76 FR 388 - Southern Nuclear Operating Company; Vogtle Electric Generating Plant, Unit Nos. 1 and 2; Notice...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-04

... Design,'' GDC 31, ``Fracture Prevention of Reactor Coolant Pressure Boundary,'' and GDC 32, ``Inspection... Operating Company; Vogtle Electric Generating Plant, Unit Nos. 1 and 2; Notice of Consideration of Issuance of Amendment to Facility Operating License, Proposed No Significant Hazards Consideration...

NOS1 mediates AP1 nuclear translocation and inflammatory response.

PubMed

Srivastava, Mansi; Baig, Mirza S

2018-06-01

A hallmark of the AP1 functioning is its nuclear translocation, which induces proinflammatory cytokine expression and hence the inflammatory response. After endotoxin shock AP1 transcription factor, which comprises Jun, ATF2, and Fos family of proteins, translocates into the nucleus and induces proinflammatory cytokine expression. In the current study, we found, NOS1 inhibition prevents nuclear translocation of the AP1 transcription factor subunits. Pharmacological inhibition of NOS1 impedes translocation of subunits into the nucleus, suppressing the transcription of inflammatory genes causing a diminished inflammatory response. In conclusion, the study shows the novel mechanism of NOS1- mediated AP1 nuclear translocation, which needs to be further explored. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Unexpected Heterodivalent Recruitment of NOS1AP to nNOS Reveals Multiple Sites for Pharmacological Intervention in Neuronal Disease Models.

PubMed

Li, Li-Li; Melero-Fernandez de Mera, Raquel M; Chen, Jia; Ba, Wei; Kasri, Nael Nadif; Zhang, Mingjie; Courtney, Michael J

2015-05-13

The protein NOS1AP/CAPON mediates signaling from a protein complex of NMDA receptor, PSD95 and nNOS. The only stroke trial for neuroprotectants that showed benefit to patients targeted this ternary complex. NOS1AP/nNOS interaction regulates small GTPases, iron transport, p38MAPK-linked excitotoxicity, and anxiety. Moreover, the nos1ap gene is linked to disorders from schizophrenia, post-traumatic stress disorder, and autism to cardiovascular disorders and breast cancer. Understanding protein interactions required for NOS1AP function, therefore, has broad implications for numerous diseases. Here we show that the interaction of NOS1AP with nNOS differs radically from the classical PDZ docking assumed to be responsible. The NOS1AP PDZ motif does not bind nNOS as measured by multiple methods. In contrast, full-length NOS1AP forms an unusually stable interaction with nNOS. We mapped the discrepancy between full-length and C-terminal PDZ motif to a novel internal region we call the ExF motif. The C-terminal PDZ motif, although neither sufficient nor necessary for binding, nevertheless promotes the stability of the complex. It therefore potentially affects signal transduction and suggests that functional interaction of nNOS with NOS1AP might be targetable at two distinct sites. We demonstrate that excitotoxic pathways can be regulated, in cortical neuron and organotypic hippocampal slice cultures from rat, either by the previously described PDZ ligand TAT-GESV or by the ExF motif-bearing region of NOS1AP, even when lacking the critical PDZ residues as long as the ExF motif is intact and not mutated. This previously unrecognized heterodivalent interaction of nNOS with NOS1AP may therefore provide distinct opportunities for pharmacological intervention in NOS1AP-dependent signaling and excitotoxicity. Copyright © 2015 the authors 0270-6474/15/357349-16$15.00/0.

48 CFR 47.303-2 - F.o.b. origin, contractor's facility.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false F.o.b. origin, contractor... REGULATION CONTRACT MANAGEMENT TRANSPORTATION Transportation in Supply Contracts 47.303-2 F.o.b. origin, contractor's facility. (a) Explanation of delivery term. F.o.b. origin, contractor's facility means free of...

9 CFR 3.1 - Housing facilities, general.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Transportation of Dogs and Cats 1 Facilities and Operating Standards § 3.1 Housing facilities, general. (a) Structure; construction. Housing facilities for dogs and cats must be designed and constructed so that they... apply only to live dogs and cats, unless stated otherwise. (b) Condition and site. Housing facilities...

9 CFR 3.1 - Housing facilities, general.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Transportation of Dogs and Cats 1 Facilities and Operating Standards § 3.1 Housing facilities, general. (a) Structure; construction. Housing facilities for dogs and cats must be designed and constructed so that they... apply only to live dogs and cats, unless stated otherwise. (b) Condition and site. Housing facilities...

7 CFR 15b.38 - Health care facilities.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 1 2012-01-01 2012-01-01 false Health care facilities. 15b.38 Section 15b.38... ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Other Aid, Benefits, or Services § 15b.38 Health care... impaired. A recipient hospital that provides health services or benefits shall establish a procedure for...

7 CFR 15b.38 - Health care facilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Health care facilities. 15b.38 Section 15b.38... ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Other Aid, Benefits, or Services § 15b.38 Health care... impaired. A recipient hospital that provides health services or benefits shall establish a procedure for...

7 CFR 15b.38 - Health care facilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 1 2011-01-01 2011-01-01 false Health care facilities. 15b.38 Section 15b.38... ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Other Aid, Benefits, or Services § 15b.38 Health care... impaired. A recipient hospital that provides health services or benefits shall establish a procedure for...

7 CFR 15b.38 - Health care facilities.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 1 2013-01-01 2013-01-01 false Health care facilities. 15b.38 Section 15b.38... ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Other Aid, Benefits, or Services § 15b.38 Health care... impaired. A recipient hospital that provides health services or benefits shall establish a procedure for...

Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-kappaB signaling.

PubMed

Cheng, Yu Wen; Chang, Ching Yi; Lin, Kou Lung; Hu, Chien Ming; Lin, Cheng Hui; Kang, Jaw Jou

2008-11-20

Shikonin/alkannin (SA) derivatives, analogs of naphthoquinone pigments, are the major components of root extracts of the Chinese medicinal herb (Lithospermum erythrorhizon; LE) and widely distributed in several folk medicines. In the present study, the effect and the underline molecular mechanism of shikonin derivatives isolated from root extracts of Lithospermum euchroma on lipopolysaccharide (LPS)-induced inflammatory response were investigated. Effects of five SA derivatives, including SA, acetylshikonin, beta,beta-dimethylacrylshikonin, 5,8-dihydroxy-1.4-naphthoquinone, and 1,4-naphthoquinone on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in mouse macrophage RAW264.7 cells were examined. Data suggested that SA derivatives inhibited LPS-induced NO and PGE(2) production, and iNOS protein expression. RT-PCR analysis showed that SA derivatives diminished LPS-induced iNOS mRNA expression. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in LPS-stimulated RAW 264.7 cells was concentration-dependently suppressed by SA derivatives. SA inhibited NF-kappaB activation by prevention of the degradation of inhibitory factor-kappaB and p65 level in nuclear fractions induced by LPS. Taken together, these results suggest that the anti-inflammatory properties of SA derivatives might result from inhibition of iNOS protein expression through the downregulation of NF-kappaB activation via suppression of phosphorylation of ERK, in LPS-stimulated RAW 264.7 cells.

E.C.I.A. Chapter 1, Part B, Institutionalized Facilities Program, 1989-90. OREA Report.

ERIC Educational Resources Information Center

Miller, Ronald C.

This report evaluates a program funded under the Educational Consolidation and Improvement Act (ECIA), Chapter 1, Part B, in New York (New York). The Program for Neglected and Delinquent Children, District 75/Citywide Institutionalized Facilities Program provides after-school supplementary instruction in prevocational skills, activities of daily…

Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation.

PubMed

Zhang, Jun-Xia; Qu, Xin-Liang; Chu, Peng; Xie, Du-Jiang; Zhu, Lin-Lin; Chao, Yue-Lin; Li, Li; Zhang, Jun-Jie; Chen, Shao-Liang

2018-05-01

Uncoupled endothelial nitric oxide synthase (eNOS) produces O 2 - instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O 2 - production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O 2 - burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O 2 - releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

77 FR 53182 - 36(b)(1) Arms Sales Notification

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2012-08-31

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-34] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...: Navy (AKL) [[Page 53184

78 FR 50047 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-21] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... Pursuant to Section 36(b) (1) Of the Arms Export Control Act, as amended (i) Prospective Purchaser: Iraq...

Protein Phosphotyrosine Phosphatase 1B (PTP1B) in Calpain-dependent Feedback Regulation of Vascular Endothelial Growth Factor Receptor (VEGFR2) in Endothelial Cells

PubMed Central

Zhang, Yixuan; Li, Qiang; Youn, Ji Youn; Cai, Hua

2017-01-01

The VEGF/VEGFR2/Akt/eNOS/NO pathway is essential to VEGF-induced angiogenesis. We have previously discovered a novel role of calpain in mediating VEGF-induced PI3K/AMPK/Akt/eNOS activation through Ezrin. Here, we sought to identify possible feedback regulation of VEGFR2 by calpain via its substrate protein phosphotyrosine phosphatase 1B (PTP1B), and the relevance of this pathway to VEGF-induced angiogenesis, especially in diabetic wound healing. Overexpression of PTP1B inhibited VEGF-induced VEGFR2 and Akt phosphorylation in bovine aortic endothelial cells, while PTP1B siRNA increased both, implicating negative regulation of VEGFR2 by PTP1B. Calpain inhibitor ALLN induced VEGFR2 activation, which can be completely blocked by PTP1B overexpression. Calpain activation induced by overexpression or Ca/A23187 resulted in PTP1B cleavage, which can be blocked by ALLN. Moreover, calpain activation inhibited VEGF-induced VEGFR2 phosphorylation, which can be restored by PTP1B siRNA. These data implicate calpain/PTP1B negative feedback regulation of VEGFR2, in addition to the primary signaling pathway of VEGF/VEGFR2/calpain/PI3K/AMPK/Akt/eNOS. We next examined a potential role of PTP1B in VEGF-induced angiogenesis. Endothelial cells transfected with PTP1B siRNA showed faster wound closure in response to VEGF. Aortic discs isolated from PTP1B siRNA-transfected mice also had augmented endothelial outgrowth. Importantly, PTP1B inhibition and/or calpain overexpression significantly accelerated wound healing in STZ-induced diabetic mice. In conclusion, our data for the first time demonstrate a calpain/PTP1B/VEGFR2 negative feedback loop in the regulation of VEGF-induced angiogenesis. Modulation of local PTP1B and/or calpain activities may prove beneficial in the treatment of impaired wound healing in diabetes. PMID:27872190

75 FR 42708 - 36(b)(1) Arms Sales Notifications

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2010-07-22

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-09, 10-33, and 10-37] 36(b)(1... Department of Defense is publishing the unclassified text of three section 36(b)(1) arms sales notifications... INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. SUPPLEMENTARY INFORMATION: The following...

75 FR 62792 - 36(b)(1) Arms Sales Notifications

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2010-10-13

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-20, 10-23, and 10-42] 36(b)(1... Department of Defense is publishing the unclassified text of three section 36(b)(1) arms sales notifications... INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. SUPPLEMENTARY INFORMATION: The following...

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... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 09-67 and 09-72] 36(b)(1) Arms... Department of Defense is publishing the unclassified text of two section 36(b)(1) arms sales notifications to... CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. SUPPLEMENTARY INFORMATION: The following are copies...

76 FR 35188 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-22] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This.... FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. The following is a copy...

Endothelial nitric-oxide synthase (eNOS) is activated through G-protein-coupled receptor kinase-interacting protein 1 (GIT1) tyrosine phosphorylation and Src protein.

PubMed

Liu, Songling; Premont, Richard T; Rockey, Don C

2014-06-27

Nitric oxide (NO) is a critical regulator of vascular tone and plays an especially prominent role in liver by controlling portal blood flow and pressure within liver sinusoids. Synthesis of NO in sinusoidal endothelial cells by endothelial nitric-oxide synthase (eNOS) is regulated in response to activation of endothelial cells by vasoactive signals such as endothelins. The endothelin B (ETB) receptor is a G-protein-coupled receptor, but the mechanisms by which it regulates eNOS activity in sinusoidal endothelial cells are not well understood. In this study, we built on two previous strands of work, the first showing that G-protein βγ subunits mediated activation of phosphatidylinositol 3-kinase and Akt to regulate eNOS and the second showing that eNOS directly bound to the G-protein-coupled receptor kinase-interacting protein 1 (GIT1) scaffold protein, and this association stimulated NO production. Here we investigated the mechanisms by which the GIT1-eNOS complex is formed and regulated. GIT1 was phosphorylated on tyrosine by Src, and Y293F and Y554F mutations reduced GIT1 phosphorylation as well as the ability of GIT1 to bind to and activate eNOS. Akt phosphorylation activated eNOS (at Ser(1177)), and Akt also regulated the ability of Src to phosphorylate GIT1 as well as GIT1-eNOS association. These pathways were activated by endothelin-1 through the ETB receptor; inhibiting receptor-activated G-protein βγ subunits blocked activation of Akt, GIT1 tyrosine phosphorylation, and ET-1-stimulated GIT1-eNOS association but did not affect Src activation. These data suggest a model in which Src and Akt cooperate to regulate association of eNOS with the GIT1 scaffold to facilitate NO production. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Aspirin prevents TNF-α-induced endothelial cell dysfunction by regulating the NF-κB-dependent miR-155/eNOS pathway: Role of a miR-155/eNOS axis in preeclampsia.

