Jin; Smolarek, Amanda K.; So, Jae Young; Simi, Barbara; Wang, Chung Xiou; Janakiram, Naveena B.; Steele, Vernon; Rao, Chinthalapally V.
2011-01-01
Evidence supports the protective role of non-steroidal anti-inflammatory drugs (NSAIDs) and statins against colon cancer. Experiments were designed to evaluate the efficacies atorvastatin and NSAIDs administered individually and in combination against colon tumor formation. F344 rats were fed AIN-76A diet and colon tumors were induced with azoxymethane (AOM). One week after the second AOM-treatment groups of rats were fed diets containing atorvastatin (200 ppm), sulindac (100 ppm) or naproxen (150 ppm), or their combinations with low-dose atorvastatin (100 ppm) for 45 weeks. Administration of atorvastatin at 200 ppm significantly suppressed both adenocarcinoma incidence (52% reduction, p=0.005) and multiplicity (58% reduction, p=0.008). Most importantly, colon tumor multiplicities were profoundly decreased (80–85% reduction, p<0.0001) when given low-dose atorvastatin with either sulindac or naproxen. Also, a significant inhibition of colon tumor incidence was observed when given a low-dose atorvastatin with either sulindac (p=0.001) or naproxen (p =0.0005). Proliferation markers, proliferating cell nuclear antigen, cyclin D1 and β-catenin in tumors of rats exposed to sulindac, naproxen, atorvastatin, and/or combinations showed a significant suppression. Importantly, colon adenocarcinomas from atorvastatin and NSAIDs fed animals showed reduced key inflammatory markers, inducible nitric oxide synthase and cyclooxygenase-2, phospho-p65, as well as inflammatory cytokines, TNF-α, IL-1β, and IL-4. Overall, this is the first report on the combination treatment using low-dose atorvastatin with either low dose sulindac or naproxen, which greatly suppress the colon adenocarcinoma incidence and multiplicity. Our results suggest that low-dose atorvastatin with sulindac or naproxen might potentially be useful combinations for colon cancer prevention in humans. PMID:21764859
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Phosphate Solubilization Potential and Phosphatase Activity Of Rhizospheric Trichoderma Spp.
Anil, Kapri; Lakshmi, Tewari
2010-01-01
Trichoderma sp., a well known biological control agent against several phytopathogens, was tested for its phosphate (P) solubilizing potential. Fourteen strains of Trichoderma sp. were isolated from the forest tree rhizospheres of pinus, deodar, bamboo, guava and oak on Trichoderma selective medium. The isolates were tested for their in-vitro P-solubilizing potential using National Botanical Research Institute Phosphate (NBRIP) broth containing tricalcium phosphate (TCP) as the sole P source, and compared with a standard culture of T. harzianum. All the cultures were found to solubilize TCP but with varying potential. The isolate DRT-1 showed maximum amount of soluble phosphate (404.07 εg.ml-1), followed by the standard culture of T. harzianum (386.42 εg.ml-1) after 96 h of incubation at 30±10C. Extra-cellular acid and alkaline phosphatases of the fungus were induced only in the presence of insoluble phosphorus source (TCP). High extra-cellular alkaline phosphatase activity was recorded for the isolate DRT-1 (14.50 U.ml-1) followed by the standard culture (13.41 U.ml-1) at 72h. The cultures showed much lesser acid phosphatase activities. Under glasshouse conditions, Trichoderma sp. inoculation increased chickpea (Cicer arietinum) growth parameters including shoot length, root length, fresh and dry weight of shoot as well as roots, in P-deficient soil containing only bound phosphate (TCP). Shoot weight was increased by 23% and 33% by inoculation with the isolate DRT-1 in the soil amended with 100 and 200 mg TCP kg-1 soil, respectively, after 60 d of sowing. The study explores high P-solubilizing potential of Trichoderma sp., which can be exploited for the solubilization of fixed phosphates present in the soil, thereby enhancing soil fertility and plant growth. PMID:24031556
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Calibration of equipment for analysis of drinking water fluoride: a comparison study.
Quock, Ryan L; Chan, Jarvis T
2012-03-01
Current American Dental Association evidence-based recommendations for prescription of dietary fluoride supplements are based in part on the fluoride concentration of a pediatric patient's drinking water. With these recommendations in mind, this study compared the relative accuracy of fluoride concentration analysis when a common apparatus is calibrated with different combinations of standard values. Fluoride solutions in increments of 0.1 ppm, from a range of 0.1 to 1.0 ppm fluoride, as well as 2.0 and 4.0 ppm, were gravimetrically prepared and fluoride concentration measured in pentad, using a fluoride ion-specific electrode and millivolt meter. Fluoride concentrations of these solutions were recorded after calibration with the following 3 different combinations of standard fluoride solutions: 0.1 ppm and 0.5 ppm, 0.1 ppm and 1.0 ppm, 0.5 ppm and 1.0 ppm. Statistical analysis showed significant differences in the fluoride content of water samples obtained with different two-standard fluoride solutions. Among the two-standard fluoride solutions tested, using 0.5 ppm and 1.0 ppm as two-standard fluoride solutions provided the most accurate fluoride measurement of water samples containing fluoride in the range of 0.1 ppm to 4.0 ppm. This information should be valuable to dental clinics or laboratories in fluoride analysis of drinking water samples.
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Sacristán-Reviriego, Almudena; Madrid, Marisa; Cansado, José; Martín, Humberto; Molina, María
2014-01-01
Dual-specificity MAPK phosphatases (MKPs) are essential for the negative regulation of MAPK pathways. Similar to other MAPK-interacting proteins, most MKPs bind MAPKs through specific docking domains known as D-motifs. However, we found that the Saccharomyces cerevisiae MKP Msg5 binds the MAPK Slt2 within the cell wall integrity (CWI) pathway through a distinct motif (IYT). Here, we demonstrate that the IYT motif mediates binding of the Msg5 paralogue Sdp1 to Slt2 as well as of the MKP Pmp1 to its CWI MAPK counterpart Pmk1 in the evolutionarily distant yeast Schizosaccharomyces pombe. As a consequence, removal of the IYT site in Msg5, Sdp1 and Pmp1 reduces MAPK trapping caused by the overexpression of catalytically inactive versions of these phosphatases. Accordingly, an intact IYT site is necessary for inactive Sdp1 to prevent nuclear accumulation of Slt2. We also show that both Ile and Tyr but not Thr are essential for the functionality of the IYT motif. These results provide mechanistic insight into MKP-MAPK interplay and stress the relevance of this conserved non-canonical docking site in the regulation of the CWI pathway in fungi. PMID:24465549
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Andersen, Melvin E; Cruzan, George; Black, Michael B; Pendse, Salil N; Dodd, Darol; Bus, James S; Sarang, Satinder S; Banton, Marcy I; Waites, Robbie; McMullen, Patrick D
2017-11-15
Styrene increased lung tumors in mice at chronic inhalation exposures of 20ppm and greater. MIEs, KEs and MFs were examined using gene expression in three strains of male mice (the parental C57BL/6 strain, a CYP2F2(-/-) knock out and a CYP2F2(-/-) transgenic containing human CYP2F1, 2A13 and 2B6). Exposures were for 1-day and 1, 4 and 26weeks. After 1-day exposures at 1, 5, 10, 20, 40 and 120ppm significant increases in differentially expressed genes (DEGs) occurred only in parental strain lungs where there was already an increase in DEGs at 5ppm and then many thousands of DEGs by 120ppm. Enrichment for 1-day and 1-week exposures included cell cycle, mitotic M-M/G1 phases, DNA-synthesis and metabolism of lipids and lipoproteins pathways. The numbers of DEGs decreased steadily over time with no DEGs meeting both statistical significance and fold-change criteria at 26weeks. At 4 and 26weeks, some key transcription factors (TFs) - Nr1d1, Nr1d2, Dbp, Tef, Hlf, Per3, Per2 and Bhlhe40 - were upregulated (|FC|>1.5), while others - Npas, Arntl, Nfil3, Nr4a1, Nr4a2, and Nr4a3 - were down-regulated. At all times, consistent changes in gene expression only occurred in the parental strain. Our results support a MIE for styrene of direct mitogenicity from mouse-specific CYP2F2-mediated metabolites activating Nr4a signaling. Longer-term MFs include down-regulation of Nr4a genes and shifts in both circadian clock TFs and other TFs, linking circadian clock to cellular metabolism. We found no gene expression changes indicative of cytotoxicity or activation of p53-mediated DNA-damage pathways. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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[Limonoids in Phellodendron amurense (Kihada)].
Miyake, M; Inaba, N; Ayano, S; Ozaki, Y; Maeda, H; Ifuku, Y; Hasegawa, S
1992-05-01
Limonoids and their glucosides in the seeds and barks of Phellondendron amurense (Kihada) were analyzed. The seeds contained limonin (1950 ppm), obakunone (20 ppm), limonin 17-beta-D-glucopyranoside (820 ppm) and obakunone 17-beta-D-glucopyranoside (1360 ppm). The barks contained limonin (6760 ppm), obakunone (1240 ppm) and nomilin (270 ppm).
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Fink, Howard A.; Litwack-Harrison, Stephanie; Taylor, Brent C.; Bauer, Douglas C.; Orwoll, Eric S.; Lee, Christine G.; Barrett-Connor, Elizabeth; Schousboe, John T.; Kado, Deborah M.; Garimella, Pranav S.; Ensrud, Kristine E.
2016-01-01
Purpose To evaluate the utility of recommended laboratory testing to identify secondary causes in older men with osteoporosis, we examined prevalence of laboratory abnormalities in older men with and without osteoporosis. Methods 1572 men aged ≥65 years in the Osteoporotic Fractures in Men study completed bone mineral density (BMD) testing and a battery of laboratory measures, including serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), 25-OH vitamin D, total testosterone, spot urine calcium/creatinine ratio, spot urine albumin-creatinine ratio, creatinine-derived estimate glomerular filtration rate, 24-hour urine calcium, and 24-hour urine free cortisol. Using cross-sectional analyses, we calculated prevalence ratios (PR) and 95% confidence intervals (CI) for the association of any and specific laboratory abnormalities with osteoporosis, and the number of men with osteoporosis needed to test to identify one additional laboratory abnormality compared to testing men without osteoporosis. Results Approximately 60% of men had ≥1 laboratory abnormality in both men with and without osteoporosis. Among individual tests, only vitamin D insufficiency (PR, 1.13; 95% CI, 1.05–1.22) and high alkaline phosphatase (PR, 3.05; 95% CI, 1.52–6.11) were more likely in men with osteoporosis. Hypercortisolism and hyperthyroidism were uncommon and not significantly more frequent in men with osteoporosis. No osteoporotic men had hypercalciuria. Conclusions Though most of these older men had ≥1 laboratory abnormality, few routinely recommended individual tests were more common in men with osteoporosis than in those without osteoporosis. Possibly excepting vitamin D and alkaline phosphatase, benefit of routine laboratory testing to identify possible secondary causes in older osteoporotic men appears low. Results may not be generalizable to younger men or to older men in whom history and exam findings raise clinical suspicion for a secondary cause of osteoporosis. PMID:26458388
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NASA Astrophysics Data System (ADS)
Parkinson, Chris; Yung, Yuk; Esposito, Larry; Gao, Peter; Bougher, Steve
2014-11-01
We use the JPL/Caltech 1-D KINETICS photochemical model to solve the continuity diffusion equation for the atmospheric constituent abundances and total number density as a function of radial distance from the planet Venus. The photochemistry of the Venus atmosphere from 58 to 112 km is modeled using an updated and expanded chemical scheme (Zhang et al., 2010; 2012), guided by the results of recent observations. We mainly follow Zhang et al. (2010; 2012) to guide our choice of boundary conditions for 40 species. We fit the SOIR Venus Express results of 1 ppm at 70-90 km (Bertaux et al (2007) by modeling water from between 10 - 35 ppm at our 58 km lower boundary and using an SO2 mixing ratio of 25 ppm as our nominal reference value. We then vary the SO2 mixing ratio at the lower boundary between 5 and 75 ppm and find that it can control the water distribution at higher altitudes.
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De-contamination of pesticide residues in food by ionizing radiation
NASA Astrophysics Data System (ADS)
Basfar, Ahmed A.; Mohamed, Khaled A.; Al-Saqer, Omar A.
2012-04-01
The role of gamma irradiation on removal of pesticides in aqueous solutions or in vegetables and fruits was investigated. Radiation - induced decontamination of pesticides is generally greater in aqueous solutions than in selected vegetables and fruits. Residues of malathion (0.5 ppm in potatoes, 8 ppm in onions and dates), pirimiphos-methyl (1 ppm in onions and grapes) and cypermethrin (0.05 ppm in potatoes and 0.1 ppm in onions) were not reduced to below maximum residue limits (MRLs) for irradiation doses up to 1 kGy. The same trend was observed when irradiation was performed for grapes fortified with malathion (8 ppm) and cypermethrin (2 ppm) for absorbed doses up to 2 kGy. Ionizing radiation reduced the residues of pirimiphos-methyl (0.05 ppm in potatoes at1 kGy, 1 ppm in grapes at 2 kGy and 0.1 ppm in dates at1 kGy), malathion (8 ppm in grapes at 7 kGy) and cypermethrin (2 ppm in grapes at 7 kGy) to below maximum residue limits (MRLs).
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Extracellular matrices for gastrointestinal surgery: Ex vivo testing and current applications
Hoeppner, Jens; Marjanovic, Goran; Helwig, Peter; Hopt, Ulrich Theodor; Keck, Tobias
2010-01-01
AIM: To assess the effects of bile and pancreatic juice on structural and mechanical resistance of extracellular matrices (ECMs) in vitro. METHODS: Small-intestinal submucosa (SIS), porcine dermal matrix (PDM), porcine pericardial matrix (PPM) and bovine pericardial matrix (BPM) were incubated in human bile and pancreatic juice in vitro. ECMs were examined by macroscopic observation, scanning electron microscopy (SEM) and testing of mechanical resistance. RESULTS: PDM dissolved within 4 d after exposure to bile or pancreatic juice. SIS, PPM and PDM retained their integrity for > 60 d when incubated in either digestive juice. The effect of bile was found to be far more detrimental to mechanical stability than pancreatic juice in all tested materials. In SIS, the loss of mechanical stability after incubation in either of the digestive secretions was less distinct than in PPM and BPM [mFmax 4.01/14.27 N (SIS) vs 2.08/5.23 N (PPM) vs 1.48/7.89 N (BPM)]. In SIS, the extent of structural damage revealed by SEM was more evident in bile than in pancreatic juice. In PPM and BPM, structural damage was comparable in both media. CONCLUSION: PDM is less suitable for support of gastrointestinal healing. Besides SIS, PPM and BPM should also be evaluated experimentally for gastrointestinal indications. PMID:20731016
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New Discoveries of Trr and Radiopactive Elements of Phosphogypsum from Romania
NASA Astrophysics Data System (ADS)
Maruta Iancu, Aurora; Georgeta Dumitras, Delia; Marincea, Stefan
2014-05-01
Phosphogypsum is a technogenic product remaining after the extraction of phosphoric acid from raw phosphate, mainly apatite. Some radioactive elements presented in the phosphate original rock, consisting in apatit, are Ra-226, th-232, U-238, Pb-210, Po-240, K-210, that can be also found in the phosphogypsum. Determination of elements has been carried out on phosphogypsum samples from Turnu Magurele (TR), Valea Calugareasca (VC), Navodari (N) and Bacau (B). The most important minor elements of phosphogypsum are Th and U. The radioactivity of isotopes from Bacau samples of phosphogypsum is: U-238 exceeding (ppm) - 40,50; 31,96; 17,49; 30,00; 31,00 and Th-232 (ppm) - 8,07; 6,07; 6,41; 7,80; 6,41. The radiometric analyzes confirmed that Bacau county phosphogypsum have higher concentrations of U, while the content in Th is lower. The radioactivity of isotopes from samples of Navodari phosphogypsum is U-238 (ppm) - 37,00; 40,97; 10,84; 25,72 and Th-232 (ppm) - 6,82; 7,04; 6,19; 7,55. The radioactivity of isotopes from Turnu Magurele phosphogypsum samples is: U-232 (ppm) - 1,51; 21,92; 28,71; 6,92, 10,79, 11,00, and Th 232 (ppm) - 3,87; 7,29; 10,65; 6,22; 6,77; 5,45. The radiaoactivity of isotopes from Valea Calugareasca samples of phosphogypsum is: U-238 (ppm) - 17,60; 22,35; 17,93; 18,78 and Th-232 (ppm) - 5,98; 7,12; 7,85; 8,07. As in the case of the phosphogypsum analyzed in Bacau, as well as in the zones TM, VC and N, the radiometric analyzes results indicate a high content of U-232 and lower in Th-232. In conclusion, based on the analyzes carried out on samples of phosphogypsum from the four areas, and the higher U and lower Th contents, it follows that we are dealing with phosphogypsum thet results from a sedimentary type rock. Inductively coupled plasma - atomic emission spectrometry (ICP-AES) analyses performed on selected samples of phosphogypsum from the four deposits showed that the contents in the main REE (cerium, erbium, neodymium, thorium, ytterbium) are specific for the phosphogypsum issued from the processing of sedimentary raw phosphates. The results are: Turnu Magurele - Ce (ppm) - (29,1-663,1); Er (ppm) - (0,9-11,7); La (ppm) - (22,7-469,0); Nd (ppm) - (21,1-260-5); Th (ppm) - (0,3-20,8); Yb (ppm) - (1,1-6,8). Valea Calugareasca - Ce (ppm) - (30,2-454,2; Er (ppm) - (0,8-7,3); La (ppm) - (35,7-322,5); Nd (ppm) - (22,3-188,2); Th (ppm) - (0,0-12,8); Yb (ppm) - (1,6-5,0). Navodari - Ce (ppm) - (3,9-165,0); Er (ppm) - (1,8-7,7); La (ppm) - (14,5-135,6); Nd (ppm) - (3,8-90,6); Th (ppm) - (0,8-6,5); Yb (ppm) - (1,8-6,1). Bacau - Ce (ppm) - (19,3-174,8); Er (ppm) - 13,1-18,8); La (ppm) - (36,2-134,2); Nd (ppm) - (24,5-104,5); Th (ppm) (1,7-5,2); Yb (ppm) - (1,9-6,6).
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Horizontal Transfer of Spinosad in Coptotermes formosanus (Isoptera: Rhinotermitidae).
Bhatta, D; Henderson, G
2016-08-01
Slow-acting and nonrepellent termiticides are possible candidates for nestmate to nestmate transfer called horizontal transfer. For the horizontal transfer study of spinosad, Coptotermes formosanus Shiraki was released in sand and soil at 1, 25, and 50 ppm Entrust(®) for 1 h and then mixed with healthy untreated termites for 21 d at the ratio of 1:1. Donor and recipient termites began to contact and groom each other immediately after release. Mortality of termites was recorded at 1, 3, 7, and 14 d after treatment. Spinosad was more effectively transferred in sand than in soil. In sand at 25 and 50 ppm, significantly high mortality of donors and recipients was observed after 7 d. When termites were exposed to treated soil at day 21, all three concentrations resulted in significantly higher mortality compared to the control. In our laboratory study, spinosad was effectively transferred by donor termites. Transfer of spinosad depended on its bioavailability and concentration. Further study is needed to address its effects against C. formosanus under field conditions. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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NASA Astrophysics Data System (ADS)
Bruna, Pablo J.; Grein, Friedrich
The ESR parameters of the cations Be 2 + , Mg 2 + , Ca 2 + , BeMg + , BeCa + , MgCa + and the mixed radicals ZBe, ZMg, ZCa (Z = Li, Na, K), all having a X 2 Σu + (1 σg 2 1 σu )/X 2 Sigma + (1 σ2 2 σ) ground state, have been studied theoretically. The A iso and A dip constants have been calculated with UHF, CISD, MP2, B3LYP, PW91PW91 wavefunctions, and 6-311+G(2df) basis sets. The electron spin g factors (magnetic moment μs) have been evaluated from correlated (MRDCI) wavefunctions, using a Hamiltonian based on Breit-Pauli theory with perturbation expansions up to second order, and 6-311+ G(2d) basis sets. As expected for s-rich radicals, the hyperfine spectra are governed by the A iso terms. Both Δg|| and Δg Υ̂values are negative, but Δg|| lies close to zero. For Δg Υ̂, the coupling with 1 2 Π(u) dominates the sum-over-states expansions. Although the singly occupied MOs (SOMO) are mostly of s character, the | Δg Υ̂| are relatively large, up to 5200 ppm for cationic, and up to 7850 ppm for neutral radicals. These large values are caused by low excitation energies and high magnetic transition moments, the latter due to the fact that the σ*( s - s ) SOMO has the same nodal properties as a p σorbital. Of the radicals considered here, an ESR spectrum is available only for Mg2+. Our theoretical A iso of-287 MHz reproduces well the matrix result (-291 MHz). Calculated values of-10 ppm for Deltag|| and of-1280 ppm for Deltag Υ̂give an average < Δg> =-860 ppm that lies within the experimental range of-600( ±300) ppm in Ne, and of-1300( ±500) ppm in Ar matrices.
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Rampy, L. W.; Quast, J. F.; Humiston, C. G.; Balmer, M. F.; Schwetz, B. A.
1977-01-01
Male and female Sprague-Dawley rats were exposed to vinylidene chloride (VDC) orally or by inhalation in 2-year toxicological studies. Interim results are included in this report. VDC was given in the drinking water at mean ± S.D. concentrations of 0, 68 ± 13, 106 ± 22, and 220 ± 35 ppm which produced mean ± S.D. dosage levels of 0, 5.9 ± 0.6, 10.0 ± 1.2, and 19.3 ± 2.7 mg/kg for male rats and 0, 7.5 ± 0.4, 12.6 ± 1.1, and 25.6 ± 2.4 mg/kg for female rats. Forty-eight rats/sex/VDC level and 80 rats/sex in the control group were used in the 2-year study with an interim kill of an additional 10 rats/sex/level at 90 days. In the inhalation study, rats were exposed to 0, 10, or 40 ppm of VDC vapor 6 hr/day, 5 days/week for 5 weeks, after which the exposure levels were changed to 0, 25, and 75 ppm of VDC. Exposure continued for a total of 18 months and the rats held for observation an additional 6 months. Interim kills occurred at 1, 6 and 12 months. A separate 90-day study using 20 rats/sex/level was conducted at 0, 25, and 75 ppm of VDC vapor. There were 86 rats/sex/level in the 2-year portion of the study. The parameters monitored were: body weight, food and water consumption (drinking water study only), hematology, clinical chemistries, cytogentics of bone marrow cells (inhalation study only), mortality, terminal organ weights, and gross and histopathology. Based on interim kills and gross pathologic observations, the main conclusions are: increased cytoplasmic vacuolation of hepatocytes was seen in the livers of rats given 200 ppm VDC in drinking water or 25 or 75 ppm VDC vapor by inhalation; based on gross tumor count, tumor incidence in VDC-exposed rats was not greater than controls. PMID:612457
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Mechanisms of Stratospheric Ozone Transport.
1982-12-03
amounts orcur too fat south and about 1 month too late. 92 CHANGE IN (740) (PPM) DIABATIC. cos ( LAT ) 70 50 ~40 (D 30_ _ _ _ _ ) 1 5 Ŗ 2.5 Z. 20 10 0 D...AD-A122 609 MECHANISMS OF STRATOSPHERIC OZONE BRANSPOR(U) NAVAL RESEARCH LAB WASHINGTON DC R B ROOD ET AL 03 DEC 82 UNCLASSIFIED F/G 4/ 1 ...NLIEIIIIEIIII EIIIIIIIIIIIIl IIIEIIIIIEEEEE IIIIIIIIIIIIIl EIIIIIIIIIIIIl EIIIIIIIIIIIIl 1111.0 112 M *0 MIt ROCLt RLS’OLU7ION TLST CHART - - - ,T 1 m -N ;’ V
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Kurnatowska, A; Białasiewicz, D
2001-01-01
Hydrolase activity of (enzymograms, biotypes) in Geotrichum candidum, one of the poorly described pathogenic fungi, was studied 81 strains were isolated from oral cavity and faeces of patients with gastrointestinal tract disorders. Axenic strains were differentiated with API 20C Aux and API ZYM tests. Then, enzymograms and biotypes were determined for all strains based on the activity of 19 hydrolases. High variability of enzymograms (17 different types) was found. The highest activity was noted in case of: e2 - alkaline phosphatase, e6 - leucine arylamidase, e11 - acid phosphatase. E5 - lipase, e7 - valine arylamidase, e12 - naphtol-AS-BI-phosphohydrolase and e17 - beta-glucosidase were used for biotyping procedures. Our own system of biotyping of 81 strains of G. candidum was based on the mathematical binominal distribution formula (1 : 4 : 6 : 4 : 1) - all "+"; one "-", three "+"; two "two "+"; three "-", one "+"; all "-". We have found: A (11.1 +/- 3.5%), BI (6.17 +/- 2.67%), B2 (1.23 +/- 1.22%), B4 (4.94 +/- 2.41%), C, (1.23 +/-1.22%), C3 (63.0 +/- 5.4%), D2 (9.88 +/-3.31%), D3 (2.47 +/- 1.72%). Among all strains from 8 various biotypes of G. candidum.
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Umano, K; Hagi, Y; Nakahara, K; Shoji, A; Shibamoto, T
2000-08-01
Extracts from leaves of Japanese mugwort (Artemisia princeps Pamp.) were obtained using two methods: steam distillation under reduced pressure followed by dichloromethane extraction (DRP) and simultaneous purging and extraction (SPSE). A total of 192 volatile chemicals were identified in the extracts obtained by both methods using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). They included 47 monoterpenoids (oxygenated monoterpenes), 26 aromatic compounds, 19 aliphatic esters, 18 aliphatic alcohols, 17 monoterpenes (hydrocarbon monoterpenes), 17 sesquiterpenes (hydrocarbon sesquiterpenes), 13 sesquiterpenoids (oxygenated sesquiterpenes), 12 aliphatic aldehydes, 8 aliphatic hydrocarbons, 7 aliphatic ketones, and 9 miscellaneous compounds. The major volatile constituents of the extract by DRP were borneol (10.27 ppm), alpha-thujone (3.49 ppm), artemisia alcohol (2.17 ppm), verbenone (1.85 ppm), yomogi alcohol (1.50 ppm), and germacren-4-ol (1.43 ppm). The major volatile constituents of the extract by SPSE were 1,8-cineole (8.12 ppm), artemisia acetate (4.22 ppm), alpha-thujone (3.20 ppm), beta-caryophyllene (2.39 ppm), bornyl acetate (2.05 ppm), borneol (1.80 ppm), and trans-beta-farnesene (1. 78 ppm).
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Toxicity of abate® 4E (temephos) in mallard ducklings and the influence of cold
Fleming, W.J.; Heinz, G.H.; Franson, J.C.; Rattner, B.A.
1985-01-01
Diets mixed to contain 0, 0.1, 1.0, 10 and 100 ppm temephos (determined chemically to contain less than 0.5, less than 0.5, 0.89, 6.0 and 59 ppm temephos, respectively) in an Abate® 4E formulation, were fed to mallard (Anas platyrhynchos) ducklings for 7 d. During this period, half of the ducklings in each dietary treatment group were housed in a heated brooder (39 to 41 °C) and half were housed in an unheated brooder (10 to 18°C). Mortality in all dietary groups in the unheated brooder was higher than in the heated brooder. High temephos-related mortality occurred in the 100 ppm group in the unheated brooder but not in any other diet-temperature groups. Ingestion of the 100 ppm temephos diet inhibited plasma Cholinesterase (ChE) activity and elevated plasma corticosterone concentration and creatine phosphokinase activity, but other selected plasma chemistries were not affected in a dose-related manner. Brain ChE activity was depressed only in the 100 ppm dietary groups; maximum inhibition of brain ChE activity was 48%. These findings suggest that diets containing up to 10 ppm temephos do not directly affect duckling survival during the first week of life and that the toxicity of 100 ppm temephos is markedly enhanced by cold.
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Methylmercury level in umbilical cords from patients with congenital Minamata disease.
Harada, M; Akagi, H; Tsuda, T; Kizaki, T; Ohno, H
1999-08-30
A total of 151 umbilical cords during the period from 1950 to 1969 were collected from the residents of the Minamata area (including 25 patients with congenital Minamata disease) for methylmercury (MeHg) analysis. When the MeHg discharge from the Chisso Company's Minamata factory into the Minamata Bay is compared with the incidence of congenital Minamata disease, the abrupt increase of the former in 1952 [Nishimura H. Chem. Today 1998;323:60-66] was found to precede that of the latter by approximately 2 years, thereby indicating that MeHg is the cause of the disaster. This was confirmed by the elevated levels of MeHg in the umbilical cords from residents of the Minamata area [from 0.35 +/- 0.30 (S.D.) ppm in 1952 to 0.96 +/- 0.75 ppm in 1955], the MeHg levels (1.60 +/- 1.00 ppm) in the cords from patients with congenital Minamata disease showing the highest values [P < 0.01 vs. acquired Minamata disease (0.72 +/- 0.65 ppm), mental retardation (0.74 +/- 0.64 ppm), other diseases (0.22 +/- 0.15 ppm), and no symptoms (0.28 +/- 0.20 ppm), respectively]. Thus, in order to fill a gap, which extends over a long period of time, in studies on environmental Hg pollution, umbilical cord samples were considered to be a useful tool.
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VERA Core Simulator Methodology for PWR Cycle Depletion
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kochunas, Brendan; Collins, Benjamin S; Jabaay, Daniel
2015-01-01
This paper describes the methodology developed and implemented in MPACT for performing high-fidelity pressurized water reactor (PWR) multi-cycle core physics calculations. MPACT is being developed primarily for application within the Consortium for the Advanced Simulation of Light Water Reactors (CASL) as one of the main components of the VERA Core Simulator, the others being COBRA-TF and ORIGEN. The methods summarized in this paper include a methodology for performing resonance self-shielding and computing macroscopic cross sections, 2-D/1-D transport, nuclide depletion, thermal-hydraulic feedback, and other supporting methods. These methods represent a minimal set needed to simulate high-fidelity models of a realistic nuclearmore » reactor. Results demonstrating this are presented from the simulation of a realistic model of the first cycle of Watts Bar Unit 1. The simulation, which approximates the cycle operation, is observed to be within 50 ppm boron (ppmB) reactivity for all simulated points in the cycle and approximately 15 ppmB for a consistent statepoint. The verification and validation of the PWR cycle depletion capability in MPACT is the focus of two companion papers.« less
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2012-07-27
induce MyD88- mediated signaling [15,16]. Seeking to improve the efficacy of Compound 1 as an inhibitor of MyD88 signaling, we synthesized a dimeric...molecule in which two Compound 1 moieties were covalently linked together, reasoning that the dimeric compound would be a more potent inhibitor of protein...pellets in 50 ml of lysis buffer (Active Motif) in the presence of DTT, protease inhibitors and phosphatase inhibitors and incubated on ice for 30–60
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A functional genomic analysis of Arabidopsis thaliana PP2C clade D
USDA-ARS?s Scientific Manuscript database
In the reference dicot plant Arabidopsis thaliana, the PP2C family of P-protein phosphatases includes the products of 80 genes that have been separated into 10 multi-protein clades plus six singletons. Clade D includes the products of nine genes distributed among 3 chromosomes (PPD1, At3g12620; PPD2...
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Hanna, G M; Lau-Cam, C A
1996-01-01
A simple, accurate, and specific 1H NMR spectroscopic method was developed for the assay of diatrizoate meglumine or the combination diatrizoate meglumine and diatrizoate sodium in commercial solutions for injection. A mixture of injectable solution and sodium acetate, the internal standard, was diluted with D2O and the 1H NMR spectrum of the solution was obtained. Two approaches were used to calculate the drug content, based on the integral values for the -N-CO-CH3 protons of diatrizoic acid at 2.23 ppm, and -N-CH3 protons of meglumine at 2.73 ppm, and the CH3-CO-protons of sodium acetate at 1.9 ppm. Recoveries (mean +/- standard deviation) of diatrizoic acid and meglumine from 10 synthetic mixtures of various amounts of these compounds with a fixed amount of internal standard were 100.3 +/- 0.55% and 100.1 +/- 0.98%, respectively. In addition to providing a direct means of simultaneously assaying diatrizoic acid and meglumine, the proposed NMR method can also be used to identify diatrizoate meglumine and each of its molecular components.
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Spectroscopic characterization of natural calcite minerals.
Gunasekaran, S; Anbalagan, G
2007-11-01
The FT-IR, FT-Raman, NMR spectral data of ten different limestone samples have been compared. FT-IR and FT-Raman spectral data show that calcium carbonate in limestone, principally in the form of calcite, as identified by its main absorption bands at 1426, 1092, 876 and 712 cm(-1). The sharp diffractions at the d-spacings, 3.0348, 1.9166 and 1.8796 confirm the presence of calcite structure and the calculated lattice parameters are: a=4.9781 A, c=17.1188 A. The range of 13C chemical shifts for different limestone samples is very small, varying from 198.38 to 198.42 ppm. The observed chemical shifts are consistent with the identical C-O bonding in different limestone samples. 27Al MAS NMR spectra of the samples exhibit a central line at 1 ppm and another line at 60 ppm corresponding to octahedral and tetrahedral Al ions, respectively. The five component resonances were observed in 29Si MAS NMR spectrum of limestone and these resonances were assigned to Si (4 Al), Si (3 Al), Si (2 Al), Si (1 Al) and Si (0 Al) from low field to high field.
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Braga, V; Dorizzi, R; Brocco, G; Rossini, M; Zamberlan, N; Gatti, D; Adami, S
1995-07-01
Bone alkaline phosphatase was evaluated by wheat-germ lectin precipitation in several clinical conditions. The study included 33 premenopausal healthy women, 46 postmenopausal apparently healthy women, 19 growing children, 24 patients with Paget's disease, 31 patients with primary hyperparathyroidism and 66 patients with hepatobiliary diseases. In postmenopausal women the mean T score (i.e.: the number of SD below or above the mean for premenopausal women) was 2.6 +/- 1.3 (SD) for bone alkaline phosphatase and 1.61 +/- 1.21 for total alkaline phosphatase (p < 0.001). The T score for bone alkaline phosphatase provided a better discrimination from normals for both Paget's disease (22.1 +/- 27.8 versus 12.8 +/- 16 p < 0.001) and primary hyperparathyroidism (8.2 +/- 4.3 versus 4.6 +/- 3.7 p < 0.005 for bone alkaline phosphatase and total alkaline phosphatase respectively). After treatment with intravenous bisphosphonate the percent decrease of bone alkaline phosphatase was larger than that of total alkaline phosphatase both in patients with Paget's disease (-46% versus -72% p < 0.01) and in patients with primary hyperparathyroidism (-21% versus -47% p < 0.02) and an estimate of the precision (delta mean/SD of the delta mean) for bone alkaline phosphatase was 1.9-3.7 times higher than that of total alkaline phosphatase. In twelve osteoporotic patients treated for six months with oral alendronate the decrease in bone turnover was detected with significantly higher precision with bone alkaline phosphatase than with total alkaline phosphatase (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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NASA Astrophysics Data System (ADS)
Rosenthal, A.; Hauri, E. H.; Hirschmann, M. M.; Davis, F. A.; Withers, A. C.; Fogel, M. L.
2012-12-01
Inventories of C in the mantle and magmatic fluxes of C between the mantle and the Earth's outer envelopes are poorly constrained in part owing to challenges in determining undegassed C concentrations of pristine basalts. Saal et al. [1] proposed that the behavior of Nb could be used as a proxy for C, owing to apparently similar behavior of the two elements in Siqueiros Transform MORB, but higher C/Nb ratios in popping rocks [2] call into question the applicability of the C/Nb proxy. Here, we present experimentally determined carbon partition coefficients (D's) between nominally volatile-free mantle minerals (olivine, OL; orthopyroxene, OPX; clinopyroxene, CPX; garnet, GA) and melts at 0.8-3 GPa, and 1250-1500°C. We conducted piston-cylinder experiments using an olivine-tholeiite + 4 wt% CO2, doped with Nb, Rb, U, Th, and 13C to enhance detection limits. To promote growth of crystals big enough for SIMS analyses, experiments were either long (<6 days), or at an initial higher temperature (T) before cooling slowly to a target T. We also produced SIMS calibration glass standards with varying amounts of C, and subject to ongoing analyses. We analyzed carbon (12C, 13C), H, F, and trace elements (Nb, Rb, Ba, U, Th, K) of both mineral phases and quenched liquids in subsets of experimental runs (21 in graphite-lined Pt-capsules, 6 in Fe-doped Pt-lined capsules) using both Cameca IMS 6F and NanoSIMS instruments. D's measured for 12C and 13C are close to 5x10-4, in most cases D13C>D12C, but a few have the opposite. Continuous exchange of the liquid (initially rich in 13C) with the graphite capsules (rich in 12C) may yield D's with 13C>12C. D's with 12C>13C are likely owing to either low count rates or comparatively high analytical contamination. Concentrations in minerals vary from 0.20-3.46 ppm for C, 25-176 ppm for H2O, and 0.05-1.21 ppm for F, whereas liquids tend to much higher values (C≤0.9 wt%; H2O≤1.5 wt%; F≤34 ppm; P≤0.25 wt%; S≤43 ppm; Cl≤77 ppm). Resulting D's indicate that C is highly incompatible in all major mantle mineral phases, with D's for OL, OPX and CPX of close to 5x10-4, and for GA ~2.2x10-4. D's for H2O (2x10-4 to ~3x10-2) and F (~2.3x10-3 to ~5.8x10-2) are comparable to those found in previous studies. Trace element partition determinations are in progress, but comparison to previous studies indicates that carbon is significantly more incompatible during mantle melting than Nb, U, or Th, and has behavior approximately similar to Ba. We therefore suggest that undegassed C/Ba ratios may be useful indicators of C fluxes and concentrations in basalt source regions where very low degrees of melting might fractionate C/Nb ratios. [1] Saal, A, Hauri, EH, Langmuir, CH, Perfit, M (2002) Nature 419, 451-455. [2] Cartigny, P, Pineau, F, Aubaud, C, Javoy, M (2008) Earth Planet Sci Lett 265, 672-685.
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Parvari, R; Lei, K J; Szonyi, L; Narkis, G; Moses, S; Chou, J Y
1997-01-01
Glycogen storage disease type 1a (von Gierke disease, GSD-1A) is caused by the deficiency of microsomal glucose-6-phosphatase (G6Pase) activity which catalyzes the final common step of glycogenolysis and gluconeogenesis. The cloning of the G6Pase cDNA and characterization of the human G6Pase gene enabled the identification of the mutations causing GSD-1a. This, in turn, allows the development of non-invasive DNA-based diagnosis that provides reliable carrier testing and prenatal diagnosis. Here we report on two new mutations E110Q and D38V causing GSD-1a in two Hungarian patients. The analyses of these mutations by site-directed mutagenesis followed by transient expression assays demonstrated that E110Q retains 17% of G6Pase enzymatic activity while the D38V abolishes the enzymatic activity. The patient with the E110Q has G222R as his other mutation. G222R was also shown to preserve about 4% of the G6Pase enzymatic activity. Nevertheless, the patient presented with the classical severe symptomatology of the GSD-1a.
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Li, Jinmei; Yan, Gonghong; Liu, Sichi; Jiang, Tong; Zhong, Mingming; Yuan, Wenjie; Chen, Shaoxian; Zheng, Yin; Jiang, Yong; Jiang, Yu
2017-12-01
In yeast target of rapamycin complex 1 (TORC1) and Tap42-associated phosphatases regulate expression of genes involved in nitrogen limitation response and the nitrogen discrimination pathway. However, it remains unclear whether TORC1 and the phosphatases are required for sensing nitrogen conditions. Utilizing temperature sensitive mutants of tor2 and tap42, we examined the role of TORC1 and Tap42 in nuclear entry of Gln3, a key transcription factor in yeast nitrogen metabolism, in response to changes in nitrogen conditions. Our data show that TORC1 is essential for Gln3 nuclear entry upon nitrogen limitation and downshift in nitrogen quality. However, Tap42-associated phosphatases are required only under nitrogen limitation condition. In cells grown in poor nitrogen medium, the nitrogen permease reactivator kinase (Npr1) inhibits TORC1 activity and alters its association with Tap42, rendering Tap42-associated phosphatases unresponsive to nitrogen limitation. These findings demonstrate a direct role for TORC1 and Tap42-associated phosphatases in sensing nitrogen conditions and unveil an Npr1-dependent mechanism that controls TORC1 and the phosphatases in response to changes in nitrogen quality. © 2017 John Wiley & Sons Ltd.
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Four diterpenoid inhibitors of Cdc25B phosphatase from a marine anemone.
Cao, Shugeng; Foster, Caleb; Lazo, John S; Kingston, David G I
2005-10-15
Three new diterpenoids and one known diterpenoid have been isolated from a sea anemone of the order Actiniara, and the structures of the new compounds, actiniarins A-C (1-3) were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. Compound 1 has a six-membered ring hemiacetal ring, and the equilibrium of this ring is discussed. All the isolates were evaluated for their inhibition of Cdc25B and for cytotoxicity against the A2780 ovarian cancer cell line.
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NASA Astrophysics Data System (ADS)
Le Voyer, M.; Kelley, K. A.; Cottrell, E.; Hauri, E. H.
2014-12-01
As carbon solubility is low in basalts, MORB contain little dissolved CO2 (189±61 ppm, 1σ, n=600 [1]). A global negative correlation between CO2/Nb (proxy for amount of CO2 lost by degassing) and Ba/La (proxy for source enrichment) indicates that depleted MORB are less affected by degassing than enriched MORB: CO2/Nb ratios range from 0-100 for samples with Ba/La>4, while CO2/Nb range from 50 to 400 for samples with Ba/La<4 [1]. To assess the CO2 content of undegassed MORB, we analyzed the volatile content of 70 olivine-hosted, glassy melt inclusions (MIs) from four basalts dredged along MAR 1-5°S, a ridge segment that produces highly depleted MORB in terms of trace element enrichment and radiogenic isotopes [2, 3]. MIs contain CO2 contents (180-1420 ppm) that are higher than their respective matrix glasses (130-220 ppm, typical for vapor-saturated melts erupted at 3-5 km b.s.l.). One of the four dredges (EN061 5D-3Ag) contains MIs that do not exhibit shrinkage bubbles. For this sample only, we find a positive correlation between the CO2 content (240-770 ppm) and the Cl content (6-20 ppm) of the MIs that is not found in the matrix glasses (see Fig.). We infer that the correlation between CO2 and Cl, both highly incompatible in silicate minerals during fractional crystallization, is strong evidence for vapor-undersaturation, as any CO2 degassing would have erased the correlation. Together with MIs from the Siqueiros Fracture Zone [4] and from northern Iceland [5], the MIs from EN061 5D-3Ag may represent another occurrence of carbon-undersaturated MORB. Our results will be used to model the primary carbon content of MORB and of the depleted upper mantle. Note that the average Cl content of the matrix glasses (20±1 ppm) is higher than those of the MIs (12±3 ppm, see Fig.). This indicates either that the matrix glasses assimilated a small amount of seawater Cl, or that the MIs are all more depleted than the matrix glass. We will acquire major and trace element data in order to further investigate the origin of the low Cl and high CO2 contents in these MIs. Ref. [1] Le Voyer et al. 2014 Goldschmidt abstr. [2] Schilling et al. 1994 JGR 99 [3] Kelley et al. 2013 G3 [4] Saal et al. 2002 Nature 419 [5] Hauri and Saal 2009 EOS Fall suppl. AGU abstr.
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Clinical Phenotype in a Toddler with a Novel Heterozygous Mutation of the Vitamin D Receptor
Dingle, Elena
2017-01-01
We present the clinical phenotype of a toddler who presented with vitamin D-resistant rickets, with one of the highest initial levels of alkaline phosphatase and parathyroid hormone (PTH) levels reported in the literature. The toddler had novel compound heterozygous mutations in the ligand-binding site of the vitamin D receptor and had an excellent response to calcitriol (1,25(OH)2D). PMID:28620554
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Molecular Cloning and Function of FAS/APO1 Associated Protein in Breast Cancer.
1996-06-01
Ariyama T, Abe T, Druck T, Ohta M, Huebner K, Yanagisawa J, Reed JC, Sato T: PTPN13, a Fas-associated protein tyrosine phosphatase, is located on...20. Yang, Q., and Tonks, N. K. (1991). Isolation of a cDNA clone encoding a human protein-tyrosine phosphatase with homology 7. Huebner, K., Druck , T...Acad. Sci. U.S.A. 91, 7477 (1994). Res. 53, 1945 (1993).(Fig. 3D ). In contrast to Jurkat cells which 13. The original description of PTP-BAS (12
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Büyükgüzel, Kemal
2006-08-01
Effects of an organophosphorus insecticide, malathion, on survivorship and lipid peroxidation of the greater wax moth, Galleria mellonella (L.), pupae were investigated by rearing the newly hatched larvae on an artificial diet containing 0.01, 0.1, 1, 10, and 100 ppm of the insecticide. As bioindicators of long-term physiological stress responses, the adult emergence rate, longevity, and fecundity associated with lipid peroxidation level and antioxidant enzyme activity in the endoparasitoid Pimpla turionellae (L.) (Hymenoptera: Ichneumonidae) were determined by rearing the parasitoid on a factitious host, G. mellonella pupae treated with malathion. At 100 ppm, malathion significantly decreased pupation rate of G. mellonella larvae and the rate of adult emergence of the parasitoid from these pupae. This concentration resulted in a significant increase in the lipid peroxidation product malondialdehyde (MDA) in both the host and the parasitoid. Malathion at 1 and 10 ppm significantly increased pupation rate and lipid peroxidation level of G. mellonella pupae. The adult emergence rate of P. turionellae was significantly decreased from 63.7 to 20% by these concentrations, whereas MDA content was increased by two- and three-fold, respectively, compared with the control (45.3 +/- 3.2 nmol/ g protein). The longevity of adults was significantly extended from 52.5 +/- 5.7 to 75.7 +/- 6.3 d when the parasitoids emerged from host pupae exposed with 0.1 ppm malathion. At low concentrations (0.01 and 0.1 ppm), malathion significantly increased the number of eggs laid per female per day. However, the lowest concentration (0.01 ppm) had no significant effect on hatchability, whereas 0.1 ppm of the insecticide resulted in significant decrease in egg hatch compared with the control. A significant increase in total superoxide dismutase (SOD) activity for low concentrations of malathion (0.01-1 ppm) was found compared with the control. There was a significant positive correlation of SOD activities with adult longevity and fecundity. This study suggested that malathion-induced oxidative stress was causative factor in the deterioration of biological fitness and that increased SOD activities may have resulted in decreased oxidative damage, which retarded the rate of deteriorative physiological changes in P. turionellae in response to sublethal doses of malathion.
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VERA Core Simulator methodology for pressurized water reactor cycle depletion
Kochunas, Brendan; Collins, Benjamin; Stimpson, Shane; ...
2017-01-12
This paper describes the methodology developed and implemented in the Virtual Environment for Reactor Applications Core Simulator (VERA-CS) to perform high-fidelity, pressurized water reactor (PWR), multicycle, core physics calculations. Depletion of the core with pin-resolved power and nuclide detail is a significant advance in the state of the art for reactor analysis, providing the level of detail necessary to address the problems of the U.S. Department of Energy Nuclear Reactor Simulation Hub, the Consortium for Advanced Simulation of Light Water Reactors (CASL). VERA-CS has three main components: the neutronics solver MPACT, the thermal-hydraulic (T-H) solver COBRA-TF (CTF), and the nuclidemore » transmutation solver ORIGEN. This paper focuses on MPACT and provides an overview of the resonance self-shielding methods, macroscopic-cross-section calculation, two-dimensional/one-dimensional (2-D/1-D) transport, nuclide depletion, T-H feedback, and other supporting methods representing a minimal set of the capabilities needed to simulate high-fidelity models of a commercial nuclear reactor. Results are presented from the simulation of a model of the first cycle of Watts Bar Unit 1. The simulation is within 16 parts per million boron (ppmB) reactivity for all state points compared to cycle measurements, with an average reactivity bias of <5 ppmB for the entire cycle. Comparisons to cycle 1 flux map data are also provided, and the average 2-D root-mean-square (rms) error during cycle 1 is 1.07%. To demonstrate the multicycle capability, a state point at beginning of cycle (BOC) 2 was also simulated and compared to plant data. The comparison of the cycle 2 BOC state has a reactivity difference of +3 ppmB from measurement, and the 2-D rms of the comparison in the flux maps is 1.77%. Lastly, these results provide confidence in VERA-CS’s capability to perform high-fidelity calculations for practical PWR reactor problems.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kochunas, Brendan; Collins, Benjamin; Stimpson, Shane
This paper describes the methodology developed and implemented in the Virtual Environment for Reactor Applications Core Simulator (VERA-CS) to perform high-fidelity, pressurized water reactor (PWR), multicycle, core physics calculations. Depletion of the core with pin-resolved power and nuclide detail is a significant advance in the state of the art for reactor analysis, providing the level of detail necessary to address the problems of the U.S. Department of Energy Nuclear Reactor Simulation Hub, the Consortium for Advanced Simulation of Light Water Reactors (CASL). VERA-CS has three main components: the neutronics solver MPACT, the thermal-hydraulic (T-H) solver COBRA-TF (CTF), and the nuclidemore » transmutation solver ORIGEN. This paper focuses on MPACT and provides an overview of the resonance self-shielding methods, macroscopic-cross-section calculation, two-dimensional/one-dimensional (2-D/1-D) transport, nuclide depletion, T-H feedback, and other supporting methods representing a minimal set of the capabilities needed to simulate high-fidelity models of a commercial nuclear reactor. Results are presented from the simulation of a model of the first cycle of Watts Bar Unit 1. The simulation is within 16 parts per million boron (ppmB) reactivity for all state points compared to cycle measurements, with an average reactivity bias of <5 ppmB for the entire cycle. Comparisons to cycle 1 flux map data are also provided, and the average 2-D root-mean-square (rms) error during cycle 1 is 1.07%. To demonstrate the multicycle capability, a state point at beginning of cycle (BOC) 2 was also simulated and compared to plant data. The comparison of the cycle 2 BOC state has a reactivity difference of +3 ppmB from measurement, and the 2-D rms of the comparison in the flux maps is 1.77%. Lastly, these results provide confidence in VERA-CS’s capability to perform high-fidelity calculations for practical PWR reactor problems.« less
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NASA Astrophysics Data System (ADS)
Kumar, Ramesh; Kaur, Amarjeet
2016-05-01
The reduced graphene oxide thin films were fabricated by using the spin coating method. The reduced graphene oxide samples were characterised by Raman studies to obtain corresponding D and G bands at 1360 and 1590 cm-1 respectively. Fourier transform infra-red (FTIR) spectra consists of peak corresponds to sp2 hybridisation of carbon atoms at 1560 cm-1. The reduced graphene oxide based chemoresistive sensor exhibited a p-type semiconductor behaviour in ambient conditions and showed good sensitivity to different concentration of ammonia from 25 ppm to 500 ppm and excellent selectivity at room temperature. The sensor displays selectivity to several hazardous vapours such as methanol, ethanol, acetone and hydrazine hydrate. The sensor demonstrated a sensitivity of 9.8 at 25 ppm concentration of ammonia with response time of 163 seconds.
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Uddin, Zia; Song, Yeong Hun; Ullah, Mahboob; Li, Zuopeng; Kim, Jeong Yoon; Park, Ki Hun
2018-01-01
Diabetes mellitus is one of a major worldwide concerns, regulated by either defects in secretion or action of insulin, or both. Insulin signaling down-regulation has been related with over activity of protein tyrosine phosphatase 1B (PTP1B) enzyme, which has been a promising target for the treatment of diabetes mellitus. Herein, activity guided separation of methanol extract (95%) of Dodonaea viscosa aerial parts afforded nine ( 1 - 9 ) polyphenolic compounds, all of them were identified through spectroscopic data including 2D NMR and HREIMS. Subsequently, their PTP1B inhibitory potentials were evaluated, in which all of the isolates exhibited significant dose-dependent inhibition with IC 50 13.5-57.9 μM. Among them, viscosol ( 4 ) was found to be the most potent compound having IC 50 13.5 μM. In order to unveil the mechanistic behavior, detailed kinetic study was carried out, in which compound 4 was observed as a reversible, and mixed type I inhibitor of PTP1B with inhibitory constant ( K i ) value of 4.6 μM. Furthermore, we annotated the major metabolites through HPLC-DAD-ESI/MS analysis, in which compounds 3 , 6 , 7 , and 9 were found to be the most abundant metabolites in D. viscosa extract.
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NASA Astrophysics Data System (ADS)
Uddin, Zia; Song, Yeong Hun; Ullah, Mahboob; Li, Zuopeng; Kim, Jeong Yoon; Park, Ki Hun
2018-03-01
Diabetes mellitus is one of a major worldwide concerns, regulated by either defects in secretion or action of insulin, or both. Insulin signaling down-regulation has been related with over activity of protein tyrosine phosphatase 1B (PTP1B) enzyme, which has been a promising target for the treatment of diabetes mellitus. Herein, activity guided separation of methanol extract (95%) of Dodonaea viscosa aerial parts afforded nine (1-9) polyphenolic compounds, all of them were identified through spectroscopic data including 2D NMR and HREIMS. Subsequently, their PTP1B inhibitory potentials were evaluated, in which all of the isolates exhibited significant dose-dependent inhibition with IC50 13.5-57.9 μM. Among them, viscosol (4) was found to be the most potent compound having IC50 13.5 μM. In order to unveil the mechanistic behavior, detailed kinetic study was carried out, in which compound 4 was observed as a reversible, and mixed type I inhibitor of PTP1B with inhibitory constant (Ki) value of 4.6 μM. Furthermore, we annotated the major metabolites through HPLC-DAD-ESI/MS analysis, in which compounds 3, 6, 7 and 9 were found to be the most abundant metabolites in D.viscosa extract.
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Optoelectronic oscillator with improved phase noise and frequency stability
NASA Astrophysics Data System (ADS)
Eliyahu, Danny; Sariri, Kouros; Taylor, Joseph; Maleki, Lute
2003-07-01
In this paper we report on recent improvements in phase noise and frequency stability of a 10 GHz opto-electronic oscillator. In our OEO loop, the high Q elements (the optical fiber and the narrow bandpass microwave filter) are thermally stabilized using resistive heaters and temperature controllers, keeping their temperature above ambient. The thermally stabilized free running OEO demonstrates a short-term frequency stability of 0.02 ppm (over several hours) and frequency vs. temperature slope of -0.1 ppm/°C (compared to -8.3 ppm/°C for non thermally stabilized OEO). We obtained an exceptional spectral purity with phase noise level of -143 dBc/Hz at 10 kHz of offset frequency. We also describe the multi-loop configuration that reduces dramatically the spurious level at offset frequencies related to the loop round trip harmonic frequency. The multi-loop configuration has stronger mode selectivity due to interference between signals having different cavity lengths. A drop of the spurious level below -90 dBc was demonstrated. The effect of the oscillator aging on the frequency stability was studied as well by recording the oscillator frequency (in a chamber) over several weeks. We observed reversal in aging direction with logarithmic behavior of A ln(B t+1)-C ln(D t+1), where t is the time and A, B, C, D are constants. Initially, in the first several days, the positive aging dominates. However, later the negative aging mechanism dominates. We have concluded that the long-term aging behavioral model is consistent with the experimental results.
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NASA Astrophysics Data System (ADS)
Ha, Nguyen Hai; Thinh, Dao Duc; Huong, Nguyen Thanh; Phuong, Nguyen Huy; Thach, Phan Duy; Hong, Hoang Si
2018-03-01
Zinc oxide (ZnO) nanoparticles loaded onto 3D reduced graphene oxide (3D-RGO) for carbon monoxide (CO) sensing were synthesized using hydrothermal method. The highly porous ZnO/3D-RGO configuration was stable without collapsing and was deposited on the micro-heater of the CO gas sensor. The resulting CO gas sensor displayed high sensitivity, fast response/recovery, and good linearity. The sensor achieved a response value of 85.2% for 1000 ppm CO at a working temperature of 200 °C. The response and recovery times of the sensor were 7 and 9 s for 1000 ppm CO at 200 °C. Similarly, the response value, response time, and recovery time of the sensor at room temperature were 27.5%, 14 s, and 15 s, respectively. The sensor demonstrated a distinct response to various CO concentrations in the range of 1-1000 ppm and good selectivity toward CO gas. In addition, the sensor exhibited good repeatability in multi-cycle and long-term stability.
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Goor, François; Thiry, Yves; Delvaux, Bruno
2007-10-01
Twenty years after the Chernobyl accident, root uptake from the surface layers of contaminated forest soils plays a major role in radiocaesium ((137)Cs) transfer to the trees and accumulation in perennial compartments, including stemwood. Trustworthy long-term predictions (modelling) of stemwood contamination with (137)Cs should accordingly be based on a reliable picture of this source-sink relationship. Considering the complexity of the processes involved in (137)Cs cycling in forest stands, elementary ratios like transfer factors (TF) were shown to be not very relevant for that purpose. At the tree level, alternatives like the wood immobilisation potential (WIP) have therefore been proposed in order to quantify the current net (137)Cs accumulation in stemwood. Our objective was here to compare WIP values determined for a series of contaminated forest stands in Belarus with the corresponding pools of (137)Cs available in the soil for root uptake. The comparison reveals that both indices are quite proportional, whatever the forest ecosystem features. This corroborates the relevancy of WIP as an indicator of the current (137)Cs root uptake by the trees, which could accordingly help to improve the existing models of (137)Cs cycling and the long-term management of contaminated forest ecosystems.
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Protein tyrosine phosphatases as potential therapeutic targets
He, Rong-jun; Yu, Zhi-hong; Zhang, Ruo-yu; Zhang, Zhong-yin
2014-01-01
Protein tyrosine phosphorylation is a key regulatory process in virtually all aspects of cellular functions. Dysregulation of protein tyrosine phosphorylation is a major cause of human diseases, such as cancers, diabetes, autoimmune disorders, and neurological diseases. Indeed, protein tyrosine phosphorylation-mediated signaling events offer ample therapeutic targets, and drug discovery efforts to date have brought over two dozen kinase inhibitors to the clinic. Accordingly, protein tyrosine phosphatases (PTPs) are considered next-generation drug targets. For instance, PTP1B is a well-known targets of type 2 diabetes and obesity, and recent studies indicate that it is also a promising target for breast cancer. SHP2 is a bona-fide oncoprotein, mutations of which cause juvenile myelomonocytic leukemia, acute myeloid leukemia, and solid tumors. In addition, LYP is strongly associated with type 1 diabetes and many other autoimmune diseases. This review summarizes recent findings on several highly recognized PTP family drug targets, including PTP1B, Src homology phosphotyrosyl phosphatase 2(SHP2), lymphoid-specific tyrosine phosphatase (LYP), CD45, Fas associated phosphatase-1 (FAP-1), striatal enriched tyrosine phosphatases (STEP), mitogen-activated protein kinase/dual-specificity phosphatase 1 (MKP-1), phosphatases of regenerating liver-1 (PRL), low molecular weight PTPs (LMWPTP), and CDC25. Given that there are over 100 family members, we hope this review will serve as a road map for innovative drug discovery targeting PTPs. PMID:25220640
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Leyria, Jimena; Fruttero, Leonardo L.; Nazar, Magalí; Canavoso, Lilián E.
2015-01-01
In this work, we have investigated the involvement of DmCatD, a cathepsin D-like peptidase, and acid phosphatase in the process of follicular atresia of Dipetalogaster maxima, a hematophagous insect vector of Chagas’ disease. For the studies, fat bodies, ovaries and hemolymph were sampled from anautogenous females at representative days of the reproductive cycle: pre-vitellogenesis, vitellogenesis as well as early and late atresia. Real time PCR (qPCR) and western blot assays showed that DmCatD was expressed in fat bodies and ovaries at all reproductive stages, being the expression of its active form significantly higher at the atretic stages. In hemolymph samples, only the immunoreactive band compatible with pro-DmCatD was observed by western blot. Acid phosphatase activity in ovarian tissues significantly increased during follicular atresia in comparison to pre-vitellogenesis and vitellogenesis. A further enzyme characterization with inhibitors showed that the high levels of acid phosphatase activity in atretic ovaries corresponded mainly to a tyrosine phosphatase. Immunofluorescence assays demonstrated that DmCatD and tyrosine phosphatase were associated with yolk bodies in vitellogenic follicles, while in atretic stages they displayed a different cellular distribution. DmCatD and tyrosine phosphatase partially co-localized with vitellin. Moreover, their interaction was supported by FRET analysis. In vitro assays using homogenates of atretic ovaries as the enzyme source and enzyme inhibitors demonstrated that DmCatD, together with a tyrosine phosphatase, were necessary to promote the degradation of vitellin. Taken together, the results strongly suggested that both acid hydrolases play a central role in early vitellin proteolysis during the process of follicular atresia. PMID:26091289
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Baker, Bradley J.; Jin, Lei; Han, Zhou; Cohen, Lawrence B.; Popovic, Marko; Platisa, Jelena; Pieribone, Vincent
2012-01-01
A substantial increase in the speed of the optical response of genetically-encoded Fluorescent Protein voltage sensors (FP voltage sensors) was achieved by using the voltage-sensing phosphatase genes of Nematostella vectensis and Danio rerio. A potential N. vectensis voltage-sensing phosphatase was identified in silico. The voltage-sensing domain (S1–S4) of the N. vectensis homolog was used to create an FP voltage sensor called Nema. By replacing the phosphatase with a cerulean/citrine FRET pair, a new FP voltage sensor was synthesized with fast off kinetics (Tauoff <5 msec). However, the signal was small (ΔF/F= 0.6%/200 mV). FP voltage sensors using the D. rerio voltage-sensing phosphatase homolog, designated Zahra and Zahra 2, exhibited fast on and off kinetics within 2 msec of the time constants observed with the organic voltage-sensitive dye, di4-ANEPPS. Mutagenesis of the S4 region of the Danio FP voltage sensor shifted the voltage dependence to more negative potentials but did not noticeably affect the kinetics of the optical signal. PMID:22634212
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N2O molecular tagging velocimetry
NASA Astrophysics Data System (ADS)
ElBaz, A. M.; Pitz, R. W.
2012-03-01
A new seeded velocity measurement technique, N2O molecular tagging velocimetry (MTV), is developed to measure velocity in wind tunnels by photochemically creating an NO tag line. Nitrous oxide "laughing gas" is seeded into the air flow. A 193 nm ArF excimer laser dissociates the N2O to O(1D) that subsequently reacts with N2O to form NO. O2 fluorescence induced by the ArF laser "writes" the original position of the NO line. After a time delay, the shifted NO line is "read" by a 226-nm laser sheet and the velocity is determined by time-of-flight. At standard atmospheric conditions with 4% N2O in air, ˜1000 ppm of NO is photochemically created in an air jet based on experiment and simulation. Chemical kinetic simulations predict 800-1200 ppm of NO for 190-750 K at 1 atm and 850-1000 ppm of NO for 0.25-1 atm at 190 K. Decreasing the gas pressure (or increasing the temperature) increases the NO ppm level. The presence of humid air has no significant effect on NO formation. The very short NO formation time (<10 ns) makes the N2O MTV method amenable to low- and high-speed air flow measurements. The N2O MTV technique is demonstrated in air jet to measure its velocity profile. The N2O MTV method should work in other gas flows as well (e.g., helium) since the NO tag line is created by chemical reaction of N2O with O(1D) from N2O photodissociation and thus does not depend on the bulk gas composition.
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Physiological aspects of fungi isolated from root nodules of faba bean (Vicia faba L.).
Omar, S A; Abd-Alla, M H
2000-03-01
The present study was made to isolate and assess some physiological characteristics of root nodule-colonizing fungi. During this study, 17 fungal species were isolated from root nodule samples taken from faba bean plants (Vicia faba L.) collected from different sites at Assiut area (Egypt). The growth of faba bean plants in pots was significantly promoted by soil inoculation with most fungi. Growth was checked in pots with inocula of Cladosporium cladosporioides, Fusarium moniliforme, F: oxysporium, F solani, Macrophominia phaseolina and Rhizoctonia solani which were added separately. All growth-promoting fungi were capable of producing cellulase, pectin lyase, polygalacturonase, protease, urease, amidase, acid phosphatase, alkaline phosphatase and arylsulfatase in growth medium supplemented with the corresponding substrates. Four fungal species, Aspergillus awamori, A. flavus, Penicillium chrysogenum and Trichoderma koningii showed the highest rates of enzyme formation. The effect of the addition of six trace elements to the growth media at 30 micromol/ml on enzyme production revealed some dependency on species, enzyme and metal ion. Cd2+, Hg2+ and Zn2+ generally inhibited enzyme activity. Cu(1+), Fe3+ and Al3+ showed a stimulatory effect. Fungicides (afugan and tilt) and herbicides (brominal and fusilade) at 50 ppm generally promoted enzyme activity, but insecticides (kelthane and fenvalerate) caused some inhibition to enzyme activities. Salinization of the growth media with NaCl strongly inhibited the enzymatic activity of all fungi at concentrations between 0.5 and 1.5%.
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Fleming, W.J.; Schuler, C.A.
1988-01-01
Young Japanese quail (Coturnix japonica) were administered NaF for 16 d either in their diet or by esophageal intubation. Based on the total fluoride ion (Emg F-) intake over the l6-d experimental period, fluoride administered by intubation was at least six times more toxic than that fed in the diet. Dietary concentrations of 1,000 ppm F- (Emg F- for 16 d = approx. 144) produced no mortality, whereas intubated doses produced 73% or greater mortality in all groups administered 54 mg F- /kg/d or more (Emg F- for 16 d _ approx. 23 mg). GraphIc companson of the regression of log F- ppm in femurs/mg F- intake showed that fluoride levels in the femurs of quail administered fluoride by intubation were higher than in those administered fluoride in the diet.
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Mendrzyk, Frank; Radlwimmer, Bernhard; Joos, Stefan; Kokocinski, Felix; Benner, Axel; Stange, Daniel E; Neben, Kai; Fiegler, Heike; Carter, Nigel P; Reifenberger, Guido; Korshunov, Andrey; Lichter, Peter
2005-12-01
Medulloblastoma is the most common malignant brain tumor in children. Despite multimodal aggressive treatment, nearly half of the patients die as a result of this tumor. Identification of molecular markers for prognosis and development of novel pathogenesis-based therapies depends crucially on a better understanding of medulloblastoma pathomechanisms. We performed genome-wide analysis of DNA copy number imbalances in 47 medulloblastomas using comparative genomic hybridization to large insert DNA microarrays (matrix-CGH). The expression of selected candidate genes identified by matrix-CGH was analyzed immunohistochemically on tissue microarrays representing medulloblastomas from 189 clinically well-documented patients. To identify novel prognostic markers, genomic findings and protein expression data were correlated to patient survival. Matrix-CGH analysis revealed frequent DNA copy number alterations of several novel candidate regions. Among these, gains at 17q23.2-qter (P < .01) and losses at 17p13.1 to 17p13.3 (P = .04) were significantly correlated to poor prognosis. Within 17q23.2-qter and 7q21.2, two of the most frequently gained chromosomal regions, confined amplicons were identified that contained the PPM1D and CDK6 genes, respectively. Immunohistochemistry revealed strong expression of PPM1D in 148 (88%) of 168 and CDK6 in 50 (30%) of 169 medulloblastomas. Overexpression of CDK6 correlated significantly with poor prognosis (P < .01) and represented an independent prognostic marker of overall survival on multivariate analysis (P = .02). We identified CDK6 as a novel molecular marker that can be determined by immunohistochemistry on routinely processed tissue specimens and may facilitate the prognostic assessment of medulloblastoma patients. Furthermore, increased protein-levels of PPM1D and CDK6 may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms.
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Liu, Jia-Ming; Liu, Zhen-Bo; Hu, Li-Xiang; He, Hang-Xia; Yang, Min-Lan; Zhou, Ping; Chen, Xin-Hua; Zheng, Min-Min; Zeng, Xiao-Yi; Xu, Yue-Long
2006-10-15
In the presence of heavy atom perturber LiAc, the silicon dioxide nanoparticle containing rhodamine 6G (R) and dibromoluciferin (D) (R-D-SiO(2)) can emit strong and stable solid-substrate room temperature phosphorescence signal of R (lambda(ex)/lambda(em)=481/648 nm) and D (lambda(ex)/lambda(em)=457/622 nm) on the surface of acetyl cellulose membrane (ACM). R-D-SiO(2) is used to label triticum vulgare lectin (WGA). Then two types of affinity adsorption reactions, R-D-SiO(2)-WGA- alkaline phosphatase (ALP) (direct method) and WGA-ALP-WGA-R-D-SiO(2) (sandwich method), are carried out on ACM. The conditions and the analytical characteristics for the determination of ALP using affinity adsorption solid-substrate room temperature phosphorimetry (AA-SS-RTP) were studied. For a 0.40-microl drop of sample, results show that the detection limits of the sandwich method are 0.16 ag spot(-1)(457/622 nm) and 0.17 ag spot(-1)(481/648 nm), and the detection limits of the direct method are 0.41 ag spot(-1) (457/622 nm) and 0.44 ag spot(-1) (481/648 nm). The contents of ALP in human serum correlated well with those obtained by enzyme-linked immunoassay. This study shows that AA-SS-RTP whether by the sandwich method or the direct method, can combine very well the characteristics of both high sensitivity of SS-RTP and specificity of the immunoreaction. Simultaneously, whether the phosphorescence excitation/emission wavelength of either R or D in R-D-SiO(2) is chosen to determine ALP, this can promote the agility and widen the adaptability of AA-SS-RTP.
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NASA Astrophysics Data System (ADS)
Feng, L.; Palmer, P. I.; Yang, Y.; Yantosca, R. M.; Kawa, S. R.; Paris, J.-D.; Matsueda, H.; Machida, T.
2010-07-01
We evaluate the GEOS-Chem atmospheric transport model (v8-02-01) of CO2 over 2003-2006, driven by GEOS-4 and GEOS-5 meteorology from the NASA Goddard Global Modelling and Assimilation Office, using surface, aircraft and space-borne concentration measurements of CO2. We use an established ensemble Kalman filter to estimate a posteriori biospheric+biomass burning (BS+BB) and oceanic (OC) CO2 fluxes from 22 geographical regions, following the TransCom 3 protocol, using boundary layer CO2 data from a subset of GLOBALVIEW surface sites. Global annual net BS+BB+OC CO2 fluxes over 2004-2006 for GEOS-4 (GEOS-5) meteorology are -4.4±0.9 (-4.2±0.9), -3.9±0.9 (-4.5±0.9), and -5.2±0.9 (-4.9±0.9) Pg C yr-1 , respectively. The regional a posteriori fluxes are broadly consistent in the sign and magnitude of the TransCom-3 study for 1992-1996, but we find larger net sinks over northern and southern continents. We find large departures from our a priori over Europe during summer 2003, over temperate Eurasia during 2004, and over North America during 2005, reflecting an incomplete description of terrestrial carbon dynamics. We find GEOS-4 (GEOS-5) a posteriori CO2 concentrations reproduce the observed surface trend of 1.91-2.43 ppm yr-1, depending on latitude, within 0.15 ppm yr-1 (0.2 ppm yr-1) and the seasonal cycle within 0.2 ppm (0.2 ppm) at all latitudes. We find the a posteriori model reproduces the aircraft vertical profile measurements of CO2 over North America and Siberia generally within 1.5 ppm in the free and upper troposphere but can be biased by up to 4-5 ppm in the boundary layer at the start and end of the growing season. The model has a small negative bias in the free troposphere CO2 trend (1.95-2.19 ppm yr-1) compared to AIRS data which has a trend of 2.21-2.63 ppm yr-1 during 2004-2006, consistent with surface data. Model CO2 concentrations in the upper troposphere, evaluated using CONTRAIL (Comprehensive Observation Network for TRace gases by AIrLiner) aircraft measurements, reproduce the magnitude and phase of the seasonal cycle of CO2 in both hemispheres. We generally find that the GEOS meteorology reproduces much of the observed tropospheric CO2 variability, suggesting that these meteorological fields will help make significant progress in understanding carbon fluxes as more data become available.
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Peng, Liu; Lei, Zhang; Xiao-na, Xie; Deli, Wang; Jing, Sun; Yong-sen, Wang; Zhi, Wang; Shu, Xing; Jun-feng, Ma; Wan-nan, Li; Xue-qi, Fu
2015-03-01
Protein tyrosine phosphatases (PTPs) are enzymes that catalyze protein tyrosine dephosphorylation of which Src homology phosphatase-1 (SHP-1) is one of the best-validated, a widely distributed intracellular tyrosine phosphatase that contains two SH2 domains. Down regulation of SHP-1 tyrosine phosphatases was significantly increased sensitivity to insulin in insulin signaling pathway. Through in vitro enzymatic reaction kinetics experiment, we found that the extract of Perilla stem was a potential inhibitor to δSHP-1, the catalytic domain of SHP-1 protein tyrosine phosphatase, and its IC(50) was 4ug/ml, and was more sensitive towards SHP-1than other PTPs, which indicated that SHP-1 might be a target of the extract of Perilla stem. It can strengthened the level of tyrosine phosphorylation of insulin receptor (IR) and extracellular signal-regulated protein kinase (ERK) in HepG2 cells, and then activated the insulin signaling pathway through inhibiting the protein phosphorylation of SHP-1. These results demonstrated that the extract of Perilla stem could play an important role for diabetes treatment through inhibiting the level of SHP-1 in insulin signaling pathway.
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The true distribution and accumulation of radiocaesium in stem of Scots pine (Pinus sylvestris L.).
Thiry, Yves; Goor, Francois; Riesen, Thomas
2002-01-01
The radial and vertical distributions of radiocaesium, potassium and calcium were determined in two Scots pine stands (17 and 58 yr old) similarly affected by the Chernobyl fallout. For both age classes, concentrations are always the lowest in the stemwood, highest in the inner bark and intermediary levels were observed for the outer bark. Due to the cumulative character of its biomass. however. stemwood is a long-term major reservoir of 137Cs. With tree development, changes in the 137Cs radial distribution are well described by variations in the sap ascent pattern and reveal an important transfer between tree rings. It is shown that. both the biomass evolution and knowledge of the evolution of the 137Cs radial gradient are important to predicting 137Cs accumulation in wood with time. According to the common transfer factor (TF) approach, one would expect a decrease in radiocaesium accumulation with time (from 0.0047 +/- 0.0013 to 0.0035 +/- 0.0008 m2kg(-1) for the 17 and 58 yr old trees, respectively). With the wood immobilisation potential (WIP) approach, it was, however, clearly shown that additional annual uptake was highest for the older stand (3.12 +/- 0.23 Bq cm(-3) yr(-1) for the 58-year-old stand compared to 1.99 +/- 0.30 Bq cm(-3) yr(-1) for the younger stand). Following the WIP approach, it was moreover possible to distinguish between the 137Cs incorporated via the root uptake process and a possible lasting effect of interception. It is shown that, whereas for the younger stand (5 yr old at the time of the accident) root uptake contributed exclusively to the wood contamination, the former process explained only 48% of the measured total 137Cs content in the wood of the older tree.
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1988-05-01
alcohol (1- octanol ) phenol n-propyl alcohol (1-propanol) isopropy1 alcohol (2-propanol) **2. Aldehydes acetaldehyde (ethanal) acrolein (propenal...59.0) D-7 MACs 7-Day ppm fmq/M^) 20 (105) 20 (82.0) 20 (70.4) 20 (70.4) Mol. Wt. methyl hexyl ketone (2- octanone ) 128.2 methyl
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Ito, Yoshihito; Yamada, Shinnosuke; Takahashi, Nagahide; Saito, Shinichi; Yoshimi, Akira; Inada, Toshiya; Noda, Yukihiro; Ozaki, Norio
2008-10-05
NRG1-ERBB signaling influences the risk for schizophrenia pathology. A recent study has reported that MAGI1, MAGI2, and protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1; located on 7q31.3) gene products regulate the NRG1-ERBB4 signaling pathway, and PTPRZ1 is associated with schizophrenia in a Caucasian population. By applying a gene-based association concept, we analyzed any association between PTPRZ1 tagging SNPs and schizophrenia in the Japanese population (576 schizophrenics and 768 controls). After linkage disequilibrium analysis, 29 single nucleotide polymorphisms (SNPs) were genotyped using a 5'-exonuclease allelic discrimination assay. We found a significant association of one tagging SNP in a genotype-wise analysis (P = 0.007); however, this might be resulted from type I error due to multiple testing (P = 0.17 after SNPSpD correction). No association was observed between schizophrenic patients and controls in either allelic, genotypic, or haplotypic analyses. Our results therefore suggest that PTPRZ1 is unlikely to be related to the development of schizophrenia in the Japanese population.
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Synthesis of C13- and N15-Labeled DNAN
2014-07-24
Multiplicities are described as singlet (s), doublet (d), triplet (t), quartet (q), doublet of doublets (dd), doublet of doublet of doublets ( ddd ), multiplet...dd, 4.8Hz, 2.6Hz, 1H), 8.40 ( ddd , 8.8Hz, 2.6Hz, 1.8Hz, 1H), and 7.81 (d, 8.8Hz, 1H) ppm. 13C NMR (CDCl3): δ 147.8 (dd, 18Hz, 3Hz), 146.3 (dd, 17Hz...Dinitroanisole mp: 86-88 °C 1H NMR (CDCl3): δ 8.77 (m, 4.8Hz, 2.6Hz, 1H), 8.46 ( ddd , 9.2Hz, 2.6Hz, 1.8Hz, 1H), 7.23 (d, 9.2Hz, 1H), and 4.10 (s, 3H
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Neem derivatives are not effective as toxic bait for tephritid fruit flies.
Silva, M A; Bezerra-Silva, G C D; Vendramim, J D; Mastrangelo, T; Forim, M R
2013-08-01
Neem derivatives have been widely touted as replacements for pesticides. A feasible replacement of synthetic insecticides in the management of fruit flies could be to use neem products in baits. This study evaluated the bioactivity of neem (Azadirachta indica A. Juss) derivatives in bait for adults of Anastrepha fraterculus (Wiedemann) and Ceratitis capitata (Wiedemann). The estimated LCs50 values for A. fraterculus and C. capitata were 7,522 ppm (18.40 ppm of azadirachtin) and 1,368 ppm (3.35 ppm of azadirachtin), respectively, using an aqueous extract of neem seeds in bait after 10 d of experimentation. No significant differences in the mortality of A. fraterculus and C. capitata adults exposed to baits made from different extracts and neem oil were observed after 3 h or 2 or 6 d; differences among the treatments were observed only on the 10th day of the evaluation. We conclude that neem derivatives applied as a bait spray over citrus plants did not demonstrate a toxic effect on A. fraterculus and C. capitata. The reasons for the low efficacy of the neem bait on Tephritid fruit flies are discussed.
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Mason, David; Mallo, Gustavo V.; Terebiznik, Mauricio R.; Payrastre, Bernard; Finlay, B. Brett; Brumell, John H.; Rameh, Lucia; Grinstein, Sergio
2007-01-01
Elucidation of the role of PtdIns(4,5)P2 in epithelial function has been hampered by the inability to selectively manipulate the cellular content of this phosphoinositide. Here we report that SigD, a phosphatase derived from Salmonella, can effectively hydrolyze PtdIns(4,5)P2, generating PtdIns(5)P. When expressed by microinjecting cDNA into epithelial cells forming confluent monolayers, wild-type SigD induced striking morphological and functional changes that were not mimicked by a phosphatase-deficient SigD mutant (C462S). Depletion of PtdIns(4,5)P2 in intact SigD-injected cells was verified by detachment from the membrane of the pleckstrin homology domain of phospholipase Cδ, used as a probe for the phosphoinositide by conjugation to green fluorescent protein. Single-cell measurements of cytosolic pH indicated that the Na+/H+ exchange activity of epithelia was markedly inhibited by depletion of PtdIns(4,5)P2. Similarly, anion permeability, measured using two different halide-sensitive probes, was depressed in cells expressing SigD. Depletion of PtdIns(4,5)P2 was associated with marked alterations in the actin cytoskeleton and its association with the plasma membrane. The junctional complexes surrounding the injected cells gradually opened and the PtdIns(4,5)P2-depleted cells eventually detached from the monolayer, which underwent rapid restitution. Similar observations were made in intestinal and renal epithelial cultures. In addition to its effects on phosphoinositides, SigD has been shown to convert inositol 1,3,4,5,6-pentakisphosphate (IP5) into inositol 1,4,5,6-tetrakisphosphate (IP4), and the latter has been postulated to mediate the diarrhea caused by Salmonella. However, the effects of SigD on epithelial cells were not mimicked by microinjection of IP4. In contrast, the cytoskeletal and ion transport effects were replicated by hydrolyzing PtdIns(4,5)P2 with a membrane-targeted 5-phosphatase or by occluding the inositide using high-avidity tandem PH domain constructs. We therefore suggest that opening of the tight junctions and inhibition of Na+/H+ exchange caused by PtdIns(4,5)P2 hydrolysis combine to account, at least in part, for the fluid loss observed during Salmonella-induced diarrhea. PMID:17389247
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Jiang, Chenyu; Sun, Meixiu; Wang, Zhennan; Chen, Zhuying; Zhao, Xiaomeng; Yuan, Yuan; Li, Yingxin; Wang, Chuji
2016-01-01
Breath analysis has been considered a suitable tool to evaluate diseases of the respiratory system and those that involve metabolic changes, such as diabetes. Breath acetone has long been known as a biomarker for diabetes. However, the results from published data by far have been inconclusive regarding whether breath acetone is a reliable index of diabetic screening. Large variations exist among the results of different studies because there has been no “best-practice method” for breath-acetone measurements as a result of technical problems of sampling and analysis. In this mini-review, we update the current status of our development of a laser-based breath acetone analyzer toward real-time, one-line diabetic screening and a point-of-care instrument for diabetic management. An integrated standalone breath acetone analyzer based on the cavity ringdown spectroscopy technique has been developed. The instrument was validated by using the certificated gas chromatography-mass spectrometry. The linear fittings suggest that the obtained acetone concentrations via both methods are consistent. Breath samples from each individual subject under various conditions in total, 1257 breath samples were taken from 22 Type 1 diabetic (T1D) patients, 312 Type 2 diabetic (T2D) patients, which is one of the largest numbers of T2D subjects ever used in a single study, and 52 non-diabetic healthy subjects. Simultaneous blood glucose (BG) levels were also tested using a standard diabetic management BG meter. The mean breath acetone concentrations were determined to be 4.9 ± 16 ppm (22 T1D), and 1.5 ± 1.3 ppm (312 T2D), which are about 4.5 and 1.4 times of the one in the 42 non-diabetic healthy subjects, 1.1 ± 0.5 ppm, respectively. A preliminary quantitative correlation (R = 0.56, p < 0.05) between the mean individual breath acetone concentration and the mean individual BG levels does exist in 20 T1D subjects with no ketoacidosis. No direct correlation is observed in T1D subjects, T2D subjects, and healthy subjects. The results from a relatively large number of subjects tested indicate that an elevated mean breath acetone concentration exists in diabetic patients in general. Although many physiological parameters affect breath acetone, under a specifically controlled condition fast (<1 min) and portable breath acetone measurement can be used for screening abnormal metabolic status including diabetes, for point-of-care monitoring status of ketone bodies which have the signature smell of breath acetone, and for breath acetone related clinical studies requiring a large number of tests. PMID:27483281
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Jiang, Chenyu; Sun, Meixiu; Wang, Zhennan; Chen, Zhuying; Zhao, Xiaomeng; Yuan, Yuan; Li, Yingxin; Wang, Chuji
2016-07-30
Breath analysis has been considered a suitable tool to evaluate diseases of the respiratory system and those that involve metabolic changes, such as diabetes. Breath acetone has long been known as a biomarker for diabetes. However, the results from published data by far have been inconclusive regarding whether breath acetone is a reliable index of diabetic screening. Large variations exist among the results of different studies because there has been no "best-practice method" for breath-acetone measurements as a result of technical problems of sampling and analysis. In this mini-review, we update the current status of our development of a laser-based breath acetone analyzer toward real-time, one-line diabetic screening and a point-of-care instrument for diabetic management. An integrated standalone breath acetone analyzer based on the cavity ringdown spectroscopy technique has been developed. The instrument was validated by using the certificated gas chromatography-mass spectrometry. The linear fittings suggest that the obtained acetone concentrations via both methods are consistent. Breath samples from each individual subject under various conditions in total, 1257 breath samples were taken from 22 Type 1 diabetic (T1D) patients, 312 Type 2 diabetic (T2D) patients, which is one of the largest numbers of T2D subjects ever used in a single study, and 52 non-diabetic healthy subjects. Simultaneous blood glucose (BG) levels were also tested using a standard diabetic management BG meter. The mean breath acetone concentrations were determined to be 4.9 ± 16 ppm (22 T1D), and 1.5 ± 1.3 ppm (312 T2D), which are about 4.5 and 1.4 times of the one in the 42 non-diabetic healthy subjects, 1.1 ± 0.5 ppm, respectively. A preliminary quantitative correlation (R = 0.56, p < 0.05) between the mean individual breath acetone concentration and the mean individual BG levels does exist in 20 T1D subjects with no ketoacidosis. No direct correlation is observed in T1D subjects, T2D subjects, and healthy subjects. The results from a relatively large number of subjects tested indicate that an elevated mean breath acetone concentration exists in diabetic patients in general. Although many physiological parameters affect breath acetone, under a specifically controlled condition fast (<1 min) and portable breath acetone measurement can be used for screening abnormal metabolic status including diabetes, for point-of-care monitoring status of ketone bodies which have the signature smell of breath acetone, and for breath acetone related clinical studies requiring a large number of tests.
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Née, Guillaume; Kramer, Katharina; Nakabayashi, Kazumi; Yuan, Bingjian; Xiang, Yong; Miatton, Emma; Finkemeier, Iris; Soppe, Wim J J
2017-07-13
The time of seed germination is a major decision point in the life of plants determining future growth and development. This timing is controlled by seed dormancy, which prevents germination under favourable conditions. The plant hormone abscisic acid (ABA) and the protein DELAY OF GERMINATION 1 (DOG1) are essential regulators of dormancy. The function of ABA in dormancy is rather well understood, but the role of DOG1 is still unknown. Here, we describe four phosphatases that interact with DOG1 in seeds. Two of them belong to clade A of type 2C protein phosphatases: ABA-HYPERSENSITIVE GERMINATION 1 (AHG1) and AHG3. These phosphatases have redundant but essential roles in the release of seed dormancy epistatic to DOG1. We propose that the ABA and DOG1 dormancy pathways converge at clade A of type 2C protein phosphatases.The DOG1 protein is a major regulator of seed dormancy in Arabidopsis. Here, Née et al. provide evidence that DOG1 can interact with the type 2C protein phosphatases AHG1 and AHG3 and that this represents the convergence point of the DOG1-regulated dormancy pathway and signalling by the plant hormone abscisic acid.
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78 FR 14461 - Fenpyrazamine; Pesticide Tolerances
Federal Register 2010, 2011, 2012, 2013, 2014
2013-03-06
... berry subgroup 13-07G at 3.0 ppm (PP 1F7841); pistachio at 0.02 ppm; Caneberry subgroup 13-07A at 7.0..., Bushberry Subgroup 13-07B, Caneberry Subgroup 13-07A, Ginseng, and Pistachio'' in docket ID number EPA-HQ..., hulls at 1.5 ppm; pistachio at 0.02 ppm; lettuce, head at 1.5 ppm; lettuce, leaf at 2 ppm; Caneberry...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kumar, Ramesh, E-mail: rameshphysicsdu@gmail.com; Kaur, Amarjeet, E-mail: amarkaur@physics.du.ac.in
The reduced graphene oxide thin films were fabricated by using the spin coating method. The reduced graphene oxide samples were characterised by Raman studies to obtain corresponding D and G bands at 1360 and 1590 cm{sup −1} respectively. Fourier transform infra-red (FTIR) spectra consists of peak corresponds to sp{sup 2} hybridisation of carbon atoms at 1560 cm{sup −1}. The reduced graphene oxide based chemoresistive sensor exhibited a p-type semiconductor behaviour in ambient conditions and showed good sensitivity to different concentration of ammonia from 25 ppm to 500 ppm and excellent selectivity at room temperature. The sensor displays selectivity to several hazardous vapours such asmore » methanol, ethanol, acetone and hydrazine hydrate. The sensor demonstrated a sensitivity of 9.8 at 25 ppm concentration of ammonia with response time of 163 seconds.« less
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What is the cause of benign transient hyperphosphatasemia? A study of 35 cases.
Crofton, P M
1988-02-01
In a study of 35 children with benign transient hyperphosphatasemia, I found a marked seasonal clustering of cases after the summer months. Furthermore, plasma 25-hydroxyvitamin D concentrations were almost twice those of controls matched for age and time of year. Many children had evidence of weight loss and one had idiopathic hypercalcemia of infancy. Activities both of liver and bone isoenzymes of alkaline phosphatase (EC 3.1.3.1) in plasma were increased. The liver and (to a lesser extent) bone isoenzymes had enhanced electrophoretic mobility, and both showed increased binding to wheat-germ lectin by affinity electrophoresis. For the liver (and probably also the bone) isoenzyme, these changes were due to an increased content of sialic acid. A possible etiology for the condition is proposed involving (a) increased synthesis of alkaline phosphatase, mediated by vitamin D metabolites, and (b) decreased hepatic clearance caused by the high sialic acid content and exacerbated in some cases by the effects of some drugs on the liver.