PubMed

Kim, Joohwan; Lee, Kyu-Sun; Kim, Ji-Hee; Lee, Dong-Keon; Park, Minsik; Choi, Seunghwan; Park, Wonjin; Kim, Suji; Choi, Yoon Kyung; Hwang, Jong Yun; Choe, Jongseon; Won, Moo-Ho; Jeoung, Dooil; Lee, Hansoo; Ryoo, Sungwoo; Ha, Kwon-Soo; Kwon, Young-Guen; Kim, Young-Myeong

2017-03-01

Preeclampsia is an inflammatory disease with endothelial cell dysfunction that occurs via decreased endothelial nitric oxide synthase/nitric oxide (eNOS/NO) activity. Aspirin reduces the incidence of hypertensive pregnancy complications. However, the underlying mechanism has not been clearly explained. Here, we found that tumor necrosis factor (TNF)-α, microRNA (miR)-155, and eNOS levels as well as endothelial redox phenotype were differentially regulated in preeclamptic patients, implying the involvement of TNF-α- and redox signal-mediated miR-155 biogenesis and eNOS downregulation in the pathogenesis of preeclampsia. Aspirin prevented the TNF-α-mediated increase in miR-155 biogenesis and decreases in eNOS expression and NO/cGMP production in cultured human umbilical vein endothelial cells (HUVECs). Similar effects of aspirin were also observed in HUVECs treated with H 2 O 2 . The preventive effects of aspirin was associated with the inhibition of nuclear factor-κB (NF-κB)-dependent MIR155HG (miR-155 host gene) expression. Aspirin recovered the TNF-α-mediated decrease in wild-type, but not mutant, eNOS 3'-untranslated region reporter activity, whose effect was blocked by miR-155 mimic. Moreover, aspirin prevented TNF-α-mediated endothelial cell dysfunction associated with impaired vasorelaxation, angiogenesis, and trophoblast invasion, and the preventive effects were blocked by miR-155 mimic or an eNOS inhibitor. Aspirin rescued TNF-α-mediated eNOS downregulation coupled with endothelial dysfunction by inhibiting NF-κB-dependent transcriptional miR-155 biogenesis. Thus, the redox-sensitive NF-κB/miR-155/eNOS axis may be crucial in the pathogenesis of vascular disorders including preeclampsia. Copyright © 2017 Elsevier Inc. All rights reserved.

Zinc regulates iNOS-derived nitric oxide formation in endothelial cells.

PubMed

Cortese-Krott, Miriam M; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D; Suschek, Christoph V

2014-01-01

Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation.

Zinc regulates iNOS-derived nitric oxide formation in endothelial cells

PubMed Central

Cortese-Krott, Miriam M.; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D.; Suschek, Christoph V.

2014-01-01

Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation. PMID:25180171

77 FR 51780 - 36(b)(1) Arms Sales Notification

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2012-08-27

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-42] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 62588 - 36(b)(1) Arms Sales Notification

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2013-10-22

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78 FR 41040 - 36(b)(1) Arms Sales Notification

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2013-07-09

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77 FR 14767 - 36(b)(1) Arms Sales Notification

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2012-03-13

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78 FR 76823 - 36(b)(1) Arms Sales Notification

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2013-12-19

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2012-12-18

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2013-06-18

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76 FR 60455 - 36(b)(1) Arms Sales Notification

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2011-09-29

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77 FR 68738 - 36(b)(1) Arms Sales Notification

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2012-11-16

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78 FR 62592 - 36(b)(1) Arms Sales Notification

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2013-10-22

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77 FR 42709 - 36(b)(1) Arms Sales Notification

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2012-07-20

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2012-07-06

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2012-06-25

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2013-03-08

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2011-09-29

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77 FR 42711 - 36(b)(1) Arms Sales Notification

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2012-07-20

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2013-11-05

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2011-09-29

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2011-09-29

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78 FR 48426 - 36(b)(1) Arms Sales Notification

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2013-08-08

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76 FR 60461 - 36(b)(1) Arms Sales Notification

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2011-09-29

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76 FR 72184 - 36(b)(1) Arms Sales Notification

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2011-11-22

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76 FR 72182 - 36(b)(1) Arms Sales Notification

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2011-11-22

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-40] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 36534 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-18

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-34] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 61673 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-30] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 60469 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-26] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 40701 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-79] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 72684 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-25

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-48] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 42707 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-20

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-35] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 71401 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-30

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-61] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 56181 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-14] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 66340 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-05

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-54] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 68740 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-49] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69922 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-50] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69938 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-44] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 74011 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-24] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69971 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-58] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 74014 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-49] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 37078 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-68] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 37071 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-03] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69931 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-46] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 29212 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-75] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69957 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-38] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69960 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-43] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 37075 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-77] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69947 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-45] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69953 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-57] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69926 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-52] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 18726 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-05

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-08] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD ACTION: Notice SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published...

75 FR 60424 - 36(b)(1) Arms Sales Notifications

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-28 and 10-30] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of two section 36(b)(1) arms sales notifications to...

High School E.C.I.A. Chapter 1, Part B, Institutionalized Facilities Program 1989-90. State Report. OREA Report.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Office of Research, Evaluation, and Assessment.

This report describes and evaluates high school programs funded under Chapter 1, Part B, of the Education Consolidation and Improvement Act (ECIA) and administered by the Institutionalized Facilities Program of the New York City Public Schools in 1989-90. The program is designed to address the educational needs of students in facilities for…

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model.

PubMed

Nunes, Ana Karolina Santana; Rapôso, Catarina; Rocha, Sura Wanessa Santos; Barbosa, Karla Patrícia de Sousa; Luna, Rayana Leal de Almeida; da Cruz-Höfling, Maria Alice; Peixoto, Christina Alves

2015-11-19

Sildenafil (Viagra®) has recently been found to have a neuroprotective effect, which occurs through the inhibition of inflammation and demyelination in the cerebellum. However, the mechanism of action of sildenafil remains unknown. AMPK, the regulatory protein of the lipid and glucose metabolism, plays a protective role by activating the eNOS enzyme. The production of a nanomolar concentration of NO by eNOS has an anti-inflammatory effect through the cGMP signaling pathway and plays an important role in the regulation of the nuclear transcription factor (NFkB), preventing the expression of inflammatory genes. The present study investigated whether AMPK-eNOS-NO-cGMP-IКβα-NFkB is involved in the mechanism of action of sildenafil in a cuprizone-demyelination model. Neuroinflammation and demyelination induced by cuprizone in rodents have been widely used as a model of MS. In the present study, five male C57BL/6 mice (7-10 weeks old) were used. Over a four week period, the groups received: cuprizone (CPZ) 0.2% mixed in feed; CPZ in the diet, combined with the administration of sildenafil (Viagra®, Pfizer, 25mg/kg) orally in drinking water, starting concurrently (sild-T0) or 15 days (sild-T15) after the start of CPZ. Control animals received pure food and water. The cerebella of the mice were dissected and processed for immunohistochemistry, immunofluorescence (frozen), western blotting and dosage of cytokines (Elisa). CPZ induced an increase in the expression of GFAP, IL-1β TNF-α, total NFkB and inactive AMPK, and prompt microglia activation. CPZ also induced a reduction of IKβα. The administration of sildenafil reduced the expression of the pro-inflammatory cytokines IL-1β and TNF-α and increased the expression of the anti-inflammatory cytokine IL-10. In addition, the administration of sildenafil reduced expression of GFAP, NFkB, inactive AMPK and iNOS, and increased IKβα. Interestingly, sildenafil also reduced levels of NGF. In general, the sild-T0 group

Enhancing eNOS activity with simultaneous inhibition of IKKβ restores vascular function in Ins2(Akita+/-) type-1 diabetic mice.

PubMed

Krishnan, Manickam; Janardhanan, Preethi; Roman, Linda; Reddick, Robert L; Natarajan, Mohan; van Haperen, Rien; Habib, Samy L; de Crom, Rini; Mohan, Sumathy

2015-10-01

The balance of nitric oxide (NO) versus superoxide generation has a major role in the initiation and progression of endothelial dysfunction. Under conditions of high glucose, endothelial nitric oxide synthase (eNOS) functions as a chief source of superoxide rather than NO. In order to improve NO bioavailability within the vessel wall in type-1 diabetes, we investigated treatment strategies that improve eNOS phosphorylation and NO-dependent vasorelaxation. We evaluated methods to increase the eNOS activity by (1) feeding Ins2(Akita) spontaneously diabetic (type-1) mice with l-arginine in the presence of sepiapterin, a precursor of tetrahydrobiopterin; (2) preventing eNOS/NO deregulation by the inclusion of inhibitor kappa B kinase beta (IKKβ) inhibitor, salsalate, in the diet regimen in combination with l-arginine and sepiapterin; and (3) independently increasing eNOS expression to improve eNOS activity and associated NO production through generating Ins2(Akita) diabetic mice that overexpress human eNOS predominantly in vascular endothelial cells. Our results clearly demonstrated that diet supplementation with l-arginine, sepiapterin along with salsalate improved phosphorylation of eNOS and enhanced vasorelaxation of thoracic/abdominal aorta in type-1 diabetic mice. More interestingly, despite the overexpression of eNOS, the in-house generated transgenic eNOS-GFP (TgeNOS-GFP)-Ins2(Akita) cross mice showed an unanticipated effect of reduced eNOS phosphorylation and enhanced superoxide production. Our results demonstrate that enhancement of endogenous eNOS activity by nutritional modulation is more beneficial than increasing the endogenous expression of eNOS by gene therapy modalities.

Tetramethylpyrazine attenuates TNF-α-induced iNOS expression in human endothelial cells: Involvement of Syk-mediated activation of PI3K-IKK-IκB signaling pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Zhen; Li, Zhiliang; Chen, Song

2013-08-15

Endothelial cells produce nitric oxide (NO) by activation of constitutive nitric oxide synthase (NOS) and transcription of inducible NO synthase (iNOS). We explored the effect of tetramethylpyrazine (TMP), a compound derived from chuanxiong, on tumor necrosis factor (TNF)-α-induced iNOS in human umbilical vein endothelial cells (HUVECs) and explored the signal pathways involved by using RT-PCR and Western blot. TMP suppressed TNF-α-induced expression of iNOS by inhibiting IκB kinase (IKK) phosphorylation, IκB degradation and nuclear factor κB (NF-κB) nuclear translocation, which were required for NO gene transcription. Exposure to wortmannin abrogated IKK/IκB/NF-κB-mediated iNOS expression, suggesting activation of such a signal pathwaymore » might be phosphoinositide-3-kinase (PI3K) dependent. Spleen tyrosine kinase (Syk) inhibitor piceatannol significantly inhibited NO production. Furthermore, piceatannol obviously suppressed TNF-α-induced IκB phosphorylation and the downstream NF-κB activation, suggesting that Syk is an upstream key regulator in the activation of PI3K/IKK/IκB-mediated signaling. TMP significantly inhibited TNF-α-induced phosphorylation of Syk and PI3K. Our data indicate that TMP might repress iNOS expression, at least in part, through its inhibitory effect of Syk-mediated PI3K phosphorylation in TNF-α-stimulated HUVECs. -- Highlights: •TMP suppressed TNF-α-induced expression of iNOS by inhibiting IKK/IκB/NF-κB pathway. •PI3K inhibitor wortmannin abrogated IKK/IκB/NF-κB-mediated iNOS expression. •Syk inhibitor piceatannol repressed PI3K/IKK/IκB mediated NO production. •Syk is an upstream regulator in the activation of PI3K/IKK/IκB-mediated signaling. •TMP might repress iNOS expression through Syk-mediated PI3K pathway.« less

78 FR 699 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-04

... proposed sale of this system will not alter the basic military balance in the region. The principal... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-02] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 48646 - 36(b)(1) Arms Sales Notifications

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-11

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-27, 10-31 and 10-41] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of three section 36(b)(1) arms sales notifications...

TOP 01-1-011B Vehicle Test Facilities at Aberdeen Test Center and Yuma Test Center

DTIC Science & Technology

2017-12-12

TYPE Final 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Test Operations Procedure (TOP) 01-1-011B Vehicle Test Facilities at Aberdeen... Test Center and Yuma Test Center 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHORS 5d. PROJECT NUMBER 5e... Test Center 400 Colleran Road Aberdeen Proving Ground, MD 21005-5059 U.S. Army Yuma Proving Ground Yuma Test Center 301 C. Street Yuma, AZ

Hemozoin Regulates iNOS Expression by Modulating the Transcription Factor NF-κB in Macrophages.