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Aral, Kübra; Alkan, Banu Arzu; Saraymen, Recep; Yay, Arzu; Şen, Ahmet; Önder, Gözde Özge
2015-05-01
The synergistic effects of vitamin D3 and vitamin K2 on bone loss prevention have been reported. This study evaluates the effects of vitamin D3 and vitamin K2 supplementation in conjunction with conventional periodontal therapy (scaling and root planing [SRP]) on gingival interleukin (IL)-1β and IL-10, serum bone alkaline phosphatase (B-ALP) and tartrate-resistant acid phosphatase 5b (TRAP-5b), and calcium and alveolar bone levels in rats with experimentally induced periodontitis. Seventy-two rats were divided into the following groups: 1) healthy; 2) periodontitis; 3) SRP; 4) SRP + vitamin D3; 5) SRP + vitamin K2; and 6) SRP + vitamins K2 and D3. Periodontitis was induced by ligature placement for 7 days, and vitamin K2 (30 mg/kg) and/or vitamin D3 (2 μg/kg) were administered for 10 days in the SRP + vitamin D3, SRP + vitamin K2, and SRP + vitamins K2 and D3 groups by oral gavage. On day 18, the animals were sacrificed, serum B-ALP, TRAP-5b, and calcium levels were measured, gingiva specimens were extracted for IL-1β and IL-10 analysis, and distances between the cemento-enamel junction and alveolar bone crest were evaluated. Alveolar bone levels in the periodontitis group were significantly greater than those in the other five groups. No significant differences were found in gingival IL-1β and IL-10, serum B-ALP and TRAP-5b, and calcium and alveolar bone levels between the groups receiving SRP and vitamins and the group receiving SRP alone. Within the limitations of this study, vitamin D3 and K2 alone or in combination did not affect gingival IL-1β and IL-10, serum B-ALP and TRAP-5b levels, or alveolar bone compared with conventional periodontal therapy alone.
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Reproduction and health of mallards fed endrin
Spann, J.W.; Heinz, G.H.; Hulse, C.S.
1986-01-01
Concentrations of 0, 1 and 3 ppm endrin in dry duck mash were fed to mallards (Anas platyrhynchos) starting in December, and health and reproduction were measured the following spring and summer. One male fed 3 ppm endrin died with 2.0 ppm endrin (wet weight), a diagnostically lethal level, in its brain. Birds fed 1 ppm endrin reproduced as well as, if not better than, controls. Birds fed 1 ppm endrin had significantly greater hatching success of fertile eggs than did those fed 0 or 3 ppm, and their clutches hatched significantly earlier than did those of birds fed 3 ppm. Mallards fed 3 ppm endrin appeared to reproduce more poorly than controls, but this finding must be regarded with caution because the results of statistical tests often were not significant. Endrin accumulated in eggs to a mean of 1.1 and 2.9 ppm (wet weight) when fed to hens at 1 and 3 ppm. The concentration of endrin in the cacasses of adults was similar to that in eggs, but the concentration in the fat of adults was about 4 to 7 times higher than in eggs.
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Investigating the Role of Cyclin D1 in the Promotion of Genomic Instability and Breast Cancer
2011-09-01
Tween-20, and protease/phosphatase inhibitors (1mM PMSF, 20U/mL aprotinin, 5mg/mL 12 leupeptin, 1mM DTT, 0.4mM NaF, and 10mM β- glycerophosphate ). Whole...inhibitors (1 mM PMSF, 20 U/ml aprotinin, 5 mg/ml leupeptin, 1 mM DTT, 0.4 mM NaF, and 10 mM b- glycerophosphate ), and protein concentration of samples was
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Bagnères, A G; Pichon, A; Hope, J; Davis, R W; Clément, J L
2009-02-01
The susceptibility to fipronil of U.S. and French populations of Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae) was evaluated in two types of laboratory bioassays: contact intoxication with 0.01-1 ppm treated sand and feeding intoxication with 0.1-10 ppm treated filter paper. Contact intoxication with 0.01 ppm fipronil caused 60% mortality after 55 and 64 h in the French and U.S. populations, respectively, whereas in the 5 ppm feeding assay 70 and 60% mortality was observed after 7 d in the French and U.S. populations, respectively. We evaluated the uptake, clearance, and transfer of fipronil among workers of French R. flavipes using [14C] fipronil in contact (0.01 ppm) and feeding (3 ppm) bioassays. Fipronil amounts were measured on their cuticle and in their bodies. Maximal uptake was observed in the contact assay. A significant uptake of fipronil occurred in the feeding assay. Transfer from exposed donors to unexposed recipients occurred within 24 h. Frequent horizontal transfer resulted in a significant uptake in recipients, particularly when donor fipronil acquisition was by feeding. Donors transferred approximately 46% of the toxicant to recipients. Social behaviors such as contact and grooming, together with internalization of the biocide, may be components of the horizontal transfer process and contribute to the efficacy of fipronil in the field.
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40 CFR 180.559 - Clodinafop-propargyl; tolerances for residues.
Code of Federal Regulations, 2010 CFR
2010-07-01
...-pyridinyl)oxy]phenoxy]-, (2R)-), in or on wheat, grain at 0.1 ppm ; wheat, forage at 0.1 ppm; wheat, hay at 0.1 ppm; and wheat, straw at 0.50 ppm. Commodity Parts per million Wheat, forage 0.1 Wheat, grain 0.1 Wheat, hay 0.1 Wheat, straw 0.5 (b) Section 18 emergency exemptions. [Reserved] (c) Tolerances...
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Goebel-Goody, Susan M.; Baum, Matthew; Paspalas, Constantinos D.; Fernandez, Stephanie M.; Carty, Niki C.; Kurup, Pradeep
2012-01-01
Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase that modulates key signaling molecules involved in synaptic plasticity and neuronal function. Targets include extracellular-regulated kinase 1 and 2 (ERK1/2), stress-activated protein kinase p38 (p38), the Src family tyrosine kinase Fyn, N-methyl-d-aspartate receptors (NMDARs), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). STEP-mediated dephosphorylation of ERK1/2, p38, and Fyn leads to inactivation of these enzymes, whereas STEP-mediated dephosphorylation of surface NMDARs and AMPARs promotes their endocytosis. Accordingly, the current model of STEP function posits that it opposes long-term potentiation and promotes long-term depression. Phosphorylation, cleavage, dimerization, ubiquitination, and local translation all converge to maintain an appropriate balance of STEP in the central nervous system. Accumulating evidence over the past decade indicates that STEP dysregulation contributes to the pathophysiology of several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, fragile X syndrome, epileptogenesis, alcohol-induced memory loss, Huntington's disease, drug abuse, stroke/ischemia, and inflammatory pain. This comprehensive review discusses STEP expression and regulation and highlights how disrupted STEP function contributes to the pathophysiology of diverse neuropsychiatric disorders. PMID:22090472
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The Saccharomyces cerevisiae Lipin Homolog is a Mg2+-dependent Phosphatidate Phosphatase Enzyme*
Han, Gil-Soo; Wu, Wen-I; Carman, George M.
2006-01-01
Mg2+-dependent phosphatidate (PA) phosphatase (3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4) catalyzes the dephosphorylation of PA to yield diacylglycerol and Pi. In this work, we identified the Saccharomyces cerevisiae PAH1 (previously known as SMP2) gene that encodes Mg2+-dependent PA phosphatase using amino acid sequence information derived from a purified preparation of the enzyme (Lin, Y.-P., and Carman, G.M. (1989) J. Biol. Chem. 264, 8641–8645). Overexpression of PAH1 in S. cerevisiae directed elevated levels of Mg2+-dependent PA phosphatase activity, whereas the pah1Δ mutation caused reduced levels of enzyme activity. Heterologous expression of PAH1 in Escherichia coli confirmed that Pah1p is a Mg2+-dependent PA phosphatase enzyme, and showed that its enzymological properties were very similar to those of the enzyme purified from S. cerevisiae. The PAH1-encoded enzyme activity was associated with both the membrane and cytosolic fractions of the cell, and the membrane-bound form of the enzyme was salt-extractable. Lipid analysis showed that mutants lacking PAH1 accumulated PA, and had reduced amounts of diacylglycerol and its derivative triacylglycerol. The PAH1-encoded Mg2+-dependent PA phosphatase shows homology to mammalian lipin, a fat-regulating protein whose molecular function is unknown. Heterologous expression of human LPIN1 in E. coli showed that lipin 1 is also a Mg2+-dependent PA phosphatase enzyme. PMID:16467296
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Construction of an efficient Escherichia coli whole-cell biocatalyst for D-mannitol production.
Reshamwala, Shamlan M S; Pagar, Sandip K; Velhal, Vishal S; Maranholakar, Vijay M; Talangkar, Vishal G; Lali, Arvind M
2014-12-01
Mannitol is a six carbon sugar alcohol that finds applications in the pharmaceutical and food industries. A novel Escherichia coli strain capable of converting D-glucose to D-mannitol has been constructed, wherein native mannitol-1-phosphate dehydrogenase (MtlD) and codon-optimized Eimeria tenella mannitol-1-phosphatase (M1Pase) have been overexpressed. Codon-optimized Pseudomonas stutzeri phosphite dehydrogenase (PtxD) was overexpressed for cofactor (NADH) regeneration with the concomitant oxidation of phosphite to phosphate. Whole-cell biotransformation using resting cells in a medium containing D-glucose and equimolar sodium phosphite resulted in d-mannitol yield of 87 mol%. Thus, production of an industrially relevant biochemical without using complex media components and elaborate process control mechanisms has been demonstrated. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
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Tian, Meng; Xu, Jian; Lei, Gang; Lombroso, Paul J.; Jackson, Michael F.; MacDonald, John F.
2016-01-01
N-methyl-D-aspartate receptors (NMDARs) are necessary for the induction of synaptic plasticity and for the consolidation of learning and memory. NMDAR function is tightly regulated by functionally opposed families of kinases and phosphatases. Herein we show that the striatal-enriched protein tyrosine phosphatase (STEP) is recruited by Gαq-coupled receptors, including the M1 muscarinic acetylcholine receptor (M1R), and opposes the Src tyrosine kinase-mediated increase in the function of NMDARs composed of GluN2A. STEP activation by M1R stimulation requires IP3Rs and can depress NMDA-evoked currents with modest intracellular Ca2+ buffering. Src recruitment by M1R stimulation requires coincident NMDAR activation and can augment NMDA-evoked currents with high intracellular Ca2+ buffering. Our findings suggest that Src and STEP recruitment is contingent on differing intracellular Ca2+ dynamics that dictate whether NMDAR function is augmented or depressed following M1R stimulation. PMID:27857196
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40 CFR 91.312 - Analytical gases.
Code of Federal Regulations, 2012 CFR
2012-07-01
... nitrogen as the predominant diluent with the balance oxygen. (e) Fuel for the hydrocarbon flame ionization... operation. (1) Purified nitrogen, also referred to as “zero-grade nitrogen” (Contamination≤1 ppm C, ≤1 ppm... mixture (40±2 percent hydrogen, balance helium) (Contamination≤1 ppm C, ≤400 ppm CO) (4) Purified...
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40 CFR 91.312 - Analytical gases.
Code of Federal Regulations, 2011 CFR
2011-07-01
... nitrogen as the predominant diluent with the balance oxygen. (e) Fuel for the hydrocarbon flame ionization... operation. (1) Purified nitrogen, also referred to as “zero-grade nitrogen” (Contamination≤1 ppm C, ≤1 ppm... mixture (40±2 percent hydrogen, balance helium) (Contamination≤1 ppm C, ≤400 ppm CO) (4) Purified...
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40 CFR 91.312 - Analytical gases.
Code of Federal Regulations, 2010 CFR
2010-07-01
... nitrogen as the predominant diluent with the balance oxygen. (e) Fuel for the hydrocarbon flame ionization... operation. (1) Purified nitrogen, also referred to as “zero-grade nitrogen” (Contamination≤1 ppm C, ≤1 ppm... mixture (40±2 percent hydrogen, balance helium) (Contamination≤1 ppm C, ≤400 ppm CO) (4) Purified...
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40 CFR 91.312 - Analytical gases.
Code of Federal Regulations, 2013 CFR
2013-07-01
... nitrogen as the predominant diluent with the balance oxygen. (e) Fuel for the hydrocarbon flame ionization... operation. (1) Purified nitrogen, also referred to as “zero-grade nitrogen” (Contamination≤1 ppm C, ≤1 ppm... mixture (40±2 percent hydrogen, balance helium) (Contamination≤1 ppm C, ≤400 ppm CO) (4) Purified...
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Matsuura, Ikuo; Saitoh, Tetsuji; Ashina, Michiko; Wako, Yumi; Iwata, Hiroshi; Toyota, Naoto; Ishizuka, Yoshihito; Namiki, Masato; Hoshino, Nobuhito; Tsuchitani, Minoru
2005-12-01
A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using vinclozolin by dietary administration at 0, 40, 200, and 1000 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed changes due to vinclozolin in the AGD, nipple development, sexual maturation, sex organ weights, and blood sex hormone concentrations in males of both parental animals and offspring, even at the lowest dose of 40 ppm, confirmed by results for the classical endpoints of histopathological examination at 200 ppm and mating at 1000 ppm. The effects on parental males included increased pituitary and testis weights, and decreased epididymis weights at 1000 ppm in both generations, and decreased prostate and epididymis weights at 200 and 1000 ppm and seminal vesicle weights at 1000 ppm in F1 males. Histopathological examination revealed hypertrophy of the basophilic cells in the pituitary at these two doses, and diffuse hyperplasia of the testicular interstitial cells and atrophy of the seminal vesicle mucosa at 1000 ppm in F0 and F1 males. In addition, F1 males demonstrated decrease in prostate fluid at 200 and 1000 ppm. Blood hormone analysis revealed increases in LH, FSH, testosterone, and DHT in F0 and F1 males at 1000 ppm. General toxicological effects included suppressed body weight gain in F0 and F1 females and in F1 males, and reduced food consumption in F0 and F1 females at 1000 ppm. Histopathological examination revealed centrilobular hepatocellular hypertrophy in males at 200 and 1000 ppm and in females at 1000 ppm, increased lipid droplets in the adrenal zona fasciculata and zona glomerulosa in males at 200 and 1000 ppm and in females at 40 ppm and above, and hyperplasia of ovarian interstitial cells and vacuolation of lutein cells in females at 1000 ppm in both generations. Almost all the tissue changes were accompanied by changes in weights. Decreases in T3 and/or T4 were observed in both sexes and generations at 1000 ppm and in F0 females at 200 ppm. However, these were presumed to be secondary to induction of hepatic drug-metabolizing enzymes, activities being increased for a range of enzymes in both sexes and generations at 1000 ppm. Rise in BROD activity was the most prominent, suggesting that vinclozolin mainly induces CYP2B. As for effects on reproductive function, a marked decrease in the fertility index caused by male infertility was observed in F1 animals at 1000 ppm. However, no effects on spermatogenesis were seen in either F0 or F1 males. Since cleft prepuce and penile hypoplasia were observed in infertile males, it is probable that the cause of infertility in F1 males was related to morphological abnormalities in the external genitalia. Vinclozolin did not affect the estrous cycle, mating, fertility, pregnancy, parturition, or nursing behavior in either F0 or F1 females. In offspring, in addition to suppressed body weight gain in F1 males and females at 1000 ppm, neonatal toxicity caused by antiandrogen activity of vinclozolin was observed in F1 and F2 males. Effects included shortened AGD in F1 males at 1000 ppm and in F2 males at 200 and 1000 ppm, and nipple/areola remnants in F1 males at 200 and 1000 ppm and in F2 males at 40 ppm and above. In addition, decreased epididymis weights at weaning and morphological abnormalities of the external genitalia, including cleft prepuce, penile hypoplasia, and vaginal pouch, were seen in F1 and F2 males at 1000 ppm.
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77 FR 14291 - Penthiopyrad; Pesticide Tolerances
Federal Register 2010, 2011, 2012, 2013, 2014
2012-03-09
...-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxamide) in animal commodities hog, meat at 0.01 ppm; hog, fat...; cattle, meat at 0.05 ppm; cattle, fat at 0.05 ppm; cattle, liver at 0.2 ppm; cattle, kidney at 0.1 ppm; cattle, meat byproducts at 0.2 ppm; sheep, meat at 0.01 ppm; sheep, fat at 0.02 ppm; sheep, liver at 0.05...
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Caldas, Justina V; Vignale, Karen; Boonsinchai, Nirun; Wang, Jinrong; Putsakum, Monticha; England, Judith A; Coon, Craig N
2018-05-11
The present study was conducted to determine whether the addition of β-mannanase in broiler feed changes hormonal profiles in the blood and broiler performance and nutrient availability. Five hundred and four Cobb male chickens were studied during d 7 to 21. Three corn-soybean meal (SBM) based diets 1) Low SBM (18% SBM); 2) High SBM (31% SBM); and 3) High SBM+GG (31% SBM + Guar Gum (GG) 0.5%) with 3 levels of β-mannanase (0, 200, and 400 ppm) were mixed to produce 9 diets. A factorial design 3 × 3 was performed with JMP pro 13 (SAS, 2017). Analysis of variance and contrast analysis were used to test significance level at P < 0.05. Glucose (190 and 188 mg/dL) was increased with 200 and 400 ppm of β-mannanase, respectively, compared to control (182 mg/dL) in the fasted state (P < 0.037). Glucose was higher in chicks fed with the High SBM and High SBM + GG diets but lower in the fasted re-fed state (P < 0.01). Insulin was higher with 200 and 400 ppm added β-mannanase in the fed state (P < 0.021). Insulin-like growth factor-1 was higher with 400 ppm added to High SBM+GG. β-mannanase improved feed conversion ratio (FCR) 9 points with 400 ppm in High SBM diet (P < 0.01) and 16 and 18 points with 200 and 400 ppm, respectively, added to the High SBM+GG diet (P < 0.01). Viscosity decreased from 19.2 to 7 cps with both enzyme doses in the High SBM + GG diet (P < 0.01). Digestible energy was +152 kcal/kg with 400 ppm β-mannanase in the High SBM diet and +200 kcal/kg with both levels of enzyme in High SBM+GG diet. Digestibility of amino acids was improved from 0.8 to 3.6% with β-mannanase in High SBM+GG diet (P < 0.05). In conclusion, chicks fed with High SBM and High SBM+GG diets with added β-mannanase significantly improved blood glucose and anabolic hormone homeostasis, FCR, digestible energy, and digestible amino acids compared to chicks fed with same diets without β-mannanase.
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Ammonia and Carbon Dioxide Concentrations in Disposable and Reusable Ventilated Mouse Cages
Silverman, Jerald; Bays, David W; Cooper, Sheldon F; Baker, Stephen P
2008-01-01
This study compares resuable and disposable individually ventilated mouse cages in terms of the formation of intracage CO2 and NH3. Crl:CD-1(ICR) female mice were placed in either disposable or reusable ventilated cages in a positive pressure animal rack. Intracage CO2 and NH3 were measured once daily for 9 d; temperature and relative humidity were monitored for the first 7 d. Results indicated higher CO2 levels in the rear of the disposable cages and in the front of the reusable cages. This pattern corresponded to where the mice tended to congregate. However, CO2 concentrations did not differ significantly between the 2 cage types. Average CO2 levels in both cage types never exceeded approximately 3000 ppm. Intracage NH3 began to rise in the reusable cages on day 4, reached approximately 50 ppm by day 5 and by day 9 was greater than 150 ppm at the cages' rear sampling port while remaining at approximately 70 ppm at the front sampling port. Intracage NH3 levels in the disposable cages remained less than or equal to 3.2 ppm. Intracage temperature and relative humidity were approximately the same in both cage types. We concluded that the disposable ventilated cage performed satisfactorily under the conditions of the study. PMID:18351723
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Occupational health concerns in the welding industry.
Korczynski, R E
2000-12-01
The Workplace Safety and Health Branch initiated a proactive study in the welding industry in Manitoba. Eight welding companies participated in this study. Health concerns raised by welders were welders' flash, sore/red/teary eyes, headaches, nosebleeds, and a black mucous discharge from their nasal membrane. Most welders expressed concern regarding excessive smoke levels in the workplace and inadequate ventilation. Types of welding identified were MIG mild steel, MIG stainless steel, and TIG aluminum. Monitoring involved an assessment of noise levels, fume composition, and carbon monoxide and ozone concentrations. Metal analyses were according to National Institute for Occupational Safety and Health (NIOSH) Method 7300. Noise dosimeters used were the Quest model 100 and Micro 14 & 15. Carbon monoxide was monitored using the Gastech Model 4700 and ozone using the AID Portable Ozone Meter Model 560. In Manitoba, a hearing conservation program is required when the equivalent sound exposure level (normalized Lex 8-hr) exceeds 80 dBA-weighted. The American Conference of Governmental Industrial Hygienists' threshold limit value-time weighted average (ACGIH TLV-TWA) for iron is 5.0 mg/m3, manganese is 0.2 mg/m3, carbon monoxide is 25 ppm, and ozone is 0.05 ppm (heavy work), 0.08 ppm (moderate work), and 0.1 ppm (light work). Welders' personal exposures to manganese ranged from 0.01-4.93 mg/m3 (N = 42; AM = 0.5; GM = 0.2; SD +/- 0.9; GSD +/- 3.2) and to iron ranged from 0.04-16.29 mg/m3 (N = 42; AM = 3.0; GM = 1.4; SD +/- 3.5; GSD +/- 2.5). Noise exposures ranged from 79-98 dBA (N = 44; AM = 88.9; GM = 88.8; SD +/- 4.2; GSD +/- 1.0). Carbon monoxide levels were less than 5.0 ppm (at source) and ozone levels varied from 0.4-0.6 ppm (at source). Ventilation upgrades in the workplace were required in most welding shops. Only 7 percent of the welders wore respiratory protection. A hearing conservation program and hearing protection were required at all monitored workplaces.
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40 CFR 91.312 - Analytical gases.
Code of Federal Regulations, 2014 CFR
2014-07-01
...) Purified nitrogen, also referred to as “zero-grade nitrogen” (Contamination≤1 ppm C, ≤1 ppm CO, ≤400 ppm... percent hydrogen, balance helium) (Contamination≤1 ppm C, ≤400 ppm CO) (4) Purified synthetic air, also... must be available: C3 H8 and purified synthetic air (dilute measurements); C3 H8 and purified nitrogen...
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40 CFR 61.67 - Emission tests.
Code of Federal Regulations, 2011 CFR
2011-07-01
... = Conversion factor from ppmw to units of emission standard, 0.001 (metric units) = 0.002 (English units) PPVC...(a), or § 61.64(a)(1), (b), (c), or (d), or from any control system to which reactor emissions are... conversion factor, 1,000 g/kg (1 lb/lb). 10−6 = Conversion factor for ppm. Z = Production rate, kg/hr (lb/hr...
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40 CFR 61.67 - Emission tests.
Code of Federal Regulations, 2012 CFR
2012-07-01
... = Conversion factor from ppmw to units of emission standard, 0.001 (metric units) = 0.002 (English units) PPVC...(a), or § 61.64(a)(1), (b), (c), or (d), or from any control system to which reactor emissions are... conversion factor, 1,000 g/kg (1 lb/lb). 10−6 = Conversion factor for ppm. Z = Production rate, kg/hr (lb/hr...
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Evaluation of salivary fluoride retention from a new high fluoride mouthrinse.
Mason, Stephen C; Shirodaria, Soha; Sufi, Farzana; Rees, Gareth D; Birkhed, Dowen
2010-11-01
To evaluate salivary fluoride retention from a new high fluoride daily use mouthrinse over a 120 min period. Sixteen subjects completed a randomised single-blind, four-treatment cross-over trial. Sensodyne® Pronamel® mouthrinse (A) contained 450 ppm fluoride; reference products were Colgate® Fluorigard® (B), Listerine® Total Care (C) and Listerine Softmint Sensation (D) containing 225, 100 and 0 ppm fluoride respectively. Salivary fluoride retention was monitored ex vivo after a single supervised use of test product (10 mL, 60 s). Samples were collected at 0, 1, 3, 5, 15, 30, 60 and 120 min post-rinse, generating fluoride clearance curves from which the area under the curve (AUC) was calculated. Differences in salivary fluoride concentrations for each product were analysed using ANCOVA at each time point using a 5% significance level, as well as lnAUC for the periods 0-120, 0-1, 1-15, 15-60 and 60-120 min. Pairwise comparisons between all treatment groups were performed. Salivary fluoride levels for A-C peaked immediately following use. Fluoride levels were statistically significantly higher for A versus B-D (p≤ 0.004), linear dose responses were apparent. AUC(0-120) was statistically significantly greater for A than for B (p = 0.035), C (p< 0.0001) and D (p< 0.0001). Post-hoc comparisons of lnAUC for the remaining time domains showed fluoride retention from A was statistically significantly greater versus B-D (p< 0.0001). Single-use treatment with the new mouthrinse containing 450 ppm fluoride resulted in statistically significantly higher salivary fluoride levels throughout the 120 min test period. Total fluoride retention (AUC(0-120)) was also statistically significantly greater versus comparator rinse treatments. Copyright © 2010 Elsevier Ltd. All rights reserved.
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Hoekstra, Elmer; Das, Asha M; Swets, Marloes; Cao, Wanlu; van der Woude, C Janneke; Bruno, Marco J; Peppelenbosch, Maikel P; Kuppen, Peter J K; Ten Hagen, Timo L M; Fuhler, Gwenny M
2016-04-19
Cell signaling is dependent on the balance between phosphorylation of proteins by kinases and dephosphorylation by phosphatases. This balance if often disrupted in colorectal cancer (CRC), leading to increased cell proliferation and invasion. For many years research has focused on the role of kinases as potential oncogenes in cancer, while phosphatases were commonly assumed to be tumor suppressive. However, this dogma is currently changing as phosphatases have also been shown to induce cancer growth. One of these phosphatases is protein tyrosine phosphatase 1B (PTP1B). Here we report that the expression of PTP1B is increased in colorectal cancer as compared to normal tissue, and that the intrinsic enzymatic activity of the protein is also enhanced. This suggests a role for PTP1B phosphatase activity in CRC formation and progression. Furthermore, we found that increased PTP1B expression is correlated to a worse patient survival and is an independent prognostic marker for overall survival and disease free survival. Knocking down PTP1B in CRC cell lines results in a less invasive phenotype with lower adhesion, migration and proliferation capabilities. Together, these results suggest that inhibition of PTP1B activity is a promising new target in the treatment of colorectal cancer and the prevention of metastasis.
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Murata, K; Sakon, M; Kambayashi, J; Yukawa, M; Yano, Y; Fujitani, K; Kawasaki, T; Shiba, E; Mori, T
1993-04-01
Protein phosphatase 1 is considered to be involved in thrombin-induced platelet activation (Murata et al., Biochem Int 26:327-334, 1992). To clarify the mechanism, we examined the effects of protein phosphatase 1 and 2A inhibitors (calyculin A, tautomycin, okadaic acid) on Ca2+ influx. In the presence of 1 mM Ca2+, thrombin- (0.1 U/ml) induced platelet aggregation and ATP release were inhibited by calyculin A, while this inhibitory effect was abolished in the absence of Ca2+ (EGTA 1 mM). Furthermore, thrombin-induced Mn2+ influx but not intracellular Ca2+ mobilization was inhibited by calyculin A in a dose-related manner. Calyculin A also blocked the ongoing Ca2+ influx when added 3 min after thrombin stimulation. Similar inhibitory effects were observed with okadaic acid and tautomycin in the same potency sequence as the reported one for protein phosphatase 1 (calyculin A > tautomycin > okadaic acid). These results suggest that the anti-platelet effects of phosphatase inhibitors are due to the inhibition of Ca2+ influx and that protein phosphatase 1 plays a key role in the regulation of receptor operated Ca2+ channel of human platelets.
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Interactions Between Vitamin D and Breast Cancer
2009-09-01
ERBB2 GRB7 B EGFR MKI67 AURKA BIRC5 CCND1 CCNA1 TP53 MMP11 CTSL2 BAX BCL2 VDR C CYP24A1 CYP27B1 HR SNAI2 MYC PTGS2 HPGD PTGER4 DUSP10 IL6 TGFB1 TNF D...BIRC5 CCND1 CCNA1 TP53 MMP11 CTSL2 BAX BCL2 VDR G CYP24A1 CYP27B1 HR SNAI2 MYC PTGS2 HPGD PTGER4 DUSP10 IL6 TGFB1 TNF H CDKN1A IGFBP3 SPP1 AR PTHLH...NAD) C08 Hs.199248 NM_000958 PTGER4 Prostaglandin E receptor 4 (subtype EP4) C09 Hs.497822 NM_007207 DUSP10 Dual specificity phosphatase 10 C10
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40 CFR 89.312 - Analytical gases.
Code of Federal Regulations, 2012 CFR
2012-07-01
... by dynamic blending. Nitrogen shall be the predominant diluent with the balance oxygen. (e) Fuel for... gases must be available for operation: (1) Purified nitrogen (Contamination ≤ 1 ppm C, ≤ 1 ppm CO, ≤ 400 ppm CO2, ≤ 0.1 ppm NO) (2) [Reserved] (3) Hydrogen-helium mixture (40 ±2 percent hydrogen, balance...
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40 CFR 89.312 - Analytical gases.
Code of Federal Regulations, 2010 CFR
2010-07-01
... by dynamic blending. Nitrogen shall be the predominant diluent with the balance oxygen. (e) Fuel for... gases must be available for operation: (1) Purified nitrogen (Contamination ≤ 1 ppm C, ≤ 1 ppm CO, ≤ 400 ppm CO2, ≤ 0.1 ppm NO) (2) [Reserved] (3) Hydrogen-helium mixture (40 ±2 percent hydrogen, balance...
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40 CFR 89.312 - Analytical gases.
Code of Federal Regulations, 2011 CFR
2011-07-01
... by dynamic blending. Nitrogen shall be the predominant diluent with the balance oxygen. (e) Fuel for... gases must be available for operation: (1) Purified nitrogen (Contamination ≤ 1 ppm C, ≤ 1 ppm CO, ≤ 400 ppm CO2, ≤ 0.1 ppm NO) (2) [Reserved] (3) Hydrogen-helium mixture (40 ±2 percent hydrogen, balance...
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40 CFR 89.312 - Analytical gases.
Code of Federal Regulations, 2013 CFR
2013-07-01
... by dynamic blending. Nitrogen shall be the predominant diluent with the balance oxygen. (e) Fuel for... gases must be available for operation: (1) Purified nitrogen (Contamination ≤ 1 ppm C, ≤ 1 ppm CO, ≤ 400 ppm CO2, ≤ 0.1 ppm NO) (2) [Reserved] (3) Hydrogen-helium mixture (40 ±2 percent hydrogen, balance...
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40 CFR 89.312 - Analytical gases.
Code of Federal Regulations, 2014 CFR
2014-07-01
... blending. Nitrogen shall be the predominant diluent with the balance oxygen. (e) Fuel for the FID shall be... be available for operation: (1) Purified nitrogen (Contamination ≤ 1 ppm C, ≤ 1 ppm CO, ≤ 400 ppm CO2, ≤ 0.1 ppm NO) (2) [Reserved] (3) Hydrogen-helium mixture (40 ±2 percent hydrogen, balance helium...
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21 CFR 74.2053 - D&C Black No. 3.
Code of Federal Regulations, 2010 CFR
2010-04-01
... may be avoided by current good manufacturing practices: (1) Calcium hydroxyapatite (CaO and P2O5), not...) Total polycyclic aromatic hydrocarbons (PAHs), not more than 5 mg/kg (5 ppm). (c) Uses and restrictions...
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Lee, Eunhee; Stafford, Walter F
2015-01-01
Scaffold proteins bind to and functionally link protein members of signaling pathways. Interaction of the scaffold proteins, myosin phosphatase target subunit (MYPT1) and myosin phosphatase-RhoA interacting protein (MRIP), causes co-localization of myosin phosphatase and RhoA to actomyosin. To examine biophysical properties of interaction of MYPT1 with MRIP, we employed analytical ultracentrifugation and surface plasmon resonance. In regard to MRIP, its residues 724-837 are sufficient for the MYPT1/MRIP interaction. Moreover, MRIP binds to MYPT1 as either a monomer or a dimer. With respect to MYPT1, its leucine repeat region, LR (residues 991-1030) is sufficient to account for the MYPT1/MRIP interaction. Furthermore, point mutations that replace glutamic acids 998-1000 within LR reduced the binding affinity toward MRIP. This suggests that the glutamic acids of MYPT1 play an important role in the interaction.
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TGF-β1/Smad3 Pathway Targets PP2A-AMPK-FoxO1 Signaling to Regulate Hepatic Gluconeogenesis.
Yadav, Hariom; Devalaraja, Samir; Chung, Stephanie T; Rane, Sushil G
2017-02-24
Maintenance of glucose homeostasis is essential for normal physiology. Deviation from normal glucose levels, in either direction, increases susceptibility to serious medical complications such as hypoglycemia and diabetes. Maintenance of glucose homeostasis is achieved via functional interactions among various organs: liver, skeletal muscle, adipose tissue, brain, and the endocrine pancreas. The liver is the primary site of endogenous glucose production, especially during states of prolonged fasting. However, enhanced gluconeogenesis is also a signature feature of type 2 diabetes (T2D). Thus, elucidating the signaling pathways that regulate hepatic gluconeogenesis would allow better insight into the process of normal endogenous glucose production as well as how this process is impaired in T2D. Here we demonstrate that the TGF-β1/Smad3 signaling pathway promotes hepatic gluconeogenesis, both upon prolonged fasting and during T2D. In contrast, genetic and pharmacological inhibition of TGF-β1/Smad3 signals suppressed endogenous glucose production. TGF-β1 and Smad3 signals achieved this effect via the targeting of key regulators of hepatic gluconeogenesis, protein phosphatase 2A (PP2A), AMP-activated protein kinase (AMPK), and FoxO1 proteins. Specifically, TGF-β1 signaling suppressed the LKB1-AMPK axis, thereby facilitating the nuclear translocation of FoxO1 and activation of key gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. These findings underscore an important role of TGF-β1/Smad3 signaling in hepatic gluconeogenesis, both in normal physiology and in the pathophysiology of metabolic diseases such as diabetes, and are thus of significant medical relevance. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
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TGF-β1/Smad3 Pathway Targets PP2A-AMPK-FoxO1 Signaling to Regulate Hepatic Gluconeogenesis*
Yadav, Hariom; Devalaraja, Samir; Chung, Stephanie T.; Rane, Sushil G.
2017-01-01
Maintenance of glucose homeostasis is essential for normal physiology. Deviation from normal glucose levels, in either direction, increases susceptibility to serious medical complications such as hypoglycemia and diabetes. Maintenance of glucose homeostasis is achieved via functional interactions among various organs: liver, skeletal muscle, adipose tissue, brain, and the endocrine pancreas. The liver is the primary site of endogenous glucose production, especially during states of prolonged fasting. However, enhanced gluconeogenesis is also a signature feature of type 2 diabetes (T2D). Thus, elucidating the signaling pathways that regulate hepatic gluconeogenesis would allow better insight into the process of normal endogenous glucose production as well as how this process is impaired in T2D. Here we demonstrate that the TGF-β1/Smad3 signaling pathway promotes hepatic gluconeogenesis, both upon prolonged fasting and during T2D. In contrast, genetic and pharmacological inhibition of TGF-β1/Smad3 signals suppressed endogenous glucose production. TGF-β1 and Smad3 signals achieved this effect via the targeting of key regulators of hepatic gluconeogenesis, protein phosphatase 2A (PP2A), AMP-activated protein kinase (AMPK), and FoxO1 proteins. Specifically, TGF-β1 signaling suppressed the LKB1-AMPK axis, thereby facilitating the nuclear translocation of FoxO1 and activation of key gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. These findings underscore an important role of TGF-β1/Smad3 signaling in hepatic gluconeogenesis, both in normal physiology and in the pathophysiology of metabolic diseases such as diabetes, and are thus of significant medical relevance. PMID:28069811
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Saha, Supradip; Mina, B L; Gopinath, K A; Kundu, S; Gupta, H S
2008-04-01
Potential impact of different levels and sources of organic composts on activities of phosphatases (acid and alkaline phosphatase, phosphodiesterase, and inorganic pyrophosphatase) was studied after three years of continuous application. Enzyme activities were compared with microbial biomass P and available P. Experimental plots were divided based on the organic source into three groups: those receiving farmyard manure (FYM), vermicompost (VC) and Lantana compost (LC). Microbial biomass P (11.7 g kg(-1) soil), available P (24.0 g kg(-1) soil) and acid phosphatase (1.3 mg g(-1) p-NP g(-1) soil h(-1)) was highest in highest dose of VC. Acid phosphatase activity was high in all plots, including those where microbial biomass P levels were low. Most of the phosphatase activities were significantly correlated with available P in FYM and VC. These relationships were negative for LC treatments. Results showed that application of earthworm casts is helpful in faster transformation of organic P by facilitating better environment to microbes and plant roots.
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Rogozinska, E; D'Amico, M I; Khan, K S; Cecatti, J G; Teede, H; Yeo, S; Vinter, C A; Rayanagoudar, G; Barakat, R; Perales, M; Dodd, J M; Devlieger, R; Bogaerts, A; van Poppel, M N M; Haakstad, L; Shen, G X; Shub, A; Luoto, R; Kinnunen, T I; Phelan, S; Poston, L; Scudeller, T T; El Beltagy, N; Stafne, S N; Tonstad, S; Geiker, N R W; Ruifrok, A E; Mol, B W; Coomarasamy, A; Thangaratinam, S
2016-01-01
To develop maternal, fetal, and neonatal composite outcomes relevant to the evaluation of diet and lifestyle interventions in pregnancy by individual patient data (IPD) meta-analysis. Delphi survey. The International Weight Management in Pregnancy (i-WIP) collaborative network. Sample Twenty-six researchers from the i-WIP collaborative network from 11 countries. A two-generational Delphi survey involving members of the i-WIP collaborative network (26 members in 11 countries) was undertaken to prioritise the individual outcomes for their importance in clinical care. The final components of the composite outcomes were identified using pre-specified criteria. Composite outcomes considered to be important for the evaluation of the effect of diet and lifestyle in pregnancy. Of the 36 maternal outcomes, nine were prioritised and the following were included in the final composite: pre-eclampsia or pregnancy-induced hypertension, gestational diabetes mellitus (GDM), elective or emergency caesarean section, and preterm delivery. Of the 27 fetal and neonatal outcomes, nine were further evaluated, with the final composite consisting of intrauterine death, small for gestational age, large for gestational age, and admission to a neonatal intensive care unit (NICU). Our work has identified the components of maternal, fetal, and neonatal composite outcomes required for the assessment of diet and lifestyle interventions in pregnancy by IPD meta-analysis. © 2015 Royal College of Obstetricians and Gynaecologists.
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NASA Astrophysics Data System (ADS)
Li, W.; Li, H.; Tao, C.; Jin, Z.
2013-12-01
Water can be present in the oceanic upper mantle as structural OH in nominally anhydrous minerals. Such water has marked effects on manlte melting and rheology properties. However, the water content of MORB source is mainly inferred from MORB glass data that the water budget of oceanic upper mantle is poorly constrained. Here we present water analysis of peridotites from different sites on the Southwest Indian Ridge. The mineral assemblages of these peridotites are olivine, orthopyroxene, clinopyroxene and spinel. As the peridotites have been serpentinized to different degrees, only water contents in orthopyroxnene can be better determined by FTIR spectrometry. The IR absorption bands of all measured orthopyroxenes can be devided into four different groups: (1)3562-3596 cm-1, (2)3515-3520 cm-1, (3)3415-3420 cm-1, (4)3200-3210 cm-1. The positions of these absorption bands are in good agreement with perivious reports. Hydrogen profile measurements performed on larger opx grains in each suite of samples show no obvious variations between core and rims regions, indicating that diffusion of H in orthopyroxene is insignificant. Preliminary measured water contents of orthopyroxene differ by up to one order of magnitude. Opx water contents (80-220 ppm) of most samples are within the range of those found in mantle xenoliths of contentinal settings [1]. Opx water contents of one sample (VM-21V-S9-D5-2: 38-64 ppm) are similar to those from Gakkel Ridge abyssal peridotites (25-60 ppm) [2] but higher than those from Mid-Atlantic Ridge ODP-Leg 209(~15 ppm) [3]. Two other samples show high water concentrations (VM-19ΙΙΙ-S3-TVG2-4: 260-275 ppm, Wb-18-b: 190-265 ppm) which compare well with those from Mid-Atlantic Ridge ODP-Leg 153(160-270 ppm) [4]. Most opx water contents decrease with increasing depletion degree (spl Cr#) consistent with an incompatible behavior of water during partial melting. Recalculated bulk water contents (27-117 ppm) of these peridotites overlap estimates for MORB source. However, estimated original bulk water contents prior to partial melting of some samples are very high (e.g. wb-18-b: 540-770 ppm) and can not simply be explained by melt extraction. Our data suggest that the water contents in the oceanic upper mantle of SWIR are heterogeneous or different post-melt depletion histories are involved. Reference [1] Peslier (2010) JVGR 197, 239-258. [2] Peslier et al. (2007) Goldschmidt. [3] Gose et al. (2009) Geology 37,543-546 [4] Schmädicke et al. (2011) Lithos 125, 308-320.
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da Silva, Cristina; Sahlen, Anders; Winter, Reidar; Bäck, Magnus; Rück, Andreas; Settergren, Magnus; Manouras, Aristomenis; Shahgaldi, Kambiz
2014-12-01
To investigate the role of 2D-transthoracic echocardiography (2D-TTE) and 3D-transesophageal echocardiography (3D-TEE) in the determination of aortic annulus size prior transcatheter aortic valve implantation (TAVI) and its' impact on the prevalence of patient prosthesis mismatch (PPM). Echocardiography plays an important role in measuring aortic annulus dimension in patients undergoing TAVI. This has great importance since it determines both eligibility for TAVI and selection of prosthesis type and size, and can be potentially important in preventing an inadequate ratio between the prosthetic valvular orifice and the patient's body surface area, concept known as prosthesis-patient mismatch (PPM). A total of 45 patients were studied pre-TAVI: 20 underwent 3D-TEE (men/women 12/8, age 84.8 ± 5.6) and 25 2D-TTE (men/women 9/16, age 84.4 ± 5.4) in order to measure aortic annulus diameter. The presence of PPM was assessed before hospital discharge and after a mean period of 3 months. Moderate PPM was defined as indexed aortic valve area (AVAi) ≤ 0.85 cm(2)/m(2) and severe PPM as AVAi < 0.65 cm(2)/m(2). Immediately post-TAVI, moderate PPM was present in 25 and 28 % of patients worked up using 3D-TEE and 2D-TTE respectively p value = n.s) and severe PPM occurred in 10 % of the patients who underwent 3D-TEE and in 20 % in those with 2D-TTE (p value = n.s). The echocardiographic evaluation 3 months post-TAVI showed 25 % moderate PPM in the 3D-TEE group compared with 24 % in the 2D-TTE group (p value = n.s) and no cases of severe PPM in the 3DTEE group comparing to 20 % in the 2D-TTE group (p = 0.032). Our results indicate a higher incidence of severe PPM in patients who performed 2DTTE compared to those performing 3DTEE prior TAVI. This suggests that the 3D technique should replace the 2DTTE analysis when investigating the aortic annulus diameter in patients undergoing TAVI.
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Brumell, J H; Chan, C K; Butler, J; Borregaard, N; Siminovitch, K A; Grinstein, S; Downey, G P
1997-01-10
The tyrosine phosphorylation of several proteins induced in neutrophils by soluble and particulate stimuli is thought to be crucial for initiating antimicrobial responses. Although activation of tyrosine kinases is thought to mediate this event, the role of tyrosine phosphatases in the initiation and modulation of neutrophil responses remains largely undefined. We investigated the role of Src homology 2-containing tyrosine phosphatase 1 (SHP-1; also known as protein tyrosine phosphatase 1C (PTP1C), hematopoetic cell phosphatase, PTP-N6, and SHPTP-1), a phosphatase expressed primarily in hemopoietic cells, in the activation of human neutrophils. SHP-1 mRNA and protein were detected in these cells, and the enzyme was found to be predominantly localized to the cytosol in unstimulated cells. Following stimulation with neutrophil agonists such as phorbol ester, chemotactic peptide, or opsonized zymosan, a fraction of the phosphatase redistributed to the cytoskeleton. Agonist treatment also induced significant decreases (30-60%) in SHP-1 activity, which correlated temporally with increases in the cellular phosphotyrosine content. Phosphorylation of SHP-1 on serine residues was associated with the inhibition of its enzymatic activity, suggesting a causal relationship. Accordingly, both the agonist-evoked phosphorylation of SHP-1 and the inhibition of its catalytic activity were blocked by treatment with bisindolylmaleimide I, a potent and specific inhibitor of protein kinase C (PKC) activity. Immunoprecipitated SHP-1 was found to be phosphorylated efficiently by purified PKC in vitro. Such phosphorylation also caused a decrease in the phosphatase activity of SHP-1. Together, these data suggest that inhibition of SHP-1 by PKC-mediated serine phosphorylation plays a role in facilitating the accumulation of tyrosine-phosphorylated proteins following neutrophil stimulation. These findings provide a new link between the PKC and tyrosine phosphorylation branches of the signaling cascade that triggers antimicrobial responses in human neutrophils.
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Voltura, M.B.; French, J.B.
1998-01-01
Contaminant exposure is an environmental factor often overlooked in ecological studies. Yet exposure to toxicants is likely to be metabolically expensive, and result in a trade-off between energy spent to detoxify an excrete contaminants, and energy allocated to growth or reproduction. To quantify the energetic cost of PCB exposure, we fed mice diets containing 0, 0.1, 10 and 25 ppm PCBs (mg PCBs/kg food). After 6 wks, there were no differences in food intake or body mass related to the level of dietary PCBs. We continued to feed mice the PCB diets for one year, and then measured food intake and resting metabolic rate. After one year, all mice had gained mass, but mice on the 25 ppm diet were significantly heavier than mice in the other groups. Mice on the 25 ppm diet also showed an increase in both food intake (p=0.06) and metabolic rate (p=0.01), after correction for differences in body mass. Food intake averaged 4.1 g/d for mice on the 25 ppm diet, compared to 3.7 gld for control mice. Oxygen consumption at 30°C averaged 40.1 ml O2/h for mice on the 25 ppm diet, compared to 36.6 ml O2/h for control mice. These results show that for white-footed mice, there is an energetic cost to contaminant exposure that when combined with other environmental stresses, will influence patterns of energy acquisition and allocation.
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Beyer, W.N.; Stafford, C.
1993-01-01
Soils derived from dredged material were collected, together with earthworms from nine confined disposal facilities located in the Great Lakes Region. These samples were analyzed for 18 elements, 11 organochlorine pesticides, PCBs, and 24 polycyclic aromatic hydrocarbons. The concentrations detected in earthworms were evaluated in terms of their potential hazard to wildlife, which for the sake of the evaluation were assumed to prey entirely either on earthworms or on other soil invertebrates having similar concentrations. The soil concentrations (dry wt.) of the contaminants of greatest concern were < 1.9 to 32 ppm Cd, < 0.053 to 0.94 ppm Hg, 4.6 to 550 ppm Pb, and < 0.1 to 1.0 ppm PCBs. The concentrations in earthworms (dry wt., ingested soil included) were as high as 91 ppm Cd, 1.6 ppm Hg, 200 ppm Pb, and 1.8 ppm PCBs. Based on laboratory toxicity studies of relatively sensitive species, and on concentration factors calculated from the earthworm and soil data, we estimated that lethal or serious sublethal effects on wildlife might be expected at concentrations of 10 ppm Cd, 3 ppm Hg, 670 ppm Pb, and 1.7 ppm PCBs in alkaline surface soils derived from dredged material. Concentrations of polycyclic aromatic hydrocarbons in earthworms were well below those in soil.
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Loveday, Chey; Tatton-Brown, Katrina; Clarke, Matthew; Westwood, Isaac; Renwick, Anthony; Ramsay, Emma; Nemeth, Andrea; Campbell, Jennifer; Joss, Shelagh; Gardner, McKinlay; Zachariou, Anna; Elliott, Anna; Ruark, Elise; van Montfort, Rob; Rahman, Nazneen
2015-09-01
Overgrowth syndromes comprise a group of heterogeneous disorders characterised by excessive growth parameters, often in association with intellectual disability. To identify new causes of human overgrowth, we have been undertaking trio-based exome sequencing studies in overgrowth patients and their unaffected parents. Prioritisation of functionally relevant genes with multiple unique de novo mutations revealed four mutations in protein phosphatase 2A (PP2A) regulatory subunit B family genes protein phosphatase 2, regulatory Subunit B', beta (PPP2R5B); protein phosphatase 2, regulatory Subunit B', gamma (PPP2R5C); and protein phosphatase 2, regulatory Subunit B', delta (PPP2R5D). This observation in 3 related genes in 111 individuals with a similar phenotype is greatly in excess of the expected number, as determined from gene-specific de novo mutation rates (P = 1.43 × 10(-10)). Analysis of exome-sequencing data from a follow-up series of overgrowth probands identified a further pathogenic mutation, bringing the total number of affected individuals to 5. Heterozygotes shared similar phenotypic features including increased height, increased head circumference and intellectual disability. The mutations clustered within a region of nine amino acid residues in the aligned protein sequences (P = 1.6 × 10(-5)). We mapped the mutations onto the crystal structure of the PP2A holoenzyme complex to predict their molecular and functional consequences. These studies suggest that the mutations may affect substrate binding, thus perturbing the ability of PP2A to dephosphorylate particular protein substrates. PP2A is a major negative regulator of v-akt murine thymoma viral oncogene homolog 1 (AKT). Thus, our data further expand the list of genes encoding components of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signalling cascade that are disrupted in human overgrowth conditions. © The Author 2015. Published by Oxford University Press.
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Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.
Huang, Ya; Chen, Huaguo; Zhou, Xin; Wu, Xingdong; Hu, Enming; Jiang, Zhengmeng
2017-08-15
This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity. Copyright © 2017. Published by Elsevier B.V.
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A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in malaria parasites
Edwards, Rachel L.; Kelly, Megan L.; Hodge, Dana M.; Tolia, Niraj H.; Odom, Audrey R.
2014-01-01
Isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway generates commercially important products and is a target for antimicrobial drug development. MEP pathway regulation is poorly understood in microorganisms. We employ a forward genetics approach to understand MEP pathway regulation in the malaria parasite, Plasmodium falciparum. The antimalarial fosmidomycin inhibits the MEP pathway enzyme deoxyxylulose 5-phosphate reductoisomerase (DXR). Fosmidomycin-resistant P. falciparum are enriched for changes in the PF3D7_1033400 locus (hereafter referred to as PfHAD1), encoding a homologue of haloacid dehalogenase (HAD)-like sugar phosphatases. We describe the structural basis for loss-of-function PfHAD1 alleles and find that PfHAD1 dephosphorylates a variety of sugar phosphates, including glycolytic intermediates. Loss of PfHAD1 is required for fosmidomycin resistance. Parasites lacking PfHAD1 have increased MEP pathway metabolites, particularly the DXR substrate, deoxyxylulose 5-phosphate. PfHAD1 therefore controls substrate availability to the MEP pathway. Because PfHAD1 has homologs in plants and bacteria, other HAD proteins may be MEP pathway regulators. PMID:25058848
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NASA Technical Reports Server (NTRS)
Kosterev, A. A.; Curl, R. F.; Tittel, F. K.; Gmachl, C.; Capasso, F.; Sivco, D. L.; Baillargeon, J. N.; Hutchinson, A. L.; Cho, A. Y.
1999-01-01
A quantum-cascade laser operating at a wavelength of 8.1 micrometers was used for high-sensitivity absorption spectroscopy of methane (CH4). The laser frequency was continuously scanned with current over more than 3 cm-1, and absorption spectra of the CH4 nu 4 P branch were recorded. The measured laser linewidth was 50 MHz. A CH4 concentration of 15.6 parts in 10(6) ( ppm) in 50 Torr of air was measured in a 43-cm path length with +/- 0.5-ppm accuracy when the signal was averaged over 400 scans. The minimum detectable absorption in such direct absorption measurements is estimated to be 1.1 x 10(-4). The content of 13CH4 and CH3D species in a CH4 sample was determined.
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Baker, Bradley J; Jin, Lei; Han, Zhou; Cohen, Lawrence B; Popovic, Marko; Platisa, Jelena; Pieribone, Vincent
2012-07-15
A substantial increase in the speed of the optical response of genetically encoded fluorescent protein voltage sensors (FP voltage sensors) was achieved by using the voltage-sensing phosphatase genes of Nematostella vectensis and Danio rerio. A potential N. vectensis voltage-sensing phosphatase was identified in silico. The voltage-sensing domain (S1-S4) of the N. vectensis homolog was used to create an FP voltage sensor called Nema. By replacing the phosphatase with a cerulean/citrine FRET pair, a new FP voltage sensor was synthesized with fast off kinetics (Tau(off)<5ms). However, the signal was small (ΔF/F=0.4%/200mV). FP voltage sensors using the D. rerio voltage-sensing phosphatase homolog, designated Zahra and Zahra 2, exhibited fast on and off kinetics within 2ms of the time constants observed with the organic voltage-sensitive dye, di4-ANEPPS. Mutagenesis of the S4 region of the Danio FP voltage sensor shifted the voltage dependence to more negative potentials but did not noticeably affect the kinetics of the optical signal. Copyright © 2012 Elsevier B.V. All rights reserved.
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Mello, Vinicius M; Oliveira, Flavia C C; Fraga, William G; do Nascimento, Claudia J; Suarez, Paulo A Z
2008-11-01
Three different calibration curves based on (1)H-NMR spectroscopy (300 MHz) were used for quantifying the reaction yield during biodiesel synthesis by esterification of fatty acids mixtures and methanol. For this purpose, the integrated intensities of the hydrogens of the ester methoxy group (3.67 ppm) were correlated with the areas related to the various protons of the alkyl chain (olefinic hydrogens: 5.30-5.46 ppm; aliphatic: 2.67-2.78 ppm, 2.30 ppm, 1.96-2.12 ppm, 1.56-1.68 ppm, 1.22-1.42 ppm, 0.98 ppm, and 0.84-0.92 ppm). The first curve was obtained using the peaks relating the olefinic hydrogens, a second with the parafinic protons and the third curve using the integrated intensities of all the hydrogens. A total of 35 samples were examined: 25 samples to build the three different calibration curves and ten samples to serve as external validation samples. The results showed no statistical differences among the three methods, and all presented prediction errors less than 2.45% with a co-efficient of variation (CV) of 4.66%. 2008 John Wiley & Sons, Ltd.
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Benini, Stefano; Caputi, Lorenzo; Cianci, Michele
2014-12-01
The Gram-negative bacterium Erwinia amylovora is a destructive pathogen of plants belonging to the Rosaceae family. Amongst its pathogenicity factors, E. amylovora produces the exopolysaccharide amylovoran, which contributes to the occlusion of plant vessels, causing wilting of shoots and eventually resulting in plant death. Amylovoran biosynthesis requires the presence of 12 genes (from amsA to amsL) clustered in the ams region of the E. amylovora genome. They mostly encode glycosyl transferases (AmsG, AmsB, AmsD, AmsE, AmsJ and AmsK), proteins involved in amylovoran translocation and assembly (AmsH, AmsL and AmsC), and also a tyrosine kinase (AmsA) and a tyrosine phosphatase (AmsI), which are both involved in the regulation of amylovoran biosynthesis. The low-molecular-weight protein tyrosine phosphatase AmsI was overexpressed as a His6-tagged protein in Escherichia coli, purified and crystallized. X-ray diffraction data were collected to a maximum resolution of 1.57 Å in space group P3121.
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Rattanachaikunsopon, Pongsak; Phumkhachorn, Parichat
2010-01-01
Nine essential oils were examined for antimicrobial activity against reference and clinical strains of Salmonella Enteritidis. Based on the size of the inhibition zone and the minimal inhibitory concentration, basil oil had the strongest antimicrobial activity against all the tested bacteria, and S. Enteritidis SE3 was the most sensitive strain to all the tested oils. Gas chromatography/mass spectrometry analysis revealed that the major constituents of the oil were linalool (64.35%), 1,8-cineole (12.28%), eugenol (3.21%), germacrene D (2.07%), alpha-terpineol (1.64%), and rho-cymene (1.03%). When applied in nham, a fermented pork sausage, experimentally inoculated with S. Enteritidis SE3 and stored at 4 degrees C, basil oil inhibited the bacterium in a dose-dependent fashion. Basil oil at a concentration of 50 ppm reduced the number of bacteria in the food from 5 to 2log cfu/g after storage for 3 d. An unmeasurable level of the bacterium in the food was observed at days 2 and 3 of storage when 100 and 150 ppm of basil oil was used, respectively. Sensory evaluation suggested that the addition of 100 but not of 150 ppm to nham would be acceptable to consumers. The results from this study confirm the potential use of basil oil as an antimicrobial agent to control S. Enteritidis in food.
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Shimano, Satoshi; Suzuki, Masahiro
2007-01-01
Two major volatiles produced by the mycelia and fruiting bodies of Tricholoma matsutake (1-octen-3-ol and methyl cinnamate) repel a mycophagous collembolan, Proisotoma minuta. Aggregation of the collembolans on their diet was significantly inhibited by exposure to 1 ppm methyl cinnamate or 10 to 100 ppm 1-octen-3-ol. The aggregation activity decreased dose-dependently upon exposure to 1-octen-3-ol at concentrations higher than 0.01 ppm. Aggregation in the presence of methyl cinnamate exhibited three phases: no significant effect at concentrations ranging from 0.001 to 0.1 ppm, significant inhibition from 1 to 100 ppm, and strong inhibition at 1,000 ppm. These results may explain why certain collembolan species do not prefer T. matsutake fruiting bodies. PMID:18066606
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Marty, Mary Sue; Neal, Barbara H; Zablotny, Carol L; Yano, Barry L; Andrus, Amanda K; Woolhiser, Michael R; Boverhof, Darrell R; Saghir, Shakil A; Perala, Adam W; Passage, Julie K; Lawson, Marie A; Bus, James S; Lamb, James C; Hammond, Larry
2013-12-01
2,4-Dichlorophenoxyacetic acid (2,4-D) was assessed for systemic toxicity, reproductive toxicity, developmental neurotoxicity (DNT), developmental immunotoxicity (DIT), and endocrine toxicity. CD rats (27/sex/dose) were exposed to 0, 100, 300, 600 (female), or 800 (male) ppm 2,4-D in diet. Nonlinear toxicokinetic behavior was shown at high doses; the renal clearance saturation threshold for 2,4-D was exceeded markedly in females and slightly exceeded in males. Exposure was 4 weeks premating, 7 weeks postmating for P1 males and through lactation for P1 females. F1 offspring were examined for survival and development, and at weaning, pups were divided in cohorts, by sex and dose, and by systemic toxicity (10), DNT (10), DIT (20), and reproductive toxicity (≥ 23). Remaining weanlings were evaluated for systemic toxicity and neuropathology (10-12). Body weight decreased during lactation in high-dose P1 females and in F1 pups. Kidney was the primary target organ, with slight degeneration of proximal convoluted tubules observed in high-dose P1 males and in high-dose F1 males and females. A slight intergenerational difference in kidney toxicity was attributed to increased intake of 2,4-D in F1 offspring. Decreased weanling testes weights and delayed preputial separation in F1 males were attributed to decreased body weights. Endocrine-related effects were limited to slight thyroid hormone changes and adaptive histopathology in high-dose GD 17 dams seen only at a nonlinear toxicokinetic dose. 2,4-D did not cause reproductive toxicity, DNT, or DIT. The "No Observed Adverse Effect Level" for systemic toxicity was 300 ppm in both males (16.6 mg/kg/day) and females (20.6 mg/kg/day), which is approximately 6700- to 93 000-fold higher than that reported for 2,4-D exposures in human biomonitoring studies.
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Marty, Mary Sue
2013-01-01
2,4-Dichlorophenoxyacetic acid (2,4-D) was assessed for systemic toxicity, reproductive toxicity, developmental neurotoxicity (DNT), developmental immunotoxicity (DIT), and endocrine toxicity. CD rats (27/sex/dose) were exposed to 0, 100, 300, 600 (female), or 800 (male) ppm 2,4-D in diet. Nonlinear toxicokinetic behavior was shown at high doses; the renal clearance saturation threshold for 2,4-D was exceeded markedly in females and slightly exceeded in males. Exposure was 4 weeks premating, 7 weeks postmating for P1 males and through lactation for P1 females. F1 offspring were examined for survival and development, and at weaning, pups were divided in cohorts, by sex and dose, and by systemic toxicity (10), DNT (10), DIT (20), and reproductive toxicity (≥ 23). Remaining weanlings were evaluated for systemic toxicity and neuropathology (10–12). Body weight decreased during lactation in high-dose P1 females and in F1 pups. Kidney was the primary target organ, with slight degeneration of proximal convoluted tubules observed in high-dose P1 males and in high-dose F1 males and females. A slight intergenerational difference in kidney toxicity was attributed to increased intake of 2,4-D in F1 offspring. Decreased weanling testes weights and delayed preputial separation in F1 males were attributed to decreased body weights. Endocrine-related effects were limited to slight thyroid hormone changes and adaptive histopathology in high-dose GD 17 dams seen only at a nonlinear toxicokinetic dose. 2,4-D did not cause reproductive toxicity, DNT, or DIT. The “No Observed Adverse Effect Level” for systemic toxicity was 300 ppm in both males (16.6mg/kg/day) and females (20.6mg/kg/day), which is approximately 6700- to 93 000-fold higher than that reported for 2,4-D exposures in human biomonitoring studies. PMID:24072463
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Protein Phosphatase 1-α Regulates AS160 Ser588 and Thr642 Dephosphorylation in Skeletal Muscle.
Sharma, Pragya; Arias, Edward B; Cartee, Gregory D
2016-09-01
Akt substrate of 160 kDa (AS160) phosphorylation on Thr(642) and Ser(588) by Akt is essential for insulin's full effect on glucose transport. However, protein phosphorylation is determined by the balance of actions by kinases and phosphatases, and the specific phosphatase(s) controlling AS160 dephosphorylation is (are) unknown. Accordingly, we assessed roles of highly expressed skeletal muscle serine/threonine phosphatases (PP1, PP2A, PP2B, and PP2C) on AS160 dephosphorylation. Preliminary screening of candidate phosphatases used an AS160 dephosphorylation assay. Lysates from insulin-stimulated skeletal muscle were treated with pharmacological phosphatase inhibitors and assessed for AS160 Ser(588) and Thr(642) dephosphorylation. AS160 dephosphorylation on both phosphorylation sites was unaltered by PP2B or PP2C inhibitors. Okadaic acid (low dose inhibits PP2A; high dose inhibits PP1) delayed AS160 Ser(588) (both doses) and Thr(642) (high dose only) dephosphorylation concomitant with greater Akt phosphorylation (both doses). AS160 was coimmunoprecipitated with PP1-α but not with PP1-β, PP1-γ1, or PP2A. Recombinant inhibitor-2 protein (a selective PP1 inhibitor) delayed AS160 dephosphorylation on both phosphorylation sites without altering Akt phosphorylation. Furthermore, knockdown of PP1-α but not PP1-β or PP1-γ1 by small interfering RNA caused greater AS160 Ser(588) and Thr(642) phosphorylation concomitant with unaltered Akt phosphorylation. Together, these results identified PP1-α as a regulator of AS160 Thr(642) and Ser(588) dephosphorylation in skeletal muscle. © 2016 by the American Diabetes Association.
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Fox, Candace R; Parks, Griffith D
2018-04-01
A parainfluenza virus 5 (PIV5) with mutations in the P/V gene (P/V-CPI - ) is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burdens in mouse model systems. Here we show that P/V-CPI - infection of HEp-2 human laryngeal cancer cells results in the majority of the cells dying, but unexpectedly, over time, there is an emergence of a population of cells that survive as P/V-CPI - persistently infected (PI) cells. P/V-CPI - PI cells had elevated levels of basal caspase activation, and viability was highly dependent on the activity of cellular inhibitor-of-apoptosis proteins (IAPs) such as Survivin and XIAP. In challenge experiments with external inducers of apoptosis, PI cells were more sensitive to cisplatin-induced DNA damage and cell death. This increased cisplatin sensitivity correlated with defects in DNA damage signaling pathways such as phosphorylation of Chk1 and translocation of damage-specific DNA binding protein 1 (DDB1) to the nucleus. Cisplatin-induced killing of PI cells was sensitive to the inhibition of wild-type (WT) p53-inducible protein 1 (WIP1), a phosphatase which acts to terminate DNA damage signaling pathways. A similar sensitivity to cisplatin was seen with cells during acute infection with P/V-CPI - as well as during acute infections with WT PIV5 and the related virus human parainfluenza virus type 2 (hPIV2). Our results have general implications for the design of safer paramyxovirus-based vectors that cannot establish PI as well as the potential for combining chemotherapy with oncolytic RNA virus vectors. IMPORTANCE There is intense interest in developing oncolytic viral vectors with increased potency against cancer cells, particularly those cancer cells that have gained resistance to chemotherapies. We have found that infection with cytoplasmically replicating parainfluenza virus can result in increases in the killing of cancer cells by agents that induce DNA damage, and this is linked to alterations to DNA damage signaling pathways that balance cell survival versus death. Our results have general implications for the design of safer paramyxovirus-based vectors that cannot establish persistent infection, the repurposing of drugs that target cellular IAPs as antivirals, and the combined use of DNA-damaging chemotherapy agents in conjunction with oncolytic RNA virus vectors. Copyright © 2018 American Society for Microbiology.
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Takeshita, Eliana M; Danelon, Marcelle; Castro, Luciene P; Sassaki, Kikue T; Delbem, Alberto C B
2015-01-01
The aim of the present study was to evaluate in situ whether a toothpaste with low fluoride associated with sodium trimetaphosphate (TMP) would provide similar effect to that of a 1,100 ppm F toothpaste. This crossover double-blind study consisted of 4 phases (14 days each), during which 10 volunteers wore oral appliances containing 4 enamel bovine blocks. The cariogenic challenge was performed by the application of a 20% sucrose solution (6×/day). The toothpaste treatments (2×/day) were: placebo, 500 ppm F, 500 ppm F plus 1% TMP, and 1,100 ppm F. At the end, enamel mineral loss and biofilm composition were analyzed. The toothpaste with 500 ppm F plus 1% TMP showed the lowest mineral loss (p < 0.05). Regarding the fluoride and calcium concentrations in the enamel and in the biofilm, there were no significant differences between 500 ppm F plus 1% TMP, and 1,100 ppm F toothpastes (p > 0.569), but they were significantly different when compared to toothpaste with 500 ppm F (p < 0.050). The addition of 1% TMP to a low-fluoride toothpaste reduces enamel demineralization in situ similar to a 1,100 ppm F toothpaste. © 2015 S. Karger AG, Basel.
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Xu, Q; Fu, H H; Gupta, R; Luan, S
1998-01-01
Protein tyrosine kinases and phosphatases play a vital role in the regulation of cell growth and differentiation in animal systems. However, none of these enzymes has been characterized from higher plants. In this study, we isolated a cDNA encoding a putative protein tyrosine phosphatase (PTPase) from Arabidopsis (referred to as AtPTP1). The expression level of AtPTP1 is highly sensitive to environmental stresses. High-salt conditions increased AtPTP1 mRNA levels, whereas cold treatment rapidly eliminated the AtPTP1 transcript. The recombinant AtPTP1 protein specifically hydrolyzed phosphotyrosine, but not phosphoserine/threonine, in protein substrates. Site-directed mutagenesis defined two highly conserved amino acids, cysteine-265 and aspartate-234, as being essential for the phosphatase activity of the AtPTP1 protein, suggesting a common catalytic mechanism for PTPases from all eukaryotic systems. In summary, we have identified AtPTP1 as a tyrosine-specific protein phosphatase that may function in stress responses of higher plants. PMID:9596642
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Impact-melt hygrometer for Mars: The case of shergottite Elephant Moraine (EETA) 79001
NASA Astrophysics Data System (ADS)
Liu, Yang; Chen, Yang; Guan, Yunbin; Ma, Chi; Rossman, George R.; Eiler, John M.; Zhang, Youxue
2018-05-01
We report volatile concentrations and hydrogen isotope compositions of impact melts and minerals in EETA 79001. We observed chemical changes in pyroxene, maskelynite (or feldspathic glass), and merrillite in contact with or inside impact melts. All pyroxene grains analyzed here are inside or close to impact melt pockets and contain 10-41 ppm H2O and enriched in D (δD = + 1729 to + 3707 ‰), with the highest values found in a grain enclosed in an impact melt pocket. Maskelynite or feldspathic glass contains 6.3 to 98 ppm H2O with δD values of +1604 to + 3938 ‰. The high H2O and δD values were obtained in those enclosed inside or in contact with the impact melts, whereas low H2O content (4 ppm) and terrestrial-like D/H value (δD of - 90 ± 82 ‰) were found in one maskelynite grain away from impact melts contains. Rims of ∼5 μm thickness of merrillite grains next to impact melts display Na-depletion by ∼0.9 wt%, and the sides in contact with impact melts show Mg-enrichment by ∼0.5 wt%. However, the H2O and δD values of merrillite interiors (39-242 ppm H2O and δD of +1682 to + 3884 ‰) do not show correlation with their proximity to the impact melts. Rather, δD and 1/H2O of merrillite form a negative trend different from that of impact melt pockets and maskelynite, suggesting post-crystallization or late-crystallization interactions with the crustal fluids. The impact melt pockets in EETA 79001 contain 121-646 ppm H2O, 4.3-13 ppm F, 13-50 ppm Cl, 707-2702 ppm S, and the δD values of +3368 to + 4639 ‰. The correlations between H2O, F, Cl, P2O5, and δD values of impact melts and feldspathic glass are consistent with mixing between a volatile-rich and high δD (+3000 to + 5000 ‰) endmember and a volatile-poor and low δD endmember. The volatile-poor and low δD endmember is consistent with magmatic volatiles stored in silicates. The volatile-rich and high δD endmember represents pre-impact alteration materials by subsurface water. Alteration from the subsurface water, equilibrated with the present-day-like Martian atmosphere, occurred after the crystallization of the rock (∼170 Ma) and before impact launch (∼0.7 Ma). Our conclusion is different from the previous suggestion of an isotopically distinct subsurface water reservoir with a δD value of +1000 to +2000‰ in EETA 79001. Although heterogeneous subsurface water on Mars is possible, the previous study was likely biased by a limited number of analyses (n = 2) and possible terrestrial contamination. The δD value of the subsurface source in EETA 79001 is ∼ + 4200 ‰, similar to those in the Tissint meteorite (crystallization at ∼600 Ma, impact launch at ∼0.7 Ma) and LAR 06319 (crystallization at ∼200 Ma, impact launch at ∼3 Ma), suggesting stable water chemistry for the subsurface environment in the last 600 Myrs.
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Magalhães, A C; Rios, D; Moino, A L; Wiegand, A; Attin, T; Buzalaf, M A R
2008-01-01
This in situ/ex vivo study assessed the effect of different concentrations of fluoride in dentifrices on dentin subjected to erosion or to erosion plus abrasion. Ten volunteers took part in this crossover and double-blind study performed in 3 phases (7 days). They wore acrylic palatal appliances containing 4 bovine dentin blocks divided in two rows: erosion and erosion plus abrasion. The blocks were subjected to erosion by immersion ex vivo in a cola drink (60 s, pH 2.6) 4 times daily. During this step, the volunteers brushed their teeth with one of three dentifrices D (5,000 ppm F, NaF, silica); C (1,100 ppm F, NaF, silica) and placebo (22 ppm F, silica). Then, the respective dentifrice slurry (1:3) was dripped on dentin surfaces. While no further treatment was performed in one row, the other row was brushed using an electric toothbrush for 30 s ex vivo. The appliances were replaced in the mouth and the volunteers rinsed with water. Dentin loss was determined by profilometry and analyzed by 2-way ANOVA/Bonferroni test (a = 0.05). Dentin loss after erosive-abrasive wear was significantly greater than after erosion alone. Wear was significantly higher for the placebo than for the D and C dentifrices, which were not significantly different from each other. It can be concluded that the presence of fluoride concentrations around 1,100 ppm in dentifrices is important to reduce dentin wear by erosion and erosion + abrasion, but the protective effect does not increase with fluoride concentration. (c) 2008 S. Karger AG, Basel
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Synthesized of 2,7 dihydroxyxanthone from xanthone and antimalarial activities
NASA Astrophysics Data System (ADS)
Amanatie; Jumina; Mustofa; Hanafi
2018-03-01
The purpose of the research is to synthesize 2,7-di-hydroxyxanthone compounds from xanthone and to evaluate antiplasmodial against activities. The synthesize of 2,7-di-hydroxyxanthone compounds worked with chromatogramphy methods including Thin Layer Chromatography (TLC), Vacuum Liquid Chromatography (VLC). A compound structures were determined based on the spectroscopic evidences including, Infrared (IR), one dimension (1-D) and two dimension (2-D) Nuclear Magnetic Resonance (NMR) spectra and comparison the spectroscopy data with related data from references. The biological properties of compounds are evaluated towards antiplasmodial against activity. The result of the product was obtained as white solid in 63.49% yield. The IR spectrum showed the absorption at 3433 cm-1 Which was reinforced with a sharp attack at 1087cm-1 indicating the stretching of OH, while the stretching of aromatic C=C appeared at 1620 cm-1. The 1H-NMR (500MHz, and DMSO –d6) spectrum showed that the aryl protons appeared in the region of δ12.98 ppm. In this region, there were 2 singlet at δH 12.98 ppm (1H, 2-OH) and (1H,7-OH) and shows the presence of two OH groups. Based on spectroscopy analyses, it could be started that the reaction of 2.7 di-aminoxanthone with NaNO2/HCl and H3PO4 produced 2.7-di-hydroxyxanthone. In vitro antiplasmodial assay of the product synthesized 2,7 di-hydroxyxanthones against. Falciparum strain of 3D7 showed that the IC50 values of 2,7-di-hydroxy xanthone, were 0.31 μg/mL, respectively.
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Rhodanine derivatives as inhibitors of JSP-1.
Cutshall, Neil S; O'Day, Christine; Prezhdo, Marina
2005-07-15
Dual-specificity phosphatases (DSPs) are a subclass within the protein tyrosine phosphatase family (PTPs). A series of rhodanine-based inhibitors was synthesized and shown to be novel, potent, and selective inhibitors against the DSP family member JNK-stimulating phosphatase-1 (JSP-1). Compounds of this class may be useful for the treatment of inflammatory and proliferative disorders.
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Tricuspid Regurgitation and Mortality in Patients with Transvenous Permanent Pacemaker Leads
Delling, Francesca N.; Hassan, Zena K.; Piatkowski, Gail; Tsao, Connie W.; Rajabali, Alefiyah; Markson, Lawrence J.; Zimetbaum, Peter J.; Manning, Warren J.; Chang, James D.; Mukamal, Kenneth J.
2016-01-01
Estimates of the prevalence and importance of significant tricuspid regurgitation (STR) related to implantable device leads are based mainly on case reports, small observational studies or mixed samples that include defibrillators. We sought to assess whether patients with permanent pacemaker (PPM) leads have an increased risk of STR and to determine mortality associated with PPM-related TR in a large longitudinal single-center cohort. We examined the prevalence of STR (defined as moderate-severe or ≥ 3+) among all echocardiograms performed between 2005 and 2011 excluding those with defibrillators. We then examined mortality risk according to the prevalence of PPM and STR after adjusting for cardiac co-morbidities, left ventricular (LV) systolic/diastolic function, and pulmonary artery hypertension. We screened 93592 echocardiograms (1245 with PPM) among 58556 individual patients (634 with PPM). The prevalence of STR was higher in patients following PPM placement (mean age 79 ± 3 years; 54% males) compared to patients without a PPM (adjusted odds ratio 2.32, 95% confidence interval [CI], 1.54–3.49; p<0.0001). Among patients with a PPM lead, the presence of STR was associated with increased mortality (adjusted hazard ratios [HR] 1.40, 95% CI 1.04–2.11, p=0.027 versus no STR). Compared to having neither a PPM lead nor STR, adjusted HR for death were 2.13 (95% CI, 1.93–2.34) for STR but no PPM, 1.04 (0.89–1.22) for PPM without STR, and 1.55 (1.13–2.14) for PPM with STR. In conclusion, in a sample comprising over 58,000 individual patients, PPM leads are associated with higher risk of STR after adjustment for LV systolic/diastolic function and pulmonary artery hypertension; similarly to STR from other cardiac pathologies, PPM-related STR is associated with increased mortality. PMID:26833208
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Dolbeare, F.A.; Phares, W.
1979-01-01
Conditions for the biochemical and flow cytometric assay of 7-bromo-3-hydroxy-2-naphtho-o-anisidine phosphatase and ..beta..-D-glucuronidase activities in Chinese hamster ovary cells were studied. In the biochemical assays, the pH optimum for the phosphatase activity was pH 4.6 with a Km of 10/sup -5/ M; the pH optimum for ..beta..-D-glucuronidase activity was pH 5.0 with a Km of 2 x 10/sup -5/ M. For intact cells the derived constants were 3 to 10 times higher. The rate of hydrolysis of both substrates was also examined by flow cytometry. Cellular fluorescence increased linearly for only about 15 min. Diffusion of the fluorescent product probablymore » caused nonlinearity of the fluorescence increase and was demonstrated by mixing cells incubated with substrate with those that had not been incubated. After 15 min, cells that had not been exposed previously to product or substrate contained the fluorescent product. Cells fractionated into size classes by centrifugal elutriation also were analyzed by flow cytometry for ..beta..-D-glucuronidase activity. The activity increased linearly with the increase in cell size corresponding to the progression from G/sub 1/ through S and into G/sub 2/-M phases of the cell cycle.« less
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Valenzuela-Melendres, Martin; Peña-Ramos, E Aida; Juneja, Vijay K; Camou, Juan Pedro; Cumplido-Barbeitia, German
2016-07-01
D- and z-values for Listeria monocytogenes were obtained for two Mexican meat entrées: pork meat marinated in tomatillo (green tomato) sauce (PTS) and beef marinated in a red chili sauce (BRCS), with addition of 0, 200, and 800 ppm of grapefruit seed extract (GSE). Meat samples inoculated with L. monocytogenes were packaged in sterile bags, immersed in a water bath, and held at 55, 57.5, 60, and 62.5°C for different periods of time. Depending upon the temperature, D-values at 0 ppm of GSE ranged from 26.19 to 2.03 min in BRCS and 26.41 to 0.8 min in PTS. Adding 800 ppm of GSE to BRCS thermally treated at 55 and 62.5°C significantly decreased inactivation time by 35%. A reduction in time of 25.9, 10.6, and 40.1% at 55, 57.5, and 60°C, respectively, was observed in PTS with 800 ppm of GSE. The z-values of L. monocytogenes were not significantly affected by GSE addition; average z-values were 7.25 and 5.09°C for BRCS and PTS, respectively. Estimated thermal lethality for a 7-D log reduction of L. monocytogenes under commercial-size sous-vide conditions at a reference temperature of 55°C was reached at 78 and 71 min for BRCS without and with 800 ppm of GSE, respectively. For PTS, 7-D reduction was attained at 69 and 61 min without and with addition of 800 ppm of GSE, respectively. Supplementing both Mexican meat entrées (BRCS and PTS) with 800 ppm of GSE rendered L. monocytogenes cells more sensitive to the lethal effect of heat. The results of this study will assist the retail food industry in designing acceptance limits on critical control points pertaining to cooking regimes to effectively eliminate L. monocytogenes in BRCS and PTS sous-vide processed Mexican meat entrées.
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Fujimoto, S; Okano, I; Tanaka, Y; Sumida, Y; Tsuda, J; Kawakami, N; Shimohama, S
1996-06-01
We have purified bovine brain Zn(2+)-dependent acid phosphatase (Zn(2+)-APase), which requires Zn2+ ions to hydrolyze the substrate p-nitrophenyl phosphate (pNPP) in an acidic environment. The substrate specificity and metal requirement of Zn(2+)-APase at a physiological pH was also studied. The enzyme exhibited hydrolytic activity on myo-inositol-1- and -2-monophosphates, 2'-adenosine monophosphate, 2'-guanosine monophosphate, and the alpha- and beta-glycerophosphates, glucose-1-phosphate, and fructose-6-phosphate in 50 mM Tris-HCl buffer (pH 7.4) in the presence of Mg2+ ions, but not on pNPP and phosphotyrosine. Zn2+, Mn2+ and Co2+ ions were less effective for activation. Among the above substrates, myo-inositol-1-phosphate was the most susceptible to hydrolysis by the enzyme in the presence of 3 mM Mg2+ ions. The enzyme exhibited an optimum pH at around 8 for myo-inositol-1-phosphate in the presence of 3 mM Mg2+ ions. The Mg(2+)-dependent myo-inositol-1-phosphatase activity of the enzyme was significantly inhibited by Li+ ions. The Zn(2+)-dependent p-nitrophenyl phosphatase activity and Mg(2+)-dependent myo-inositol-1-phosphatase activity of the purified enzyme fraction exhibited similar behavior on Sephadex G-100 and Mono Q colomns. These findings suggest that Zn(2+)-APase also exhibits Mg(2+)-dependent myo-inositol-1-phosphatase activity under physiological conditions.
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Neumann, Z L; Pondenis, H C; Masyr, A; Byrum, M L; Wycislo, K L; Fan, T M
2015-01-01
Canine osteosarcoma (OS) is an aggressive sarcoma characterized by pathologic skeletal resorption and pulmonary metastases. A number of negative prognostic factors, including bone alkaline phosphatase, have been identified in dogs with OS, but the underlying biologic factors responsible for such observations have not been thoroughly investigated. Endothelin-1-mediated signaling is active during bone repair, and is responsible for osteoblast migration, survival, proliferation, and bone alkaline phosphatase expression. The endothelin-1 signaling axis is active in canine OS cells, and this pathway is utilized by malignant osteoblasts for promoting cellular migration, survival, proliferation, and bone alkaline phosphatase activities. 45 dogs with appendicular OS. The expressions of endothelin-1 and endothelin A receptor were studied in OS cell lines and in samples from spontaneously occurring tumors. Activities mediated by endothelin-1 signaling were investigated by characterizing responses in 3 OS cell lines. In 45 dogs with OS, bone alkaline phosphatase concentrations were correlated with primary tumor osteoproductivity. Canine OS cells express endothelin-1 and endothelin A receptor, and this signaling axis mediates OS migration, survival, proliferation, and bone alkaline phosphatase activities. In OS-bearing dogs, circulating bone alkaline phosphatase activities were positively correlated with primary tumor relative bone mineral densities. Canine OS cells express endothelin-1 and functional endothelin A receptors, with the potential for a protumorigenic signaling loop. Increases in bone alkaline phosphatase activity are associated with osteoblastic OS lesions, and might be an epiphenomenon of active endothelin-1 signaling or excessive osteoproduction within the localized bone microenvironment. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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Code of Federal Regulations, 2011 CFR
2011-07-01
... Results for Methods for SO 2, CO, O 3, NO 2 C Figure C-1 to Subpart C of Part 53 Protection of Environment... Pt. 53, Subpt. C, Fig. C-1 Figure C-1 to Subpart C of Part 53—Suggested Format for Reporting Test... Difference Table C-1 spec. Pass or fail Low 1 ____ ppm 2 to ____ ppm 3 4 5 6 Medium 1 ____ ppm 2 to ____ ppm...
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Code of Federal Regulations, 2014 CFR
2014-07-01
... Results for Methods for SO 2, CO, O 3, NO 2 C Figure C-1 to Subpart C of Part 53 Protection of Environment... Pt. 53, Subpt. C, Fig. C-1 Figure C-1 to Subpart C of Part 53—Suggested Format for Reporting Test... Difference Table C-1 spec. Pass or fail Low 1 ____ ppm 2 to ____ ppm 3 4 5 6 Medium 1 ____ ppm 2 to ____ ppm...
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Code of Federal Regulations, 2012 CFR
2012-07-01
... Results for Methods for SO 2, CO, O 3, NO 2 C Figure C-1 to Subpart C of Part 53 Protection of Environment... Pt. 53, Subpt. C, Fig. C-1 Figure C-1 to Subpart C of Part 53—Suggested Format for Reporting Test... Difference Table C-1 spec. Pass or fail Low 1 ____ ppm 2 to ____ ppm 3 4 5 6 Medium 1 ____ ppm 2 to ____ ppm...
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Code of Federal Regulations, 2010 CFR
2010-07-01
... Results for Methods for SO 2, CO, O 3, NO 2 C Figure C-1 to Subpart C of Part 53 Protection of Environment... Pt. 53, Subpt. C, Fig. C-1 Figure C-1 to Subpart C of Part 53—Suggested Format for Reporting Test... Difference Table C-1 spec. Pass or fail Low 1 ____ ppm 2 to ____ ppm 3 4 5 6 Medium 1 ____ ppm 2 to ____ ppm...
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Searing, Daniel A; Zhang, Yong; Murphy, James R; Hauk, Pia J; Goleva, Elena; Leung, Donald Y M
2010-05-01
There is little knowledge about clinical variables associated with vitamin D (VitD) insufficiency in asthmatic children. We sought to investigate disease variables associated with VitD insufficiency in patients with childhood asthma and interaction of VitD with corticosteroid-mediated anti-inflammatory responses. We analyzed 25-hydroxyvitamin D serum levels in 100 asthmatic children to investigate relationships between 25-hydroxyvitamin D levels and patients' characteristics. We determined VitD's effects on dexamethasone (DEX) induction of mitogen-activated protein kinase phosphatase 1 and IL-10 in PBMCs. The median 25-hydroxyvitamin D serum level was 31 ng/mL. Forty-seven percent of subjects had VitD levels in the insufficient range (<30 ng/mL), whereas 17% were VitD deficient (<20 ng/mL). Log(10) IgE (P = .01, rho = -0.25) and the number of positive aeroallergen skin prick test responses (P = .02, rho = -0.23) showed a significant inverse correlation with VitD levels, whereas FEV(1) percent predicted (P = .004, rho = 0.34) and FEV(1)/forced vital capacity ratio (P = .01, rho = 0.30) showed a significant positive correlation with VitD levels. The use of inhaled steroids (P = .0475), use of oral steroids (P = .02), and total steroid dose (P = .001) all showed significant inverse correlations with VitD levels. The amount of mitogen-activated protein kinase phosphatase 1 and IL10 mRNA induced by VitD plus DEX was significantly greater than that induced by DEX alone (P < .01). In an experimental model of steroid resistance in which DEX alone did not inhibit T-cell proliferation, addition of VitD to DEX resulted in significant dose-dependent suppression of cell proliferation. Corticosteroid use and worsening airflow limitation are associated with lower VitD serum levels in asthmatic patients. VitD enhances glucocorticoid action in PBMCs from asthmatic patients and enhances the immunosuppressive function of DEX in vitro. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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Grausova, Lubica; Kromka, Alexander; Burdikova, Zuzana; Eckhardt, Adam; Rezek, Bohuslav; Vacik, Jiri; Haenen, Ken; Lisa, Vera; Bacakova, Lucie
2011-01-01
Intrinsic nanocrystalline diamond (NCD) films have been proven to be promising substrates for the adhesion, growth and osteogenic differentiation of bone-derived cells. To understand the role of various degrees of doping (semiconducting to metallic-like), the NCD films were deposited on silicon substrates by a microwave plasma-enhanced CVD process and their boron doping was achieved by adding trimethylboron to the CH(4):H(2) gas mixture, the B∶C ratio was 133, 1000 and 6700 ppm. The room temperature electrical resistivity of the films decreased from >10 MΩ (undoped films) to 55 kΩ, 0.6 kΩ, and 0.3 kΩ (doped films with 133, 1000 and 6700 ppm of B, respectively). The increase in the number of human osteoblast-like MG 63 cells in 7-day-old cultures on NCD films was most apparent on the NCD films doped with 133 and 1000 ppm of B (153,000 ± 14,000 and 152,000 ± 10,000 cells/cm(2), respectively, compared to 113,000 ± 10,000 cells/cm(2) on undoped NCD films). As measured by ELISA per mg of total protein, the cells on NCD with 133 and 1000 ppm of B also contained the highest concentrations of collagen I and alkaline phosphatase, respectively. On the NCD films with 6700 ppm of B, the cells contained the highest concentration of focal adhesion protein vinculin, and the highest amount of collagen I was adsorbed. The concentration of osteocalcin also increased with increasing level of B doping. The cell viability on all tested NCD films was almost 100%. Measurements of the concentration of ICAM-1, i.e. an immunoglobuline adhesion molecule binding inflammatory cells, suggested that the cells on the NCD films did not undergo significant immune activation. Thus, the potential of NCD films for bone tissue regeneration can be further enhanced and tailored by B doping and that B doping up to metallic-like levels is not detrimental for cells.