PubMed

Ranjan, Ravi; Karpurapu, Manjula; Rani, Asha; Chishti, Athar H; Christman, John W

2016-01-01

Hemozoin (Hz) is released from ruptured erythrocytes during malaria infection caused by Plasmodium sp., in addition the malaria infected individuals are prone to bacterial sepsis. The molecular interactions between Hz, bacterial components and macrophages remains poorly investigated. In this report, we investigated the combinatorial immune-modulatory effects of phagocytosed Hz, Interferon gamma (IFNγ) or lipopolysaccharide (LPS) in macrophages. Macrophages were treated with various concentrations of commercial synthetic Hz, and surprisingly it did not result in inducible nitric oxide synthase (iNOS) expression. However, when macrophages were pretreated with Hz and then challenged with IFNγ or LPS, there was a differential impact on iNOS expression. There was an increase in iNOS expression when macrophages were pre-treated with Hz and subsequently treated with IFNγ when compared to IFNγ alone. Whereas iNOS expression was reduced when Hz phagocytosed macrophages were stimulated with LPS compared to LPS alone. Furthermore, there was an increased activation of NF-κB in Hz phagocytosed macrophages that were challenged with IFNγ. The interaction between Hz and macrophages has an impact on iNOS expression.

15 CFR 807.1 - Public Reference Facility.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) BUREAU OF ECONOMIC ANALYSIS, DEPARTMENT OF COMMERCE PUBLIC INFORMATION § 807.1 Public Reference Facility. The Public Reference Facility of the Bureau of Economic Analysis is located in room B7 of the Tower...

15 CFR 807.1 - Public Reference Facility.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) BUREAU OF ECONOMIC ANALYSIS, DEPARTMENT OF COMMERCE PUBLIC INFORMATION § 807.1 Public Reference Facility. The Public Reference Facility of the Bureau of Economic Analysis is located in room B7 of the Tower...

15 CFR 807.1 - Public Reference Facility.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) BUREAU OF ECONOMIC ANALYSIS, DEPARTMENT OF COMMERCE PUBLIC INFORMATION § 807.1 Public Reference Facility. The Public Reference Facility of the Bureau of Economic Analysis is located in room B7 of the Tower...

78 FR 76110 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-58] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... any: Multiple cases date back to 1997; most recent FMS case is GGT-$100M-08Nov11 (vi) Sales Commission...

15 CFR Supplement Nos.1-3 to Part 746 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false [Reserved] Nos.1 Supplement Nos.1-3 to Part 746 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS EMBARGOES AND...

eNOS gene T786C, G894T and 4a4b polymorphisms and male infertility susceptibility: a meta-analysis.

PubMed

Chang, J; Pan, F; Tang, Q; Wu, W; Chen, M; Lu, C; Ding, H; Hu, L; Chen, D; Xia, Y; Wang, X

2017-05-01

The association between polymorphism of eNOS and male infertility in several studies was controversial. To explore a more precise estimation of the association, a meta-analysis of eight case-control studies, including 1,968 cases and 1,539 controls, were selected. The meta-analysis was conducted by calculating the pooled odds ratio (OR) with a 95% confidence interval (95% CI). Overall, the association between T786C and risk of male infertility was obvious (TC vs. TT: OR, 1.20; 95% CI, 1.01-1.42; CC vs. TT: OR, 3.37; 95% CI, 1.65-6.87; TC/CC vs. TT: OR, 1.47; 95% CI, 1.25-1.73; CC vs. OR, 3.18; 95% CI, 1.54-6.56; TC vs. TT: OR, 1.65; 95% CI, 1.27-2.03). However, no overall association was observed between the other two polymorphisms of eNOS (G894T and 4a4b) and male infertility. Stratified analysis showed that significantly strong association between T786C polymorphism and semen quality was present in all three types of male infertility (azoospermia, oligozoospermia and asthenozoospermia). In the subgroup analysis based on ethnicity, both T786C and 4a4b could influence the risk of male infertility in Asian and Caucasian. Further studies of polymorphisms of eNOS with their biological functions are needed to understand the role in the development of male infertility. © 2016 Blackwell Verlag GmbH.

75 FR 75706 - Dresden Nuclear Power Station, Units 2 and 3 and Quad Cities Nuclear Power Station, Unit Nos. 1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-06

...- 2010-0373] Dresden Nuclear Power Station, Units 2 and 3 and Quad Cities Nuclear Power Station, Unit Nos... and DPR-25 for Dresden Nuclear Power Station, Units 2 and 3, respectively, located in Grundy County, Illinois, and to Renewed Facility Operating License Nos. DPR-29 and DPR-30 for Quad Cities Nuclear Power...

NOS1AP is associated with increased severity of PTSD and depression in untreated combat veterans.

PubMed

Lawford, Bruce R; Morris, Charles P; Swagell, Christopher D; Hughes, Ian P; Young, Ross McD; Voisey, Joanne

2013-05-01

Posttraumatic stress disorder (PTSD) and depressive disorder are over represented in combat veterans. Veterans with both disorders have an increased risk of suicide. The nitric oxide synthase 1 adaptor protein (NOS1AP) gene, which modulates stress-evoked N-methyl-d-aspartate (NMDA) activity, was investigated in combat veterans. A comprehensive genetic analysis of NOS1AP and its association with PTSD was investigated in Vietnam combat veterans with PTSD (n=121) and a group of healthy control individuals (n=237). PTSD patients were assessed for symptom severity and level of depression using the Mississippi Scale for Combat-Related PTSD and the Beck Depression Inventory-II (BDI). The G allele of NOS1AP SNP rs386231 was significantly associated with PTSD (p=0.002). Analysis of variance revealed significant differences in BDI-II and Mississippi scores between genotypes for rs386231 with the GG genotype associated with increased severity of depression (p=0.002 F=6.839) and higher Mississippi Scale for Combat-Related PTSD scores (p=0.033). Haplotype analysis revealed that the C/G haplotype (rs451275/rs386231) was significantly associated with PTSD (p=0.001). The sample sizes in our study were not sufficient to detect SNP associations with very small effects. In addition the study was limited by its cross sectional design. This is the first study reporting that a variant of the NOS1AP gene is associated with PTSD. Our data also suggest that a genetic variant in NOS1AP may increase the susceptibility to severe depression in patients with PTSD and increased risk for suicide. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Overview taken from Facility 2 looking east down Avenue E ...

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

Overview taken from Facility 2 looking east down Avenue E (Russell Avenue). Facility 1 is on left, Facility 1G and 1C in center. View facing east - U.S. Naval Base, Pearl Harbor, Administration Annex, Near Russell Avenue (previously Avenue E), between of Facility Nos. 1C & 1E , Pearl City, Honolulu County, HI

Rosmanol potently inhibits lipopolysaccharide-induced iNOS and COX-2 expression through downregulating MAPK, NF-kappaB, STAT3 and C/EBP signaling pathways.

PubMed

Lai, Ching-Shu; Lee, Jong Hun; Ho, Chi-Tang; Liu, Cheng Bin; Wang, Ju-Ming; Wang, Ying-Jan; Pan, Min-Hsiung

2009-11-25

Rosmanol is a natural polyphenol from the herb rosemary (Rosmarinus officinalis L.) with high antioxidant activity. In this study, we investigated the inhibitory effects of rosmanol on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells induced by lipopolysaccharide (LPS). Rosmanol markedly inhibited LPS-stimulated iNOS and COX-2 protein and gene expression, as well as the downstream products, NO and PGE2. Treatment with rosmanol also reduced translocation of the nuclear factor-kappaB (NF-kappaB) subunits by prevention of the degradation and phosphorylation of inhibitor kappaB (IkappaB). Western blot analysis showed that rosmanol significantly inhibited translocation and phosphorylation of NF-kappaB, signal transducer and activator of transcription-3 (STAT3), and the protein expression of C/EBPbeta and C/EBPdelta. We also found that rosmanol suppressed LPS-induced phosphorylation of ERK1/2, p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Our results demonstrate that rosmanol downregulates inflammatory iNOS and COX-2 gene expression by inhibiting the activation of NF-kappaB and STAT3 through interfering with the activation of PI3K/Akt and MAPK signaling. Taken together, rosmanol might contribute to the potent anti-inflammatory effect of rosemary and may have potential to be developed into an effective anti-inflammatory agent.

District 75/Citywide E.C.I.A. Chapter 1, Part B, Institutionalized Facilities Program. Summer 1989. OREA Report.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Office of Research, Evaluation, and Assessment.

This report evaluates a program funded under Chapter 1, Part B, of the Education Consolidation and Improvement Act in New York (New York). The New York City Division of Special Education administers the Institutionalized Facilities Program to provide instruction to neglected and delinquent children and adolescents residing in group homes and…

Retinoic acid-induced nNOS expression depends on a novel PI3K/Akt/DAX1 pathway in human TGW-nu-I neuroblastoma cells.

PubMed

Nagl, Florian; Schönhofer, Katrin; Seidler, Barbara; Mages, Jörg; Allescher, Hans-Dieter; Schmid, Roland M; Schneider, Günter; Saur, Dieter

2009-11-01

Neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. NO regulates multiple processes like neuronal development, plasticity, and differentiation and is a mediator of neurotoxicity. The nNOS gene is highly complex with 12 alternative first exons, exon 1a-1l, transcribed from distinct promoters, leading to nNOS variants with different 5'-untranslated regions. Transcriptional control of the nNOS gene is not understood in detail. To investigate regulation of nNOS gene expression by retinoic acid (RA), we used the human neuroblastoma cell line TGW-nu-I as a model system. We show that RA induces nNOS transcription in a protein synthesis-dependent fashion. We identify the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and the atypical orphan nuclear receptor DAX1 (NR0B1) as critical mediators involved in RA-induced nNOS gene transcription. RA treatment increases DAX1 expression via PI3K/Akt signaling. Upregulation of DAX1 expression in turn induces nNOS transcription in response to RA. These results identify nNOS as a target gene of a novel RA/PI3K/Akt/DAX1-dependent pathway in human neuroblastoma cells and stress the functional importance of the transcriptional regulator DAX1 for nNOS gene expression in response to RA treatment.

PGC-1α dictates endothelial function through regulation of eNOS expression

PubMed Central

Craige, Siobhan M.; Kröller-Schön, Swenja; Li, Chunying; Kant, Shashi; Cai, Shenghe; Chen, Kai; Contractor, Mayur M.; Pei, Yongmei; Schulz, Eberhard; Keaney, John F.

2016-01-01

Endothelial dysfunction is a characteristic of many vascular related diseases such as hypertension. Peroxisome proliferator activated receptor gamma, coactivator 1α (PGC-1α) is a unique stress sensor that largely acts to promote adaptive responses. Therefore, we sought to define the role of endothelial PGC-1α in vascular function using mice with endothelial specific loss of function (PGC-1α EC KO) and endothelial specific gain of function (PGC-1α EC TG). Here we report that endothelial PGC-1α is suppressed in angiotensin-II (ATII)-induced hypertension. Deletion of endothelial PGC-1α sensitized mice to endothelial dysfunction and hypertension in response to ATII, whereas PGC-1α EC TG mice were protected. Mechanistically, PGC-1α promotes eNOS expression and activity, which is necessary for protection from ATII-induced dysfunction as mice either treated with an eNOS inhibitor (LNAME) or lacking eNOS were no longer responsive to transgenic endothelial PGC-1α expression. Finally, we determined that the orphan nuclear receptor, estrogen related receptor α (ERRα) is required to coordinate the PGC-1α -induced eNOS expression. In conclusion, endothelial PGC-1α expression protects from vascular dysfunction by promoting NO• bioactivity through ERRα induced expression of eNOS. PMID:27910955

NASA Plum Brook's B-2 Test Facility: Thermal Vacuum and Propellant Test Facility

NASA Technical Reports Server (NTRS)

Kudlac, Maureen T.; Weaver, Harold F.; Cmar, Mark D.

2012-01-01

The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) Plum Brook Station (PBS) Spacecraft Propulsion Research Facility, commonly referred to as B-2, is NASA's third largest thermal vacuum facility. It is the largest designed to store and transfer large quantities of liquid hydrogen and liquid oxygen, and is perfectly suited to support developmental testing of upper stage chemical propulsion systems as well as fully integrated stages. The facility is also capable of providing thermal-vacuum simulation services to support testing of large lightweight structures, Cryogenic Fluid Management (CFM) systems, electric propulsion test programs, and other In-Space propulsion programs. A recently completed integrated system test demonstrated the refurbished thermal vacuum capabilities of the facility. The test used the modernized data acquisition and control system to monitor the facility. The heat sink provided a uniform temperature environment of approximately 77 K. The modernized infrared lamp array produced a nominal heat flux of 1.4 kW/sq m. With the lamp array and heat sink operating simultaneously, the thermal systems produced a heat flux pattern simulating radiation to space on one surface and solar exposure on the other surface.

D-limonene suppresses doxorubicin-induced oxidative stress and inflammation via repression of COX-2, iNOS, and NFκB in kidneys of Wistar rats.