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Grausova, Lubica; Kromka, Alexander; Burdikova, Zuzana; Eckhardt, Adam; Rezek, Bohuslav; Vacik, Jiri; Haenen, Ken; Lisa, Vera; Bacakova, Lucie
2011-01-01
Intrinsic nanocrystalline diamond (NCD) films have been proven to be promising substrates for the adhesion, growth and osteogenic differentiation of bone-derived cells. To understand the role of various degrees of doping (semiconducting to metallic-like), the NCD films were deposited on silicon substrates by a microwave plasma-enhanced CVD process and their boron doping was achieved by adding trimethylboron to the CH4:H2 gas mixture, the B∶C ratio was 133, 1000 and 6700 ppm. The room temperature electrical resistivity of the films decreased from >10 MΩ (undoped films) to 55 kΩ, 0.6 kΩ, and 0.3 kΩ (doped films with 133, 1000 and 6700 ppm of B, respectively). The increase in the number of human osteoblast-like MG 63 cells in 7-day-old cultures on NCD films was most apparent on the NCD films doped with 133 and 1000 ppm of B (153,000±14,000 and 152,000±10,000 cells/cm2, respectively, compared to 113,000±10,000 cells/cm2 on undoped NCD films). As measured by ELISA per mg of total protein, the cells on NCD with 133 and 1000 ppm of B also contained the highest concentrations of collagen I and alkaline phosphatase, respectively. On the NCD films with 6700 ppm of B, the cells contained the highest concentration of focal adhesion protein vinculin, and the highest amount of collagen I was adsorbed. The concentration of osteocalcin also increased with increasing level of B doping. The cell viability on all tested NCD films was almost 100%. Measurements of the concentration of ICAM-1, i.e. an immunoglobuline adhesion molecule binding inflammatory cells, suggested that the cells on the NCD films did not undergo significant immune activation. Thus, the potential of NCD films for bone tissue regeneration can be further enhanced and tailored by B doping and that B doping up to metallic-like levels is not detrimental for cells. PMID:21695172
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Gurtler, Joshua B; Bailey, Rebecca B; Jin, Tony Z; Fan, Xuetong
2014-10-17
A 2011 outbreak of hemorrhagic colitis, which resulted in the death of two individuals, was associated with contaminated strawberries. A study was conducted to identify antimicrobial washes effective at reducing E. coli O157:H7 and Salmonella enterica from the surface of fresh whole strawberries during two-minute immersion washes. Twenty-seven antimicrobial treatments were tested. Vacuum perfusion was applied to strawberries during chlorine and peracetic acid treatments to promote infiltration of sanitizer into porous strawberry tissue. Strawberries were inoculated to 7.1logCFU/strawberry with a seven-strain bacterial composite, consisting of three strains of E. coli O157:H7 and four serovars of Salmonella enterica. Berries were air-dried for 2h and immersed in circulating antimicrobial solutions for 120s at 22°C. Four treatments reduced ≥3.0logCFU/strawberry, including (a) 1% acetic acid+1% H2O2, (b) 30% ethanol+1% H2O2, (c) 90ppm peracetic acid, and (d) 1% lactic acid+1% H2O2. Two additional treatments that reduced 2.8logCFU/strawberry were (a) 40% ethanol, and (b) 1% each of phosphoric+fumaric acids. Eight treatments reduced 2.0-2.6logCFU/strawberry. Five treatments reduced <1.45CFU/strawberry, including (a) 1% citric acid, (b) 1% lactic acid, (c) 1% acetic acid, (d) 0.5% each of acetic+citric acids and (e) 0.5% each of acetic+lactic acids. The use of vacuum perfusion with 200ppm chlorine or 90ppm peracetic acid did not reduce greater populations of pathogens than did the same treatments without vacuum perfusion. Fourteen treatments reduced no more pathogens (p<0.05) than did sterile deionized water. Results from this study provide some options for end-point decontamination of strawberries for retail operations just prior to serving to customers. Published by Elsevier B.V.
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Sopina, V A
2001-01-01
Activity and thermoresistance of acid phosphatase were determined in supernatant of Amoeba proteus homogenates using 1-naphthyl phosphate (pH 4.0) and p-nitrophenyl phosphate (pH 5.5). Although tartrate-resistant and tartrate-sensitive acid phosphatases hydrolyse both substrates, the former mainly hydrolyses p-nitrophenyl phosphate and the latter 1-naphthyl phosphate. A decrease in the activity of the total and tartrate-sensitive acid phosphatases, when using 1-naphthyl phosphate, and of the total and tartrate-resistant acid phosphatases, when using p-nitrophenyl phosphate, was found in amoebae acclimated to 10 degrees C (10 degrees-amoebae) compared to those acclimated to 25 degrees C (25 degrees-amoebae). Using 1-naphthyl phosphate, the thermoresistance of the total acid phosphatase was lower in 10 degrees-amoebae than in 25 degrees-amoebae, but the thermostability of tartrate-resistant enzyme was the same in both groups of amoebae. Using p-nitrophenyl phosphate, the thermoresistance of the total and tartrate-resistant acid phosphatases was lower (the latter only slightly) in 10 degrees-amoebae than in 25 degrees-amoebae. It is suggested that at least with the use of 1-naphthyl phosphate a decrease in thermostability of the total acid phosphatase may be due to a decrease in thermoresistance of tartrate-sensitive enzyme. The results obtained confirm the author's previous data on the activity and thermostability of electrophoretic forms of acid phosphatase using 2-naphthyl phosphate in 10- and 25 degrees-amoebae (Sopina, 2001). It is the first case of discovering a correlation between changes in primary cell thermoresistance of amoebae cultured at different temperatures and changes in the activity and thermostability of acid phosphatase in their homogenates, with the number of electrophoretic forms of this enzyme and their mobility being permanent.
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Yamada, Takayuki; Ezura, Yoichi; Hayata, Tadayoshi; Moriya, Shuichi; Shirakawa, Jumpei; Notomi, Takuya; Arayal, Smriti; Kawasaki, Makiri; Izu, Yayoi; Harada, Kiyoshi; Noda, Masaki
2015-06-01
β adrenergic stimulation suppresses bone formation in vivo while its actions in osteoblastic differentiation are still incompletely understood. We therefore examined the effects of β2 adrenergic stimulation on osteoblast-like MC3T3-E1 cells focusing on BMP-induced alkaline phosphatase expression. Morphologically, isoproterenol treatment suppresses BMP-induced increase in the numbers of alkaline phosphatase-positive small foci in the cultures of MC3T3-E1 cells. Biochemically, isoproterenol treatment suppresses BMP-induced enzymatic activity of alkaline phosphatase in a dose-dependent manner. Isoproterenol suppression of alkaline phosphatase activity is observed even when the cells are treated with high concentrations of BMP. With respect to cell density, isoproterenol treatment tends to suppress BMP-induced increase in alkaline phosphatase expression more in osteoblasts cultured at higher cell density. In terms of treatment protocol, continuous isoproterenol treatment is compared to cyclic treatment. Continuous isoproterenol treatment is more suppressive against BMP-induced increase in alkaline phosphatase expression than cyclic regimen. At molecular level, isoproterenol treatment suppresses BMP-induced enhancement of alkaline phosphatase mRNA expression. Regarding the mode of isoproterenol action, isoproterenol suppresses BMP-induced BRE-luciferase activity. These data indicate that isoproterenol regulates BMP-induced alkaline phosphatase expression in osteoblast-like MC3T3E1 cells. © 2014 Wiley Periodicals, Inc.
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Jiang, Cheng-shi; Liang, Lin-fu; Guo, Yue-wei
2012-01-01
This article provides an overview of approximately 300 secondary metabolites with inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), which were isolated from various natural sources or derived from synthetic process in the last decades. The structure-activity relationship and the selectivity of some compounds against other protein phosphatases were also discussed. Potential pharmaceutical applications of several PTP1B inhibitors were presented. PMID:22941286
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Spomer, Neil A; Kamble, Shripat T; Warriner, Richard A; Davis, Robert W
2008-06-01
The effect of temperature on [14C]fipronil uptake and transfer from donor (D) to recipient (R) Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae) workers was evaluated. Test chambers used in the fipronil uptake study were constructed from petri dishes containing autoclaved soil treated with 1 ppm [14C]fipronil (1.14 microCi of total radioactivity per petri dish), distilled water, and R. flavipes workers. Test chambers were held in environmental growth chambers preset at 12, 17, 22, 27, and 32 degrees C. For the fipronil transfer study, donor termites stained with Nile blue-A were exposed to soil treated with 1 ppm [14C]fipronil for 2 h. Donors were then combined with unexposed recipient termite workers at either 1D:5R, 1D:10R, or 1D:20R ratios. Test chambers consisted of a nest and feeding chamber connected by a piece of polyethylene tube and held in growth chambers at 12, 17, 22, 27, and 32 degrees C. Worker termites were sampled over time and the amount of [14C]fipronil present was measured by scintillation counting. Some degree of uptake and transfer occurred at all temperatures and ratios in this study. The highest level of uptake occurred by termites held at 22-32 degrees C, followed decreasingly by 17 and 12 degrees C. Maximum transfer of [14C]fipronil occurred at the higher ratios (1:5 > 1:10 > 1:20) of donors to recipients. Data presented in this study suggest that temperature is one of the key factors affecting the rate of uptake and subsequent horizontal transfer of [14C]fipronil in subterranean termites.
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Xiong, Qi; Chai, Jin; Deng, Changyan; Jiang, Siwen; Liu, Yang; Huang, Tao; Suo, Xiaojun; Zhang, Nian; Li, Xiaofeng; Yang, Qianping; Chen, Mingxin; Zheng, Rong
2012-12-01
Skeletal muscle and kidney-enriched inositol phosphatase (SKIP) was identified as a 5'-inositol phosphatase that hydrolyzes phosphatidylinositol (3,4,5)-triphosphate (PI(3,4,5)P3) to PI(3,4)P2 and negatively regulates insulin-induced phosphatidylinositol 3-kinase signaling in skeletal muscle. In this study, two new single nucleotide polymorphisms (SNPs) in porcine SKIP introns 1 and 6 were detected. The C1092T locus in intron 1 showed significant associations with some meat traits, whereas the A17G locus in intron 6 showed significant associations with some carcass traits. Expression analysis showed that porcine SKIP is upregulated at d 65 of gestation and Meishan fetuses have higher and prolonged expression of SKIP compared to Large White at d 100 of gestation. Ectopic expression of porcine SKIP decreased insulin-induced cell proliferation and promoted serum starvation-induced cell cycle arrest in G0/G1 phase in C2C12. Our results suggest that SKIP plays a negative regulatory role in skeletal muscle development partly by preventing cell proliferation. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.
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Jerez-Timaure, Nancy; Rivero, Janeth Colina; Araque, Humberto; Jiménez, Paola; Velazco, Mariela; Colmenares, Ciolys
2011-03-01
Two experiments were conducted to evaluate the proximal composition, lipids and cholesterol content of meat from pigs fed diets with peach-palm meal (PPM), with or without addition of synthetic lysine (LYS). In experiment 1, 24 pigs were randomly allotted into six treatments with three levels of PPM (0.16 and 32%) and two levels of LYS (0 and 0.27%). In experiment II, 16 finishing pigs were fed with two levels of PPM (0 and 17.50%) and two levels of LYS (0 and 0.27%). At the end of each experiment (42 and 35 d, respectively), pigs were slaughtered and loin samples were obtained to determine crude protein, dry matter, moisture, ash, total lipids, and cholesterol content. In experiment I, pork loin from 16% PPM had more dry matter (26.45 g/100 g) and less moisture (73.49 g/100g) than pork loin from 32% PPM (25.11 y 75.03 g/100g, respectively). Meat samples from pigs without LYS had higher (p < 0.05) content of lipids (2.11 g/100 g) than meat from pigs that consumed LYS (1.72 g/100 g). In experiment II, the proximal, lipids and cholesterol content were similar among treatments. The PPM addition to pig diets did not affect the proximal composition of pork, while LYS addition indicated a reduction of total lipids, which could result as an alternative to obtain leaner meat.
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Recurring sets of recurring starspot occultations on exoplanet host Qatar-2
NASA Astrophysics Data System (ADS)
Močnik, T.; Southworth, J.; Hellier, C.
2017-10-01
We announce the detection of recurring sets of recurring starspot occultation events in the short-cadence K2 light curve of Qatar-2, a K dwarf star transited every 1.34 d by a hot Jupiter. In total, we detect 34 individual starspot occultation events, caused by five different starspots, occulted in up to five consecutive transits or after a full stellar rotation. The longest recurring set of recurring starspot occultations spans over three stellar rotations, setting a lower limit for the longest starspot lifetime of 58 d. Starspot analysis provided a robust stellar rotational period measurement of 18.0 ± 0.2 d and indicates that the system is aligned, having a sky-projected obliquity of 0° ± 8°. A pronounced rotational modulation in the light curve has a period of 18.2 ± 1.6 d, in agreement with the rotational period derived from the starspot occultations. We tentatively detect an ellipsoidal modulation in the phase curve, with a semi-amplitude of 18 ppm, but cannot exclude the possibility that this is the result of red noise or imperfect removal of the rotational modulation. We detect no transit-timing and transit-duration variations with upper limits of 15 s and 1 min, respectively. We also reject any additional transiting planets with transit depths above 280 ppm in the orbital period region 0.5-30 d.
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Sklan, D; Shelly, M; Makovsky, B; Geyra, A; Klipper, E; Friedman, A
2003-03-01
1. The effects of feeding T-2 toxin or diacetoxyscirpenol (DAS) at levels up to 1 ppm for 32 d on performance, health, small intestinal physiology and immune response to enteral and parenteral immunisation were examined in young poults. 2. Slight improvement in growth was observed in some groups of poults fed T-2 or DAS mycotoxins for 32 d, with no change in feed efficiency. Feeding both T-2 and DAS resulted in oral lesions which had maximal severity after 7-15 d. 3. Mild intestinal changes were observed at 32 d but no pathological or histopathological lesions were found. Both mycotoxins altered small intestinal morphology, especially in the jejunum where villi were shorter and thinner. In addition, both DAS and T-2 mycotoxins enhanced the proportion of proliferating cells both in the crypts and along the villi. Migration rates were reduced in the jejunum of poults fed T-2 toxin but did not change in the duodenum or in poults fed DAS. 4. No significant effects of T-2 or DAS were observed on antibody production to antigens administered by enteral or parenteral routes. 5. This study indicates that tricothecene toxins at concentrations of up to 1 ppm for more than 30 d influenced small intestinal morphology but did not affect growth or antibody production.
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Secchi, Francesca; Schubert, Andrea; Lovisolo, Claudio
2016-04-14
The aquaporin specific control on water versus carbon pathways in leaves is pivotal in controlling gas exchange and leaf hydraulics. We investigated whether Nicotiana tabacum aquaporin 1 (NtAQP1) and Nicotiana tabacum plasma membrane intrinsic protein 2;1 (NtPIP2;1) gene expression varies in tobacco leaves subjected to treatments with different CO₂ concentrations (ranging from 0 to 800 ppm), inducing changes in photosynthesis, stomatal regulation and water evaporation from the leaf. Changes in air CO₂ concentration ([CO₂]) affected net photosynthesis (Pn) and leaf substomatal [CO₂] (Ci). Pn was slightly negative at 0 ppm air CO₂; it was one-third that of ambient controls at 200 ppm, and not different from controls at 800 ppm. Leaves fed with 800 ppm [CO₂] showed one-third reduced stomatal conductance (gs) and transpiration (E), and their gs was in turn slightly lower than in 200 ppm- and in 0 ppm-treated leaves. The 800 ppm air [CO₂] strongly impaired both NtAQP1 and NtPIP2;1 gene expression, whereas 0 ppm air [CO₂], a concentration below any in vivo possible conditions and specifically chosen to maximize the gene expression alteration, increased only the NtAQP1 transcript level. We propose that NtAQP1 expression, an aquaporin devoted to CO₂ transport, positively responds to CO₂ scarcity in the air in the whole range 0-800 ppm. On the contrary, expression of NtPIP2;1, an aquaporin not devoted to CO₂ transport, is related to water balance in the leaf, and changes in parallel with gs. These observations fit in a model where upregulation of leaf aquaporins is activated at low Ci, while downregulation occurs when high Ci saturates photosynthesis and causes stomatal closure.
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NASA Technical Reports Server (NTRS)
Lam, Chiu-Wing; James, John T.; Dodd, Darol; Stuart, Bruce; Rothenberg, Simon; Kershaw, Mary Ann; Thilagar, A.
1993-01-01
DMES, a volatile liquid, is used by NASA to waterproof the Orbiter thermal protective system. During waterproofing operations at the Oribter Processing Facility at KSC, workers could be exposed to DMES vapor. To assess the toxicity of DMES, acute and subchronic (2-week and 13-week) inhalation studies were conducted with rats. Studies were also conducted to assess the potential of DMES. Inhalation exposure concentrations ranged from 40 ppm to 4000 ppm. No mortality was observed during the studies. Exposures to 2100 ppm produced narcosis and ataxia. Post-exposure recovery from these CNS effects was rapid (less than 1 hr). These effects were concentration-dependent and relatively independent of exposure length. Exposure to 3000 ppm for 2 weeks (5 h/d, 5 d/wk) produced testicular toxicity. The 13-week study yielded similar results. Results from the genotoxicity assays (in vivo/in vitro unscheduled DNA synthesis in rat primary heptaocytes, chromosomal aberrations in rat bone marrow cells; reverse gene mutation in Salmonella typhimurium; and forward mutation in Chinese hamster culture cells) were negative. These studies indicated that DMES is mildly to moderately toxic but not a multagen.
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Hepatic pathology in mice after continuous inhalation exposure to 1, 1, 1-trichloroethane
NASA Technical Reports Server (NTRS)
Mcnutt, N. S.; Master, R. L.; Mcconnell, E. E.; Morris, F.
1974-01-01
Mice exposed to either 250ppm or 1,000ppm 1,1,1-trichloroethane in air continuously for 14 weeks demonstrated significant changes in the centrilobular hepatocytes for the 1,000ppm group. Moderate liver triglyceride accumulation was evident in the 1,000ppm group and peaked at 40mg/gm of tissue after 7 weeks of exposure. Focal hepatocyte necrosis occurred in 40% of the mice exposed to 1,000ppm for 12 weeks. This necrosis was associated with an acute inflammatory infiltrate and hypertrophy of Kupffer cells. These findings indicate that the pathological alternations observed with 1,1,1-trichloroethane are similar to those observed with dichloromethane except for different time courses of the effects and different degrees of recovery. The toxic effects of 1,1,1-trichloroethane are of a similar type to those produced by carbon tetrachloride but appear much less severe.
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Reproductive toxicity evaluation of dietary butyl benzyl phthalate (BBP) in rats.
Tyl, Rochelle W; Myers, Christina B; Marr, Melissa C; Fail, Patricia A; Seely, John C; Brine, Dolores R; Barter, Robert A; Butala, John H
2004-01-01
Butyl benzyl phthalate (BBP) was administered in the diet at 0, 750, 3750, and 11,250 ppm ad libitum to 30 rats per sex per dose for two offspring generations, one litter/breeding pair/generation, through weaning of F2 litters. Adult F0 systemic toxicity and adult F1 systemic and reproductive toxicity were present at 11,250 ppm (750 mg/kg per day). At 11,250 ppm, there were reduced F1 and F2 male anogenital distance (AGD) and body weights/litter during lactation, delayed acquisition of puberty in F1 males and females, retention of nipples and areolae in F1 and F2 males, and male reproductive system malformations. At 3750 ppm (250 mg/kg per day), only reduced F1 and F2 offspring male AGD was present. There were no effects on parents or offspring at 750 ppm (50 mg/kg per day). The F1 parental systemic and reproductive toxicity no observable adverse effect level (NOAEL) was 3750 ppm. The offspring toxicity NOAEL was 3750 ppm. The offspring toxicity no observable effect level (NOEL) was 750 ppm, based on the presence of reduced AGD in F1 and F2 males at birth at 3750 ppm, but no effects on reproductive development, structures, or functions.
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Uhrig, R Glen; Moorhead, Greg B
2011-12-01
Protein phosphorylation, catalyzed by the opposing actions of protein kinases and phosphatases, is a cornerstone of cellular signaling and regulation. Since their discovery, protein phosphatases have emerged as highly regulated enzymes with specificity that rivals their counteracting kinase partners. However, despite years of focused characterization in mammalian and yeast systems, many protein phosphatases in plants remain poorly or incompletely characterized. Here, we describe a bioinformatic, biochemical, and cellular examination of an ancient, Bacterial-like subclass of the phosphoprotein phosphatase (PPP) family designated the Shewanella-like protein phosphatases (SLP phosphatases). The SLP phosphatase subcluster is highly conserved in all plants, mosses, and green algae, with members also found in select fungi, protists, and bacteria. As in other plant species, the nucleus-encoded Arabidopsis (Arabidopsis thaliana) SLP phosphatases (AtSLP1 and AtSLP2) lack genetic redundancy and phylogenetically cluster into two distinct groups that maintain different subcellular localizations, with SLP1 being chloroplastic and SLP2 being cytosolic. Using heterologously expressed and purified protein, the enzymatic properties of both AtSLP1 and AtSLP2 were examined, revealing unique metal cation preferences in addition to a complete insensitivity to the classic serine/threonine PPP protein phosphatase inhibitors okadaic acid and microcystin. The unique properties and high conservation of the plant SLP phosphatases, coupled to their exclusion from animals, red algae, cyanobacteria, archaea, and most bacteria, render understanding the function(s) of this new subclass of PPP family protein phosphatases of particular interest.
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Protein Phosphatase 1ß Limits Ring Canal Constriction during Drosophila Germline Cyst Formation
Yamamoto, Shinya; Bayat, Vafa; Bellen, Hugo J.; Tan, Change
2013-01-01
Germline cyst formation is essential for the propagation of many organisms including humans and flies. The cytoplasm of germline cyst cells communicate with each other directly via large intercellular bridges called ring canals. Ring canals are often derived from arrested contractile rings during incomplete cytokinesis. However how ring canal formation, maintenance and growth are regulated remains unclear. To better understand this process, we carried out an unbiased genetic screen in Drosophila melanogaster germ cells and identified multiple alleles of flapwing (flw), a conserved serine/threonine-specific protein phosphatase. Flw had previously been reported to be unnecessary for early D. melanogaster oogenesis using a hypomorphic allele. We found that loss of Flw leads to over-constricted nascent ring canals and subsequently tiny mature ring canals, through which cytoplasmic transfer from nurse cells to the oocyte is impaired, resulting in small, non-functional eggs. Flw is expressed in germ cells undergoing incomplete cytokinesis, completely colocalized with the Drosophila myosin binding subunit of myosin phosphatase (DMYPT). This colocalization, together with genetic interaction studies, suggests that Flw functions together with DMYPT to negatively regulate myosin activity during ring canal formation. The identification of two subunits of the tripartite myosin phosphatase as the first two main players required for ring canal constriction indicates that tight regulation of myosin activity is essential for germline cyst formation and reproduction in D. melanogaster and probably other species as well. PMID:23936219
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Patterned basal seismicity shows sub-ice stream bedforms
NASA Astrophysics Data System (ADS)
Barcheck, C. G.; Tulaczyk, S. M.; Schwartz, S. Y.
2017-12-01
Patterns in seismicity emanating from the bottom of fast-moving ice streams and glaciers may indicate localized patches of higher basal resistance— sometimes called 'sticky spots', or otherwise varying basal properties. These seismogenic basal areas resist an unknown portion of the total driving stress of the Whillans Ice Plain (WIP), in West Antarctica, but may play an important role in the WIP stick-slip cycle and ice stream slowdown. To better understand the mechanism and importance of basal seismicity beneath the WIP, we analyze seismic data collected by a small aperture (< 3km) network of 8 surface and 5 borehole seismometers installed in the main central sticky spot of the WIP. We use a network beamforming technique to detect and roughly locate thousands of small (magnitude < 0), local basal micro-earthquakes in Dec 2014, and we compare the resulting map of seismicity to ice bottom depth measured by airborne radar. The number of basal earthquakes per area within the network is spatially heterogeneous, but a pattern of two 400m wide streaks of high seismicity rates is evident, with >50-500 earthquakes detected per 50x50m grid cell in 2 weeks. These seismically active streaks are elongated approximately in the ice flow direction with a spacing of 750m. Independent airborne radar measurements of ice bottom depth from Jan 2013 show a low-amplitude ( 5m) undulation in the basal topography superposed on a regional gradient in ice bottom depth. The flow-perpendicular wavelength of these low-amplitude undulations is comparable to the spacing of the high seismicity bands, and the streaks of high seismicity intersect local lows in the undulating basal topography. We interpret these seismic and radar observations as showing seismically active sub-ice stream bedforms that are low amplitude and elongated in the direction of ice flow, comparable to the morphology of mega scale glacial lineations (MSGLs), with high basal seismicity rates observed in the MSGL troughs. These results have implications for understanding the formation mechanism of MSGLS and well as understanding the interplay between basal topographic roughness, spatially varying basal till and hydrologic properties, basal resistance to fast ice flow, and ice stream stick-slip.
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Stick-slip Cycles and Tidal Modulation of Ice Stream Flow
NASA Astrophysics Data System (ADS)
Lipovsky, B.; Dunham, E. M.
2016-12-01
The reactivation of a single dormant Antarctic ice stream would double the continent's mass imbalance. Despite importance of understanding the likelihood of such an event, direct observation of the basal processes that lead to the activation and stagnation of streaming ice are minimal. As the only ice stream undergoing stagnation, the Whillans Ice Plain (WIP) occupies a central role in our understanding of these subglacial processes. Complicating matters is the observation, from GPS records, that the WIP experiences most of its motion during episodes of rapid sliding. These sliding events are tidally modulated and separated by 12 hour periods of quiescence. We conduct numerical simulations of ice stream stick-slip cycles. Our simulations include rate- and state-dependent frictional sliding, tidal forcing, inertia, upstream loading in a cross-stream, thickness-averaged formulation. Our principal finding is that ice stream motion may respond to ocean tidal forcing with one of two end member behaviors. In one limit, tidally modulated slip events have rupture velocities that approach the shear wave speed and slip events have a duration that scales with the ice stream width divided by the shear wave speed. In the other limit, tidal modulation results in ice stream sliding velocities with lower amplitude variation but at much longer timescales, i.e. semi-diurnal and longer. This latter behavior more closely mimics the behavior of several active ice streams (Bindschadler, Rutford). We find that WIP slip events exist between these two end member behaviors: rupture velocities are far below the inertial limit yet sliding occurs only episodically. The continuum of sliding behaviors is governed by a critical ice stream width over which slip event nucleate. When the critical width is much longer than the ice stream width, slip events are unable to nucleate. The critical width depends on the subglacial effective pressure, ice thickness, and frictional and elastic constitutive parameters. One implication of our work is that, because the transition from steady to episodic sliding may occur by changing subglacial effective pressure, changing effective pressure may be responsible for the stagnation of the WIP.
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Mauderly, J L; Kracko, D; Brower, J; Doyle-Eisele, M; McDonald, J D; Lund, A K; Seilkop, S K
2014-09-01
An experiment was conducted to test the hypothesis that a mixture of five inorganic gases could reproduce certain central vascular effects of repeated inhalation exposure of apolipoprotein E-deficient mice to diesel or gasoline engine exhaust. The hypothesis resulted from preceding multiple additive regression tree (MART) analysis of a composition-concentration-response database of mice exposed by inhalation to the exhausts and other complex mixtures. The five gases were the predictors most important to MART models best fitting the vascular responses. Mice on high-fat diet were exposed 6 h/d, 7 d/week for 50 d to clean air or a mixture containing 30.6 ppm CO, 20.5 ppm NO, 1.4 ppm NO₂, 0.5 ppm SO₂, and 2.0 ppm NH₃ in air. The gas concentrations were below the maxima in the preceding studies but in the range of those in exhaust exposure levels that caused significant effects. Five indicators of stress and pro-atherosclerotic responses were measured in aortic tissue. The exposure increased all five response indicators, with the magnitude of effect and statistical significance varying among the indicators and depending on inclusion or exclusion of an apparent outlying control. With the outlier excluded, three responses approximated predicted values and two fell below predictions. The results generally supported evidence that the five gases drove the effects of exhaust, and thus supported the potential of the MART approach for identifying putative causal components of complex mixtures.
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Hurricane Katrina Wind Investigation Report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Desjarlais, A. O.
This investigation of roof damage caused by Hurricane Katrina is a joint effort of the Roofing Industry Committee on Weather Issues, Inc. (RICOWI) and the Oak Ridge National Laboratory/U.S. Department of Energy (ORNL/DOE). The Wind Investigation Program (WIP) was initiated in 1996. Hurricane damage that met the criteria of a major windstorm event did not materialize until Hurricanes Charley and Ivan occurred in August 2004. Hurricane Katrina presented a third opportunity for a wind damage investigation in August 29, 2005. The major objectives of the WIP are as follows: (1) to investigate the field performance of roofing assemblies after majormore » wind events; (2) to factually describe roofing assembly performance and modes of failure; and (3) to formally report results of the investigations and damage modes for substantial wind speeds The goal of the WIP is to perform unbiased, detailed investigations by credible personnel from the roofing industry, the insurance industry, and academia. Data from these investigations will, it is hoped, lead to overall improvement in roofing products, systems, roofing application, and durability and a reduction in losses, which may lead to lower overall costs to the public. This report documents the results of an extensive and well-planned investigative effort. The following program changes were implemented as a result of the lessons learned during the Hurricane Charley and Ivan investigations: (1) A logistics team was deployed to damage areas immediately following landfall; (2) Aerial surveillance--imperative to target wind damage areas--was conducted; (3) Investigation teams were in place within 8 days; (4) Teams collected more detailed data; and (5) Teams took improved photographs and completed more detailed photo logs. Participating associations reviewed the results and lessons learned from the previous investigations and many have taken the following actions: (1) Moved forward with recommendations for new installation procedures; (2) Updated and improved application guidelines and manuals from associations and manufacturers; (3) Launched certified product installer programs; and (4) Submitted building code changes to improve product installation. Estimated wind speeds at the damage locations came from simulated hurricane models prepared by Applied Research Associates of Raleigh, North Carolina. A dynamic hurricane wind field model was calibrated to actual wind speeds measured at 12 inland and offshore stations. The maximum estimated peak gust wind speeds in Katrina were in the 120-130 mph range. Hurricane Katrina made landfall near Grand Isle, Louisiana, and traveled almost due north across the city of New Orleans. Hurricane winds hammered the coastline from Houma, Louisiana, to Pensacola, Florida. The severe flooding problems in New Orleans made it almost impossible for the investigating teams to function inside the city. Thus the WIP investigations were all conducted in areas east of the city. The six teams covered the coastal areas from Bay Saint Louis, Mississippi, on the west to Pascagoula, Mississippi, on the east. Six teams involving a total of 25 persons documented damage to both low slope and steep slope roofing systems. The teams collected specific information on each building examined, including type of structure (use or occupancy), wall construction, roof type, roof slope, building dimensions, roof deck, insulation, construction, and method of roof attachment. In addition, the teams noted terrain exposure and the estimated wind speeds at the building site from the Katrina wind speed map. With each team member assigned a specific duty, they described the damage in detail and illustrated important features with numerous color photos. Where possible, the points of damage initiation were identified and damage propagation described. Because the wind speeds in Katrina at landfall, where the investigations took place, were less than code-specified design speeds, one would expect roof damage to be minimal. One team speculated that damage to all roofs in the area they examined was less than 10% when improper installation and deterioration were eliminated as causes. Roofs designed to code and installed according to manufacturers recommendations performed very well.« less
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Smiderle, Fhernanda R; Sassaki, Guilherme L; van Arkel, Jeroen; Iacomini, Marcello; Wichers, Harry J; Van Griensven, Leo J L D
2010-08-25
An alpha-glucan was isolated from the culinary medicinal mushroom A. bisporus by hot water extraction, ethanol precipitation and DEAE-cellulose chromatography. The resulting material showed a single HMW peak excluded from a Sephadex G50 column that could completely be degraded by alpha-amylase treatment. After heating in 1% SDS a small additional peak of low MW eluted from the G50 column. The monosaccharide composition of the main peak was evaluated by HPLC, and was found to consist of a majority of glucose (97.6%), and a minor proportion of galactose (2.4%). Methylation analysis and degradation by alpha-amylase indicated the presence of an alpha-glucan with a main chain consisting of (1(R)4)-linked units, substituted at O-6 by alpha-D-glucopyranose single-units in the relation 1:8. Mono- (13C-, 1H-NMR) and bidimensional [1H (obs.),13C-HSQC] spectroscopy analysis confirmed the alpha-configuration of the Glcp residues by low frequency resonances of C-1 at delta 100.6, 100.2, and 98.8 ppm and H-1 high field ones at delta 5.06, 5.11, and 4.74 ppm. The DEPT-13C-NMR allowed assigning the non-substituted and O-substituted -CH(2) signals at delta 60.3/60.8 and 66.2 ppm, respectively. Other assignments were attributed to C-2, C-3, C-4, C-5 and C-6 of the non-reducing ends at delta 71.8; 72.8; 70.0; 71.3 and 60.3/60.8 ppm, respectively. The minor proportion of galactose that was demonstrated was probably derived from a complex between the alpha-glucan and a low molecular weight galactan.
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Preparation of special purity Ge - S - I and Ge - Se - I glasses
NASA Astrophysics Data System (ADS)
Velmuzhov, A. P.; Sukhanov, M. V.; Shiryaev, V. S.; Kotereva, T. V.; Snopatin, G. E.; Churbanov, M. F.
2017-05-01
The paper considers the new approaches for the production of special pure Ge - S - I and Ge - Se - I glasses via the germanium(IV) iodide, germanium(II) sulfide, as well as the Ge2S3, Ge2S3I2 and Ge2Se3I2 glassy alloys. The glass samples containing 0.03-0.17 ppm(wt) hydrogen impurity in the form of SH-group, 0.04-0.15 ppm(wt) hydrogen impurity in the form of SeH-group, and 0.5-7.8 ppm(wt) oxygen impurity in the form of Ge-O were produced. Using a crucible technique, the single-index [GeSe4]95I5 glass fibers of 300-400 μm diameter were drawn. The minimum optical losses in the best fiber were 1.7 dB/m at a wavelength of 5.5 μm; the background optical losses were within 2-3 dB/m in the spectral range of 2.5-8 μm.
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High-voltage measurements on the 5 ppm relative uncertainty level with collinear laser spectroscopy
NASA Astrophysics Data System (ADS)
Krämer, J.; König, K.; Geppert, Ch; Imgram, P.; Maaß, B.; Meisner, J.; Otten, E. W.; Passon, S.; Ratajczyk, T.; Ullmann, J.; Nörtershäuser, W.
2018-04-01
We present the results of high-voltage collinear laser spectroscopy measurements on the 5 ppm relative uncertainty level using a pump and probe scheme at the 4s ^2S1/2 → 4p ^2P3/2 transition of {\\hspace{0pt}}40Ca+ involving the 3d ^2D5/2 metastable state. With two-stage laser interaction and a reference measurement we can eliminate systematic effects such as differences in the contact potentials due to different electrode materials and thermoelectric voltages, and the unknown starting potential of the ions in the ion source. Voltage measurements were performed between -5 kV and -19 kV and parallel measurements with stable high-voltage dividers calibrated to 5 ppm relative uncertainty were used as a reference. Our measurements are compatible with the uncertainty limits of the high-voltage dividers and demonstrate an unprecedented (factor of 20) increase in the precision of direct laser-based high-voltage measurements.
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Etienne-Julan, Maryse; Gotoh, Akihiko; Braun, Stephen E.; Lu, Li; Cooper, Scott; Feng, Gen-Sheng; Li, Xing Jun
2013-01-01
The protein tyrosine phosphatase, SHP2, is widely expressed; however, previous studies demonstrated that hematopoietic cell development more stringently requires Shp2 expression compared to other tissues. Furthermore, somatic gain-of-function SHP2 mutants are commonly found in human myeloid leukemias. Given that pharmacologic inhibitors to SHP2 phosphatase activity are currently in development as putative antileukemic agents, we conducted a series of experiments examining the necessity of SHP2 phosphatase activity for human hematopoiesis. Anti-sense oligonucleotides to human SHP2 coding sequences reduced human cord blood- and human cell line, TF1-derived colony formation. Expression of truncated SHP2 bearing its Src homology 2 (SH2) domains, but lacking the phosphatase domain similarly reduced human cord blood- and TF1-derived colony formation. Mechanistically, expression of truncated SHP2 reduced the interaction between endogenous, full-length SHP2 with the adapter protein, Grb2. To verify the role of SHP2 phosphatase function in human hematopoietic cell development, human cord blood CD34+ cells were transduced with a leukemia-associated phosphatase gain-of-function SHP2 mutant or with a phosphatase dead SHP2 mutant, which indicated that increased phosphatase function enhanced, while decreased SHP2 phosphatase function reduced, human cord blood-derived colonies. Collectively, these findings indicate that SHP2 phosphatase function regulates human hematopoietic cell development and imply that the phosphatase component of SHP2 may serve as a pharmacologic target in human leukemias bearing increased SHP2 phosphatase activity. PMID:23082805
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Broxmeyer, Hal E; Etienne-Julan, Maryse; Gotoh, Akihiko; Braun, Stephen E; Lu, Li; Cooper, Scott; Feng, Gen-Sheng; Li, Xing Jun; Chan, Rebecca J
2013-03-15
The protein tyrosine phosphatase, SHP2, is widely expressed; however, previous studies demonstrated that hematopoietic cell development more stringently requires Shp2 expression compared to other tissues. Furthermore, somatic gain-of-function SHP2 mutants are commonly found in human myeloid leukemias. Given that pharmacologic inhibitors to SHP2 phosphatase activity are currently in development as putative antileukemic agents, we conducted a series of experiments examining the necessity of SHP2 phosphatase activity for human hematopoiesis. Anti-sense oligonucleotides to human SHP2 coding sequences reduced human cord blood- and human cell line, TF1-derived colony formation. Expression of truncated SHP2 bearing its Src homology 2 (SH2) domains, but lacking the phosphatase domain similarly reduced human cord blood- and TF1-derived colony formation. Mechanistically, expression of truncated SHP2 reduced the interaction between endogenous, full-length SHP2 with the adapter protein, Grb2. To verify the role of SHP2 phosphatase function in human hematopoietic cell development, human cord blood CD34+ cells were transduced with a leukemia-associated phosphatase gain-of-function SHP2 mutant or with a phosphatase dead SHP2 mutant, which indicated that increased phosphatase function enhanced, while decreased SHP2 phosphatase function reduced, human cord blood-derived colonies. Collectively, these findings indicate that SHP2 phosphatase function regulates human hematopoietic cell development and imply that the phosphatase component of SHP2 may serve as a pharmacologic target in human leukemias bearing increased SHP2 phosphatase activity.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Fauziah, Faiza, E-mail: faiza.fauziah@gmail.com; Choesin, Devi N., E-mail: faiza.fauziah@gmail.com
2014-03-24
Banten Bay in Indonesia is a coastal area which has been highly affected by human activity. Previous studies have reported the presence of lead (Pb) and copper (Cu) heavy metals in the seawater of this area. This study was conducted to measure the accumulation of Pb and Cu in seawater, sediment, leaf tissue, and root tissue of the seagrass species Enhalus sp. Sampling was conducted at two observation stations in Banten Bay: Station 1 (St.1) was located closer to the coastline and to industrial plants as source of pollution, while Station 2 (St.2) was located farther away offshore. At eachmore » station, three sampling points were established by random sampling. Field sampling was conducted at two different dates, i.e., on 29 May 2012 and 30 June 2012. Samples were processed by wet ashing using concentrated HNO{sub 3} acid and measured using Atomic Absorption Spectrometry (AAS). Accumulation of Pb was only detected in sediment samples in St.1, while Cu was detected in all samples. Average concentrations of Cu in May were as follows: sediment St.1 = 0.731 ppm, sediment St.2 = 0.383 ppm, seawater St.1 = 0.163 ppm, seawater St.2 = 0.174 ppm, leaf St.1 = 0.102 ppm, leaf St.2 = 0.132 ppm, root St.1= 0.139 ppm, and root St.2 = 0.075 ppm. Average measurements of Cu in June were: sediment St.1 = 0.260 ppm, leaf St.1 = 0.335 ppm, leaf St.2 = 0.301 ppm, root St.1= 0.047 ppm, and root St.2 = 0.060 ppm. In June, Cu was undetected in St.2 sediment and seawater at both stations. In May, Cu concentration in seawater exceeded the maximum allowable threshold for water as determined by the Ministry of the Environment. Spatial and temporal variation in Pb and Cu accumulation were most probably affected by distance from source and physical conditions of the environment (e.g., water current and mixing)« less
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Agarwal, Silky; Changotra, Harish
2017-01-01
Protein tyrosine phosphatase, non-receptor type 22 gene, which translates to lymphoid tyrosine phosphatase, is considered to be a susceptibility gene marker associated with several autoimmune diseases. Several studies have demonstrated the association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism with vitiligo. However, these studies showed conflicting results. Meta-analysis of the same was conducted earlier that included fewer number of publications in their study. We performed a meta-analysis of a total of seven studies consisting of 2094 cases and 3613 controls to evaluate the possible association of protein tyrosine phosphatase, non-receptor type 22 +1858C>T polymorphism with vitiligo susceptibility. We conducted a literature search in PubMed, Google Scholar and Dogpile for all published paper on protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism and vitiligo risk till June 2016. Data analysis was performed by RevMan 5.3 and comprehensive meta-analysis v3.0 software. Meta-analysis showed an overall significant association of protein tyrosine phosphatase, non- receptor type 22 +1858C→T polymorphism with vitiligo in all models (allelic model [T vs. C]: odds ratio = 1.50, 95% confidence interval [1.32-1.71], P< 0.001; dominant model [TT + CT vs. CC]: odds ratio = 1.61, 95% confidence interval [1.16-2.24], P = 0.004; recessive model [TT vs. CT + CC]: odds ratio = 4.82, 95% confidence interval [1.11-20.92], P = 0.04; homozygous model [TT vs. CC]: odds ratio = 5.34, 95% confidence interval [1.23-23.24], P = 0.03; co-dominant model [CT vs. CC]: odds ratio = 1.52, 95% confidence interval [1.09-2.13], P = 0.01). No publication bias was detected in the funnel plot study. Limited ethnic-based studies, unable to satisfy data by gender or vitiligo-type are some limitations of the present meta-analysis. Stratifying data by ethnicity showed an association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T with vitiligo in European population (odds ratio = 1.53, 95% confidence interval [1.34-1.75], P< 0.001) but not in Asian population (odds ratio = 0.59, 95% confidence interval [0.26-1.32], P = 0.2). In conclusion, protein tyrosine phosphatase, non-receptor type 22 +1858 T allele predisposes European individuals to vitiligo.
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Memantine Attenuates Alzheimer’s Disease-Like Pathology and Cognitive Impairment
Wang, Xiaochuan; Blanchard, Julie; Iqbal, Khalid
2015-01-01
Deficiency of protein phosphatase-2A is a key event in Alzheimer’s disease. An endogenous inhibitor of protein phosphatase-2A, inhibitor-1, I1 PP2A, which inhibits the phosphatase activity by interacting with its catalytic subunit protein phosphatase-2Ac, is known to be upregulated in Alzheimer’s disease brain. In the present study, we overexpressed I1 PP2A by intracerebroventricular injection with adeno-associated virus vector-1-I1 PP2A in Wistar rats. The I1 PP2A rats showed a decrease in brain protein phosphatase-2A activity, abnormal hyperphosphorylation of tau, neurodegeneration, an increase in the level of activated glycogen synthase kinase-3beta, enhanced expression of intraneuronal amyloid-beta and spatial reference memory deficit; littermates treated identically but with vector only, i.e., adeno-associated virus vector-1-enhanced GFP, served as a control. Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer’s disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer’s disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1 PP2A rats. These findings provide new clues into the possible mechanism of the beneficial therapeutic effect of memantine in Alzheimer’s disease patients. PMID:26697860
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Hubel, F.; Beck, E.
1996-01-01
Three phytase (EC 3.1.3.26) isoforms from the roots of 8-d-old maize (Zea mays L. var Consul) seedlings were separated from phosphatases and purified to near homogeneity. The molecular mass of the native protein was 71 kD, and the isoelectric points of the three isoforms were pH 5.0, 4.9, and 4.8. Each of the three isoforms consisted of two subunits with a molecular mass of 38 kD. The temperature and pH optima (40[deg]C, pH 5.0) of these three isoforms, as well as the apparent Michaelis constants for sodium inositol hexakisphosphate (phytate) (43, 25, and 24 [mu]M) as determined by the release of inorganic phosphate, were only slightly different. Phytate concentrations higher than 300 [mu]M were inhibitory to all three isoforms. In contrast, the dephosphorylation of 4-nitrophenyl phosphate was not inhibited by any substrate concentration, but the Michaelis constants for this substrate were considerably higher (137-157 [mu]M). Hydrolysis of phytate by the phytase isoforms is a nonrandom reaction. D/L-Inositol-1,2,3,4,5- pentakisphosphate was identified as the first and D/L-inositol-1,2,5,6-tetrakisphosphate as the second intermediate in phytate hydrolysis. Phytase activity was localized in root slices. Although phosphatase activity was present in the stele and the cortex of the primary root, phytase activity was confined to the endodermis. Phytate was identified as the putative native substrate in maize roots (45 [mu]g P g-1 dry matter). It was readily labeled upon supplying [32P]phosphate to the roots. PMID:12226456
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Tastan, Yasemin; Kann, Peter Herbert; Tinneberg, Hans-Rudolf; Hadji, Peyman; Müller-Ladner, Ulf; Lange, Uwe
2016-11-01
Patients with osteoporosis have a low bone mass resulting in an increased risk for bone fractures, morbidity and mortality. One hundred thirty-one female pre-menopausal participants (98 Turkish immigrants living in Germany in comparison with 33 age-matched healthy Germans) were recruited for this study which explored vitamin D deficiency and specific genetic modifications of bone metabolism. The subjects were investigated for their femoral and lumbar bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) of the right total femur and the lumbar spine. Serum levels of osteologic parameters were determined: parathormone (PTH), calcium (Ca), osteocalcin (OC), phosphate (P), alkaline phosphatase (AP), beta-crossLaps (CL), tartrate-resistant acid phosphatase isoform 5b (TRAP5b), and 25-vitamin D 3 (25-OH D 3 ). The Bsml- and Fokl-polymorphisms of the vitamin D receptor (VDR) gene and the collagen type I alpha 1 (COLIA1)-gene polymorphism were also genotyped. An extremely high prevalence of vitamin D deficiency could be found in the immigrant cohort (87.8 %). Osteoporosis but not osteopenia was more prevalent in this group. Among immigrants with osteoporosis, TRAP5b was elevated in 42.9 % and beta-CL in 28.6 %. Only the Fokl FF-genotype of the VDR polymorphism was significantly more prevalent among the Turkish women, Ff-genotyped immigrants showed significantly decreased BMD. A significant correlation between the COLIA1-gene polymorphism and BMD could not be identified in the two groups. Vitamin D deficiency and osteoporosis appear to be dominant and unrecognized problem among female Turkish immigrants in Germany. Therefore, in this population, osteologic parameters and BMD should be routinely analyzed and deficiencies be treated immediately.
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Nguyen, Hung; Do, Nhat; Phan, Tuyn; Pham, Tri
2018-02-01
The aim of this study is to use steered molecular dynamics to investigate the dissociation process between IRK and PTP1Bs for wild type and five mutants (consisting of p.D181E, p.D181A, p.Q262A, p.D181A-Y46F, and p.D181A-Q262A). The gained results are observed not only the unbinding mechanism of IRK-PTP1B complexes came from pulling force profile, number of hydrogen bonds, and interaction energy between IRK and PTP1Bs but also described PTP1B's point mutations could variably change its binding affinity towards IRK. Additionally, the binding free energy calculated by Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) is also revealed that electrostatic energy and polar solvation energy mainly made up the binding free energy of PTP1B-IRK complexes.
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Bai, Bingyang; Qiao, Qi; Arandiyan, Hamidreza; Li, Junhua; Hao, Jiming
2016-03-01
Three-dimensional (3D) ordered mesoporous Ag/MnO2 catalyst was prepared by impregnation method based on 3D-MnO2 and used for catalytic oxidation of HCHO. Ag nanoparticles are uniformly distributed on the polycrystalline wall of 3D-MnO2. The addition of Ag does not change the 3D ordered mesoporous structure of the Ag/MnO2, but does reduce the pore size and surface area. Ag nanoparticles provide sufficient active site for the oxidation reaction of HCHO, and Ag (111) crystal facets in the Ag/MnO2 are active faces. The 8.9% Ag/MnO2 catalyst shows a higher normalized rate (10.1 nmol·s(-1)·m(-2) at 110 °C) and TOF (0.007 s(-1) at 110 °C) under 1300 ppm of HCHO and 150 000 h(-1) of GHSV, and its apparent activation energy of the reaction is the lowest (39.1 kJ/mol). More Ag active sites, higher low-temperature reducibility, more abundant surface lattice oxygen species, oxygen vacancies, and lattice defects generated from interaction Ag with MnO2 are responsible for the excellent catalytic performance of HCHO oxidation on the 8.9% Ag/MnO2 catalyst. The 8.9% Ag/MnO2 catalyst remained highly active and stable under space velocity increasing from 60 000 to 150 000 h(-1), under initial HCHO concentration increasing from 500 to 1300 ppm, and under the presence of humidity, respectively.
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Ripoche, N; Ferchaud-Roucher, V; Krempf, M; Ritz, P
2006-09-01
In doubly labelled water studies, biological sample enrichments are mainly measured using off-line techniques (equilibration followed by dual-inlet introduction) or high-temperature elemental analysis (HT-EA), coupled with an isotope-ratio mass spectrometer (IRMS). Here another continuous-flow method, (CF-EA/IRMS), initially dedicated to water, is tested for plasma and urine analyses. The elemental analyser configuration is adapted for each stable isotope: chromium tube for deuterium reduction and glassy carbon reactor for 18O pyrolysis. Before on-line conversion of water into gas, each matrix is submitted to a short and easy treatment, which is the same for the analysis of the two isotopes. Plasma is passed through centrifugal filters. Urine is cleaned with black carbon and filtered (0.45 microm diameter). Tested between 150 and 300 ppm in these fluids, the D/H ratio response is linear with good repeatability (SD<0.2 ppm) and reproducibility (SD<0.5 ppm). For 18O/16O ratios (from 2000 to 2200 ppm), the same repeatability is obtained with a between-day precision lower than 1.4 ppm. The accuracy on biological samples is validated by comparison to classical dual-inlet methods: 18O analyses give more accurate results. The data show that enriched physiological fluids can be successfully analysed in CF-EA/IRMS. Copyright (c) 2006 John Wiley & Sons, Ltd.
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Domingo-Sananes, Maria Rosa; Kapuy, Orsolya; Hunt, Tim; Novak, Bela
2011-12-27
Activation of the cyclin-dependent kinase (Cdk1) cyclin B (CycB) complex (Cdk1:CycB) in mitosis brings about a remarkable extent of protein phosphorylation. Cdk1:CycB activation is switch-like, controlled by two auto-amplification loops--Cdk1:CycB activates its activating phosphatase, Cdc25, and inhibits its inhibiting kinase, Wee1. Recent experimental evidence suggests that parallel to Cdk1:CycB activation during mitosis, there is inhibition of its counteracting phosphatase activity. We argue that the downregulation of the phosphatase is not just a simple latch that suppresses futile cycles of phosphorylation/dephosphorylation during mitosis. Instead, we propose that phosphatase regulation creates coherent feed-forward loops and adds extra amplification loops to the Cdk1:CycB regulatory network, thus forming an integral part of the mitotic switch. These network motifs further strengthen the bistable characteristic of the mitotic switch, which is based on the antagonistic interaction of two groups of proteins: M-phase promoting factors (Cdk1:CycB, Cdc25, Greatwall and Endosulfine/Arpp19) and interphase promoting factors (Wee1, PP2A-B55 and a Greatwall counteracting phosphatase, probably PP1). The bistable character of the switch implies the existence of a CycB threshold for entry into mitosis. The end of G2 phase is determined by the point where CycB level crosses the CycB threshold for Cdk1 activation.
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Code of Federal Regulations, 2013 CFR
2013-07-01
... Results for Methods for SO 2, CO, O 3, NO 2 C Figure C-1 to Subpart C of Part 53 Protection of Environment... Pt. 53, Subpt. C, Fig. C-1 Figure C-1 to Subpart C of Part 53—Suggested Format for Reporting Test... Difference Table C-1 spec. Pass or fail Low 1 ____ pPM 2 to ____ pPM 3 4 5 6 Medium 1 ____ pPM 2 to ____ pPM...
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Reactivation of oxidized PTP1B and PTEN by Thioredoxin 1
Schwertassek, Ulla; Haque, Aftabul; Krishnan, Navasona; Greiner, Romy; Weingarten, Lars; Dick, Tobias P.; Tonks, Nicholas K.
2014-01-01
The transient inactivation of protein phosphatases contributes to the efficiency and temporal control of kinase-dependent signal transduction. In particular, members of the protein tyrosine phosphatase family are known to undergo reversible oxidation of their active site cysteine. The thiol oxidation step requires activation of co-localized NADPH oxidases and is mediated by locally produced ROS, in particular H2O2. How oxidized phosphatases are returned to the reduced active state is less well studied. Both major thiol reductive systems, the thioredoxin and the glutathione systems, have been implicated in the reactivation of phosphatases. Here, we show that the protein tyrosine phosphatase PTP1B and the dual-specificity phosphatase PTEN are preferentially reactivated by the thioredoxin system. We show that inducible depletion of TRX1 slows down PTEN re-activation in intact living cells. Finally, using a mechanism-based trapping approach we demonstrate direct thiol disulfide exchange between the active sites of thioredoxin and either phosphatase. The application of thioredoxin trapping mutants represents a complementary approach to direct assays of PTP oxidation in elucidating the significance of redox regulation of PTP function in the control of cell signaling. PMID:24976139
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NASA Technical Reports Server (NTRS)
Rashotte, A. M.; DeLong, A.; Muday, G. K.; Brown, C. S. (Principal Investigator)
2001-01-01
Auxin transport is required for important growth and developmental processes in plants, including gravity response and lateral root growth. Several lines of evidence suggest that reversible protein phosphorylation regulates auxin transport. Arabidopsis rcn1 mutant seedlings exhibit reduced protein phosphatase 2A activity and defects in differential cell elongation. Here we report that reduced phosphatase activity alters auxin transport and dependent physiological processes in the seedling root. Root basipetal transport was increased in rcn1 or phosphatase inhibitor-treated seedlings but showed normal sensitivity to the auxin transport inhibitor naphthylphthalamic acid (NPA). Phosphatase inhibition reduced root gravity response and delayed the establishment of differential auxin-induced gene expression across a gravity-stimulated root tip. An NPA treatment that reduced basipetal transport in rcn1 and cantharidin-treated wild-type plants also restored a normal gravity response and asymmetric auxin-induced gene expression, indicating that increased basipetal auxin transport impedes gravitropism. Increased auxin transport in rcn1 or phosphatase inhibitor-treated seedlings did not require the AGR1/EIR1/PIN2/WAV6 or AUX1 gene products. In contrast to basipetal transport, root acropetal transport was normal in phosphatase-inhibited seedlings in the absence of NPA, although it showed reduced NPA sensitivity. Lateral root growth also exhibited reduced NPA sensitivity in rcn1 seedlings, consistent with acropetal transport controlling lateral root growth. These results support the role of protein phosphorylation in regulating auxin transport and suggest that the acropetal and basipetal auxin transport streams are differentially regulated.
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Vitamin D and gene networks in human osteoblasts
van de Peppel, Jeroen; van Leeuwen, Johannes P. T. M.
2014-01-01
Bone formation is indirectly influenced by 1,25-dihydroxyvitamin D3 (1,25D3) through the stimulation of calcium uptake in the intestine and re-absorption in the kidneys. Direct effects on osteoblasts and bone formation have also been established. The vitamin D receptor (VDR) is expressed in osteoblasts and 1,25D3 modifies gene expression of various osteoblast differentiation and mineralization-related genes, such as alkaline phosphatase (ALPL), osteocalcin (BGLAP), and osteopontin (SPP1). 1,25D3 is known to stimulate mineralization of human osteoblasts in vitro, and recently it was shown that 1,25D3 induces mineralization via effects in the period preceding mineralization during the pre-mineralization period. For a full understanding of the action of 1,25D3 in osteoblasts it is important to get an integrated network view of the 1,25D3-regulated genes during osteoblast differentiation and mineralization. The current data will be presented and discussed alluding to future studies to fully delineate the 1,25D3 action in osteoblast. Describing and understanding the vitamin D regulatory networks and identifying the dominant players in these networks may help develop novel (personalized) vitamin D-based treatments. The following topics will be discussed in this overview: (1) Bone metabolism and osteoblasts, (2) Vitamin D, bone metabolism and osteoblast function, (3) Vitamin D induced transcriptional networks in the context of osteoblast differentiation and bone formation. PMID:24782782
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Yamburenko, Maria V; Zubo, Yan O; Börner, Thomas
2015-06-01
Abscisic acid (ABA) represses the transcriptional activity of chloroplast genes (determined by run-on assays), with the exception of psbD and a few other genes in wild-type Arabidopsis seedlings and mature rosette leaves. Abscisic acid does not influence chloroplast transcription in the mutant lines abi1-1 and abi2-1 with constitutive protein phosphatase 2C (PP2C) activity, suggesting that ABA affects chloroplast gene activity by binding to the pyrabactin resistance (PYR)/PYR1-like or regulatory component of ABA receptor protein family (PYR/PYL/RCAR) and signaling via PP2Cs and sucrose non-fermenting protein-related kinases 2 (SnRK2s). Further we show by quantitative PCR that ABA enhances the transcript levels of RSH2, RSH3, PTF1 and SIG5. RelA/SpoT homolog 2 (RSH2) and RSH3 are known to synthesize guanosine-3'-5'-bisdiphosphate (ppGpp), an inhibitor of the plastid-gene-encoded chloroplast RNA polymerase. We propose, therefore, that ABA leads to an inhibition of chloroplast gene expression via stimulation of ppGpp synthesis. On the other hand, sigma factor 5 (SIG5) and plastid transcription factor 1 (PTF1) are known to be necessary for the transcription of psbD from a specific light- and stress-induced promoter (the blue light responsive promoter, BLRP). We demonstrate that ABA activates the psbD gene by stimulation of transcription initiation at BLRP. Taken together, our data suggest that ABA affects the transcription of chloroplast genes by a PP2C-dependent activation of nuclear genes encoding proteins involved in chloroplast transcription. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.
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Kurnatowski, Piotr; Wójcik, Anna; Błaszkowska, Joanna; Góralska, Katarzyna
2016-10-01
The pathogenicity of fungi depends on, inter alia, the secretion of hydrolytic enzymes. The aim of this study was to determine the enzymatic activity of yeasts and yeast-like fungi isolated from children’s recreation areas, and compare the results with literature data of strains obtained from patients with mycoses. The enzymatic activity of 96 strains was assessed using an API ZYM kit (bioMerieux, France) and their biotypes were established. The fungal species were found to produce from 16 to 19 hydrolases: the most active were: leucine arylamidase (e5), acid phosphatase (e10), alkaline phosphatase (e1), naphthol-AS-BI-phosphohydrolase (e11), esterase – C4 (e2), β-galac - tosidase (e13) and β-glucosidase (e16). In addition, 13 biotypes characteristic of particular species of fungi were defined. Most strains could be categorized as biotypes C2 – 39.5% and A – 26%. The examined fungal strains isolated from recreational areas have selected biochemical characteristics i.e. production of hydrolases, which demonstrate their pathogenicity. They produce a number of enzymes which are also present in strains isolated from patients with mycoses, including: leucine arylamidase (e5), acid phosphatase (e10), naphthol-AS-BI-phosphohydrolase (e11) and alkaline phosphatase (e1). The biotypes identified in the course of this study (A, B3, B4, C1, C6 and D3) have been also reported in cases of fungal infection. Therefore, the fungi present in the sand and soil of recreational have pathogenic properties and are possible factors of fungal infection among children.
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Tanabe, Rieko; Kawamura, Yuka; Tsugawa, Naoko; Haraikawa, Mayu; Sogabe, Natsuko; Okano, Toshio; Hosoi, Takayuki; Goseki-Sone, Masae
2015-01-01
Several genes have been implicated as genetic determinants of osteoporosis. Vitamin D receptor (VDR) is an intracellular hormone receptor that specifically binds to the biologically active form of vitamin D, 1-alpha, 25- dihydroxyvitamin D3 [1, 25(OH)2D], and mediates its effects. One of the most frequently studied single nucleotide polymorphisms is the restriction fragment length polymorphism (RFLP) Fok-I (rs2228570). The presence of a Fok-I site, designated f, allows protein translation to initiate from the first ATG. An allele lacking the site (ATG>ACG: designated F), initiates from a second ATG site. In the present study, we explored the effect of the VDR Fok-I genotype on associations among serum bone-specific alkaline phosphatase (ALP), 25- hydroxyvitamin D3 [25(OH)D], 1, 25(OH)2D, and the dietary nutrient intake in healthy young Japanese subjects (n=193). Dietary nutrient intakes were calculated based on 3-day food records before the day of blood examinations. Quantitative ultrasound (QUS) parameters at the right calcaneus (heel bone) were measured. The allele frequencies were 0.622 for the F allele and 0.378 for the f allele in all subjects. Grouped by the VDR genotype, a significant positive correlation between the levels of serum bone-specific ALP and 25(OH)D was observed in the FF-type (p=0.005), but not in the ff-type. In addition, there was a significant positive correlation between the level of serum 25(OH)D and osteo-sono assessment index (OSI) in the FF-type (p=0.008), but not in the ff-type. These results suggest that the level of circulating 25(OH)D is an important factor when assessing the VDR Fok-I polymorphism to prevent osteoporosis.
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Martins, ML; Watral, V; Rodrigues-Soares, JP; Kent, ML
2016-01-01
Pseudocapillaria tomentosa is a common pathogen of zebrafish (Danio rerio) in research facilities. We developed a method to collect and concentrate the nematode eggs using a modified sugar centrifugation method, and documented their normal development. Embryonating stages with blastomere formation followed by elongation of the embryo prior to larva formation cumulated in developed larvae inside the eggs and hatching after 5–10 d. We then evaluated the efficacy of heat and chlorine to kill them based on a larva development assay. Eggs were exposed to 40, 50, 60°C for 30 min and 1 h. Chlorine treatment was performed at 100, 250, 500, 1000, 3000 and 6000 ppm for 10 min. Samples exposed to 40°C for 30 min or 1 h showed incidences of larvated eggs similar to controls. In contrast, no larvation occurred with eggs exposed to either 50 or 60°C for 30 min or 1 h. Remarkably, in repeated assays, samples exposed to low doses of chlorine (100, 250, 500 and 1000 ppm for 10 min) showed significantly higher incidence of larvation than controls. Eggs treated with 3,000 ppm for 10 min did not develop larvae and no eggs were found after 6,000 ppm treatment. PMID:27334246
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Concentrations of methoxyflurane and nitrous oxide in veterinary operating rooms
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ward, G.S.; Byland, R.R.
1982-02-01
The surgical rooms of 14 private veterinary practices were monitored to determined methoxyflurane (MOF) concentrations during surgical procedure under routine working conditions. The average room volume for these 14 rooms was 29 m3. The average MOF value for all rooms was 2.3 ppm, with a range of 0.7 to 7.4 ppm. Four of the 14 rooms exceeded the maximum recommended concentration of 2 ppm. Six rooms which had 6 or more air changes/hr averaged 1.1 ppm, whereas 8 rooms with less than 6 measurable air changes/hr averaged 3.2 ppm. Operating rooms that had oxygen flows of more than 1,000 cm3/minmore » averaged 4.4 ppm, whereas those with flows of less than 1,000 cm3/min averaged 1.5 ppm. The average time spent during a surgical procedure using MOF, for all 14 facilities, was 2 hours. Nitrous oxide (N/sub 2/O) concentrations were determined in 4 veterinary surgical rooms. The average N/sub 2/O concentration for 3 rooms without waste anesthetic gas scavenging was 138 ppm. Concentration of N/sub 2/O in the waste anesthetic gas-scavenged surgical room was 14 ppm, which was below the maximum recommended concentration of 25 ppm.« less
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Ramalingam, N; Prasanna, B Gowtham
2006-09-01
The impact of insoluble phosphorus such as aluminum and rock phosphate on alkaline phosphatase activity of polyurethane foam immobilized cyanobacteria was assessed. Polyurethane foam immobilized Nodularia recorded the highest alkaline phosphatase activity of 9.04 (m. mol p-nitrophenol released h(-1) mg(-1) protein) in vitro. A higher concentration of aluminum phosphate was recorded a 25% reduction in alkaline phosphatase activity, ammonia content, and available phosphorus in culture filtrate of polyurethane foam immobilized cyanobacteria. In general, immobilized cyanobacteria exhibited a higher alkaline phosphatase activity in rock phosphate than aluminum phosphate.
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Modelling of Tc migration in an un-oxidized fractured drill core from Äspö, Sweden
NASA Astrophysics Data System (ADS)
Huber, F. M.; Totskiy, Y.; Montoya Garcia, V.; Enzmann, F.; Trumm, M.; Wenka, A.; Geckeis, H.; Schaefer, T.
2015-12-01
The radionuclide retention of redox sensitive radionuclides (e.g. Pu, Np, U, Tc) in crystalline host rock greatly depends on the rock matrix and the rock redox capacity. Preservation of drill cores concerning oxidation is therefore of paramount importance to reliably predict the near-natural radionuclide retention properties. Here, experimental results of HTO and Tc laboratory migration experiments in a naturally single fractured Äspö un-oxidized drill core are modelled using two different 2D models. Both models employ geometrical information obtained by μ-computed tomography (μCT) scanning of the drill core. The models differ in geometrical complexity meaning the first model (PPM-MD) consists of a simple parallel plate with a porous matrix adjacent to the fracture whereas the second model (MPM) uses the mid-plane of the 3D fracture only (no porous matrix). Simulation results show that for higher flow rates (Peclet number > 1), the MPM satisfactorily describes the HTO breakthrough curves (BTC) whereas the PPM-MD model nicely reproduces the HTO BTC for small Pe numbers (<1). These findings clearly highlight the influence of fracture geometry/flow field complexity on solute transport for Pe numbers > 1 and the dominating effect of matrix diffusion for Peclet numbers < 1. Retention of Tc is modelled using a simple Kd-approach in case of the PPM-MD and including 1st order sorptive reduction/desorption kinetics in case of the MPM. Batch determined sorptive reduction/desorption kinetic rates and Kd values for Tc on non-oxidized Äspö diorite are used in the model and compared to best fit values. By this approach, the transferability of kinetic data concerning sorptive reduction determined in static batch experiments to dynamic transport experiments is examined.
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Pulmonary sensitivity to ozone exposure in sedentary versus chronically trained, female rats.
Gordon, Christopher J; Phillips, Pamela M; Beasley, Tracey E; Ledbetter, A; Aydin, Cenk; Snow, Samantha J; Kodavanti, Urmila P; Johnstone, Andrew F
2016-06-01
Epidemiological data suggest that a sedentary lifestyle may contribute to increased susceptibility for some environmental toxicants. We developed an animal model of active versus sedentary life style by providing female Sprague-Dawley rats with continuous access to running wheels. Sedentary rats were housed in standard cages without wheels. After training for 12 wks, rats were exposed to 0, 0.25, 0.5 or 1.0 ppm ozone [O3 for 5 h/d, 1 d/wk, for 6 wk (N = 10 per group)]. Body composition (%fat, lean and fluid) was monitored noninvasively over the course of the study. Ventilatory parameters [tidal volume, minute ventilation, frequency and enhanced pause (Penh)] were assessed using whole-body plethysmography prior to O3 and 24 h after the 5th O3 exposure. Trained rats lost ∼2% body fat after 12 wk of access to running wheels. Peak wheel activity was reduced by 40% after exposure to 1.0 ppm O3. After the 5th O3 exposure, body weight and %fat were reduced in sedentary but not trained rats. Penh was significantly elevated in sedentary but not trained rats the day after exposure to 1.0 ppm O3. However, lung lavage cell counts and biomarkers of pulmonary inflammation measured 1 day after the final exposure were inconsistently affected by training. Wheel running led to marked physiological responses along with some indication of improved pulmonary recovery from O3 exposure. However, wheel running with O3 exposure may also be a detriment for some pulmonary endpoints. Overall, a sedentary lifestyle may increase susceptibility to O3, but additional studies are needed.
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Liang, Lin-Fu; Chen, Wen-Ting; Mollo, Ernesto; Yao, Li-Gong; Wang, He-Yao; Xiao, Wei; Guo, Yue-Wei
2017-06-01
Minor metabolic components, six new cembranoids sarcophytrols G - L (1 - 6) along with two known related analogues 7 and 8, were isolated from the South China Sea soft coral Sarcophyton trocheliophorum. Their structures were elucidated by extensive spectroscopic analyses (1D-, 2D-NMR, and ESI-MS) as well as comparison with literature data. As part of our ongoing research project for discovering bioactive substances from Chinese marine invertebrates, compounds 1 - 8 were tested for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of Type-II diabetes and obesity. However, none of them exhibited potent PTP1B inhibitory activities. © 2017 Wiley-VHCA AG, Zurich, Switzerland.
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1986-09-01
60 48.4 Systems 200/400 15 12.1 Contract Administration (PPM 152) 13 10.5 Logistics Management (Log 224) 2 1.6 Government Contract Law (PPM 302) 20...detail. 1. Systems 200/400 2. Contract Administration (PPM 152) 3. Logistics Management (LOG 224) 4. Government Contract Law (PPM 302) 5. Technical...152 Contract Administration o Log 224 Logistics Management o PPM 302 Government Contract Law o QMT 345 Quantitative Technical, Cost, and Price Analysis
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Sridharan, Srirangarajan; Sravani, Paruchuri; Satyanarayan, Aparna; Kiran, K; Shetty, Varun
The aim of this pilot study was to determine whether salivary alkaline phosphatase levels can be a non invasive marker for early inflammatory periodontal disease in children with uncontrolled type 1 diabetes mellitus. 10 healthy children (group 1), 10 children with recently diagnosed type 1 diabetes mellitus (group 2) and 10 children with type 1 diabetes mellitus for more than 4 years (group 3) were recruited for the study. All three groups were matched for age, gender and socioeconomic status. Periodontal health was assessed by plaque index, gingival index and probing pocket depth. Metabolic status was assessed by glycosylated hemoglobin levels, salivary alkaline phosphatase levels were determined by spectrophotometer. Data was analyzed by Kruskal Wallis ANOVA, Mann-Whitney U test and Spearman's rank correlation method. Salivary alkaline phosphatase levels correlated significantly with the periodontal parameters in the diabetic group. An increase in salivary alkaline phosphatase levels increased with increased values of gingival index and probing pocket depth. Group 3 showed greater correlation than group 2 and group 1. At p value p<0.05. The glycemic status of the children affects the periodontal disease parameters. Salivary alkaline phosphatase levels could be a useful tool in analyzing periodontal status of children with uncontrolled type I diabetes mellitus.
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1 ALPHA-Hydroxyvitamin D5 as a Chemotherapeutic and Possibly Chemopreventive Agent
2004-09-01
with differential, platelets, PT, and PTT. 7.1.4 Serum chemistries : glucose, electrolytes (Na+, K+, Cl-, C0 2), BUN, creatinine, total protein... chemistries : glucose, electrolytes (Na+, K+, Cl-, and C02), BUN, creatinine, total protein, albumin, bilirubin, alkaline phosphatase, LDH, SGOT, SGPT, calcium...Roberts AB, Goodman DS (eds) The Retinoids: Biology, Chemistry , and Medicine. New York: Raven, 1994, pp. 573-596. 3. Hong WK, Itri LM. Retinoids and human
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NASA Astrophysics Data System (ADS)
Feng, L.; Palmer, P. I.; Yang, Y.; Yantosca, R. M.; Kawa, S. R.; Paris, J.-D.; Matsueda, H.; Machida, T.
2011-03-01
We evaluate the GEOS-Chem atmospheric transport model (v8-02-01) of CO2 over 2003-2006, driven by GEOS-4 and GEOS-5 meteorology from the NASA Goddard Global Modeling and Assimilation Office, using surface, aircraft and space-borne concentration measurements of CO2. We use an established ensemble Kalman Filter to estimate a posteriori biospheric+biomass burning (BS + BB) and oceanic (OC) CO2 fluxes from 22 geographical regions, following the TransCom-3 protocol, using boundary layer CO2 data from a subset of GLOBALVIEW surface sites. Global annual net BS + BB + OC CO2 fluxes over 2004-2006 for GEOS-4 (GEOS-5) meteorology are -4.4 ± 0.9 (-4.2 ± 0.9), -3.9 ± 0.9 (-4.5 ± 0.9), and -5.2 ± 0.9 (-4.9 ± 0.9) PgC yr-1, respectively. After taking into account anthropogenic fossil fuel and bio-fuel emissions, the global annual net CO2 emissions for 2004-2006 are estimated to be 4.0 ± 0.9 (4.2 ± 0.9), 4.8 ± 0.9 (4.2 ± 0.9), and 3.8 ± 0.9 (4.1 ± 0.9) PgC yr-1, respectively. The estimated 3-yr total net emission for GEOS-4 (GEOS-5) meteorology is equal to 12.5 (12.4) PgC, agreeing with other recent top-down estimates (12-13 PgC). The regional a posteriori fluxes are broadly consistent in the sign and magnitude of the TransCom-3 study for 1992-1996, but we find larger net sinks over northern and southern continents. We find large departures from our a priori over Europe during summer 2003, over temperate Eurasia during 2004, and over North America during 2005, reflecting an incomplete description of terrestrial carbon dynamics. We find GEOS-4 (GEOS-5) a posteriori CO2 concentrations reproduce the observed surface trend of 1.91-2.43 ppm yr-1 (parts per million per year), depending on latitude, within 0.15 ppm yr-1 (0.2 ppm yr-1) and the seasonal cycle within 0.2 ppm (0.2 ppm) at all latitudes. We find the a posteriori model reproduces the aircraft vertical profile measurements of CO2 over North America and Siberia generally within 1.5 ppm in the free and upper troposphere but can be biased by up to 4-5 ppm in the boundary layer at the start and end of the growing season. The model has a small negative bias in the free troposphere CO2 trend (1.95-2.19 ppm yr-1) compared to AIRS data which has a trend of 2.21-2.63 ppm yr-1 during 2004-2006, consistent with surface data. Model CO2 concentrations in the upper troposphere, evaluated using CONTRAIL (Comprehensive Observation Network for TRace gases by AIrLiner) aircraft measurements, reproduce the magnitude and phase of the seasonal cycle of CO2 in both hemispheres. We generally find that the GEOS meteorology reproduces much of the observed tropospheric CO2 variability, suggesting that these meteorological fields will help make significant progress in understanding carbon fluxes as more data become available.
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Issa, Jaqueline S; Abe, Tania M O; Pereira, Alexandre C; Megid, Maria Cristina; Shimabukuro, Cristina E; Valentin, Luis Sergio O; Ferreira, Marizete M da C; Nobre, Moacyr R C; Lancarotte, Ines; Barretto, Antonio Carlos Pereira
2011-03-01
Studies have shown that there is no safe level of secondhand smoke (SHS) exposure and there is a close link between SHS and the risk of coronary heart disease and stroke. Carbon monoxide (CO) is one of the most important components present in SHS. To evaluate the impact of the smoking ban law in the city of Sao Paulo, Brazil, on the CO concentration in restaurants, bars, night clubs and similar venues and in their workers. In the present study we measured CO concentration in 585 hospitality venues. CO concentration was measured in different environments (indoor, semi-open and open areas) from visited venues, as well as, in the exhaled air from approximately 627 workers of such venues. Measurements were performed twice, before and 12 weeks after the law implementation. In addition, the quality of the air in the city during the same period of our study was verified. RESULTS The CO concentration pre-ban and pot-ban in hospitality venues was indoor area 4.57 (3.70) ppm vs 1.35 (1.66) ppm (p<0.0001); semi-open 3.79 (2.49) ppm vs 1.16 (1.14) ppm (p<0.0001); open area 3.31(2.2) ppm vs 1.31 (1.39) ppm (p<0.0001); smoking employees 15.78 (9.76) ppm vs 11.50 (7.53) ppm (p<0.0001) and non-smoking employees 6.88 (5.32) ppm vs 3.50 (2.21) ppm (p<0.0001). The average CO concentration measured in the city was lower than 1 ppm during both pre-ban and post-ban periods. São Paulo's smoking-free legislation reduced significantly the CO concentration in hospitality venues and in their workers, whether they smoke or not.
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Pola-Gallego-de-Guzmán, María Dolores; Ruiz-Bailén, Manuel; Martínez-Arcos, Maria-Angeles; Gómez-Blizniak, Artur; Castillo Rivera, Ana-Maria; Molinos, Jesus Cobo
2018-04-01
Patients with acute coronary syndrome complicated with high degree atrioventricular block still have a high mortality. A low percentage of these patients need a permanent pacemaker (PPM) but mortality and associated factors with the PPM implant in acute coronary syndrome patients are not known. We assess whether PPM implant is an independent variable in the mortality of acute coronary syndrome patients. Also, we explored the variables that remain independently associated with PPM implantation. This was an observational study on the Spanish ARIAM register. The inclusion period was from January 2001 to December 2011. This registry included all Andalusian acute coronary syndrome patients. Follow-up for global mortality was until November 2013. We selected 27,608 cases. In 62 patients a PPM was implanted (0.024%). The mean age in PPM patients was 70.71±11.214 years versus 64.46±12.985 years in patients with no PPM. PPM implant was associated independently with age (odds ratio (OR) 1.031, 95% confidence interval (CI) 1.007-1.055), with left ventricular branch block (OR 6.622, 95% CI 2.439-18.181), with any arrhythmia at intensive care unit admission (OR 2.754, 95% CI 1.506-5.025) and with heart failure (OR 3.344, 95% CI 1.78-8.333). PPM implant was independently associated with mortality (OR 11.436, 95% CI 1.576-83.009). In propensity score analysis PPM implant was still associated with mortality (OR 5.79, 95% CI 3.27-25.63). PPM implant is associated with mortality in the acute coronary syndrome population in the ARIAM registry. Advanced age, heart failure, arrhythmias and left ventricular branch block at intensive care unit admission were found associated factors with PPM implant in acute coronary syndrome patient.
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Yokoyama, Victoria Y
2014-06-01
A multiple quarantine treatment was developed to control Hessian fly puparia, Mayetiola destructor (Say), the stage of regulatory concern in exported hay. In a commercial test using 51.589 puparia, no insects survived to the adult stage after exposure to bale compression at 137 kg/cm2 and fumigation with 61 g/28.3 m3 hydrogen phosphide for 3d. The puparia were fumigated in infested wheat seedlings in cloth bags inside compressed timothy bales placed in different locations in three replicate freight containers in a heated building. Fumigant concentrations were 345-522 ppm on day 1; 580-824 ppm on day 2; and 680-861 ppm on day 3. Monitored temperatures were < 20 degrees C in all locations allowing the fumigation temperature to be established at > or = 20 degrees C. Copper detection plate corrosion values were severe inside the freight container doors, and moderate in the middle of bales in all locations, providing visual confirmation of exposure to hydrogen phosphide. Hydrogen phosphide residues in exposed hay bales were found in trace amounts, below the U.S. Environmental Protection Agency tolerance of 0.1 ppm for animal feeds. Timothy hay used in the commercial test is the representative species for all previously exported hay and straw species. The new multiple quarantine treatment is proposed for use with all previously tested bale sizes and wrapper styles for which 3-d fumigation data has been reported, and for bales and wrappers derived from those tested.
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1998-09-01
Chloroprene is used almost exclusively in the manufacture of neoprene (polychloroprene). Chloroprene was chosen for study because it is a high-volume production chemical with limited information on its carcinogenic potential and because it is the 2-chloro analogue of 1,3-butadiene, a potent, multi-species, multi-organ carcinogen. Male and female F344/N rats and B6C3F1 mice were exposed to chloroprene (greater than 96% pure) by inhalation for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Drosophila melanogaster, and B6C3F1 mice (bone marrow cells and peripheral blood erythrocytes). 16-Day Study in Rats: Groups of 10 male and 10 female F344/N rats were exposed to 0, 32, 80, 200, or 500 ppm chloroprene by inhalation, 6 hours per day, 5 days per week, for 16 days. Three 500 ppm males died on day 2 or 3 of the study. Mean body weight gains of 200 ppm males and females and 500 ppm females were significantly less than those of the chamber control groups. On the first day of exposure, rats exposed to 500 ppm were hypoactive and unsteady and had rapid shallow breathing. These effects were also observed to some degree in animals exposed to 200 ppm. After the second day of exposure, the effects in these groups worsened, and hemorrhage from the nose was observed. A normocytic, normochromic, responsive anemia; thrombocytopenia; and increases in serum activities of alanine aminotransferase, glutamate dehydrogenase, and sorbitol dehydrogenase occurred on day 4 in 200 ppm females and 500 ppm males. Kidney weights of 80 and 500 ppm females were significantly greater than those of the chamber control group, as were the liver weights of 200 and 500 ppm females. The incidences of minimal to mild olfactory epithelial degeneration of the nose in all exposed groups of males and females were significantly greater than those in the chamber control groups. The incidence of squamous metaplasia of the respiratory epithelium was significantly increased in 500 ppm males. The incidences of centrilobular to random hepatocellular necrosis in 500 ppm males and 200 ppm females were significantly greater than those in the chamber control groups. 16-Day Study in Mice: Groups of 10 male and 10 female B6C3F1 mice were exposed to 0, 12, 32, 80, or 200 ppm chloroprene by inhalation, 6 hours per day, 5 days per week, for 16 days. All males and females exposed to 200 ppm died on day 2 or day 3 of the study. Mean body weight gains of males exposed to 32 or 80 ppm were significantly less than that of the chamber control group. Mice exposed to 200 ppm exhibited narcosis during exposure and were hypoactive with reduced body tone after the first day of exposure. In general, hematology and clinical chemistry parameters measured for exposed males and females were similar to those of the chamber control groups. Thymus weights of 80 ppm males and females were significantly less than those of the chamber control groups. Liver weights of 80 ppm females were significantly greater than those of the chamber control groups. Increased incidences of multifocal random hepatocellular necrosis occurred in males and females exposed to 200 ppm. Hypertrophy of the myocardium, foci of hemorrhage, and mucosal erosion were observed in three males and three females exposed to 200 ppm. Squamous epithelial hyperplasia of the forestomach was observed in two males and two females exposed to 80 ppm. Thymic necrosis, characterized by karyorrhexis of thymic lymphocytes, was observed in all males and females in the 200 ppm groups. 13-Week Study in Rats: Groups of 10 male and 10 female F344/N rats were exposed to chloroprene at concentrations of 0, 5, 12, 32, 80, or 200 ppm by inhalation, 6 hours per day, 5 days per week, for 13 weeks. One male exposed to 200 ppm died during the study. The final mean body weights and body weight gains of all exposed groups of males and females were similar to those of the chamber control groups. Clinical findings in 200 ppm males included red or clear discharge around the nose and eye region. At week 13, a norm a normocytic, normochromic, and non-responsive anemia occurred in 200 ppm males and females. A thrombocytopenia occurred in 200 ppm males and females on day 2 and in 80 and 200 ppm females on day 22. However, at week 13, platelet counts rebounded and were minimally increased in 200 ppm males and females. On day 2, a minimal to mild increase in activated partial thromboplastin time and prothrombin time occurred in 200 ppm males and females. The 200 ppm males and females also had increased activities of serum alanine aminotransferase, glutamate dehydrogenase, and sorbitol dehydrogenase on day 22; these increases were transient, and by week 13 the serum activities of these enzymes were similar to those of the chamber controls. An alkaline phosphatase enzymeuria occurred in 200 ppm females on day 22; at week 13, an alkaline phosphatase enzymeuria oc-curred in 32, 80, and 200 ppm males and 200 ppm females. At week 13, a proteinuria occurred in 200 ppm males. Liver nonprotein sulfhydryl concentrations in male rats immediately following 1 day or 12 weeks of exposure to 200 ppm and in females exposed to 200 ppm for 12 weeks were significantly less than those of the chamber control groups. Kidney weights of 200 ppm males and females and 80 ppm females were significantly greater than those of the chamber control groups. Sperm motility of 200 ppm males was significantly less than that of the controls. In neurobehavioral assessments, horizontal activity was increased in male rats exposed to 32 ppm or greater and total activity was increased in 32 and 200 ppm males. Increased incidences of minimal to mild olfactory epithelial degeneration and respiratory metaplasia occurred in males and females exposed to 80 or 200 ppm. The incidence of olfactory epithelial degeneration in 32 ppm females was also significantly greater than that in the chamber control group. The incidence of hepatocellular necrosis in 200 ppm females was significantly greater than that in the chamber control group. Scattered chronic inflammation also occurred in the liver of male and female rats in the 200 ppm groups; the incidence in 200 ppm females was significantly greater than that in the chamber control group. The incidences of hemosiderin pigmentation were significantly increased in males and females exposed to 200 ppm. 13-Week Study in Mice: Groups of 10 male and 10 female B6C3F1 mice were exposed to chloroprene at concentrations of 0, 5, 12, 32, or 80 ppm by inhalation, 6 hours per day, 5 days per week, for 13 weeks. All male and female mice survived to the end of the study. The final mean body weight and body weight gain of males exposed to 80 ppm were significantly less than those of the chamber control group. Hematocrit concentrations of females exposed to 32 or 80 ppm and erythrocyte counts of 80 ppm females were significantly less than those of the chamber control group. Platelet counts of 32 and 80 ppm females were also greater than that of the chamber control group. Increased incidences of squamous epithelial hyperplasia of the forestomach occurred in males and females exposed to 80 ppm. 2-Year Study in Rats: Groups of 50 male and 50 female F344/N rats were exposed to chloroprene at concentrations of 0, 12.8, 32, or 80 ppm by inhalation, 6 hours per day, 5 days per week, for 2 years. Survival, Body Weights, and Clinical Findings: Survival of males exposed to 32 or 80 ppm was significantly less than that of the chamber control group. Mean body weights of males exposed to 80 ppm were less than those of the chamber controls after week 93. Masses of the torso were observed during the study in exposed female groups, and these clinical findings correlated with mammary gland fibroadenomas observed at necropsy. Pathology Findings: The incidences of squamous cell papilloma and squamous cell papilloma or squamous cell carcinoma (combined) of the oral cavity in male rats exposed to 32 ppm and male and female rats exposed to 80 ppm were significantly greater than those in the chamber controls and exceeded the historical control ranges. The incidences of thyroid gland follicular cell adenoma or carcinoma (combined) in males exposed to 32 or 80 ppm were significantly greater than that in the chamber control group and exceeded the historical control range. Although the incidences of follicular cell adenoma and follicular cell adenoma or carcinoma (combined) in 80 ppm females were not significantly greater than those in the chamber controls, they did exceed the historical control range for these neoplasms. The incidences of alveolar epithelial hyperplasia of the lung were significantly greater in all exposed groups of males and females than in the chamber control groups. The incidences of alveolar/bronchiolar carcinoma and alveolar/bronchiolar adenoma or carcinoma (combined) in 80 ppm males were slightly greater than those in the chamber control group. Although these neoplasm incidences were not significant, they exceeded the historical control range. The incidence of alveolar/bronchiolar adenoma, although not significant, was greater in 80 ppm females than in the chamber control group. The incidences of multiple fibroadenoma of the mammary gland in all exposed groups of females were greater than that in the chamber control group. The incidences of fibroadenoma (including multiple fibroadenoma) in 32 and 80 ppm females were significantly greater than that in the chamber controls. The incidences of fibroadenoma in the chamber control group and in all exposed groups of females exceeded the historical control range. The severity of nephropathy in exposed groups of male and female rats was slightly greater than in the chamber controls. Renal tubule adenoma and hyperplasia were observed in males and females. Additional kidney sections from male and female control and exposed rats were examined to provide a clearer indication of the potential effects of chloroprene on the kidney. The combined single- and step-section incidences of renal tubule hyperplasia in 32 and 80 ppm males and 80 ppm females and the incidences of adenoma and adenoma or carcinoma (combined) in all exposed males were significantly greater than those in the chamber controls. A slight increase in the incidence of transitional epithelium carcinoma of the urinary bladder was observed in 80 ppm females. In addition, one 32 ppm male had a transitional epithelium carcinoma and one 80 ppm male had a transitional cell papilloma. These findings are noteworthy because no urinary bladder neoplasms have been observed in chamber control male or female F344/N rats. In the nose, the incidences of atrophy, basal cell hyperplasia, metaplasia, and necrosis of the olfactory epithelium in 32 and 80 ppm males and females and of atrophy and necrosis in 12.8 ppm males were significantly greater than those in the chamber control groups. The incidences of chronic inflammation were significantly increased in males exposed to 12.8 or 32 ppm and in males and females exposed to 80 ppm. The incidences of fibrosis and adenomatous hyperplasia in 80 ppm males and females were significantly greater than those in the chamber controls. Generally, lesions in the nasal cavity were mild to moderate in severity. 2-Year Study in Mice: Groups of 50 male and 50 female B6C3F1 mice were exposed to chloroprene at concentrations of 0, 12.8, 32, or 80 ppm by inhalation, 6 hours per day, 5 days per week, for 2 years. Survival, Body Weights, and Clinical Findings: Survival of males exposed to 32 or 80 ppm and of all exposed female groups was significantly less than that of the chamber controls. The mean body weights of 80 ppm females were significantly less than those of the chamber control group after week 75. Clinical findings included masses of the head, which correlated with harderian gland adenoma and/or carcinoma in 32 ppm males and 80 ppm males and fe-males. Dorsal and lateral torso masses of female mice correlated with mammary gland neoplasms in 32 and 80 ppm females and subcutaneous sarcomas in 12.8, 32, and 80 ppm females. Pathology Findings: The incidences of alveolar/bronchiolar neoplasms in the lungs of all groups of exposed males and females were significantly greater than those in the chamber control groups and generally exceeded the historical control ranges. The incidences of multiple alveolar/bronchiolar adenoma and alveolar/bronchiolar carcinoma were increased in all exposed groups of males and females. The incidences of bronchiolar hyperplasia in all exposed groups of males and females were significantly greater than those in the chamber control groups. Male mice had a pattern of nonneoplastic liver lesions along with silver-staining helical organisms within the liver consistent with infection with Helicobacter hepaticus. An organism compatible with H. hepaticus was confirmed with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based assay. In NTP studies with H. hepaticus-associated hepatitis, increased incidences of hemangiosarcoma have been seen in the livers of male mice. Therefore, hemangiosarcomas of the liver were excluded from the analyses of circulatory (endothelial) neoplasms in males in this study. Even with this exclusion, the combined occurrence of hemangioma or hemangiosarcoma at other sites was significantly increased at all chloroprene exposure concentrations in males and in 32 ppm females. Incidences of neoplasms at other sites in this study of chloroprene were not considered to have been significantly impacted by the infection with H. hepaticus or its associated hepatitis. The incidences of harderian gland adenoma and harderian gland adenoma or carcinoma (combined) in males exposed to 32 or 80 ppm and females exposed to 80 ppm were significantly greater than those in the chamber controls. The incidences of harderian gland adenoma or carcinoma (combined) in 32 ppm males and 80 ppm males and females exceeded the historical control ranges. The incidences of mammary gland carcinoma and adenoacanthoma or carcinoma (combined) in 80 ppm females were significantly greater than those in the chamber control group. The incidences of mammary gland carcinoma and of adenoacanthoma in 32 and 80 ppm females exceeded the historical control ranges. Multiple mammary gland carcinomas occurred in exposed females. The incidences of hepatocellular carcinoma in all exposed female groups and hepatocellular adenoma or carcinoma (combined) in 32 and 80 ppm females were significantly greater than those in the chamber controls; in the 80 ppm group, the incidence exceeded the historical control ranges for carcinoma and adenoma or carcinoma (combined). The incidence of eosinophilic foci in 80 ppm females was also significantly greater than that in the chamber controls. The incidences of sarcoma of the skin were significantly greater in all exposed groups of females than in the chamber controls. The incidences of sarcoma of the mesentery were also increased in all exposed groups of females. The incidence of squamous cell papilloma in 80 ppm females was greater than that in the chamber controls; the difference was not significant, but the incidence exceeded the historical control range. Males also showed a positive trend in the incidence of squamous cell papilloma of the forestomach. In males and females exposed to 80 ppm, the incidences of hyperplasia of the forestomach epithelium were significantly greater than those in the chamber controls. Carcinomas of the Zymbal's gland were seen in three 80 ppm females, and two carcinomas metastasized to the lung. Zymbal's gland carcinomas have not been reported in control female mice in the NTP historical database. The incidence of renal tubule adenoma in 80 ppm males was greater than that in the chamber controls. Though this difference was not significant, the incidence of this rare neoplasm exceeded the historical control range. The incidences of renal tubule hyperplasia in males exposed to 32 or 80 ppm were significantly greater than that in the chamber controls. Additional sections of kidney were examined from control and exposed males to verify these findings. The combined single- and step-section incidence of renal tubule adenoma in 80 ppm males and the combined incidences of renal tubule hyperplasia in all groups of exposed male mice were greater than those in the chamber controls. The incidences of olfactory epithelial atrophy, adenomatous hyperplasia, and metaplasia in 80 ppm males and females were significantly greater than those in the chamber controls. The incidences of hematopoietic proliferation of the spleen in 32 and 80 ppm males and in all groups of exposed females were significantly greater than those in the chamber controls. Genetic Toxicology: Chloroprene was not mutagenic in any of the tests performed by the NTP. No induction of mutations was noted in any of four strains of S. typhimurium in the presence or the absence of S9 metabolic activation enzymes, and no induction of sex-linked recessive lethal mutations was observed in germ cells of male D. melanogaster treated with chloroprene via feeding or injection. In male mice exposed to chloroprene by inhalation for 12 days over a 16-day period, no induction of chromosomal aberrations, sister chromatid exchanges, or micronucleated erythrocytes in bone marrow or peripheral blood occurred. Results of a second micronucleus assay in male and female mice after 13 weeks of exposure to chloroprene via inhalation were also negative. Conclusion: Under the conditions of these 2-year inhalation studies, there was clear evidence of carcinogenic activity of chloroprene in male F344/N rats based on increased incidences of neoplasms of the oral cavity; increased incidences of neoplasms of the thyroid gland, lung, and kidney were also attributed to chloroprene exposure. There was clear evidence of carcinogenic activity of chloroprene in female F344/N rats based on increased incidences of neoplasms of the oral cavity; increased incidences of neoplasms of the thyroid gland, mammary gland, and kidney were also attributed to exposure to chloroprene. Low incidences of urinary bladder neoplasms in male and female rats and lung neoplasms in female rats may also have been related to exposure to chloroprene. There was clear evidence of carcinogenic activity of chloroprene in male B6C3F1 mice based on increased incidences of neoplasms of the lung, circulatory system (hemangiomas and hemangiosarcomas), and harderian gland; increased incidences of neoplasms of the forestomach and kidney were also attributed to exposure to chloroprene. There was clear evidence of carcinogenic activity of chloroprene in female B6C3F1 mice based on increased incidences of neoplasms of the lung, circulatory system (hemangiomas and hemangiosarcomas), harderian gland, mammary gland, liver, skin, and mesentery; increased incidences of neoplasms of the forestomach and Zymbal's gland were also attributed to exposure to chloroprene. Exposure of male and female rats to chloroprene was associated with increased incidences of alveolar epithelial hyperplasia in the lung; nephropathy; and several nonneoplastic effects in the nose including olfactory epithelial atrophy, fibrosis, adenomatous hyperplasia, basal cell hyperplasia, chronic inflammation, respiratory metaplasia, and necrosis. Exposure of male and female mice to chloroprene was associated with increased incidences of bronchiolar hyperplasia and histiocytic cell infiltration in the lung; epithelial hyperplasia in the forestomach; renal tubule hyperplasia (males only); several effects in the nose including olfactory epithelial atrophy, respiratory metaplasia, and adenomatous hyperplasia; and hematopoietic cell proliferation in the spleen. Synonyms: Chlorobutadiene, 2-chlorobuta-1,3-diene, 2-chloro-1,3-butadiene, -chloroprene
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bleavins, M.R.; Bursian, S.J.; Brewster, J.S.