PubMed

Rehman, Muneeb U; Tahir, Mir; Khan, Abdul Quaiyoom; Khan, Rehan; Oday-O-Hamiza; Lateef, Abdul; Hassan, Syed Kazim; Rashid, Sumaya; Ali, Nemat; Zeeshan, Mirza; Sultana, Sarwat

2014-04-01

D-limonene is a naturally occurring monoterpene and has been found to posses numerous therapeutic properties. In this study, we used D-limonene as a protective agent against the nephrotoxic effects of anticancer drug doxorubicin (Dox). Rats were given D-limonene at doses of 5% and 10% mixed with diet for 20 consecutive days. Dox was give at the dose of 20 mg/kg body weight intraperitoneally. The protective effects of D-limonene on Dox-induced oxidative stress and inflammation were investigated by assaying oxidative stress biomarkers, lipid peroxidation, serum toxicity markers, proinflammatory cytokines, and expression of nuclear factor kappa B (NFκB), cyclo-oxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and Nitrite levels. Administration of Dox (20 mg/kg body weight) in rats enhanced renal lipid peroxidation; depleted glutathione content and anti-oxidant enzymes; elevated levels of kidney toxicity markers viz. kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine; enhanced expression of NFκB, COX-2, and iNOS and nitric oxide. Treatment with D-limonene prevented oxidative stress by restoring the levels of antioxidant enzymes, further both doses of 5% and 10% showed significant decrease in inflammatory response. Both the doses of D-limonene significantly decreased the levels of kidney toxicity markers KIM-1, BUN, and creatinine. D-limonene also effectively decreased the Dox induced overexpression of NF-κB, COX-2, and iNOS and nitric oxide. Data from the present study indicate the protective role of D-limonene against Dox-induced renal damage.

Protein Phosphotyrosine Phosphatase 1B (PTP1B) in Calpain-dependent Feedback Regulation of Vascular Endothelial Growth Factor Receptor (VEGFR2) in Endothelial Cells: IMPLICATIONS IN VEGF-DEPENDENT ANGIOGENESIS AND DIABETIC WOUND HEALING.

PubMed

Zhang, Yixuan; Li, Qiang; Youn, Ji Youn; Cai, Hua

2017-01-13

The VEGF/VEGFR2/Akt/eNOS/NO pathway is essential to VEGF-induced angiogenesis. We have previously discovered a novel role of calpain in mediating VEGF-induced PI3K/AMPK/Akt/eNOS activation through Ezrin. Here, we sought to identify possible feedback regulation of VEGFR2 by calpain via its substrate protein phosphotyrosine phosphatase 1B (PTP1B), and the relevance of this pathway to VEGF-induced angiogenesis, especially in diabetic wound healing. Overexpression of PTP1B inhibited VEGF-induced VEGFR2 and Akt phosphorylation in bovine aortic endothelial cells, while PTP1B siRNA increased both, implicating negative regulation of VEGFR2 by PTP1B. Calpain inhibitor ALLN induced VEGFR2 activation, which can be completely blocked by PTP1B overexpression. Calpain activation induced by overexpression or Ca/A23187 resulted in PTP1B cleavage, which can be blocked by ALLN. Moreover, calpain activation inhibited VEGF-induced VEGFR2 phosphorylation, which can be restored by PTP1B siRNA. These data implicate calpain/PTP1B negative feedback regulation of VEGFR2, in addition to the primary signaling pathway of VEGF/VEGFR2/calpain/PI3K/AMPK/Akt/eNOS. We next examined a potential role of PTP1B in VEGF-induced angiogenesis. Endothelial cells transfected with PTP1B siRNA showed faster wound closure in response to VEGF. Aortic discs isolated from PTP1B siRNA-transfected mice also had augmented endothelial outgrowth. Importantly, PTP1B inhibition and/or calpain overexpression significantly accelerated wound healing in STZ-induced diabetic mice. In conclusion, our data for the first time demonstrate a calpain/PTP1B/VEGFR2 negative feedback loop in the regulation of VEGF-induced angiogenesis. Modulation of local PTP1B and/or calpain activities may prove beneficial in the treatment of impaired wound healing in diabetes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

B-1 and B-3 Test Stands at NASA’s Plum Brook Station

NASA Image and Video Library

1966-09-21

Operation of the High Energy Rocket Engine Research Facility (B-1), left, and Nuclear Rocket Dynamics and Control Facility (B-3) at the National Aeronautics and Space Administration’s (NASA) Plum Brook Station in Sandusky, Ohio. The test stands were constructed in the early 1960s to test full-scale liquid hydrogen fuel systems in simulated altitude conditions. Over the next decade each stand was used for two major series of liquid hydrogen rocket tests: the Nuclear Engine for Rocket Vehicle Application (NERVA) and the Centaur second-stage rocket program. The different components of these rocket engines could be studied under flight conditions and adjusted without having to fire the engine. Once the preliminary studies were complete, the entire engine could be fired in larger facilities. The test stands were vertical towers with cryogenic fuel and steam ejector systems. B-1 was 135 feet tall, and B-3 was 210 feet tall. Each test stand had several levels, a test section, and ground floor shop areas. The test stands relied on an array of support buildings to conduct their tests, including a control building, steam exhaust system, and fuel storage and pumping facilities. A large steam-powered altitude exhaust system reduced the pressure at the exhaust nozzle exit of each test stand. This allowed B-1 and B-3 to test turbopump performance in conditions that matched the altitudes of space.

Poly(ADP-ribose) polymerase-1 and its cleavage products differentially modulate cellular protection through NF-kB-dependent signaling

PubMed Central

Castri, Paola; Lee, Yang-ja; Ponzio, Todd; Maric, Dragan; Spatz, Maria; Bembry, Joliet; Hallenbeck, John

2014-01-01

Poly(ADP-ribose) polymerase-1 (PARP-1) and its cleavage products regulate cell viability and NF-kB activity when expressed in neurons. PARP-1 cleavage generates a 24kDa (PARP-124) and an 89kDa fragment (PARP-189). Compared to WT (PARP-1WT), the expression of an uncleavable PARP-1 (PARP-1UNCL) or of PARP-124 conferred protection from oxygen/glucose deprivation (OGD) or OGD/restoration of oxygen and glucose (ROG) damage in vitro, whereas expression of PARP-189 was cytotoxic. Viability experiments were performed in SH-SY5Y, a human neuroblastoma cell line, as well as in rat primary cortical neurons. Following OGD, the higher viability in the presence of PARP-1UNCL or PARP-124 was not accompanied with decreased formation of poly(ADP-riboses) or higher NAD levels. PARP-1 is a known cofactor for NF-kB, hence we investigated whether PARP-1 cleavage influences the inflammatory response. All PARP-1 constructs mimicked PARP-1WT in regards to induction of NF-kB translocation into the nucleus and its increased activation during ischemic challenge. However, expression of PARP-189 construct induced significantly higher NF-kB activity than PARP-1WT; and the same was true for NF-kB-dependent iNOS promoter binding activity. At a protein level, PARP-1UNCL and PARP-124 decreased iNOS (and lower levels of iNOS transcript) and COX-2, and increased Bcl-xL. The increased levels of NF-kB and iNOS transcriptional activities, seen with cytotoxic PARP-189, were accompanied by higher protein expression of COX-2 and iNOS (and higher levels of iNOS transcript) and lower protein expression of Bcl-xL. Taken together, these findings suggest that PARP-1 cleavage products may regulate cellular viability and inflammatory responses in opposing ways during in vitro models of “ischemia”. PMID:24333653

Genetic association of NOS1 exon18, NOS1 exon29, ABCB1 1236C/T, and ABCB1 3435C/T polymorphisms with the risk of Parkinson's disease

PubMed Central

Huang, Hongbin; Peng, Cong; Liu, Yong; Liu, Xu; Chen, Qicong; Huang, Zunnan

2016-01-01

Abstract Background: Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. Previous publications have investigated the association of NOS1 and ABCB1 polymorphisms with PD risk. However, those studies have provided some contradictory results. Methods: Literature searches were performed using PubMed, Embase, PDgene, China National Knowledge Infrastructure database, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to evaluate the strength of association. Results: The analysis results indicated that NOS1 exon18 polymorphism was associated with developing PD in 4 genetic models (allelic: OR = 1.25, 95%CI 1.09–1.44, P = 0.001; homozygous: OR = 1.79, 95%CI 1.32–2.45, P < 0.001; recessive: OR = 1.70, 95%CI 1.26–2.28, P < 0.001; dominant: OR = 1.22, 95%CI 1.02–1.46, P = 0.03), whereas exon29 polymorphism was not correlated to PD susceptibility. In addition, ABCB1 1236C/T polymorphism was related to PD in the recessive (OR = 0.80, 95%CI 0.66–0.97, P = 0.025) and overdominant (OR = 1.21, 95%CI 1.03–1.43, P = 0.02) models, which might indicate the opposite effects of 2 minor variants of this locus on Parkinson's disease. However, this associated result was not robust enough to withstand statistically significant correction. On the other hand, no association was found between ABCB1 3435C/T polymorphism and the predisposition to PD in 5 genetic models, and such an absence of relationship was further confirmed by subgroup analysis in Caucasians and Asians. Whether the polymorphisms of these 4 loci were linked to PD or not, our study provided some interesting findings that differ from the previous results with regard to their genetic susceptibility. Conclusion: The NOS1 exon18 and ABCB1 1236C/T variants might play a role in the risk of Parkinson's disease, whereas NOS1 exon29 and ABCB1 3435C/T polymorphisms might not contribute to PD susceptibility. PMID

Characterization of Short Range DNA Looping in Endotoxin-mediated Transcription of the Murine Inducible Nitric-oxide Synthase (iNOS) Gene*

PubMed Central

Guo, Hongtao; Mi, Zhiyong; Kuo, Paul C.

2008-01-01

The local structural properties and spatial conformations of chromosomes are intimately associated with gene expression. The spatial associations of critical genomic elements in inducible nitric-oxide synthase (iNOS) transcription have not been previously examined. In this regard, the murine iNOS promoter contains 2 NF-κB binding sites (nt –86 and nt –972) that are essential for maximal transactivation of iNOS by LPS. Although AP-1 is commonly listed as an essential transcription factor for LPS-mediated iNOS transactivation, the relationship between AP-1 and NF-κB in this setting is not well studied. In this study using a model of LPS-stimulated ANA-1 murine macrophages, we demonstrate that short range DNA looping occurs at the iNOS promoter. This looping requires the presence of AP-1, c-Jun, NF-κB p65, and p300-associated acetyltransferase activity. The distal AP-1 binding site interacts via p300 with the proximal NF-κB binding site to create this DNA loop to participate in iNOS transcription. Other geographically distant AP-1 and NF-κB sites are certainly occupied, but selected sites are critical for iNOS transcription and the formation of the c-Jun, p65, and p300 transcriptional complex. In this “simplified” model of murine iNOS promoter, numerous transcription factors recognize and bind to various response elements, but these locales do not equally contribute to iNOS gene transcription. PMID:18596035

iNOS expression in CD4+ T cells limits Treg induction by repressing TGFβ1: combined iNOS inhibition and Treg depletion unmask endogenous antitumor immunity.

PubMed

Jayaraman, Padmini; Alfarano, Matthew G; Svider, Peter F; Parikh, Falguni; Lu, Geming; Kidwai, Sarah; Xiong, Huabao; Sikora, Andrew G

2014-12-15

Expression of inducible nitric oxide synthase (iNOS) in different cellular compartments may have divergent effects on immune function. We used a syngeneic tumor model to functionally characterize the role of iNOS in regulation of CD4(+)FOXP3(+) regulatory T cells (Treg), and optimize the beneficial effects of iNOS inhibition on antitumor immunity. Wild-type (WT) or iNOS knockout mice bearing established MT-RET-1 melanoma were treated with the small-molecule iNOS inhibitor L-NIL and/or cyclophosphamide alone or in combination. The effect of iNOS inhibition or knockout on induction of Treg from mouse and human CD4(+) T cells in ex vivo culture was determined in parallel in the presence or absence of TGFβ1-depleting antibodies, and TGFβ1 levels were assessed by ELISA. Whereas intratumoral myeloid-derived suppressor cells (MDSC) were suppressed by iNOS inhibition or knockout, systemic and intratumoral FOXP3(+) Treg levels increased in tumor-bearing mice. iNOS inhibition or knockout similarly enhanced induction of Treg from activated cultured mouse splenocytes or purified human or mouse CD4(+) T cells in a TGFβ1-dependent manner. Although either iNOS inhibition or Treg depletion with low-dose cyclophosphamide alone had little effect on growth of established MT-RET1 melanoma, combination treatment potently inhibited MDSC and Treg, boosted tumor-infiltrating CD8(+) T-cell levels, and arrested tumor growth in an immune-dependent fashion. iNOS expression in CD4(+) T cells suppresses Treg induction by inhibiting TGFβ1 production. Our data suggest that iNOS expression has divergent effects on induction of myeloid and lymphoid-derived regulatory populations, and strongly support development of combinatorial treatment approaches that target these populations simultaneously. ©2014 American Association for Cancer Research.

The protein inhibitor of nNOS (PIN/DLC1/LC8) binding does not inhibit the NADPH-dependent heme reduction in nNOS, a key step in NO synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parhad, Swapnil S.; Jaiswal, Deepa; TIFR Centre for Interdisciplinary Sciences, 21 Brundavan Colony, Narsingi, Hyderabad 500075

The neuronal nitric oxide synthase (nNOS) is an essential enzyme involved in the synthesis of nitric oxide (NO), a potent neurotransmitter. Although previous studies have indicated that the dynein light chain 1 (DLC1) binding to nNOS could inhibit the NO synthesis, the claim is challenged by contradicting reports. Thus, the mechanism of nNOS regulation remained unclear. nNOS has a heme-bearing, Cytochrome P450 core, and the functional enzyme is a dimer. The electron flow from NADPH to Flavin, and finally to the heme of the paired nNOS subunit within a dimer, is facilitated upon calmodulin (CaM) binding. Here, we show thatmore » DLC1 binding to nNOS-CaM complex does not affect the electron transport from the reductase to the oxygenase domain. Therefore, it cannot inhibit the rate of NADPH-dependent heme reduction in nNOS, which results in L-Arginine oxidation. Also, the NO release activity does not decrease with increasing DLC1 concentration in the reaction mix, which further confirmed that DLC1 does not inhibit nNOS activity. These findings suggest that the DLC1 binding may have other implications for the nNOS function in the cell. - Highlights: • The effect of interaction of nNOS with DLC1 has been debatable with contradicting reports in literature. • Purified DLC1 has no effect on electron transport between reductase and oxygenase domain of purified nNOS-CaM. • The NO release activity of nNOS was not altered by DLC1, supporting that DLC1 does not inhibit the enzyme. • These findings suggest that the DLC1 binding may have other implications for the nNOS function in the cell.« less

Pterostilbene is equally potent as resveratrol in inhibiting 12-O-tetradecanoylphorbol-13-acetate activated NFkappaB, AP-1, COX-2, and iNOS in mouse epidermis.

PubMed

Cichocki, Michal; Paluszczak, Jaroslaw; Szaefer, Hanna; Piechowiak, Adriana; Rimando, Agnes M; Baer-Dubowska, Wanda

2008-06-01

Resveratrol, a phytoalexin present in grapes, has been reported to inhibit multistage mouse skin carcinogenesis. Recent studies showed that topically applied resveratrol significantly inhibited cyclooxygenase-2 (COX-2) expression and activation of nuclear factor-kappaB (NF-kappaB) induced by tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis. The aim of the present study was to further explore the effect of resveratrol on TPA-induced signaling pathways in mouse epidermis and to compare with its dimethylether, pterostilbene. Resveratrol and pterostilbene significantly reduced activator protein 1 (AP-1) and NF-kappaB activation. In the case of AP-1, the binding of c-Jun subunit was particularly affected, while only slight effect on c-Fos binding to TPA-responsive element (AP-1 binding consensus sequence) (TRE) site was observed. Both stilbenes inhibited the activation of NF-kappaB by blocking the translocation of p65 to the nucleus and increasing the retention of IkappaBa in the cytosol. The latter might be related to decreased activity of IkappaB kinase and/or proteasome 20S. Reduced activation of transcription factors decreased the expression and activity of COX-2 and inducible nitric oxide synthase (iNOS). In most assays, pterostilbene was either equally or significantly more potent than resveratrol. Pterostilbene might show higher biological activity due to its possible better bioavailability, since substitution of hydroxy with methoxy group increases lipophilicity.

Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus.

PubMed

Sutton, Amy K; Pei, Hongjuan; Burnett, Korri H; Myers, Martin G; Rhodes, Christopher J; Olson, David P

2014-11-12

The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of Sim1-expressing cell types that comprise a major autonomic output nucleus and play critical roles in the control of food intake and energy homeostasis. The roles of specific PVH neuronal subtypes in energy balance have yet to be defined, however. The PVH contains nitric oxide synthase-1 (Nos1)-expressing (Nos1(PVH)) neurons of unknown function; these represent a subset of the larger population of Sim1-expressing PVH (Sim1(PVH)) neurons. To determine the role of Nos1(PVH) neurons in energy balance, we used Cre-dependent viral vectors to both map their efferent projections and test their functional output in mice. Here we show that Nos1(PVH) neurons project to hindbrain and spinal cord regions important for food intake and energy expenditure control. Moreover, pharmacogenetic activation of Nos1(PVH) neurons suppresses feeding to a similar extent as Sim1(PVH) neurons, and increases energy expenditure and activity. Furthermore, we found that oxytocin-expressing PVH neurons (OXT(PVH)) are a subset of Nos1(PVH) neurons. OXT(PVH) cells project to preganglionic, sympathetic neurons in the thoracic spinal cord and increase energy expenditure upon activation, though not to the same extent as Nos1(PVH) neurons; their activation fails to alter feeding, however. Thus, Nos1(PVH) neurons promote negative energy balance through changes in feeding and energy expenditure, whereas OXT(PVH) neurons regulate energy expenditure alone, suggesting a crucial role for non-OXT Nos1(PVH) neurons in feeding regulation. Copyright © 2014 the authors 0270-6474/14/3415306-13$15.00/0.

The Akt1-eNOS axis illustrates the specificity of kinase-substrate relationships in vivo.

PubMed

Schleicher, Michael; Yu, Jun; Murata, Takahisa; Derakhshan, Berhad; Atochin, Dimitriy; Qian, Li; Kashiwagi, Satoshi; Di Lorenzo, Annarita; Harrison, Kenneth D; Huang, Paul L; Sessa, William C

2009-08-04

Akt1 is critical for many in vivo functions; however, the cell-specific substrates responsible remain to be defined. Here, we examine the importance of endothelial nitric oxide synthase (eNOS) as an Akt1 substrate by generating Akt1-deficient mice (Akt1(-/-) mice) carrying knock-in mutations (serine to aspartate or serine to alanine substitutions) of the critical Akt1 phosphorylation site on eNOS (serine 1176) that render the enzyme "constitutively active" or "less active." The eNOS mutations did not influence several phenotypes in Akt1(-/-) mice; however, the defective postnatal angiogenesis characteristic of Akt1(-/-) mice was rescued by crossing the Akt1(-/-) mice with mice carrying the constitutively active form of eNOS, but not by crossing with mice carrying the less active eNOS mutant. This genetic rescue resulted in the stabilization of hypoxia-inducible factor 1alpha (HIF-1alpha) and increased production of HIF-1alpha-responsive genes in vivo and in vitro. Thus, Akt1 regulates angiogenesis largely through phosphorylation of eNOS and NO-dependent signaling.

Exposure to diesel exhaust up-regulates iNOS expression in ApoE knockout mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai Ni; James Hogg Research Centre, Providence Heart and Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC; Kido, Takashi

Traffic related particulate matter air pollution is a risk factor for cardiovascular events; however, the biological mechanisms are unclear. We hypothesize that diesel exhaust (DE) inhalation induces up-regulation of inducible nitric oxide synthase (iNOS), which is known to contribute to vascular dysfunction, progression of atherosclerosis and ultimately cardiovascular morbidity and mortality. Methods: ApoE knockout mice (30-week) were exposed to DE (at 200 {mu}g/m{sup 3} of particulate matter) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week). iNOS expression in the blood vessels and heart was evaluated by immunohistochemistry and western blotting analysis. To examine iNOS activity, thoracic aortae weremore » mounted in a wire myograph, and vasoconstriction stimulated by phenylephrine (PE) was measured with and without the presence of the specific inhibitor for iNOS (1400 W). NF-{kappa}B (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-{kappa}B (p65) was determined by real-time PCR. Results: DE exposure significantly enhanced iNOS expression in the thoracic aorta (4-fold) and heart (1.5 fold). DE exposure significantly attenuated PE-stimulated vasoconstriction by {approx} 20%, which was partly reversed by 1400 W. The mRNA expression of iNOS and NF-{kappa}B was significantly augmented after DE exposure. NF-{kappa}B activity was enhanced 2-fold after DE inhalation, and the augmented NF-{kappa}B activity was positively correlated with iNOS expression (R{sup 2} = 0.5998). Conclusions: We show that exposure to DE increases iNOS expression and activity possibly via NF-{kappa}B-mediated pathway. We suspect that DE exposure-caused up-regulation of iNOS contributes to vascular dysfunction and atherogenesis, which could ultimately lead to urban air pollution-associated cardiovascular morbidity and mortality. - Highlights: > Exposed ApoE knockout mice (30-week) to diesel exhaust (DE) for 7 weeks. > Examine iNOS expression and activity in

Gigantol isolated from the whole plants of Cymbidium goeringii inhibits the LPS-induced iNOS and COX-2 expression via NF-kappaB inactivation in RAW 264.7 macrophages cells.

PubMed

Won, Jong-Heon; Kim, Ji-Yeon; Yun, Kyung-Jin; Lee, Jin-Hee; Back, Nam-In; Chung, Hae-Gon; Chung, Sun A; Jeong, Tae-Sook; Choi, Myung-Sook; Lee, Kyung-Tae

2006-10-01

During our efforts to find bioactive natural products with anti-inflammatory activity, we isolated gigantol from the whole plants of Cymbidium goeringii (Orchidaceae) by activity-guided chromatographic fractionation. Gigantol was found to have potent inhibitory effects on LPS-induced nitric oxide (NO) and prostaglandin E (2) (PGE (2)) production in RAW 264.7 cells. Consistent with these findings, gigantol suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in RAW 264.7 cells in a concentration-dependent manner. Our data also indicate that gigantol is a potent inhibitor of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) release and influenced the mRNA expression levels of these cytokines in a dose-dependent manner. Furthermore, a reporter gene assay for nuclear factor kappa B (NF-kappaB) and an electromobility shift assay (EMSA) demonstrated that gigantol effectively inhibited the activation of NF-kappaB, which is necessary for the expression of iNOS, COX-2, TNF-alpha, IL-1beta and IL-6. Thus, our studies suggest that gigantol inhibits LPS-induced iNOS and COX-2 expression by blocking NF- kappaB activation.

Angiotensin II modulates interleukin-1{beta}-induced inflammatory gene expression in vascular smooth muscle cells via interfering with ERK-NF-{kappa}B crosstalk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Shanqin; Zhi, Hui; Hou, Xiuyun

2011-07-08

Highlights: {yields} We examine how angiotensin II modulates ERK-NF-{kappa}B crosstalk and gene expression. {yields} Angiotensin II suppresses IL-1{beta}-induced prolonged ERK and NF-{kappa}B activation. {yields} ERK-RSK1 signaling is required for IL-1{beta}-induced prolonged NF-{kappa}B activation. {yields} Angiotensin II modulates NF-{kappa}B responsive genes via regulating ERK-NF-{kappa}B crosstalk. {yields} ERK-NF-{kappa}B crosstalk is a novel mechanism regulating inflammatory gene expression. -- Abstract: Angiotensin II is implicated in cardiovascular diseases, which is associated with a role in increasing vascular inflammation. The present study investigated how angiotensin II modulates vascular inflammatory signaling and expression of inducible nitric oxide synthase (iNOS) and vascular cell adhesion molecule (VCAM)-1. Inmore » cultured rat aortic vascular smooth muscle cells (VSMCs), angiotensin II suppressed interleukin-1{beta}-induced prolonged phosphorylation of extracellular signal-regulated kinase (ERK) and ribosomal S6 kinase (RSK)-1, and nuclear translocation of nuclear factor (NF)-{kappa}B, leading to decreased iNOS but enhanced VCAM-1 expression, associated with an up-regulation of mitogen-activated protein kinase phosphatase-1 expression. Knock-down of RSK1 selectively down regulated interleukin-1{beta}-induced iNOS expression without influencing VCAM-1 expression. In vivo experiments showed that interleukin-1{beta}, iNOS, and VCAM-1 expression were detectable in the aortic arches of both wild-type and apolipoprotein E-deficient (ApoE{sup -/-}) mice. VCAM-1 and iNOS expression were higher in ApoE{sup -/-} than in wild type mouse aortic arches. Angiotensin II infusion (3.2 mg/kg/day, for 6 days, via subcutaneous osmotic pump) in ApoE{sup -/-} mice enhanced endothelial and adventitial VCAM-1 and iNOS expression, but reduced medial smooth muscle iNOS expression associated with reduced phosphorylation of ERK and RSK-1. These results indicate that

The Akt1-eNOS Axis Illustrates the Specificity of Kinase-Substrate Relationships in Vivo

PubMed Central

Schleicher, Michael; Yu, Jun; Murata, Takahisa; Derakhshan, Berhad; Atochin, Dimitriy; Qian, Li; Kashiwagi, Satoshi; Lorenzo, Annarita Di; Harrison, Kenneth D.; Huang, Paul L.; Sessa, William C.