1984-01-01
In the initial trial, adult mink and ferrets were administered hexachlorobenzene (HCB) via the feed at concentrations of 1, 5, or 25 ppm for 47 wk. Animals receiving 125 and 625 ppm HCB in the diet died before termination of the experiment, with female ferrets at the 125 ppm level displaying abnormal aggressiveness and hyperexcitability just prior to death. Hypothalamic serotonin (5-HT) was significantly elevated at all dose levels in mink, and cerebellar 5-HT was significantly elevated at 1 ppm in the ferret. Regional brain biogenic amine concentrations were also determined in the offspring of the female mink that weremore » administered 1 and 5 ppm HCB. Hypothalamic dopamine (DA) concentrations were significantly depressed by 1 and 5 ppm in these kits. In a second study, adult male and female ferrets were administered 250 or 500 ppm HCB via the diet for 7 wk. Two animals at the 250-ppm level and 3 animals at the 500-ppm level died before termination of the experiment without showing behavioral changes. Of the remaining animals, 3 ferrets at 250 ppm and 1 ferret at 500 ppm showed slight aggressiveness and hyperexcitability during the last week of the experiment. Concentrations of 5-HT were significantly elevated at 500 ppm in the cerebral hemispheres and at 250 ppm in the midbrain of male ferrets, while in the females, 5-HT was elevated in the cerebral hemispheres at 250 ppm and in the hypothalamus at both 250 and 500 ppm. Norepinephrine (NE) concentrations were significantly elevated in the cerebellum of males exposed to 250 and 500 ppm, as were NE concentrations in the midbrain. HCB at 500 ppm caused a significant increase in medullary NE, while 250 ppm caused an increase in hypothalamic NE in males. The only change in regional brain dopamine (DA) concentrations occurred at 500 ppm HCB in the midbrain of males, where there was a significant elevation of this neurotransmitter. 34 references, 7 tables.« less
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Conkle, Jeremy L; Lattao, Charisma; White, John R; Cook, Robert L
2010-09-01
Significant amounts of pharmaceuticals are discharged into the environment through wastewater effluent. Sorption has been shown to be a significant aqueous removal pathway for many of these compounds. Competition between ciprofloxacin (CIP), ofloxacin (OFL) and norfloxacin (NOR) and their sorption to, and desorption from, a surrogate Louisiana wastewater treatment wetland soil were investigated to gain insight into the fate and transport of the pollutants within wastewater treatment wetlands. This study was undertaken in the context of a treatment wetland that continuously receives pharmaceuticals. Therefore it is important to understand the total capacity of this soil to sorb these compounds. Sorption to this treatment wetland soil was found to provide a major and potentially long-term removal pathway for these antibiotics from wastewater. LogK(F) values for all three compounds were between 4.09 and 3.90 for sorption and 4.24 and 4.05 microg(1-1/)(n)(cm(3))(1/)(n)g(-1) for desorption. The compounds were sorbed in amounts ranging from 60% to 90% for high and low loading, respectively. The majority of the compounds were sorbed to the soil within the first 20h, indicating that treatment wetland may not need long retention times (weeks to months) in order to remove these compounds. Sorption K(D) values for competition (20 ppm of each compound for 60 ppm of total fluoroquinolones) ranged from 2300 to 3800 cm(3)g(-1) which is between both the 20 (4300-5800 cm(3)g(-1)) and 60 (1300-3000 cm(3)g(-1)) ppm single compound K(D) values, indicating that there is competition between these three compound for sorption sites. Sorption and desorption data (single component and mixture) collectively provide the following evidence: (1) NOR and, to a lesser extent, CIP outcompete OFL for sorption sites, (2) OFL sorbes to its share of "quality" sorption sites, and (3) competition only occurs for lesser "quality" binding sites. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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Van Speybroeck, Alexander; Mueske, Nicole M; Mittelman, Steven D; Kremer, Richard K; Ryan, Deirdre D; Wren, Tishya A L
2017-03-01
This study examined serum levels in children with myelomeningocele to identify the prevalence of pre-clinical signs of disease. A prospective, cross-sectional study. Patients were actively recruited from multidisciplinary care clinics at tertiary children's hospitals from 2010-2012. The control comparison group was recruited by word-of-mouth. Twenty-eight children with myelomeningocele (93% Hispanic; 17 males; 10.0 ± 2.1 years) and 58 controls (84% Hispanic; 30 males; 10.4 ± 2.4 years) provided ≥ 8-hour fasting blood samples with concomitant dual-energy x-ray absorptiometry measurements of body fat. Not applicable. The serum analysis included a lipid panel (cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein), insulin, glucose, leptin, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, albumin, creatinine, calcium, phosphatase, parathyroid hormone, and vitamin D. Children with myelomeningocele had higher body fat (35.2% versus 29.9%, p=0.01) and altered lipid profiles (lower high-density lipoprotein levels, 43.9 mg/dL versus 51.6 mg/dL, P = 0.03) suggesting elevated risk of metabolic syndrome. They also had a higher prevalence of vitamin D deficiency (43% versus 17%, p=0.02) and significantly lower levels of calcium (9.4 mg/dL versus 9.7 mg/dL, P = 0.003) and alkaline phosphatase (187.0 U/L versus 237.0 U/L, P = 0.003). Unexpectedly children with myelomeningocele had lower parathyroid hormone levels (14.5 pg/mL versus 18.4 pg/mL, P = 0.02) than controls despite lower calcium, vitamin D and alkaline phosphatase levels. This suggests an alteration in the sensing mechanism or response of the parathyroid gland to normal physiological stimuli in patients with myelomeningocele. Children with myelomeningocele have abnormal biochemical markers for cardiovascular disease, insulin resistance and bone and mineral metabolism. Early recognition and monitoring of these risk factors in patients with myelomeningocele may help prevent later complications.
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Uhrig, R Glen; Moorhead, Greg B
2011-12-01
Reversible protein phosphorylation is of central importance to the proper cellular functioning of all living organisms. Catalyzed by the opposing reactions of protein kinases and phosphatases, dysfunction in reversible protein phosphorylation can result in a wide variety of cellular aberrations. In eukaryotic organisms there exists four classes of protein phosphatases, of which the PPP-family protein phosphatases have documented susceptibility to a range of protein and small molecule inhibitors. These inhibitors have been of great importance to the biochemical characterization of PPP-family protein phosphatases since their discovery, but also maintain in natura biological significance with their endogenous regulatory properties (protein inhibitors) and toxicity (small molecule inhibitors). Recently, two unique PPP-family protein phosphatases, named the Shewanella-like protein phosphatases (SLP phosphatases), from Arabidopsis thaliana were characterized and found to be phylogenetically similar to the PPP-family protein phosphatases protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), while completely lacking sensitivity to the classic PPP-family phosphatase small molecule inhibitors okadaic acid and microcystin-LR. SLP phosphatases were also found to be absent in metazoans, but present in a wide range of bacteria, fungi and protozoa responsible for human disease. The unique biochemical properties and evolutionary heritage of SLP phosphatases suggests they could not only be potential biotechnology targets for agriculture, but may also prove to be of interest for future therapeutic drug development. © 2011 Landes Bioscience
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Xu, Sa; Labuza, Theodore P.; Diez-Gonzalez, Francisco
2008-01-01
The milk supply is considered a primary route for a bioterrorism attack with Bacillus anthracis spores because typical high-temperature short-time (HTST) pasteurization conditions cannot inactivate spores. In the event of intentional contamination, an effective method to inactivate the spores in milk under HTST processing conditions is needed. This study was undertaken to identify combinations and concentrations of biocides that can inactivate B. anthracis spores at temperatures in the HTST range in less than 1 min. Hydrogen peroxide (HP), sodium hypochlorite (SH), and peroxyacetic acid (PA) were evaluated for their efficacy in inactivating spores of strains 7702, ANR-1, and 9131 in milk at 72, 80, and 85°C using a sealed capillary tube technique. Strains ANR-1 and 9131 were more resistant to all of the biocide treatments than strain 7702. Addition of 1,260 ppm SH to milk reduced the number of viable spores of each strain by 6 log CFU/ml in less than 90 and 60 s at 72 and 80°C, respectively. After neutralization, 1,260 ppm SH reduced the time necessary to inactivate 6 log CFU/ml (TTI6-log) at 80°C to less than 20 s. Treatment of milk with 7,000 ppm HP resulted in a similar level of inactivation in 60 s. Combined treatment with 1,260 ppm SH and 1,800 ppm HP inactivated spores of all strains in less than 20 s at 80°C. Mixing 15 ppm PA with milk containing 1,260 ppm SH resulted in TTI6-log of 25 and 12 s at 72 and 80°C, respectively. TTI6-log of less than 20 s were also achieved at 80°C by using two combinations of biocides: 250 ppm SH, 700 ppm HP, and 150 ppm PA; and 420 ppm SH (pH 7), 1,100 ppm HP, and 15 ppm PA. These results indicated that different combinations of biocides could consistently result in 6-log reductions in the number of B. anthracis spores in less than 1 min at temperatures in the HTST range. This information could be useful for developing more effective thermal treatment strategies which could be used in HTST milk plants to process contaminated milk for disposal and decontamination, as well as for potential protective measures. PMID:18390680
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Xu, Sa; Labuza, Theodore P; Diez-Gonzalez, Francisco
2008-06-01
The milk supply is considered a primary route for a bioterrorism attack with Bacillus anthracis spores because typical high-temperature short-time (HTST) pasteurization conditions cannot inactivate spores. In the event of intentional contamination, an effective method to inactivate the spores in milk under HTST processing conditions is needed. This study was undertaken to identify combinations and concentrations of biocides that can inactivate B. anthracis spores at temperatures in the HTST range in less than 1 min. Hydrogen peroxide (HP), sodium hypochlorite (SH), and peroxyacetic acid (PA) were evaluated for their efficacy in inactivating spores of strains 7702, ANR-1, and 9131 in milk at 72, 80, and 85 degrees C using a sealed capillary tube technique. Strains ANR-1 and 9131 were more resistant to all of the biocide treatments than strain 7702. Addition of 1,260 ppm SH to milk reduced the number of viable spores of each strain by 6 log CFU/ml in less than 90 and 60 s at 72 and 80 degrees C, respectively. After neutralization, 1,260 ppm SH reduced the time necessary to inactivate 6 log CFU/ml (TTI6-log) at 80 degrees C to less than 20 s. Treatment of milk with 7,000 ppm HP resulted in a similar level of inactivation in 60 s. Combined treatment with 1,260 ppm SH and 1,800 ppm HP inactivated spores of all strains in less than 20 s at 80 degrees C. Mixing 15 ppm PA with milk containing 1,260 ppm SH resulted in TTI6-log of 25 and 12 s at 72 and 80 degrees C, respectively. TTI6-log of less than 20 s were also achieved at 80 degrees C by using two combinations of biocides: 250 ppm SH, 700 ppm HP, and 150 ppm PA; and 420 ppm SH (pH 7), 1,100 ppm HP, and 15 ppm PA. These results indicated that different combinations of biocides could consistently result in 6-log reductions in the number of B. anthracis spores in less than 1 min at temperatures in the HTST range. This information could be useful for developing more effective thermal treatment strategies which could be used in HTST milk plants to process contaminated milk for disposal and decontamination, as well as for potential protective measures.
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EPA Evaluations of Phase I Watershed Implementation Plans in the Chesapeake Bay Watershed
This page provides the PDF documents of EPA's evaluation of the Phase I WIPs submitted by the jurisdictions (Delaware, District of Columbia, Maryland, New York, Pennsylvania, Virginia and West Virginia).
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Effects of air, ozone, and nitrogen dioxide exposure on the oxidation of corn and soybean lipids
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brooks, R.I.; Csallany, A.S.
1978-01-01
Whole, halves and ground samples of soybean seeds and whole corn kernels were exposed to air, 15 ppm NO2, or 1.5 ppm O3 continuously for 100 h at room temperature. Lipid oxidation was measured by polyunsaturated fatty acid (PUFA) and tocopherol destruction and formation of fluorescent lipofuscin-like pigments. Exposure of whole soybean and corn seeds to air, 15 ppm NO2, or 1.5 ppm O3 was found to induce no PUFA and tocopherol destruction and no formation of lipofuscin-like pigments. Tocopherol and PUFA destruction and lipofuscin-like pigment formation were detected in samples of soybean seed halves exposed to 15 ppm NO2more » or 1.5 ppm O3; however, only tocopherol destruction occurred in soybean halves exposed to air. Ground soybean samples exposed to air, 15 ppm NO2, or 1.5 ppm O3 incurred the greatest PUFA and tocopherol destruction and lipofuscin-like pigment formation. 25 references, 3 figures, 4 tables.« less
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Spiker, J K; Crawford, D L; Crawford, R L
1992-01-01
The ability of Phanerochaete chrysosporium to bioremediate TNT (2,4,6-trinitrotoluene) in a soil containing 12,000 ppm of TNT and the explosives RDX (hexahydro-1,3,5-trinitro-1,3,5- triazine; 3,000 ppm) and HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine; 300 ppm) was investigated. The fungus did not grow in malt extract broth containing more than 0.02% (wt/vol; 24 ppm of TNT) soil. Pure TNT or explosives extracted from the soil were degraded by P. chrysosporium spore-inoculated cultures at TNT concentrations of up to 20 ppm. Mycelium-inoculated cultures degraded 100 ppm of TNT, but further growth was inhibited above 20 ppm. In malt extract broth, spore-inoculated cultures mineralized 10% of added [14C]TNT (5 ppm) in 27 days at 37 degrees C. No mineralization occurred during [14C]TNT biotransformation by mycelium-inoculated cultures, although the TNT was transformed. PMID:1444437
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-02-04
... on banana at 0.05 parts per million (ppm). An adequate, validated method (GRM006.01B) is available... insecticide fluazifop-p-butyl, in or on potato, tuber at 1.1 ppm; potato, peel (wet) at 1.1 ppm; potato, chips...
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Michael, Helana Naguib; Salib, Josline Yehia; Eskander, Emad Fawzi
2013-05-01
The new natural flavonoid compounds - diosmetin 7-O-β-L-arabinofuranosyl (1 → 2) β-D-apiofuranoside (1) and diosmetin 7-O-β-D-apiofuranoside (2) - were isolated from the acetone extract of date fruits epicarp belonging to family Arecaceae (Palmae). Elucidation of their chemical structures was determined by different spectroscopic methods in addition to the chemical and physical methods of analysis. These compounds were assessed for their biological activity on alloxan diabetic rats. A dose of 1.5 ml of (1) and (2) suspensions/100 gm b. wt were orally administrated to alloxan diabetic rats for 30 days. The treatment of diabetic rats with these compounds resulted in marked improvement of the different biochemical results, i.e. the serum glucose level (highly significant, from 330 + 5.5 mg/dL to 140 + 1.2 mg/dL) treated with (1); liver functions markedly developed both by AST and ALT levels, (reduced significantly from 68.3 + 4.8 μ/L to 54 + 5.5 μ/L and from 61.0 + 3.6 μ/L to 40.1 + 3.6 μ/L, respectively) treated with (2), accompanying with mild decrease in both cholesterol and triglycerides levels with (1) or (2). Decrease of TBARS level was observed in whole blood when treated with (1) or (2), while levels of glutathione peroxidase and superoxide dismutase were increased in liver. Serum testosterone level was highly significantly increased (from 705.1 + 3.6 mg/100 ml to 720 + 4.7 mg/100 ml), total acid phosphatase and prostate acid phosphatase activities were highly significantly decreased (from 16.9 + 0.28 μ/L to 10.7 + 1.2 μ/L and from 9.7 + 0.7 μ/L to 6.5 + 1 μ/L, respectively) for compound (1). Copyright © 2012 John Wiley & Sons, Ltd.
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Detection of trace nitric oxide concentrations using 1-D laser-induced fluorescence imaging
NASA Astrophysics Data System (ADS)
Yoo, J.; Lee, T.; Jeffries, J. B.; Hanson, R. K.
2008-06-01
Spectrally resolved laser-induced fluorescence (LIF) with one-dimensional spatial imaging was investigated as a technique for detection of trace concentrations of nitric oxide (NO) in high-pressure flames. Experiments were performed in the burnt gases of premixed methane/argon/oxygen flames with seeded NO (15 to 50 ppm), pressures of 10 to 60 bar, and an equivalence ratio of 0.9. LIF signals were dispersed with a spectrometer and recorded on a 2-D intensified CCD array yielding both spectral resolution and 1-D spatial resolution. This method allows isolation of NO-LIF from interference signals due to alternative species (mainly hot O2 and CO2) while providing spatial resolution along the line of the excitation laser. A fast data analysis strategy was developed to enable pulse-by-pulse NO concentration measurements from these images. Statistical analyses as a function of laser energy of these single-shot data were used to determine the detection limits for NO concentration as well as the measurement precision. Extrapolating these results to pulse energies of ˜ 16 mJ/pulse yielded a predicted detection limit of ˜ 10 ppm for pressures up to 60 bar. Quantitative 1-D LIF measurements were performed in CH4/air flames to validate capability for detection of nascent NO in flames at 10-60 bar.
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NASA Astrophysics Data System (ADS)
Muhsin Ithnin, Ahmad; Jazair Yahya, Wira; Baun Fletcher, Jasmine; Kadir, Hasannuddin Abd
2017-10-01
Water-in-diesel emulsion fuel (W/D) is one of the alternative fuels that capable to reduce the exhaust emission of diesel engine significantly especially the nitrogen oxides (NOx) and particulate matter (PM). However, the usage of W/D emulsion fuels contributed to higher CO emissions. Supplementing metal additive into the fuel is the alternate way to reduce the CO emissions and improve performance. The present paper investigates the effect of using W/D blended with organic based manganese metal additives on the diesel engine performance and exhaust emission. The test were carried out by preparing and analysing the results observed from five different tested fuel which were D2, emulsion fuel (E10: 89% D2, 10% - water, 1% - surfactant), E10Mn100, E10Mn150, E10Mn200. Organic based Manganese (100ppm, 150ppm, 200ppm) used as the additive in the three samples of the experiments. E10Mn200 achieved the maximum reduction of BSFC up to 13.66% and has the highest exhaust gas temperature. Whereas, E10Mn150 achieved the highest reduction of CO by 14.67%, and slightly increased of NOx emissions as compared to other emulsion fuels. Organic based manganese which act as catalyst promotes improvement of the emulsion fuel performance and reduced the harmful emissions discharged.
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Trembacz, H; Jezewska, M M
1990-01-01
Spontaneous decomposition of 5-phosphoribosyl 1-pyrophosphate at pH 5.5 was established to occur as follows: 5-Phosphoribosyl 1-pyrophosphate----5-phosphoribosyl 1,2-(cyclic)phosphate----ribose 1-phosphate----ribose Enzymic degradation of 5-phosphoribosyl 1-pyrophosphate by alkaline phosphatase from calf intestine and by acid phosphatases from potato and Aspergillus niger was found to proceed according to this pathway within the pH range 2.5-7.4 with accumulation of ribose 1-phosphate. In the case of alkaline phosphatase, Mg2+ ions inhibit the pyrophosphorolysis of 5-phosphoribosyl 1-pyrophosphate and stimulate the hydrolysis of ribose 1-phosphate. PMID:1700897
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Boron content and isotopic composition of ocean basalts: Geochemical and cosmochemical implications
NASA Astrophysics Data System (ADS)
Chaussidon, Marc; Jambon, Albert
1994-02-01
Ion microprobe determination of boron content and delta B-11 values has been performed for a set of 40 oceanic basalt glasses (N-MORB, E-MORB, BABB and OIB) whose chemical characteristics (major and trace elements and isotopic ratios) are well documented. Boron contents, determined at +/- 10% relative, range from 0.34 to 0.74 ppm in N-MORB, whereas E-MORB, BABB and OIB extend to higher concentrations (0.5-2.4 ppm). After correction for crystal fractionation, this range is reduced to 0.5-1.3 ppm. N-MORB and E-MORB also exhibit different B/K ratios, 1.0 +/- 0.3 x 10(exp -3) and 0.2 to 1.4 x 10(exp -3) respectively. This can be interpreted as resulting from the incorporation into the upper mantle of a K-rich and B-poor component (e.g., subducted oceanic crust having lost most of its initial boron). Delta B-11 values range between -7.40 +/- 2 and +0.6 +/- 2 per mill, with no significant difference between N-MORB, E-MORB, OIB or BABB. The Hawaiian samples define a strong linear correlation between boron contents, delta B-11 values, MgO and water contents and delta D values. This is interpreted as resulting from assimilation-fractionation processes which occurred within a water-rich oceanic crust, and which produced high delta B-11 values associated with high delta D values. The low level of B-11 enrichment in the upper mantle constraints the amount of boron reinjected by subduction to a maximum of about 2% of the boron present in the subducted slab. This in turn corresponds to a maximum net Boron transfer of about 3 x 10(exp 10) g/a towards the surface reservoirs. Finally, a boron content of 0.25 +/- 0.1 ppm is estimated for the bulk silicate Earth (i.e., primitive mantle), corresponding to a depletion factor relative to C1 chondrites of about 0.15 and suggesting that B was moderately volatile upon terrestrial accretion.
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Toxicity of a hazardous chemical mixture in the planarian, Dugesia dorotocephala
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ramsdell, H.S.; Matthews, C.M.
1995-12-31
The responses of the planarian, Dugesia dorotocephala to toxic chemical mixtures representative of water contaminants associated with hazardous waste sites have been studied in laboratory experiments. These free-living flatworms are readily maintained under laboratory conditions and are a useful invertebrate model for toxicology studies. Their widespread occurrence also makes them potentially useful for environmental studies. Mature asexual Dugesia dorotocephala were exposed for 14 days to mixtures of seven contaminants frequently detected in water at hazardous waste sites. The complete 1X mixture contained both metals (As, 3.1 ppm; Cr, 0.7 ppm; Pb, 3.7 ppm) and organics (chloroform, 1.5 ppm; benzene, 5.0more » ppm; phenol, 3.4 ppm; trichloroethylene, 3.8 ppm). Groups of planaria were treated with the complete mixture at 0.1X, 1X and 10X concentrations. Additional groups were exposed to the metals-only or organics-only submixtures, also at 0.1X, 1X and 10X concentrations. Treatment solutions were renewed daily. Suppression of fissioning was observed in all of the 1X and 10X treatment groups. Significant mortality occurred only in the 10X complete and 1 0X metals-only treatments. It appears that the toxic effects of the complete mixture are primarily associated with the metal components.« less
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Nishi, Akinori; Matamales, Miriam; Musante, Veronica; Valjent, Emmanuel; Kuroiwa, Mahomi; Kitahara, Yosuke; Rebholz, Heike; Greengard, Paul; Girault, Jean-Antoine; Nairn, Angus C
2017-01-27
The interaction of glutamate and dopamine in the striatum is heavily dependent on signaling pathways that converge on the regulatory protein DARPP-32. The efficacy of dopamine/D1 receptor/PKA signaling is regulated by DARPP-32 phosphorylated at Thr-34 (the PKA site), a process that inhibits protein phosphatase 1 (PP1) and potentiates PKA action. Activation of dopamine/D1 receptor/PKA signaling also leads to dephosphorylation of DARPP-32 at Ser-97 (the CK2 site), leading to localization of phospho-Thr-34 DARPP-32 in the nucleus where it also inhibits PP1. In this study the role of glutamate in the regulation of DARPP-32 phosphorylation at four major sites was further investigated. Experiments using striatal slices revealed that glutamate decreased the phosphorylation states of DARPP-32 at Ser-97 as well as Thr-34, Thr-75, and Ser-130 by activating NMDA or AMPA receptors in both direct and indirect pathway striatal neurons. The effect of glutamate in decreasing Ser-97 phosphorylation was mediated by activation of PP2A. In vitro phosphatase assays indicated that the PP2A/PR72 heterotrimer complex was likely responsible for glutamate/Ca 2+ -regulated dephosphorylation of DARPP-32 at Ser-97. As a consequence of Ser-97 dephosphorylation, glutamate induced the nuclear localization in cultured striatal neurons of dephospho-Thr-34/dephospho-Ser-97 DARPP-32. It also reduced PKA-dependent DARPP-32 signaling in slices and in vivo Taken together, the results suggest that by inducing dephosphorylation of DARPP-32 at Ser-97 and altering its cytonuclear distribution, glutamate may counteract dopamine/D1 receptor/PKA signaling at multiple cellular levels. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
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Nishi, Akinori; Matamales, Miriam; Musante, Veronica; Valjent, Emmanuel; Kuroiwa, Mahomi; Kitahara, Yosuke; Rebholz, Heike; Greengard, Paul; Girault, Jean-Antoine; Nairn, Angus C.
2017-01-01
The interaction of glutamate and dopamine in the striatum is heavily dependent on signaling pathways that converge on the regulatory protein DARPP-32. The efficacy of dopamine/D1 receptor/PKA signaling is regulated by DARPP-32 phosphorylated at Thr-34 (the PKA site), a process that inhibits protein phosphatase 1 (PP1) and potentiates PKA action. Activation of dopamine/D1 receptor/PKA signaling also leads to dephosphorylation of DARPP-32 at Ser-97 (the CK2 site), leading to localization of phospho-Thr-34 DARPP-32 in the nucleus where it also inhibits PP1. In this study the role of glutamate in the regulation of DARPP-32 phosphorylation at four major sites was further investigated. Experiments using striatal slices revealed that glutamate decreased the phosphorylation states of DARPP-32 at Ser-97 as well as Thr-34, Thr-75, and Ser-130 by activating NMDA or AMPA receptors in both direct and indirect pathway striatal neurons. The effect of glutamate in decreasing Ser-97 phosphorylation was mediated by activation of PP2A. In vitro phosphatase assays indicated that the PP2A/PR72 heterotrimer complex was likely responsible for glutamate/Ca2+-regulated dephosphorylation of DARPP-32 at Ser-97. As a consequence of Ser-97 dephosphorylation, glutamate induced the nuclear localization in cultured striatal neurons of dephospho-Thr-34/dephospho-Ser-97 DARPP-32. It also reduced PKA-dependent DARPP-32 signaling in slices and in vivo. Taken together, the results suggest that by inducing dephosphorylation of DARPP-32 at Ser-97 and altering its cytonuclear distribution, glutamate may counteract dopamine/D1 receptor/PKA signaling at multiple cellular levels. PMID:27998980
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Resin-modified glass ionomer cements: fluoride release and influence on Streptococcus mutans growth.
Friedl, K H; Schmalz, G; Hiller, K A; Shams, M
1997-02-01
The aims of the present study were to measure the fluoride release of 1 glass ionomer cement, 1 cermet, 3 resin-modified glass ionomer cements and 1 compomer, and to determine the influence of each material on bacterial growth. Test specimens were eluted in saline for 180 days. Every 2 days, the specimens were transferred into fresh saline and the fluoride content of the solution was measured. Furthermore, 48-h, 14-d, 90-d, and 180-d eluates were inoculated with Streptococcus mutans and bacterial growth was recorded nephelometrically. Fluoride release dropped significantly over time for each material with values between 6.2 (Ketac-Silver) and 29.3 (Photac-Fil) ppm after 48 h to values between 0.6 (Ketac-Silver) and 1.7 (Ketac-Fil, Vitremer) ppm after 180 days. Each material reduced bacterial growth at each time of examination, but the effect decreased significantly over time with a maximum growth of 71.7% (Ketac-Fil) to 85.6% (Ketac-Silver) after 48 h and 94.7 (Vitremer) to 99.0% (Ketac-Silver) after 180 days (growth control = 100%). Both Ketac-Silver and Dyract showed a significantly lower inhibiting effect on bacterial growth than the other materials. The tested materials showed a good correlation between fluoride release and influence on bacterial growth. However, both effects dropped dramatically over the 180-days period.
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Orlando, Kelly A; Iosue, Christine L; Leone, Sarah G; Davies, Danielle L; Wykoff, Dennis D
2015-10-15
Inorganic phosphate is required for a range of cellular processes, such as DNA/RNA synthesis and intracellular signalling. The phosphate starvation-inducible phosphatase activity of Candida glabrata is encoded by the gene CgPMU2 (C. glabrata phosphomutase-like protein). CgPMU2 is part of a three-gene family (∼75% identical) created through gene duplication in the C. glabrata clade; only CgPmu2 is a PHO-regulated broad range acid phosphatase. We identified amino acids that confer broad range phosphatase activity on CgPmu2 by creating fusions of sections of CgPMU2 with CgPMU1, a paralogue with little broad range phosphatase activity. We used site-directed mutagenesis on various fusions to sequentially convert CgPmu1 to CgPmu2. Based on molecular modelling of the Pmu proteins on to a histidine phosphatase crystal structure, clusters of amino acids were found in two distinct regions that were able to confer phosphatase activity. Substitutions in these two regions together conferred broad phosphatase activity on CgPmu1. Interestingly, one change is a histidine adjacent to the active site histidine of CgPmu2 and it exhibits a novel ability to partially replace the conserved active site histidine in CgPmu2. Additionally, a second amino acid change was able to confer nt phosphatase activity to CgPmu1, suggesting single amino acid changes neofunctionalize CgPmu2. © 2015 Authors; published by Portland Press Limited.
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King, J A; Ball, J K
1993-09-01
An extremely sensitive and convenient microtiter plate solution hybridisation assay for the detection of HIV-1 PCR products was developed. The PCR product is labelled by direct incorporation of digoxigenin-dUTP and after denaturation is captured by a microtitre plate coated with a streptavidin-linked biotinylated probe. The PCR/probe hybrids are reacted with an alkaline phosphate conjugated anti-digoxigenin antibody and detected using an alkaline phosphatase enzyme amplification system. The use of uracil-N-glycosylase and dUTP instead of dTTP in the PCR is used to effectively control carry-over from previous PCR products. The assay can detect single HIV-1 DNA molecules in a background DNA of 0.75 microgram.
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Knockaert, Marie; Sapkota, Gopal; Alarcón, Claudio; Massagué, Joan; Brivanlou, Ali H.
2006-01-01
Smad transcription factors are key signal transducers for the TGF-β/bone morphogenetic protein (BMP) family of cytokines and morphogens. C-terminal serine phosphorylation by TGF-β and BMP membrane receptors drives Smads into the nucleus as transcriptional regulators. Dephosphorylation and recycling of activated Smads is an integral part of this process, which is critical for agonist sensing by the cell. However, the nuclear phosphatases involved have remained unknown. Here we provide functional, biochemical, and embryological evidence identifying the SCP (small C-terminal domain phosphatase) family of nuclear phosphatases as mediators of Smad1 dephosphorylation in the BMP signaling pathway in vertebrates. Xenopus SCP2/Os4 inhibits BMP activity in the presumptive ectoderm and leads to neuralization. In Xenopus embryos, SCP2/Os4 and human SCP1, 2, and 3 cause selective dephosphorylation of Smad1 compared with Smad2, inhibiting BMP- and Smad1-dependent transcription and leading to the induction of the secondary dorsal axis. In human cells, RNAi-mediated depletion of SCP1 and SCP2 increases the extent and duration of Smad1 phosphorylation in response to BMP, the transcriptional action of Smad1, and the strength of endogenous BMP gene responses. The present identification of the SCP family as Smad C-terminal phosphatases sheds light on the events that attenuate Smad signaling and reveals unexpected links to the essential phosphatases that control RNA polymerase II in eukaryotes. PMID:16882717
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Fire Effects on Microbial Enzyme Activities in Larch Forests of the Siberian Arctic
NASA Astrophysics Data System (ADS)
Ludwig, S.; Alexander, H. D.; Bulygina, E. B.; Mann, P. J.; Natali, S.
2012-12-01
Arctic forest ecosystems are warming at an accelerated rate relative to lower latitudes, with global implications for C cycling within these regions. As climate continues to warm and dry, wildfire frequency and severity are predicted to increase, creating a positive feedback to climate warming. Increased fire activity will also influence the microenvironment experienced by soil microbes in disturbed soils. Because soil microbes regulate carbon (C) and nitrogen (N) cycling between terrestrial ecosystems and the atmosphere, it is important to understand microbial response to fires, particularly in the understudied larch forests in the Siberian Arctic. In this project, we created experimental burn plots in a mature larch forest in the Kolyma River watershed of Northeastern Siberia. Plots were burned at several treatments: control (no burn), low, moderate, and severe. After, 1 and 8 d post-fire, we measured soil organic layer depth, soil organic matter (SOM) content, soil moisture, and CO2 flux from the plots. Additionally, we leached soils and measured dissolved organic carbon (DOC), total dissolved nitrogen (TDN), NH4, NO3, soluble reactive phosphorus (SRP), and chromophoric dissolved organic matter (CDOM). Furthermore, we measured extracellular activity of four enzymes involved in soil C and nutrient cycling (leucine aminopeptidase (LAP), β-glucosidase, phosphatase, and phenol oxidase). One day post-fire, LAP activity was similarly low in all treatments, but by 8 d post-fire, LAP activity was lower in burned plots compared to control plots, likely due to increased nitrogen content with increasing burn severity. Phosphatase activity decreased with burn severity 1 d post-fire, but after 8 d, moderate and severe burn plots exhibited increased phosphatase activity. Coupled with trends in LAP activity, this suggests a switch in nutrient limitation from N to phosphorus that is more pronounced with burn severity. β-glucosidase activity similarly decreased with burn severity 1 d post-fire, but by 8 d post-fire activity was the same in all treatments, indicating complete recovery of the microbial population. Phenol oxidase activity was low in all treatments 1 d post-fire, but by 8 d post-fire, severe plots had substantially increased phenol oxidase activity, likely due to microbial efforts to mitigate phenolic compound toxicity following severe fires. Both DOC and the slope ratio of CDOM absorbance increased with burn severity 1 d post-fire, indicating higher extractability of lighter molecular weight C from severe burns. These results imply that black C created from fires remains as a stable C pool while more labile C is mobilized with increasing burn severity. Our results suggest that the immediate effects of fire severity on microbial communities have the potential to change both nutrient use and the form and concentration of C being processed and mobilized from larch forest ecosystems. These findings highlight the importance of changing fire regimes on soil dynamics with implications for forest re-growth, soil-atmospheric feedbacks, and terrestrial inputs to aquatic ecosystems.
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Coating compositions and method for the treatment of metal surfaces
DOE Office of Scientific and Technical Information (OSTI.GOV)
Das, N.; Stastny, P.M.
1984-09-11
An aqeuous acidic composition provides improved coating for aluminum. The composition comprises from about 10 to about 150 ppm zirconium, from about 20 to about 250 ppm fluoride, from 30 to about 125 ppm tannin, from about about 15 to about 100 ppm phosphate and from about 5 to about 50 ppm zinc, said coating solution having a tannin to phosphate ratio in the range of at least about 1:1 to about 2:1 and a pH in the range of about 2.3 to about 2.95.
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Optimization of sputter deposition parameters for magnetostrictive Fe62Co19Ga19/Si(100) films
NASA Astrophysics Data System (ADS)
Jen, S. U.; Tsai, T. L.
2012-04-01
A good magnetostrictive material should have large saturation magnetostriction (λS) and low saturation (or anisotropy) field (HS), such that its magnetostriction susceptibility (SH) can be as large as possible. In this study, we have made Fe62Co19Ga19/Si(100) nano-crystalline films by using the dc magnetron sputtering technique under various deposition conditions: Ar working gas pressure (pAr) was varied from 1 to 15 mTorr; sputtering power (Pw) was from 10 to 120 W; deposition temperature (TS) was from room temperature (RT) to 300 °C, The film thickness (tf) was fixed at 175 nm. Each magnetic domain looked like a long leaf, with a long-axis of about 12-15 μm and a short-axis of about 1.5 μm. The optimal magnetic and electrical properties were found from the Fe62Co19Ga19 film made with the sputter deposition parameters of pAr = 5 mTorr, Pw = 80 W, and TS = RT. Those optimal properties include λS = 80 ppm, HS = 19.8 Oe, SH = 6.1 ppm/Oe, and electrical resistivity ρ = 57.0 μΩ cm. Note that SH for the conventional magnetostrictive Terfenol-D film is, in general, equal to 1.5 ppm/Oe only.
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Waadt, Rainer; Manalansan, Bianca; Rauniyar, Navin; Munemasa, Shintaro; Booker, Matthew A.; Brandt, Benjamin; Waadt, Christian; Nusinow, Dmitri A.; Kay, Steve A.; Kunz, Hans-Henning; Schumacher, Karin; DeLong, Alison; Yates, John R.; Schroeder, Julian I.
2015-01-01
The plant hormone abscisic acid (ABA) controls growth and development and regulates plant water status through an established signaling pathway. In the presence of ABA, pyrabactin resistance/regulatory component of ABA receptor proteins inhibit type 2C protein phosphatases (PP2Cs). This, in turn, enables the activation of Sucrose Nonfermenting1-Related Protein Kinases2 (SnRK2). Open Stomata1 (OST1)/SnRK2.6/SRK2E is a major SnRK2-type protein kinase responsible for mediating ABA responses. Arabidopsis (Arabidopsis thaliana) expressing an epitope-tagged OST1 in the recessive ost1-3 mutant background was used for the copurification and identification of OST1-interacting proteins after osmotic stress and ABA treatments. These analyses, which were confirmed using bimolecular fluorescence complementation and coimmunoprecipitation, unexpectedly revealed homo- and heteromerization of OST1 with SnRK2.2, SnRK2.3, OST1, and SnRK2.8. Furthermore, several OST1-complexed proteins were identified as type 2A protein phosphatase (PP2A) subunits and as proteins involved in lipid and galactolipid metabolism. More detailed analyses suggested an interaction network between ABA-activated SnRK2-type protein kinases and several PP2A-type protein phosphatase regulatory subunits. pp2a double mutants exhibited a reduced sensitivity to ABA during seed germination and stomatal closure and an enhanced ABA sensitivity in root growth regulation. These analyses add PP2A-type protein phosphatases as another class of protein phosphatases to the interaction network of SnRK2-type protein kinases. PMID:26175513
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Enzyme-linked immunosorbent assays for Z-DNA.
Thomas, M J; Strobl, J S
1988-10-01
Dot blot and transblot enzyme-linked immunosorbent assays (e.l.i.s.a.) are described which provide sensitive non-radioactive methods for screening Z-DNA-specific antisera and for detecting Z-DNA in polydeoxyribonucleotides and supercoiled plasmids. In the alkaline phosphatase dot blot e.l.i.s.a., Z-DNA, Br-poly(dG-dC).poly(dG-dC), or B-DNA, poly(dG-dC).poly(dG-dC), poly(dA-dT).poly(dA-dT), Br-poly(dI-dC).poly(dI-dC), or salmon sperm DNA were spotted onto nitrocellulose discs and baked. The e.l.i.s.a. was conducted in 48-well culture dishes at 37 degrees C using a rabbit polyclonal antiserum developed against Br-poly(dG-dC).poly(dG-dC), an alkaline phosphatase-conjugated second antibody, and p-nitrophenol as the substrate. Under conditions where antibody concentrations were not limiting, alkaline phosphatase activity was linear for 2 h. Dot blot e.l.i.s.a. conditions are described which allow quantification of Z-DNA [Br-poly(dG-dC).poly(dG-dC)] within the range 5-250 ng. Dot blot and transblot horseradish peroxidase e.l.i.s.a. are described that detect Z-DNA within supercoiled plasmid DNAs immobilized on diazophenylthioether (DPT) paper. In the transblot e.l.i.s.a., plasmid pUC8 derivatives containing 16, 24, or 32 residues of Z-DNA were electrophoresed in agarose gels and electrophoretically transferred to DPT paper. Z-DNA-antibody complexes were detected by the horseradish peroxidase-catalysed conversion of 4-chloro-1-naphthol to a coloured product that was covalently bound to the DPT paper. Z-DNA antibody reactivity was specific for supercoiled Z-DNA containing plasmids after removal of the antibodies cross-reactive with B-DNA by absorption onto native DNA-cellulose. The transblot e.l.i.s.a. was sensitive enough to detect 16 base pairs of alternating G-C residues in 100 ng of pUC8 DNA.
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40 CFR 90.312 - Analytical gases.
Code of Federal Regulations, 2014 CFR
2014-07-01
... contentration must be between 0 and 1 percent O2. Nitrogen must be the predominant diluent with the balance... for operation: (1) Purified nitrogen, also referred to as “zero-grade nitrogen” (Contamination ≤ 1 ppm...) Hydrogen-helium mixture (40 ±2 percent hydrogen, balance helium) (Contamination ≤ 1 ppm C, ≤ 400 ppm CO...