2016-01-01

Akt1 is critical for many in vivo functions; however, the cell-specific substrates responsible remain to be defined. Here, we examine the importance of endothelial nitric oxide synthase (eNOS) as an Akt1 substrate by generating Akt1-deficient mice (Akt1−/− mice) carrying knock-in mutations (serine to aspartate or serine to alanine substitutions) of the critical Akt1 phosphorylation site on eNOS (serine 1176) that render the enzyme “constitutively active” or “less active.” The eNOS mutations did not influence several phenotypes in Akt1−/− mice; however, the defective postnatal angiogenesis characteristic of Akt1−/− mice was rescued by crossing the Akt1−/− mice with mice carrying the constitutively active form of eNOS, but not by crossing with mice carrying the less active eNOS mutant. This genetic rescue resulted in the stabilization of hypoxia-inducible factor 1α (HIF-1α) and increased production of HIF-1α–responsive genes in vivo and in vitro. Thus, Akt1 regulates angiogenesis largely through phosphorylation of eNOS and NO-dependent signaling. PMID:19654415

SOD1 suppresses maternal hyperglycemia-increased iNOS expression and consequent nitrosative stress in diabetic embryopathy

PubMed Central

Weng, Hongbo; Li, Xuezheng; Reece, E. Albert; Yang, Peixin

2012-01-01

Objectives Hyperglycemia induces oxidative stress and increases inducible nitric oxide synthase (iNOS) expression. We hypothesized that oxidative stress is responsible for hyperglycemia-induced iNOS expression. Study Design iNOS-luciferase activities, nitrosylated protein, lipidperoxidation markers 4-HNE and MDA were determined in PYS-2 cells exposed to 5 mM glucose or high glucose (25 mM) with or without SOD1 (copper zinc superoxide dismutase 1) treatment. Levels of iNOS protein and mRNA, nitrosylated protein, and cleaved caspase-3 and -8 were assessed in wild-type embryos and SOD1 overexpressing embryos from non-diabetic and diabetic dams. Results SOD1 treatment diminished high glucose-induced oxidative stress, as evidenced by 4-HNE and MDA reductions, and it blocked high glucose-increased iNOS expression, iNOS-luciferase activities, and nitrosylated protein. in vivo SOD1 overexpression suppressed hyperglycemia-increased iNOS expression and nitrosylated protein, and it blocked caspase-3 and -8 cleavage. Conclusions We conclude that oxidative stress induces iNOS expression, nitrosative stress, and apoptosis in diabetic embryopathy. PMID:22425406

SOD1 suppresses maternal hyperglycemia-increased iNOS expression and consequent nitrosative stress in diabetic embryopathy.

PubMed

Weng, Hongbo; Li, Xuezheng; Reece, E Albert; Yang, Peixin

2012-05-01

Hyperglycemia induces oxidative stress and increases inducible nitric oxide synthase (iNOS) expression. We hypothesized that oxidative stress is responsible for hyperglycemia-induced iNOS expression. iNOS-luciferase activities, nitrosylated protein, and lipid peroxidation markers 4-hydroxynonenal and malondialdehyde were determined in parietal yolk sac-2 cells exposed to 5 mmol/L glucose or high glucose (25 mmol/L) with or without copper zinc superoxide dismutase 1 (SOD1) treatment. Levels of iNOS protein and messenger RNA, nitrosylated protein, and cleaved caspase-3 and -8 were assessed in wild-type embryos and SOD1-overexpressing embryos from nondiabetic and diabetic dams. SOD1 treatment diminished high glucose-induced oxidative stress, as evidenced by 4-hydroxynonenal and malondialdehyde reductions, and it blocked high glucose-increased iNOS expression, iNOS-luciferase activities, and nitrosylated protein. In vivo SOD1 overexpression suppressed hyperglycemia-increased iNOS expression and nitrosylated protein, and it blocked caspase-3 and -8 cleavage. We conclude that oxidative stress induces iNOS expression, nitrosative stress, and apoptosis in diabetic embryopathy. Copyright © 2012 Mosby, Inc. All rights reserved.

Space Propulsion Research Facility (B-2): An Innovative, Multi-Purpose Test Facility

NASA Technical Reports Server (NTRS)

Hill, Gerald M.; Weaver, Harold F.; Kudlac, Maureen T.; Maloney, Christian T.; Evans, Richard K.

2011-01-01

The Space Propulsion Research Facility, commonly referred to as B-2, is designed to hot fire rocket engines or upper stage launch vehicles with up to 890,000 N force (200,000 lb force), after environmental conditioning of the test article in simulated thermal vacuum space environment. As NASA s third largest thermal vacuum facility, and the largest designed to store and transfer large quantities of propellant, it is uniquely suited to support developmental testing associated with large lightweight structures and Cryogenic Fluid Management (CFM) systems, as well as non-traditional propulsion test programs such as Electric and In-Space propulsion. B-2 has undergone refurbishment of key subsystems to support the NASA s future test needs, including data acquisition and controls, vacuum, and propellant systems. This paper details the modernization efforts at B-2 to support the Nation s thermal vacuum/propellant test capabilities, the unique design considerations implemented for efficient operations and maintenance, and ultimately to reduce test costs.

Inhibition by antioxidants of nitric oxide synthase expression in murine macrophages: role of nuclear factor kappa B and interferon regulatory factor 1.

PubMed Central

Hecker, M.; Preiss, C.; Klemm, P.; Busse, R.

1996-01-01

1. In view of the potential deleterious effects of high amounts of nitric oxide (NO) produced by the inducible isoform of NO synthase (iNOS) in inflammation, the prevention of the expression of this enzyme represents an important therapeutic goal. In cytokine-stimulated cells, activation of nuclear factor kappa B (NF-kappa B) is crucial for the increase in iNOS gene expression. Since NF-kappa B activation appears to involve a redox-sensitive step, we have investigated whether three structurally unrelated antioxidants, 5,7-dihydroxyflavone (chrysin), 3,4-dichloroisocoumarin (DCI) and N-acetyl 5-hydroxytryptamine (N-acetylserotonin, NAS), affect iNOS expression in cultured RAW 264.7 monocyte/macrophages stimulated with bacterial lipopolysaccharide (LPS, 140 ng ml-1) and interferon-gamma (IFN gamma, 5 u ml-1). 2. During a 6 h incubation period neither LPS nor IFN gamma alone exerted a significant effect but when combined, caused a prominent increase in nitrite formation, iNOS mRNA and protein abundance. Co-incubation with chrysin (50 microM), DCI (50 microM) or NAS (1 mM) markedly attenuated this increase in iNOS gene expression. 3. DCI, but not chrysin or NAS, prevented the activation of NF-kappa B in cells exposed to LPS plus IFN gamma for 30 min. In contrast, all three antioxidants significantly blunted the DNA-binding activity of interferon regulatory factor 1 (IRF-1), which mediates the synergistic effect of IFN gamma on iNOS gene expression in cells treated for 2 h with LPS plus IFN gamma. 4. DCI thus appears to inhibit iNOS gene expression at the transcriptional level by preventing the activation of both NF-kappa B and IRF-1. The inhibitory effect of DCI on NF-kappa B activation, however, does not seem to be related to its antioxidative properties, since DCI, unlike chrysin or NAS, is a potent serine protease inhibitor which stabilizes the inactive NF-kappa B complex by protecting the inhibitory I kappa B-alpha subunit from proteolytic degradation. 5. The

Lectin purified from Musca domestica pupa up-regulates NO and iNOS production via TLR4/NF-κB signaling pathway in macrophages.

PubMed

Cao, Xiaohong; Zhou, Minghui; Wang, Chunling; Hou, Lihua; Zeng, Bin

2011-04-01

The present study reported that nitric oxide (NO) was up-regulated by the induction of lectin purified from Musca domestica pupa (MPL) in macrophages without cytotoxicity. The mRNA expression and protein secretion of inducible nitric oxide synthase (iNOS) were strongly induced by MPL treatments. Subsequent investigation revealed that the nuclear factor-κB (NF-κB) inhibitory κB (IκB) in endochylema was inhibited and NF-κB translocated into the nucleus after MPL treatment. Meanwhile, the IKKβ was strongly induced and the production of the toll-like receptor 4 (TLR4) was significantly up-regulated. Moreover, MPL increased NO production via inducing the expression of iNOS through the activation of NF-κB, which suggested that MPL probably acted as an activating agent of the NF-κB activation. Copyright © 2010 Elsevier B.V. All rights reserved.

48 CFR 52.247-30 - F.o.b. Origin, Contractor's Facility.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false F.o.b. Origin, Contractor... Clauses 52.247-30 F.o.b. Origin, Contractor's Facility. As prescribed in 47.303-2(c), insert the following clause in solicitations and contracts when the delivery term is f.o.b. origin, contractor's facility: F.o...

Imbalance of caveolin-1 and eNOS expression in the pulmonary vasculature of experimental diaphragmatic hernia.

PubMed

Hofmann, Alejandro; Gosemann, Jan-Hendrik; Takahashi, Toshiaki; Friedmacher, Florian; Duess, Johannes W; Puri, Prem

2014-08-01

Caveolin-1 (Cav-1) exerts major regulatory functions on intracellular signaling pathways originating at the plasma membrane. Cav-1 is a key regulator in adverse lung remodeling and the development of pulmonary hypertension (PH) regulating vasomotor tone through its ability to reduce nitric oxide (NO) production. This low-output endothelial NO synthase (eNOS) derived NO maintains normal pulmonary vascular homeostasis. Cav-1 deficiency leads to increased bioavailability of NO, which has been linked to increased nitrosative stress. Inhibition of eNOS reduced oxidant production and reversed PH, supporting the concept that Cav-1 regulation of eNOS activity is crucial to endothelial homeostasis in lungs. We designed this study to investigate the hypothesis that expression of Cav-1 is downregulated while eNOS expression is upregulated by the pulmonary endothelium in the nitrofen-induced congenital diaphragmatic hernia (CDH). Pregnant rats were exposed to nitrofen or vehicle on day 9.5 (D9.5). Fetuses were sacrificed on D21 and divided into nitrofen and control groups. Quantitative real-time polymerase chain reaction, Western blotting, and confocal immunofluorescence were performed to determine pulmonary gene expression levels and protein expression of Cav-1 and eNOS. Pulmonary Cav-1 gene expression levels were significantly decreased, while eNOS gene expression was significantly increased in nitrofen-induced CDH(+). Western blotting and confocal microscopy revealed decreased pulmonary Cav-1 protein expression, while eNOS protein expression was increased in CDH(+) compared to controls. The striking evidence of markedly decreased gene and protein expression of Cav-1 with concurrently increased eNOS gene and protein expression in the pulmonary vasculature suggests that activation of eNOS secondary to Cav-1 deficiency may play an important role in the pathogenesis of PH in the nitrofen-induced CDH. © 2014 Wiley Periodicals, Inc.

40 CFR Appendix B to Subpart I of... - Allowance for Facilities Planning and Design

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Allowance for Facilities Planning and Design B Appendix B to Subpart I of Part 35 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works Pt. 35, Subpt. I, App. B Appendix B to...

26 CFR 1.141-8 - $15 million limitation for output facilities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 2 2011-04-01 2011-04-01 false $15 million limitation for output facilities. 1....141-8 $15 million limitation for output facilities. (a) In general—(1) General rule. Section 141(b)(4... million output limitation, the benefits and burdens test of § 1.141-7 applies, except that “$15 million...

26 CFR 1.141-8 - $15 million limitation for output facilities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false $15 million limitation for output facilities. 1....141-8 $15 million limitation for output facilities. (a) In general—(1) General rule. Section 141(b)(4... million output limitation, the benefits and burdens test of § 1.141-7 applies, except that “$15 million...

Preinduction of heat shock protein 70 protects mice against post-infection irritable bowel syndrome via NF-κB and NOS/NO signaling pathways.

PubMed

Zhou, Xuchun; Dong, Liwei; Yang, Bo; He, Zhoutao; Chen, Yiyao; Deng, Taozhi; Huang, Baili; Lan, Cheng

2015-12-01

This study aimed to investigate the protective effects of preinduction of heat shock protein 70 (HSP70) on Trichinella spiralis infection-induced post-infectious irritable bowel syndrome (PI-IBS) in mice. Trichinella spiralis infection significantly reduced HSP70 abundance, ileal villus height and crypt depth, expression of tight junctions, serum lysine and arginine concentrations, and ileal SCL7A6 and SCL7A7 mRNA levels, induced inflammatory response, and activated NF-κB signaling pathway. Meanwhile, the heat treatment upregulated HSP70 expression, and then reversed intestinal dysfunction and inflammatory response. Preinduction of HSP70 enhanced serum arginine and intestinal SCL7A7 expression and inhibited NF-κB activation compared with PI-IBS model. Treatment with pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) and N-nitro-L-arginine methyl ester hydrochloride (L-NAME, a nitric oxide synthase inhibitor, NOS) further demonstrated that preinduction of HSP70 might inhibit NF-κB and activated NOS/nitric oxide (NO) signaling pathways. In conclusion, preinduction of HSP70 by heat treatment may confer beneficial effects on Trichinella spiralis infection-induced PI-IBS in mice, and the protective effect of HSP70 may be associated with inhibition of NF-κB and stimulation of NOS/NO signaling pathways.

Modulation of Lipopolysaccharide Stimulated Nuclear Factor kappa B Mediated iNOS/NO Production by Bromelain in Rat Primary Microglial Cells.

PubMed

Abbasi Habashi, Soraya; Sabouni, Farzaneh; Moghimi, Ali; Ansari Majd, Saeed

2016-01-01

Microglial cells act as the sentinel of the central nervous system .They are involved in neuroprotection but are highly implicated in neurodegeneration of the aging brain. When over-activated, microglia release pro-inflammatory factors, such as nitric oxide (NO) and cytokines, which are critical in eliciting neuroinflammatory responses associated with neurodegenerative diseases. This study examined whether bromelain, the pineapple-derived extract, may exert an anti-inflammatory effect in primary microglia and may be neuroprotective by regulating microglial activation. Following the isolation of neonatal rat primary microglial cells, the activation profile of microglia was investigated by studying the effects of bromelain (5, 10, 20, and 30 µg/ml) on the levels of NO, inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) in microglia treated with lipopolysaccharide (LPS) (1 µg/ml). Data were analyzed using Student's t-test. P values less than 0.05 were considered to be statistically significant, compared with the LPS-treated group without bromelain. Results showed that pretreatment of rat primary microglia with bromelain, decreased the production of NO induced by LPS (1 µg/ml) treatment in a dose-dependent manner. Bromelain (30 µg/ml) also significantly reduced the expression of iNOS at mRNA level and NF-κB at protein level. Moreover, the study of mitochondrial activity in microglia indicated that bromelain had no cytotoxicity at any of the applied doses, suggesting that the anti-inflammatory effects of bromelain are not due to cell death. Bromelain can be of potential use as an agent for alleviation of symptoms in neurodegenerative diseases.

The role of nNOS and PGC-1α in skeletal muscle cells.

PubMed

Baldelli, Sara; Lettieri Barbato, Daniele; Tatulli, Giuseppe; Aquilano, Katia; Ciriolo, Maria Rosa

2014-11-15

Neuronal nitric oxide synthase (nNOS) and peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α) are two fundamental factors involved in the regulation of skeletal muscle cell metabolism. nNOS exists as several alternatively spliced variants, each having a specific pattern of subcellular localisation. Nitric oxide (NO) functions as a second messenger in signal transduction pathways that lead to the expression of metabolic genes involved in oxidative metabolism, vasodilatation and skeletal muscle contraction. PGC-1α is a transcriptional coactivator and represents a master regulator of mitochondrial biogenesis by promoting the transcription of mitochondrial genes. PGC-1α can be induced during physical exercise, and it plays a key role in coordinating the oxidation of intracellular fatty acids with mitochondrial remodelling. Several lines of evidence demonstrate that NO could act as a key regulator of PGC-1α expression; however, the link between nNOS and PGC-1α in skeletal muscle remains only poorly understood. In this Commentary, we review important metabolic pathways that are governed by nNOS and PGC-1α, and aim to highlight how they might intersect and cooperatively regulate skeletal muscle mitochondrial and lipid energetic metabolism and contraction. © 2014. Published by The Company of Biologists Ltd.

10. "TEST STANDS NOS. 11, 13, & 15; CONCRETE STRUCTURAL ...

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

10. "TEST STANDS NOS. 1-1, 1-3, & 1-5; CONCRETE STRUCTURAL SECTIONS AND DETAILS." Specifications No. OC12-50-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/14, Rev. B. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04353 Eng. 177, Rev. B; Date: 21 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans

PubMed Central

Velez, Digna Rosa; Hulme, William F.; Myers, Jamie L.; Weinberg, J. Brice; Levesque, Marc C.; Stryjewski, Martin E.; Abbate, Eduardo; Estevan, Rosa; Patillo, Sara G.; Gilbert, John R; Hamilton, Carol D.; Scott, William K.

2010-01-01

Tuberculosis (TB) has substantial mortality worldwide with 5-10% of those exposed progressing to active TB disease. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS) molecule plays an important role in immune response to TB. A mixed case-control association study of individuals with TB, relatives, or close contact controls was performed in 726 individuals (279 case and 166 control African-Americans; 198 case and 123 control Caucasians). Thirty-nine single nucleotide polymorphisms (SNPs) were selected from the NOS2A gene for single SNP, haplotype, and multilocus interaction analyses with other typed candidate genes using generalized estimating equations. In African-Americans, ten NOS2A SNPs were associated with TB. The strongest associations were observed at rs2274894 (odds ratio (OR) = 1.84, 95% confidence interval (CI) [1.23-2.77], p = 0.003) and rs7215373 (OR 1.67, 95% CI [1.17-2.37], p = 0.004), both of which passed a false discovery rate (FDR) correction for multiple comparisons (q*=0.20). The strongest gene-gene interactions were observed between NOS2A rs2248814 and IFNGR1 rs1327474 (p = 0.0004) and NOS2A rs944722 and IFNGR1 rs1327474 (p = 0.0006). Three other SNPs in NOS2A interacted with TLR4 rs5030729 and five other NOS2A SNPs interacted with IFNGR1 rs1327474. No significant associations were observed in Caucasians. These results suggest that NOS2A variants may contribute to TB susceptibility, particularly in individuals of African descent, and may act synergistically with SNPs in TLR4 and IFNGR1. PMID:19575238

42 CFR 52b.7 - How is the grantee obligated to use the facility?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false How is the grantee obligated to use the facility? 52b.7 Section 52b.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.7 How is the grantee obligated to use the...

42 CFR 52b.7 - How is the grantee obligated to use the facility?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false How is the grantee obligated to use the facility? 52b.7 Section 52b.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.7 How is the grantee obligated to use the...

42 CFR 52b.7 - How is the grantee obligated to use the facility?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false How is the grantee obligated to use the facility? 52b.7 Section 52b.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.7 How is the grantee obligated to use the...

42 CFR 52b.7 - How is the grantee obligated to use the facility?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false How is the grantee obligated to use the facility? 52b.7 Section 52b.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.7 How is the grantee obligated to use the...

ET-1 Stimulates Superoxide Production by eNOS Following Exposure of Vascular Endothelial Cells to Endotoxin.

PubMed

Gopalakrishna, Deepak; Pennington, Samantha; Karaa, Amel; Clemens, Mark G

2016-07-01

It has been shown that microcirculation is hypersensitized to endothelin1 (ET-1) following endotoxin (lipopolysaccharide [LPS]) treatment leading to an increased vasopressor response. This may be related in part to decreased activation of endothelial nitric oxide synthase (eNOS) by ET-1. eNOS can also be uncoupled to produce superoxide (O2). This aberrant eNOS activity could further contribute to the hyperconstriction and injury caused by ET-1 following LPS. We therefore tested whether LPS affects ROS production by vascular endothelial cells and whether and how this effect is altered by ET-1. Human umbilical vein endothelial cells (HUVEC) or human microvascular endothelial cells (HMEC) were subjected to a 6-h treatment with LPS (250 ng/mL) or LPS and sepiapterin (100 μM) followed by a 30-min treatment with 100 μM L-Iminoethyl Ornithine (L-NIO) an irreversible eNOS inhibitor and 30-min treatment with ET-1 (10 nM). Conversion of [H]L-arginine to [H]L-citrulline was used to measure eNOS activity. Superoxide dismutase (SOD) inhibitable reduction of Cytochrome-C, dihydro carboxy fluorescein (DCF), and Mitosox was used to estimate ROS. LT-SDS PAGE was used to assess the degree of monomerization of the eNOS homodimer. Stimulation of HUVECs with ET-1 significantly increased NO synthesis by 1.4-fold (P < 0.05). ET-1 stimulation of LPS-treated HUVECs failed to increase NO production. Western blot for eNOS protein showed no change in eNOS protein levels. LPS alone resulted in an insignificant increase in ROS production as measured by cytochrome C that was increased 4.6-fold by ET-1 stimulation (P < 0.05). L-NIO significantly decreased ET-1-induced ROS production (P < 0.05). Sepiapterin significantly decreased ROS production in both; unstimulated and ET-1-stimulated LPS-treated groups, but did not restore NO production. DCF experiments confirmed intracellular ROS while Mitosox suggested a non-mitochondrial source. ET-1 treatment following a chronic LPS stress

7 CFR 15b.18 - Existing facilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Accessibility § 15b.18 Existing facilities. (a) Accessibility. A recipient shall operate each assisted program or activity so that when each part is viewed in... results in making its program or activity accessible to qualified handicapped persons. A recipient is not...

36. ISLAND PLANT: Nos. 1 AND 2 TWENTYSIX INCH HORIZONTAL ...

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

36. ISLAND PLANT: Nos. 1 AND 2 TWENTY-SIX INCH HORIZONTAL SAMSON TURBINES - American Falls Water, Power & Light Company, Island Power Plant, Snake River, below American Falls Dam, American Falls, Power County, ID

75 FR 13600 - Virginia Electric and Power Company, North Anna Power Station, Unit Nos. 1 and 2, Surry Power...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

...- 2010-0116] Virginia Electric and Power Company, North Anna Power Station, Unit Nos. 1 and 2, Surry Power Station, Unit Nos. 1 and 2; Environmental Assessment and Finding of No Significant Impact The U.S... Anna Power Station, Unit Nos. 1 and 2 (NAPS), and Surry Power Station, Unit Nos. 1 and 2 (SPS), located...

Modulation of Lipopolysaccharide Stimulated Nuclear Factor kappa B Mediated iNOS/NO Production by Bromelain in Rat Primary Microglial Cells

PubMed Central

Abbasi Habashi, Soraya; Sabouni, Farzaneh; Moghimi, Ali; Ansari Majd, Saeed

2016-01-01

Background: Microglial cells act as the sentinel of the central nervous system .They are involved in neuroprotection but are highly implicated in neurodegeneration of the aging brain. When over-activated, microglia release pro-inflammatory factors, such as nitric oxide (NO) and cytokines, which are critical in eliciting neuroinflammatory responses associated with neurodegenerative diseases. This study examined whether bromelain, the pineapple-derived extract, may exert an anti-inflammatory effect in primary microglia and may be neuroprotective by regulating microglial activation. Methods: Following the isolation of neonatal rat primary microglial cells, the activation profile of microglia was investigated by studying the effects of bromelain (5, 10, 20, and 30 µg/ml) on the levels of NO, inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) in microglia treated with lipopolysaccharide (LPS) (1 µg/ml). Data were analyzed using Student's t-test. P values less than 0.05 were considered to be statistically significant, compared with the LPS-treated group without bromelain. Results: Results showed that pretreatment of rat primary microglia with bromelain, decreased the production of NO induced by LPS (1 µg/ml) treatment in a dose-dependent manner. Bromelain (30 µg/ml) also significantly reduced the expression of iNOS at mRNA level and NF-κB at protein level. Moreover, the study of mitochondrial activity in microglia indicated that bromelain had no cytotoxicity at any of the applied doses, suggesting that the anti-inflammatory effects of bromelain are not due to cell death. Conclusion: Bromelain can be of potential use as an agent for alleviation of symptoms in neurodegenerative diseases. PMID:26459398

5. POWERHOUSE, PELTONFRANCIS TURBINES (GENERATORS) UNITS NOS. 1 AND 2 ...

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

5. POWERHOUSE, PELTON-FRANCIS TURBINES (GENERATORS) UNITS NOS. 1 AND 2 WITH REGULATOR PANEL AT LEFT AND GATE VALVE IN CENTER FOREGROUND - Yosemite Hydroelectric Power Plant, Highways 120 & 140, Yosemite Village, Mariposa County, CA

Relationship between soil type and N₂O reductase genotype (nosZ) of indigenous soybean bradyrhizobia: nosZ-minus populations are dominant in Andosols.

PubMed

Shiina, Yoko; Itakura, Manabu; Choi, Hyunseok; Saeki, Yuichi; Hayatsu, Masahito; Minamisawa, Kiwamu

2014-01-01

Bradyrhizobium japonicum strains that have the nosZ gene, which encodes N2O reductase, are able to mitigate N2O emissions from soils (15). To examine the distribution of nosZ genotypes among Japanese indigenous soybean bradyrhizobia, we isolated bradyrhizobia from the root nodules of soybean plants inoculated with 32 different soils and analyzed their nosZ and nodC genotypes. The 1556 resultant isolates were classified into the nosZ+/nodC+ genotype (855 isolates) and nosZ-/nodC+ genotype (701 isolates). The 11 soil samples in which nosZ- isolates significantly dominated (P < 0.05; the χ(2) test) were all Andosols (a volcanic ash soil prevalent in agricultural fields in Japan), whereas the 17 soil samples in which nosZ+ isolates significantly dominated were mainly alluvial soils (non-volcanic ash soils). This result was supported by a principal component analysis of environmental factors: the dominance of the nosZ- genotype was positively correlated with total N, total C, and the phosphate absorption coefficient in the soils, which are soil properties typical of Andosols. Internal transcribed spacer sequencing of representative isolates showed that the nosZ+ and nosZ- isolates of B. japonicum fell mainly into the USDA110 (BJ1) and USDA6 (BJ2) groups, respectively. These results demonstrated that the group lacking nosZ was dominant in Andosols, which can be a target soil type for an N2O mitigation strategy in soybean fields. We herein discussed how the nosZ genotypes of soybean bradyrhizobia depended on soil types in terms of N2O respiration selection and genomic determinants for soil adaptation.