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Dynamics of Nafion membrane swelling in H2O/D2O mixtures as studied using FTIR technique
NASA Astrophysics Data System (ADS)
Bunkin, Nikolai F.; Kozlov, Valeriy A.; Shkirin, Alexey V.; Ninham, Barry W.; Balashov, Anatoliy A.; Gudkov, Sergey V.
2018-03-01
Experiments with Fourier transform spectrometry of Nafion, a water-swollen polymeric membrane, are described. The transmittance spectra of liquid samples and Nafion, soaked in these samples, were studied, depending on the deuterium content in water in the spectral range 1.8-2.15 μm. The experiments were carried out using two protocols: in the first protocol we studied the dynamics of Nafion swelling in H2O + D2O mixtures for the deuterium concentrations 3 < C < 104 ppm, and in the second protocol we studied the dynamics of swelling in pure heavy water (C = 106 ppm). For liquid mixtures in the concentration range 3 < C < 104 ppm, the transmittance spectra are the same, but for Nafion soaked in these fluids, the corresponding spectra are different. It is shown that, in the range of deuterium contents C = 90-500 ppm, the behavior of transmittance of the polymer membrane is non-monotonic. In experiments using the second protocol, the dynamics of diffusion replacement of residual water, which is always present in the bulk of the polymer membrane inside closed cavities (i.e., without access to atmospheric air), were studied. The experimentally estimated diffusion coefficient for this process is ≈6.10-11 cm2/s.
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Xu, Xuehua; Gera, Nidhi; Li, Hongyan; Yun, Michelle; Zhang, Liyong; Wang, Youhong; Wang, Q. Jane; Jin, Tian
2015-01-01
Chemotaxis requires precisely coordinated polymerization and depolymerization of the actin cytoskeleton at leading fronts of migrating cells. However, GPCR activation-controlled F-actin depolymerization remains largely elusive. Here, we reveal a novel signaling pathway, including Gαi, PLC, PKCβ, protein kinase D (PKD), and SSH2, in control of cofilin phosphorylation and actin cytoskeletal reorganization, which is essential for neutrophil chemotaxis. We show that PKD is essential for neutrophil chemotaxis and that GPCR-mediated PKD activation depends on PLC/PKC signaling. More importantly, we discover that GPCR activation recruits/activates PLCγ2 in a PI3K-dependent manner. We further verify that PKCβ specifically interacts with PKD1 and is required for chemotaxis. Finally, we identify slingshot 2 (SSH2), a phosphatase of cofilin (actin depolymerization factor), as a target of PKD1 that regulates cofilin phosphorylation and remodeling of the actin cytoskeleton during neutrophil chemotaxis. PMID:25568344
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Pal, Ravi Prakash; Mani, Veena; Tripathi, Deepika; Kumar, Rajesh; Kewalramani, Neelam J
2018-04-01
The nutritional essentialities of transition element vanadium (V) as micro-nutrient in farm animals have not yet been established, though in rat model, vanadium as vanadate has been reported to exert insulin-mimetic effect and shown to be needed for proper development of bones. The objective of this study was to determine the effect of V supplementation on growth performance, plasma hormones and bone health status in calves. Twenty-four crossbred calves (body weight 72.83 ± 2.5 kg; age 3-9 months) were blocked in four groups and randomly assigned to four treatment groups (n = 6) on body weight and age basis. Experimental animals were kept on similar feeding regimen except that different groups were supplemented with either 0, 3, 6 or 9 ppm inorganic V/kg DM. Effect of supplementation during 150-day experimental period was observed on feed intake, body weight gain, feed efficiency, body measures, endocrine variables, plasma glucose and biomarkers of bone health status. Supplementation of V did not change average daily gain (ADG), dry matter intake (DMI), feed efficiency and body measures during the experimental period. During the post-V supplementation period plasma insulin-like growth factor-1 (IGF-1), triiodothyronine (T 3 ) and thyroxin (T 4 ) concentrations were increased and observed highest in 9 mg V/kg DM fed calves; however, levels of insulin, glucose, parathyroid hormone (PTH) and calcitonin hormones remained similar among calves fed on basal or V-supplemented diets. Bone alkaline phosphatase (Bone-ALP) concentration was increased (P < 0.05); however, plasma protein tyrosine phosphatase (PTP) level decreased (P < 0.05) in 6 and 9 mg V/kg DM supplemented groups. Plasma hydroxyproline (Hyp) and tartrate-resistant acid phosphatase (TRAP) concentration were unchanged by V supplementation. Blood V concentration showed positive correlation with supplemental V levels. These results suggest that V may play a role in modulation of the action of certain endocrine variables and biomarkers of bone health status in growing crossbred calves.
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Natural gas pipeline leaks across Washington, DC.
Jackson, Robert B; Down, Adrian; Phillips, Nathan G; Ackley, Robert C; Cook, Charles W; Plata, Desiree L; Zhao, Kaiguang
2014-01-01
Pipeline safety in the United States has increased in recent decades, but incidents involving natural gas pipelines still cause an average of 17 fatalities and $133 M in property damage annually. Natural gas leaks are also the largest anthropogenic source of the greenhouse gas methane (CH4) in the U.S. To reduce pipeline leakage and increase consumer safety, we deployed a Picarro G2301 Cavity Ring-Down Spectrometer in a car, mapping 5893 natural gas leaks (2.5 to 88.6 ppm CH4) across 1500 road miles of Washington, DC. The δ(13)C-isotopic signatures of the methane (-38.2‰ ± 3.9‰ s.d.) and ethane (-36.5 ± 1.1 s.d.) and the CH4:C2H6 ratios (25.5 ± 8.9 s.d.) closely matched the pipeline gas (-39.0‰ and -36.2‰ for methane and ethane; 19.0 for CH4/C2H6). Emissions from four street leaks ranged from 9200 to 38,200 L CH4 day(-1) each, comparable to natural gas used by 1.7 to 7.0 homes, respectively. At 19 tested locations, 12 potentially explosive (Grade 1) methane concentrations of 50,000 to 500,000 ppm were detected in manholes. Financial incentives and targeted programs among companies, public utility commissions, and scientists to reduce leaks and replace old cast-iron pipes will improve consumer safety and air quality, save money, and lower greenhouse gas emissions.
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Romá-Mateo, Carlos; Sacristán-Reviriego, Almudena; Beresford, Nicola J; Caparrós-Martín, José Antonio; Culiáñez-Macià, Francisco A; Martín, Humberto; Molina, María; Tabernero, Lydia; Pulido, Rafael
2011-04-01
Dual-specificity phosphatases (DSPs) constitute a large protein tyrosine phosphatase (PTP) family, with examples in distant evolutive phyla. PFA-DSPs (Plant and Fungi Atypical DSPs) are a group of atypical DSPs present in plants, fungi, kinetoplastids, and slime molds, the members of which share structural similarity with atypical- and lipid phosphatase DSPs from mammals. The analysis of the PFA-DSPs from the plant Arabidopsis thaliana (AtPFA-DSPs) showed differential tissue mRNA expression, substrate specificity, and catalytic activity for these proteins, suggesting different functional roles among plant PFA-DSPs. Bioinformatic analysis revealed the existence of novel PFA-DSP-related proteins in fungi (Oca1, Oca2, Oca4 and Oca6 in Saccharomyces cerevisiae) and protozoa, which were segregated from plant PFA-DSPs. The closest yeast homolog for these proteins was the PFA-DSP from S. cerevisiae ScPFA-DSP1/Siw14/Oca3. Oca1, Oca2, Siw14/Oca3, Oca4, and Oca6 were involved in the yeast response to caffeine and rapamycin stresses. Siw14/Oca3 was an active phosphatase in vitro, whereas no phosphatase activity could be detected for Oca1. Remarkably, overexpression of Siw14/Oca3 suppressed the caffeine sensitivity of oca1, oca2, oca4, and oca6 deleted strains, indicating a genetic linkage and suggesting a functional relationship for these proteins. Functional studies on mutations targeting putative catalytic residues from the A. thaliana AtPFA-DSP1/At1g05000 protein indicated the absence of canonical amino acids acting as the general acid/base in the phosphor-ester hydrolysis, which suggests a specific mechanism of reaction for PFA-DSPs and related enzymes. Our studies demonstrate the existence of novel phosphatase protein families in fungi and protozoa, with active and inactive enzymes linked in common signaling pathways. This illustrates the catalytic and functional complexity of the expanding family of atypical dual-specificity phosphatases in non-metazoans, including parasite organisms responsible for infectious human diseases.
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Protein phosphatase 2A in stretch-induced endothelial cell proliferation
NASA Technical Reports Server (NTRS)
Murata, K.; Mills, I.; Sumpio, B. E.
1996-01-01
We previously proposed that activation of protein kinase C is a key mechanism for control of cell growth enhanced by cyclic strain [Rosales and Sumpio (1992): Surgery 112:459-466]. Here we examined protein phosphatase 1 and 2A activity in bovine aortic endothelial cells exposed to cyclic stain. Protein phosphatase 2A activity in the cytosol was decreased by 36.1% in response to cyclic strain for 60 min, whereas the activity in the membrane did not change. Treatment with low concentration (0.1 nM) of okadaic acid enhanced proliferation of both static and stretched endothelial cells in 10% fetal bovine serum. These data suggest that protein phosphatase 2A acts as a growth suppressor and cyclic strain may enhance cellular proliferation by inhibiting protein phosphatase 2A as well as stimulating protein kinase C.
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Neurotoxicity of 2-bromopropane and 1-bromopropane, alternative solvents for chlorofluorocarbons.
Yu, X; Ichihara, G; Kitoh, J; Xie, Z; Shibata, E; Kamijima, M; Takeuchi, Y
2001-01-01
To clarify the neurotoxicity of 2-bromopropane (2-BP) in comparison with 1-bromopropane (1-BP), 36 Wistar strain male rats were divided into 4 groups of 9 and exposed daily to 100-ppm 2-BP, 1000-ppm 2-BP, 1000-ppm 1-BP, or fresh air for 8 h a day. Exposure to 1000 ppm of 1-BP was discontinued after 5 or 7 weeks' exposure because of the unexpected appearance of incomplete hindlimb paralysis followed by serious emaciation. The other groups were sacrificed at the end of 12 weeks' exposure. Exposure to 1000 ppm of 2-BP resulted in significant decreases in body weight and motor nerve conduction velocity (MCV) and elongation in distal latency (DL). A ball-like enlargement of myelin sheaths was observed. Significant reductions in the number of erythrocytes, platelets, and leukocytes, testicular germ cell loss, and seminiferous atrophy were also observed in this group, but not in 100-ppm 2-BP group. Exposure to 1000 ppm of 1-BP for 5 or 7 weeks caused a significant decrease in body weight and MCV and elongation in DL. Linearly arranged ovoid- or bubble-like debris of the axons and myelin sheaths in the teased tibial nerves and axonal swelling in gracilis nucleus were found in this group. No significant changes in hematological indices or histopathological findings of the testis were found in this group. In conclusion, 2-BP is neurotoxic to the peripheral nerves in addition to its toxic effects on the reproductive and hematopoietic systems at 1000 ppm. No noticeable changes were found in the rats exposed to 100 ppm of 2-BP. 1-BP is a potent neurotoxicant at 1000 ppm for 5 or 7 weeks, while testicular and hematopoietic toxicity was not found. Copyright 2001 Academic Press.
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NASA Astrophysics Data System (ADS)
Ferris, Thomas D.; Farrar, Thomas C.
The temperature dependence of the hydroxyl proton chemical shift and deuterium quadrupolar relaxation time of neat ethanol were measured over the temperature range 190-350 K. The proton isotropic chemical shift varies from 6.2 ppm at 190 K to 4.7 ppm at 350 K. The deuterium NMR relaxation time in ethanol- d 1 varies from 6.2 ms to 309 ms over the same range. Ab initio calculations performed on various ethanol clusters ranging in size from monomer to hexamer show a linear correlation ( R 2 = 0.99) between ≤D, the deuterium quadrupole coupling parameter, and δH, the isotropic proton chemical shift in ppm relative to TMS: ≤D(kHz) = 297.60 - 15.28 δH. The temperature dependence of ≤D ranges from 199.5 kHz at 190 K to 221.4 kHz at 350 K. Using the values for ≤D and the relaxation time data, the temperature dependence of the OD rotational correlation time was found to vary from 282 ps at 190 K to 4.5 ps near the boiling point (350 K). Using these correlation times and bulk viscosity data, the Gierer-Wirtz model predicts a supramolecular cluster volume of about 317 A 3 , the approximate volume of a cyclic pentamer cluter of ethanol molecules. The cluster volume was nearly constant from 340 K to about 290 K.
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Fragale, Alessandra; Tartaglia, Marco; Wu, Jie; Gelb, Bruce D
2004-03-01
Noonan syndrome is a developmental disorder with dysmorphic facies, short stature, cardiac defects, and skeletal anomalies, which can be caused by missense PTPN11 mutations. PTPN11 encodes Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2 or SHP-2), a protein tyrosine phosphatase that acts in signal transduction downstream to growth factor, hormone, and cytokine receptors. We compared the functional effects of three Noonan syndrome-causative PTPN11 mutations on SHP2's phosphatase activity, interaction with a binding partner, and signal transduction. All SHP2 mutants had significantly increased basal phosphatase activity compared to wild type, but that activity varied significantly between mutants and was further increased after epidermal growth factor stimulation. Cells expressing SHP2 mutants had prolonged extracellular signal-regulated kinase 2 activation, which was ligand-dependent. Binding of SHP2 mutants to Grb2-associated binder-1 was increased and sustained, and tyrosine phosphorylation of both proteins was prolonged. Coexpression of Grb2-associated binder-1-FF, which lacks SHP2 binding motifs, blocked the epidermal growth factor-mediated increase in SHP2's phosphatase activity and resulted in a dramatic reduction of extracellular signal-regulated kinase 2 activation. Taken together, these results document that Noonan syndrome-associated PTPN11 mutations increase SHP2's basal phosphatase activity, with greater activation when residues directly involved in binding at the interface between the N-terminal Src homology 2 and protein tyrosine phosphatase domains are altered. The SHP2 mutants prolonged signal flux through the RAS/mitogen-activated protein kinase (ERK2/MAPK1) pathway in a ligand-dependent manner that required docking through Grb2-associated binder-1 (GAB1), leading to increased cell proliferation. Copyright 2004 Wiley-Liss, Inc.
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Some Pb and Sr isotopic measurements on eclogites from the Roberts Victor mine, South Africa
Manton, W.I.; Tatsumoto, M.
1971-01-01
Five nodules of eclogite, one nodule of garnet peridotite and one sample of kimberlite from the Roberts Victor mine were analyzed for concentrations of U, Th, Pb, Rb and Sr and isotopic compositions of Pb and Sr. In the eclogites, U content ranges from 0.09 to 0.26 ppm, Th from 0.35 to 1.1 ppm, Pb from 0.79 to 5.5 ppm, Rb from 2.1 to 28 ppm and Sr from 133 to 346 ppm; 206Pb/204Pb ratios range from 14.8 to 18.5, 207Pb/204Pb from 14.9 to 15.7, 208Pb/204Pb from 35.2 to 38.5. The garnet peridotite contains 0.22 ppm U, 0.97 ppm Th, 1.05 ppm Pb, 6.9 ppm Rb and 108 ppm Sr and the kimberlite contains 2.5 ppm U, 30 ppm Th, 37 ppm Pb, 113 ppm Rb and 2040 ppm Sr. The lead in the eclogites has two components, a lead pyroextractable at 1100-1200?? and a non-pyroextractable residual lead. In three of the eclogites, which are to some extent altered, a proportion of the pyroextractable lead may be contaminating lead from the kimberlite, but an altered kyanite eclogite does not appear to be contaminated by this same kimberlite. The pyroextractable lead from a less altered eclogite contains a much larger proportion of 206Pb. Compositions calculated for the residual leads vary greatly. In many of the pyroextraction runs the primary eclogitic phases disappeared and the new phases plagioclase, clinopyroxene and a magnetic iron compound were formed. Why part of the lead should have been retained by these new phases is not understood. ?? 1971.
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Cell death features induced in Leishmania major by 1,3,4-thiadiazole derivatives.
Ardestani, Sussan K; Poorrajab, Fatemeh; Razmi, Sepideh; Foroumadi, Alireza; Ajdary, Soheila; Gharegozlou, Behnaz; Behrouzi-Fardmoghadam, Mina; Shafiee, Abbas
2012-10-01
Under a variety of stress conditions, Leishmania species display some morphological and biochemical features characteristic of mammalian programmed cell death or necrosis. Nitroheteroaryl-1,3,4-thiadiazoles induce cell death in Leishmania major (L. major). Putative mechanisms of action of these compounds were investigated in vitro at cellular and molecular levels. We used colorimetric assay to measure acid phosphatase activity which is an indicator of cell viability in the promastigotes. The mode of toxicity was determined by detection of phosphatidylserine translocation to the surface, evaluation of cell membrane integrity, and in situ dUTP nick end-labeling assay. We also determined poly-ADP-ribose polymerase-like protein (PARP) level in the parasites after treatment. A significant reduction of acid phosphatase level, one of the most crucial and virulent factors of the parasite was found in parasites treated with 1,3,4-thiadiazole derivatives. In addition, 1,3,4-thiadiazole derivatives induced loss of plasma membrane integrity, DNA breakage, proteolysis of PARP and necrotic-like death in the parasites. Copyright © 2012 Elsevier Inc. All rights reserved.
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Measurement of the 3 s 1 / 2 - 3 p 3 / 2 resonance line of sodiumlike Eu 52 +
DOE Office of Scientific and Technical Information (OSTI.GOV)
Träbert, E.; Beiersdorfer, P.; Hell, N.
2015-08-01
We have measured the 3 s 1 / 2 - 3 p 3 / 2 transition in sodiumlike Eu 52 + situated at 41.232 Å with an uncertainty of 73 ppm. Our measurement extends previous high-precision measurements into the 56 < Z < 78 range of atomic numbers. We also present measurements of 3 s 1 / 2 - 3 p 3 / 2 and 3 p 1 / 2 - 3 d 3 / 2 transitions in the neighboring magnesiumlike, aluminumlike, and siliconlike europium ions.
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Measurement of the 3 s 1 / 2 - 3 p 3 / 2 resonance line of sodiumlike Eu 52 +
DOE Office of Scientific and Technical Information (OSTI.GOV)
Träbert, E.; Beiersdorfer, P.; Hell, N.
2015-08-20
We have measured the 3s 1/2-3p 3/2 transition in sodiumlike Eu 52+ situated at 41.232 Å with an uncertainty of 73 ppm. Our measurement extends previous high-precision measurements into the 56< Z< 78 range of atomic numbers. We also present measurements of 3s 1/2-3p 3/2 and 3p 1/2-3d 3/2 transitions in the neighboring magnesiumlike, aluminumlike, and siliconlike europium ions.
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Error Rates and Channel Capacities in Multipulse PPM
NASA Technical Reports Server (NTRS)
Hamkins, Jon; Moision, Bruce
2007-01-01
A method of computing channel capacities and error rates in multipulse pulse-position modulation (multipulse PPM) has been developed. The method makes it possible, when designing an optical PPM communication system, to determine whether and under what conditions a given multipulse PPM scheme would be more or less advantageous, relative to other candidate modulation schemes. In conventional M-ary PPM, each symbol is transmitted in a time frame that is divided into M time slots (where M is an integer >1), defining an M-symbol alphabet. A symbol is represented by transmitting a pulse (representing 1) during one of the time slots and no pulse (representing 0 ) during the other M 1 time slots. Multipulse PPM is a generalization of PPM in which pulses are transmitted during two or more of the M time slots.
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Inclusion of phytogenic blends in different nutrient density diets of meat-type ducks.
Gheisar, Mohsen Mohammadi; Im, Yong Woon; Lee, Hae Hyoung; Choi, Yang Il; Kim, In Ho
2015-12-01
A total of 160 1-day-old ducklings (average initial body weight of 53 g), were used in a 42-d feeding trial to evaluate the effects of reducing nutrient density of diets, and supplementing the diets with a phytogenic blend (quillaja, anise, and thyme) on their growth, carcass quality, and nutrient digestibility. After checking body weight on d 1, the birds were sorted into pens with 5 birds/pen and 8 pens/treatment. The treatments were: T1, Basal diet; T2, T1+150 ppm phytogenic blend; T3, T1-(1% CP, 0.04% Lys, 0.05% Met+Cys, 0.02% Ca, and 0.02% P, and 50 kcal ME); T4, T3+150 ppm phytogenic blend. The results indicated that reducing nutrient density of the diets had an adverse effect (P<0.05) on body weight gain (BWG) on d 1 to 21, d 21 to 42, and the overall experimental period. Supplementing the diets with the phytogenic blend improved (P<0.05) BWG and feed conversion ratio (FCR) on d 21 to 42 and the overall experimental period. Feed intake was not affected by treatments. Low nutrient density diets increased (P<0.05) the cooking loss percentage of breast meat. Supplementing the diets with the phytogenic blend decreased (P<0.05) the lightness of breast meat. The percentage of drip loss was influenced (P<0.05) by nutrient density and the phytogenic blend on d 1 and d 7. The relative weights of breast meat, abdominal fat, gizzard, liver, spleen, and bursa of Fabricius, pH, and TBARS values were not affected by the treatments. The digestibility of dry matter, energy, nitrogen, ADF, and NDF was decreased (P<0.05) by reducing nutrients density of the diets, but addition of the phytogenic blend alleviated (P<0.05) the negative effects of lowering the nutrient density. The results indicated that the ducks fed high nutrient density diets supplemented with the phytogenic blend showed higher BWG and nutrient digestibility and lower FCR, cooking loss, drip loss, and TBARS value, without any negative effect on meat quality and relative organs weights. © 2015 Poultry Science Association Inc.
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Kerekes, Éva; Kókai, Endre; Páldy, Ferenc Sándor; Dombrádi, Viktor
2014-06-01
The product of the CG9238 gene that we termed glycogen binding subunit 70E (Gbs-70E) was characterized by biochemical and molecular genetics methods. The interaction between Gbs-70E and all catalytic subunits of protein phosphatase 1 (Pp1-87B, Pp1-9C, Pp1-96A and Pp1-13C) of Drosophila melanogaster was confirmed by pairwise yeast two-hybrid tests, co-immunoprecipitation and pull down experiments. The binding of Gbs-70E to glycogen was demonstrated by sedimentation analysis. With RT-PCR we found that the mRNAs coding for the longer Gbs-70E PB/PC protein were expressed in all developmental stages of the fruit flies while the mRNA for the shorter Gbs-70E PA was restricted to the eggs and the ovaries of the adult females. The development specific expression of the shorter splice variant was not conserved in different Drosophila species. The expression level of the gene was manipulated by P-element insertions and gene deletion to analyze the functions of the gene product. A small or moderate reduction in the gene expression resulted in no significant changes, however, a deletion mutant expressing very low level of the transcript lived shorter and exhibited reduced glycogen content in the imagos. In addition, the gene deletion decreased the fertility of the fruit flies. Our results prove that Gbs-70E functions as the glycogen binding subunit of protein phosphatase 1 that regulates glycogen content and plays a role in the development of eggs in D. melanogaster. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Characterization of air contaminants formed by the interaction of lava and sea water.
Kullman, G J; Jones, W G; Cornwell, R J; Parker, J E
1994-01-01
We made environmental measurements to characterize contaminants generated when basaltic lava from Hawaii's Kilauea volcano enters sea water. This interaction of lava with sea water produces large clouds of mist (LAZE). Island winds occasionally directed the LAZE toward the adjacent village of Kalapana and the Hawaii Volcanos National Park, creating health concerns. Environmental samples were taken to measure airborne concentrations of respirable dust, crystalline silica and other mineral compounds, fibers, trace metals, inorganic acids, and organic and inorganic gases. The LAZE contained quantifiable concentrations of hydrochloric acid (HCl) and hydrofluoric acid (HF); HCl was predominant. HCl and HF concentrations were highest in dense plumes of LAZE near the sea. The HCl concentration at this sampling location averaged 7.1 ppm; this exceeds the current occupational exposure ceiling of 5 ppm. HF was detected in nearly half the samples, but all concentrations were <1 ppm Sulfur dioxide was detected in one of four short-term indicator tube samples at approximately 1.5 ppm. Airborne particulates were composed largely of chloride salts (predominantly sodium chloride). Crystalline silica concentrations were below detectable limits, less than approximately 0.03 mg/m3 of air. Settled dust samples showed a predominance of glass flakes and glass fibers. Airborne fibers were detected at quantifiable levels in 1 of 11 samples. These fibers were composed largely of hydrated calcium sulfate. These findings suggest that individuals should avoid concentrated plumes of LAZE near its origin to prevent over exposure to inorganic acids, specifically HCl. Images Figure 1. Figure 2. Figure 3. Figure 4. A Figure 4. B Figure 4. C Figure 4. D PMID:8593853
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Waadt, Rainer; Manalansan, Bianca; Rauniyar, Navin; ...
2015-09-04
The plant hormone abscisic acid (ABA) controls growth and development and regulates plant water status through an established signaling pathway. In the presence of ABA, pyrabactin resistance/regulatory component of ABA receptor proteins inhibit type 2C protein phosphatases (PP2Cs). This, in turn, enables the activation of Sucrose Nonfermenting1-Related Protein Kinases2 (SnRK2). Open Stomata1 (OST1)/SnRK2.6/SRK2E is a major SnRK2-type protein kinase responsible for mediating ABA responses. Arabidopsis (Arabidopsis thaliana) expressing an epitope-tagged OST1 in the recessive ost1-3 mutant background was used for the copurification and identification of OST1-interacting proteins after osmotic stress and ABA treatments. Furthemore, these analyses, which were confirmed usingmore » bimolecular fluorescence complementation and coimmunoprecipitation, unexpectedly revealed homo- and heteromerization of OST1 with SnRK2.2, SnRK2.3, OST1, and SnRK2.8. Furthermore, several OST1-complexed proteins were identified as type 2A protein phosphatase (PP2A) subunits and as proteins involved in lipid and galactolipid metabolism. More detailed analyses suggested an interaction network between ABA-activated SnRK2-type protein kinases and several PP2A-type protein phosphatase regulatory subunits. pp2a double mutants exhibited a reduced sensitivity to ABA during seed germination and stomatal closure and an enhanced ABA sensitivity in root growth regulation. Our analyses add PP2A-type protein phosphatases as another class of protein phosphatases to the interaction network of SnRK2-type protein kinases.« less
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Łopieńska-Biernat, Elżbieta; Molcan, Tomasz; Paukszto, Łukasz; Jastrzębski, Jan Paweł; Myszczyński, Kamil
2018-01-01
The trehalose-6-phosphate phosphatase (TPP) enzyme is involved in the synthesis of trehalose, the main sugar in the energy metabolism of nematodes. TPP is a member of the HAD-like hydrolase superfamily and shows a robust and specific phosphatase activity for the substrate trehalose-6-phosphate. The presence of conserved active sites of TPP in closely related nematodes and its absence in humans makes it a promising target for antiparasitic drugs. In the present study, homology modeling, molecular docking and MD simulation techniques were used to explore the structure and dynamics of TPP. In the active site, a magnesium ion is stabilized by 3 coordinate bonds formed by D 189 , D 191 and D 400 . The key amino acids involved in ligand binding by the enzyme are C 198 , Y 201 ,T 357 , D 191 and Y 197 . This study relied on docking to select potential inhibitors of TPP which were tested in vitro for sensitivity to anthelmintic drugs such as levamisole and ivermectin targeting Anisakis simplex. The higher toxicity of LEV than IVM was demonstrated after 96 h, 30% of larvae were motile in cultures with 100 μg/ml of LEV and 1000 μg/ml of IVM. We identified drug combination of LEV-IVM against in vitro A. simplex as agonistic effect (CI = 1.1). Levamisole appeared to be a more effective drug which inhibited enzyme activity after 48 h and expression of mRNA after 96 h at a concentration of 10 μg/ml. This preliminary study predicted the structure of TPP, and the results of an in vitro experiment involving A. simplex will contribute to the development of effective inhibitors with potential antiparasitic activity in the future. Copyright © 2017 Elsevier Inc. All rights reserved.
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Capacity of Pulse-Position Modulation (PPM) on Gaussian and Webb Channels
NASA Technical Reports Server (NTRS)
Dolinar, S.; Divsalar, D.; Hamkins, J.; Pollara, F.
2000-01-01
This article computes the capacity of various idealized soft-decision channels modeling an optical channel using an avalanche photodiode detector (APD) and pulse-position modulation (PPM). The capacity of this optical channel depends in a complicated way on the physical parameters of the APD and the constraints imposed by the PPM orthogonal signaling set. This article attempts to identify and separate the effects of several fundamental parameters on the capacity of the APD-detected optical PPM channel. First, an overall signal-to-noise ratio (SNR) parameter is de ned such that the capacity as a function of a bit-normalized version of this SNR drops precipitously toward zero at quasi-brick-wall limits on bit SNR that are numerically the same as the well-understood brick-wall limits for the standard additive white Gaussian noise (AWGN) channel. A second parameter is used to quantify the effects on capacity of one unique facet of the optical PPM channel (as compared with the standard AWGN channel) that causes the noise variance to be higher in signal slots than in nonsignal slots. This nonuniform noise variance yields interesting capacity effects even when the channel model is AWGN. A third parameter is used to measure the effects on capacity of the difference between an AWGN model and a non-Gaussian model proposed by Webb (see reference in [2]) for approximating the statistics of the APD-detected optical channel. Finally, a fourth parameter is used to quantify the blending of a Webb model with a pure AWGN model to account for thermal noise. Numerical results show that the capacity of M-ary orthogonal signaling on the Webb channel exhibits the same brick-wall Shannon limit, (M ln 2)=(M 1), as on the AWGN channel ( 1:59 dB for large M). Results also compare the capacity obtained by hard- and soft-output channels and indicate that soft-output channels o er a 3-dB advantage.
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An, Jianguo; Sun, Mingjiang; Bai, Lin; Chen, Ted; Liu, David Q; Kord, Alireza
2008-11-04
Derivatization LC/MS methodology has been developed for the determination of a group of commonly encountered alkyl esters of sulfonates or sulfates in drug substances at low ppm levels. This general method uses trimethylamine as the derivatizing reagent for ethyl/propyl/isopropyl esters and triethylamine for methyl esters. The resulting quaternary ammonium derivatization products are highly polar (ionic) and can be retained by a hydrophilic interaction liquid chromatography (HILIC) column and readily separated from the main interfering active pharmaceutical ingredient (API) peak that is usually present at very high concentration. The method gives excellent sensitivity for all the alkyl esters at typical target analyte level of 1-2 ppm when the API samples were prepared at 5mg/mL. The recoveries at 1-2 ppm were generally above 85% for all the alkyl esters in the various APIs tested. The injection precisions of the lowest concentration standards were excellent with R.S.D.=0.4-4%. A linear range for concentrations from 0.2 to 20 ppm has been established with R(2)>or=0.99. This general method has been tested in a number of API matrices and used successfully for determination of alkyl sulfonates or dialkyl sulfates in support of API batch releases at GlaxoSmithKline.
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Gracia, Louise H; Rees, Gareth D; Brown, Alan; Fowler, Christabel E
2010-11-01
Firstly, to evaluate the in vitro anti-erosion efficacy of a new mouthrinse formulation containing 450 ppm fluoride using profilometry and microindentation. Secondly, to compare fluoride uptake by erosive lesions from two mouthrinses containing different fluoride sources using dynamic secondary ion mass spectrometry (DSIMS). Sound human enamel was treated (60s) with mouthrinses containing different fluoride concentrations, then immersed in 1.0% citric acid pH 3.8 for either 300 s or 30 min (Studies 1 & 2 respectively). Surface roughness and erosion depth were determined profilometrically in Study 1, and surface microhardness monitored as a function of time in Study 2. Lesion rehardening was monitored following a 60 s rinse and immersion in artificial saliva for 48 h (Study 3), whilst Study 4 employed DSIMS to quantify fluoride uptake by lesions treated (60s) with rinses containing either sodium fluoride (NaF) or a NaF/Olaflur/stannous chloride combination. The test rinse (450 ppm fluoride) suppressed surface roughening and bulk tissue loss versus all comparators (p< 0.0001), except in the latter measure for the rinse containing 112 ppm fluoride. The test rinse significantly inhibited enamel surface softening versus the three rinses containing ≤112 ppm fluoride (as NaF) at 30 min (p<0.05), but was not statistically significantly different from the 225 ppm fluoride rinse. The test rinse conferred statistically superior lesion rehardening versus all comparators at both 24 and 48 h (p< 0.0001). DSIMS demonstrated statistically significantly higher fluoride uptake by incipient erosive lesions treated with the test rinse versus the NaF/Olaflur/stannous rinse. Anti-erosion efficacy was positively correlated with fluoride concentration. DSIMS showed significantly higher levels of fluoride uptake by incipient erosive lesions treated with the 450 ppm fluoride rinse versus the NaF/Olaflur/stannous rinse. Copyright © 2010 Elsevier Ltd. All rights reserved.
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Regulation of Na+-K+-2Cl− cotransport by protein phosphorylation in ferret erythrocytes
Flatman, Peter W; Creanor, James
1999-01-01
Na+-K+-2Cl− cotransport in ferret erythrocytes was measured as the bumetanide-sensitive uptake of 86Rb. The resting cotransport rate was high but could be increased threefold by treating erythrocytes with calyculin A, a potent inhibitor of serine/threonine phosphatases. Twenty nanomolar was sufficient to maximally and rapidly (within 4 min) stimulate transport. The effects of several kinase inhibitors were tested. High concentrations of K-252a, K-252b, calphostin C and hypericin caused less than 20 % inhibition. Staurosporine (IC50, 0.06 μm) and 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1; IC50, 2.5 μm) were more potent but still only partially (40–50 %) inhibited transport, an effect mimicked by reducing ionized intracellular Mg2+ concentration to submicromolar levels. Genistein may inhibit all transport at a sufficiently high dose (IC50, 0.36 mM) perhaps by directly inhibiting the transporter. Staurosporine, PP1 and the removal of Mg2+ all prevented subsequent stimulation by calyculin A, and all inhibited calyculin-stimulated transport by 20–30 %. The effects of staurosporine, PP1 and Mg2+ removal were not additive. The phosphatase that dephosphorylates the cotransporter is probably Mg2+ (or possibly Ca2+ or Mn2+) sensitive and not the target for calyculin A. The data suggest that this phosphatase is inhibited by phosphorylation, and that it is the regulation of this process which is affected by calyculin A and the kinase inhibitors tested here. Phosphorylation of the phosphatase is probably regulated by members of the Src family of tyrosine kinases. PMID:10358111
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Xu, Jian; Chatterjee, Manavi; Baguley, Tyler D.; Brouillette, Jonathan; Kurup, Pradeep; Ghosh, Debolina; Kanyo, Jean; Zhang, Yang; Seyb, Kathleen; Ononenyi, Chimezie; Foscue, Ethan; Anderson, George M.; Gresack, Jodi; Cuny, Gregory D.; Glicksman, Marcie A.; Greengard, Paul; Lam, TuKiet T.; Tautz, Lutz; Nairn, Angus C.; Ellman, Jonathan A.; Lombroso, Paul J.
2014-01-01
STEP (STriatal-Enriched protein tyrosine Phosphatase) is a neuron-specific phosphatase that regulates N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking, as well as ERK1/2, p38, Fyn, and Pyk2 activity. STEP is overactive in several neuropsychiatric and neurodegenerative disorders, including Alzheimer's disease (AD). The increase in STEP activity likely disrupts synaptic function and contributes to the cognitive deficits in AD. AD mice lacking STEP have restored levels of glutamate receptors on synaptosomal membranes and improved cognitive function, results that suggest STEP as a novel therapeutic target for AD. Here we describe the first large-scale effort to identify and characterize small-molecule STEP inhibitors. We identified the benzopentathiepin 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (known as TC-2153) as an inhibitor of STEP with an IC50 of 24.6 nM. TC-2153 represents a novel class of PTP inhibitors based upon a cyclic polysulfide pharmacophore that forms a reversible covalent bond with the catalytic cysteine in STEP. In cell-based secondary assays, TC-2153 increased tyrosine phosphorylation of STEP substrates ERK1/2, Pyk2, and GluN2B, and exhibited no toxicity in cortical cultures. Validation and specificity experiments performed in wild-type (WT) and STEP knockout (KO) cortical cells and in vivo in WT and STEP KO mice suggest specificity of inhibitors towards STEP compared to highly homologous tyrosine phosphatases. Furthermore, TC-2153 improved cognitive function in several cognitive tasks in 6- and 12-mo-old triple transgenic AD (3xTg-AD) mice, with no change in beta amyloid and phospho-tau levels. PMID:25093460
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Regulation of Mih1/Cdc25 by protein phosphatase 2A and casein kinase 1
Pal, Gayatri; Paraz, Maria T.Z.; Kellogg, Douglas R.
2008-01-01
The Cdc25 phosphatase promotes entry into mitosis by removing cyclin-dependent kinase 1 (Cdk1) inhibitory phosphorylation. Previous work suggested that Cdc25 is activated by Cdk1 in a positive feedback loop promoting entry into mitosis; however, it has remained unclear how the feedback loop is initiated. To learn more about the mechanisms that regulate entry into mitosis, we have characterized the function and regulation of Mih1, the budding yeast homologue of Cdc25. We found that Mih1 is hyperphosphorylated early in the cell cycle and is dephosphorylated as cells enter mitosis. Casein kinase 1 is responsible for most of the hyperphosphorylation of Mih1, whereas protein phosphatase 2A associated with Cdc55 dephosphorylates Mih1. Cdk1 appears to directly phosphorylate Mih1 and is required for initiation of Mih1 dephosphorylation as cells enter mitosis. Collectively, these observations suggest that Mih1 regulation is achieved by a balance of opposing kinase and phosphatase activities. Because casein kinase 1 is associated with sites of polar growth, it may regulate Mih1 as part of a signaling mechanism that links successful completion of growth-related events to cell cycle progression. PMID:18316413
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Majumder, Shyam Prasad; Das, Amal Chandra
2016-04-01
An experiment was conducted under laboratory conditions to investigate the effect of four organophosphate insecticides, viz. monocrotophos, profenophos, quinalphos and triazophos at their field application rates (0.75, 1.0, 0.5 and 0.6 kg a.i.ha(-1), respectively), on the growth and activities of phosphate solubilizing microorganisms in relation to availability of insoluble phosphates in the Gangetic alluvial soil of West Bengal, India. The proliferation of phosphate solubilizing microorganisms was highly induced with profenophos (38.3%), while monocrotophos exerted maximum stimulation (20.8%) towards the solubility of insoluble phosphates in soil. The phosphatase activities of the soil (both acid phosphatase and alkaline phosphatase) were significantly increased due to the incorporation of the insecticides in general, and the augmentation was more pronounced with quinalphos (43.1%) followed by profenophos (27.6%) for acid phosphatase, and with monocrotophos (25.2%) followed by profenophos (16.1%) for alkaline phosphatase activity in soil. The total phosphorus was highly retained by triazophos (19.9%) followed by monocrotophos (16.5%), while incorporation of triazophos and quinalphos manifested greater availability of water soluble phosphorus in soil. Copyright © 2015 Elsevier Inc. All rights reserved.
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Geno, K. Aaron; Hauser, Jocelyn R.; Gupta, Kanupriya
2014-01-01
Streptococcus pneumoniae produces a protective capsular polysaccharide whose production must be modulated for bacterial survival within various host niches. Capsule production is affected in part by a phosphoregulatory system comprised of CpsB, CpsC, and CpsD. Here, we found that growth of serotype 2 strain D39 under conditions of increased oxygen availability resulted in decreased capsule levels concurrent with an ∼5-fold increase in Cps2B-mediated phosphatase activity. The change in Cps2B phosphatase activity did not result from alterations in the levels of either the cps2B transcript or the Cps2B protein. Recombinant Cps2B expressed in Escherichia coli similarly exhibited increased phosphatase activity under conditions of high-oxygen growth. S. pneumoniae D39 derivatives with defined deletion or point mutations in cps2B demonstrated reduced phosphatase activity with corresponding increases in levels of Cps2D tyrosine phosphorylation. There was, however, no correlation between these phenotypes and the level of capsule production. During growth under reduced-oxygen conditions, the Cps2B protein was essential for parental levels of capsule, but phosphatase activity alone could be eliminated without an effect on capsule. Under increased-oxygen conditions, deletion of cps2B did not affect capsule levels. These results indicate that neither Cps2B phosphatase activity nor Cps2D phosphorylation levels per se are determinants of capsule levels, whereas the Cps2B protein is important for capsule production during growth under conditions of reduced but not enhanced oxygen availability. Roles for factors outside the capsule locus, possible interactions between capsule regulatory proteins, and links to other cellular processes are also suggested by the results described in this study. PMID:24659769
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STRIATAL-ENRICHED PROTEIN TYROSINE PHOSPHATASE (STEP) KNOCKOUT MICE HAVE ENHANCED HIPPOCAMPAL MEMORY
Venkitaramani, Deepa V.; Moura, Paula J.; Picciotto, Marina R.; Lombroso, Paul J.
2011-01-01
STEP is a brain-specific phosphatase that opposes synaptic strengthening by the regulation of key synaptic signaling proteins. Previous studies suggest a possible role for STriatal-Enriched protein tyrosine Phosphatase (STEP) in learning and memory. To demonstrate the functional importance of STEP in learning and memory, we generated STEP knockout (KO) mice and examined the effect of deletion of STEP on behavioral performance, as well as the phosphorylation and expression of its substrates. Here we report that loss of STEP leads to significantly enhanced performance in hippocampal-dependent learning and memory tasks. In addition, STEP KO mice displayed greater dominance behavior, although they were normal in their motivation, motor coordination, visual acuity and social interactions. STEP KO mice displayed enhanced tyrosine phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2), the NR2B subunit of the N-methyl-D-aspartate receptor (NMDAR), Proline-rich tyrosine kinase (Pyk2), as well as an increased phosphorylation of ERK1/2 substrates. Concomitant to the increased phosphorylation of NR2B, synaptosomal expression of NR1/NR2B NMDARs was increased in STEP KO mice, as was the GluR1/GluR2 containing α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPAR), providing a potential molecular mechanism for the improved cognitive performance. The data support a role for STEP in the regulation of synaptic strengthening. The absence of STEP improves cognitive performance, and may do so by the regulation of downstream effectors necessary for synaptic transmission. PMID:21501258
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The relation of the European Datum to a geocentric reference system
NASA Technical Reports Server (NTRS)
Marsh, J. G.; Douglas, B. C.; Klosko, S. M.
1971-01-01
Over 31,000 precision reduced optical observations of GEOS-1 and 2 in 70 two-day orbital arcs were used at Goddard Space Flight Center (GSFC) in a dynamical solution to determine center-of-mass coordinates for 15 tracking stations on the European Datum. Comparisons with the results obtained at Centre National d'Etudes Spatiales (CNES) give agreement of about 1.5 ppm for chord lengths. After considering a scale correction to the European Datum (ED) of 1950 to account for the absence of geoid heights at the time of its reduction, agreement to a few ppm between the CNES/GSFC and the ED chords is obtained. However, a small systematic difference between survey and satellite results remains for stations in southeastern France and Switzerland.
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Abe, Tania M O; Pereira, Alexandre C; Megid, Maria Cristina; Shimabukuro, Cristina E; Valentin, Luis Sergio O; da C Ferreira, Marizete M; Nobre, Moacyr R C; Lancarotte, Ines; Barretto, Antonio Carlos Pereira
2010-01-01
Background Studies have shown that there is no safe level of secondhand smoke (SHS) exposure and there is a close link between SHS and the risk of coronary heart disease and stroke. Carbon monoxide (CO) is one of the most important components present in SHS. Objective To evaluate the impact of the smoking ban law in the city of Sao Paulo, Brazil, on the CO concentration in restaurants, bars, night clubs and similar venues and in their workers. Methods In the present study we measured CO concentration in 585 hospitality venues. CO concentration was measured in different environments (indoor, semi-open and open areas) from visited venues, as well as, in the exhaled air from approximately 627 workers of such venues. Measurements were performed twice, before and 12 weeks after the law implementation. In addition, the quality of the air in the city during the same period of our study was verified. Results The CO concentration pre-ban and pot-ban in hospitality venues was indoor area 4.57 (3.70) ppm vs 1.35 (1.66) ppm (p<0.0001); semi-open 3.79 (2.49) ppm vs 1.16 (1.14) ppm (p<0.0001); open area 3.31(2.2) ppm vs 1.31 (1.39) ppm (p<0.0001); smoking employees 15.78 (9.76) ppm vs 11.50 (7.53) ppm (p<0.0001) and non-smoking employees 6.88 (5.32) ppm vs 3.50 (2.21) ppm (p<0.0001). The average CO concentration measured in the city was lower than 1 ppm during both pre-ban and post-ban periods. Conclusion São Paulo's smoking-free legislation reduced significantly the CO concentration in hospitality venues and in their workers, whether they smoke or not. PMID:21109684