109(b) State Training Center Facility Assessment, Program Evaluation, and Guide Development. Final Report.

ERIC Educational Resources Information Center

Miklas, Michael P., Jr.

Section 109(b) of the 1972 Federal Water Pollution Control Act Amendments authorized funding for the construction of statewide water treatment training facilities. Described in this report is work conducted by Southwest Research Institute (SwRI) to: (1) aid in developing updated 109(b) Guidance Documents; (2) characterize and evaluate existing…

NOS1 ex1f-VNTR polymorphism influences prefrontal brain oxygenation during a working memory task.

PubMed

Kopf, Juliane; Schecklmann, Martin; Hahn, Tim; Dresler, Thomas; Dieler, Alica C; Herrmann, Martin J; Fallgatter, Andreas J; Reif, Andreas

2011-08-15

Nitric oxide (NO) synthase produces NO, which serves as first and second messenger in neurons, where the protein is encoded by the NOS1 gene. A functional variable number of tandem repeats (VNTR) polymorphism in the promoter region of the alternative first exon 1f of NOS1 is associated with various functions of human behavior, for example increased impulsivity, while another, non-functional variant was linked to decreased verbal working memory and a heightened risk for schizophrenia. We therefore investigated the influence of NOS1 ex 1f-VNTR on working memory function as reflected by both behavioral measures and prefrontal oxygenation. We hypothesized that homozygous short allele carriers exhibit altered brain oxygenation in task-related areas, namely the dorsolateral and ventrolateral prefrontal cortex and the parietal cortex. To this end, 56 healthy subjects were stratified into a homozygous long allele group and a homozygous short allele group comparable for age, sex and intelligence. All subjects completed a letter n-back task (one-, two-, and three-back), while concentration changes of oxygenated (O(2)Hb) hemoglobin in the prefrontal cortex were measured with functional near-infrared spectroscopy (fNIRS). We found load-associated O(2)Hb increases in the prefrontal and parts of the parietal cortex. Significant load-associated oxygenation differences between the two genotype groups could be shown for the dorsolateral prefrontal cortex and the parietal cortex. Specifically, short allele carriers showed a significantly larger increase in oxygenation in all three n-back tasks. This suggests a potential compensatory mechanism, with task-related brain regions being more active in short allele carriers to compensate for reduced NOS1 expression. Copyright © 2011 Elsevier Inc. All rights reserved.

MGE-derived nNOS+ interneurons promote fear acquisition in nNOS-/- mice.

PubMed

Zhang, Lin; Yuan, Hong-Jin; Cao, Bo; Kong, Cheng-Cheng; Yuan, Fang; Li, Jun; Ni, Huan-Yu; Wu, Hai-Yin; Chang, Lei; Liu, Yan; Luo, Chun-Xia

2017-12-02

Neuronal nitric oxide synthase (nNOS) 1 , mainly responsible for NO release in central nervous system (CNS) 2 , plays a significant role in multiple physiological functions. However, the function of nNOS + interneurons in fear learning has not been much explored. Here we focused on the medial ganglionic eminences (MGE) 3 -derived nNOS + interneurons in fear learning. To determine the origin of nNOS + interneurons, we cultured neurons in vitro from MGE, cortex, lateral ganglionic eminence (LGE) 4 , caudal ganglionic eminences (CGE) 5 and preoptic area (POA) 6 . The results showed that MGE contained the most abundant precursors of nNOS + interneurons. Moreover, donor cells from E12.5 embryos demonstrated the highest positive rate of nNOS + interneurons compared with other embryonic periods (E11.5, E12, E13, E13.5 and E14). Additionally, these cells from E12.5 embryos showed long axonal and abundant dendritic arbors after 10 days culture, indicating the capability to disperse and integrate in host neural circuits after transplantation. To investigate the role of MGE-derived nNOS + interneurons in fear learning, donor MGE cells were transplanted into dentate gyrus (DG) 7 of nNOS knock-out (nNOS -/- ) or wild-type mice. Results showed that the transplantation of MGE cells promoted the acquisition of nNOS -/- but not the wild-type mice, suggesting the importance of nNOS + neurons in fear acquisition. Moreover, we transplanted MGE cells from nNOS -/- mice or wild-type mice into DG of the nNOS -/- mice and found that only MGE cells from wild-type mice but not the nNOS -/- mice rescued the deficit in acquisition of the nNOS -/- mice, further confirming the positive role of nNOS + neurons in fear learning. Copyright © 2017 Elsevier Inc. All rights reserved.

37. ISLAND PLANT: Nos. 1 AND 2 TWENTYSIX INCH SPECIAL ...

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

37. ISLAND PLANT: Nos. 1 AND 2 TWENTY-SIX INCH SPECIAL HORIZONTAL SAMSON TURBINE (RIVITED CASE) - American Falls Water, Power & Light Company, Island Power Plant, Snake River, below American Falls Dam, American Falls, Power County, ID

A noninhibitory mutant of the caveolin-1 scaffolding domain enhances eNOS-derived NO synthesis and vasodilation in mice

PubMed Central

Bernatchez, Pascal; Sharma, Arpeeta; Bauer, Philip M.; Marin, Ethan; Sessa, William C.

2011-01-01

Aberrant regulation of eNOS and associated NO release are directly linked with various vascular diseases. Caveolin-1 (Cav-1), the main coat protein of caveolae, is highly expressed in endothelial cells. Its scaffolding domain serves as an endogenous negative regulator of eNOS function. Structure-function analysis of Cav-1 has shown that phenylalanine 92 (F92) is critical for the inhibitory actions of Cav-1 toward eNOS. Herein, we show that F92A–Cav-1 and a mutant cell–permeable scaffolding domain peptide called Cavnoxin can increase basal NO release in eNOS-expressing cells. Cavnoxin reduced vascular tone ex vivo and lowered blood pressure in normal mice. In contrast, similar experiments performed with eNOS- or Cav-1–deficient mice showed that the vasodilatory effect of Cavnoxin is abolished in the absence of these gene products, which indicates a high level of eNOS/Cav-1 specificity. Mechanistically, biochemical assays indicated that noninhibitory F92A–Cav-1 and Cavnoxin specifically disrupted the inhibitory actions of endogenous Cav-1 toward eNOS and thereby enhanced basal NO release. Collectively, these data raise the possibility of studying the inhibitory influence of Cav-1 on eNOS without interfering with the other actions of endogenous Cav-1. They also suggest a therapeutic application for regulating the eNOS/Cav-1 interaction in diseases characterized by decreased NO release. PMID:21804187

Relationship Between Soil Type and N2O Reductase Genotype (nosZ) of Indigenous Soybean Bradyrhizobia: nosZ-minus Populations are Dominant in Andosols

PubMed Central

Shiina, Yoko; Itakura, Manabu; Choi, Hyunseok; Saeki, Yuichi; Hayatsu, Masahito; Minamisawa, Kiwamu

2014-01-01

Bradyrhizobium japonicum strains that have the nosZ gene, which encodes N2O reductase, are able to mitigate N2O emissions from soils (15). To examine the distribution of nosZ genotypes among Japanese indigenous soybean bradyrhizobia, we isolated bradyrhizobia from the root nodules of soybean plants inoculated with 32 different soils and analyzed their nosZ and nodC genotypes. The 1556 resultant isolates were classified into the nosZ+/nodC+ genotype (855 isolates) and nosZ−/nodC+ genotype (701 isolates). The 11 soil samples in which nosZ− isolates significantly dominated (P < 0.05; the χ2 test) were all Andosols (a volcanic ash soil prevalent in agricultural fields in Japan), whereas the 17 soil samples in which nosZ+ isolates significantly dominated were mainly alluvial soils (non-volcanic ash soils). This result was supported by a principal component analysis of environmental factors: the dominance of the nosZ− genotype was positively correlated with total N, total C, and the phosphate absorption coefficient in the soils, which are soil properties typical of Andosols. Internal transcribed spacer sequencing of representative isolates showed that the nosZ+ and nosZ− isolates of B. japonicum fell mainly into the USDA110 (BJ1) and USDA6 (BJ2) groups, respectively. These results demonstrated that the group lacking nosZ was dominant in Andosols, which can be a target soil type for an N2O mitigation strategy in soybean fields. We herein discussed how the nosZ genotypes of soybean bradyrhizobia depended on soil types in terms of N2O respiration selection and genomic determinants for soil adaptation. PMID:25476067

Centaur Rocket in Space Propulsion Research Facility (B-2)

NASA Image and Video Library

1969-07-21

A Centaur second-stage rocket in the Space Propulsion Research Facility, better known as B‒2, operating at NASA’s Plum Brook Station in Sandusky, Ohio. Centaur was designed to be used with an Atlas booster to send the Surveyor spacecraft to the moon in the mid-1960s. After those missions, the rocket was modified to launch a series of astronomical observation satellites into orbit and send space probes to other planets. Researchers conducted a series of systems tests at the Plum Brook test stands to improve the Centaur fuel pumping system. Follow up full-scale tests in the B-2 facility led to the eventual removal of the boost pumps from the design. This reduced the system’s complexity and significantly reduced the cost of a Centaur rocket. The Centaur tests were the first use of the new B-2 facility. B‒2 was the world's only high altitude test facility capable of full-scale rocket engine and launch vehicle system level tests. It was created to test rocket propulsion systems with up to 100,000 pounds of thrust in a simulated space environment. The facility has the unique ability to maintain a vacuum at the rocket’s nozzle while the engine is firing. The rocket fires into a 120-foot deep spray chamber which cools the exhaust before it is ejected outside the facility. B‒2 simulated space using giant diffusion pumps to reduce chamber pressure 10-6 torr, nitrogen-filled cold walls create cryogenic temperatures, and quartz lamps replicate the radiation of the sun.

10 CFR 140.13b - Amount of liability insurance required for uranium enrichment facilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... enrichment facilities. 140.13b Section 140.13b Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FINANCIAL... required for uranium enrichment facilities. Each holder of a license issued under Parts 40 or 70 of this chapter for a uranium enrichment facility that involves the use of source material or special nuclear...

Grb-2–associated binder 1 (Gab1) regulates postnatal ischemic and VEGF-induced angiogenesis through the protein kinase A–endothelial NOS pathway

PubMed Central

Xiong, Yan; Huo, Yingqing; Han, Jingyan; Yang, Xiao; Zhang, Rongli; Zhu, De-Sheng; Klein-Heßling, Stefan; Zhang, Xiaoyu; Han, Xiaofan; Li, Yanli; Shen, Bin; He, Yulong; Shibuya, Masabumi; Feng, Gen-Sheng; Luo, Jincai

2011-01-01

The intracellular signaling mechanisms underlying postnatal angiogenesis are incompletely understood. Herein we show that Grb-2–associated binder 1 (Gab1) plays a critical role in ischemic and VEGF-induced angiogenesis. Endothelium-specific Gab1 KO (EGKO) mice displayed impaired angiogenesis in the ischemic hindlimb despite normal induction of VEGF expression. Matrigel plugs with VEGF implanted in EGKO mice induced fewer capillaries than those in control mice. The vessels and endothelial cells (ECs) derived from EGKO mice were defective in vascular sprouting and tube formation induced by VEGF. Biochemical analyses revealed a substantial reduction of endothelial NOS (eNOS) activation in Gab1-deficient vessels and ECs following VEGF stimulation. Interestingly, the phosphorylation of Akt, an enzyme known to promote VEGF-induced eNOS activation, was increased in Gab1-deficient vessels and ECs whereas protein kinase A (PKA) activity was significantly decreased. Introduction of an active form of PKA rescued VEGF-induced eNOS activation and tube formation in EGKO ECs. Reexpression of WT or mutant Gab1 molecules in EGKO ECs revealed requirement of Gab1/Shp2 association for the activation of PKA and eNOS. Taken together, these results identify Gab1 as a critical upstream signaling component in VEGF-induced eNOS activation and tube formation, which is dependent on PKA. Of note, this pathway is conserved in primary human ECs for VEGF-induced eNOS activation and tube formation, suggesting considerable potential in treatment of human ischemic diseases. PMID:21282639

Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum.

PubMed

Di Girolamo, G; Farina, M; Riberio, M L; Ogando, D; Aisemberg, J; de los Santos, A R; Martí, M L; Franchi, A M

2003-07-01

1. The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins. 2. Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions such as Parkinson and Alzheimer disease, and Huntington's chorea. 3. In the present study, the in vivo effect of three NSAIDs (lysine clonixinate (LC), indomethacine (INDO) and meloxicam (MELO)) on NO production and nitric oxide synthase expression in rat cerebellar slices was analysed. Rats were treated with (a) saline, (b) lipopolysaccharide (LPS) (5 mg kg(-1), i.p.), (c) saline in combination with different doses of NSAIDs and (d) LPS in combination with different doses of NSAIDs and then killed 6 h after treatment. 4. NO synthesis, evaluated by Bred and Snyder technique, was increased by LPS. This augmentation was inhibited by coadministration of the three NSAIDs assayed. None of the NSAIDs tested was able to modify control NO synthesis. 5. Expression of iNOS and neural NOS (nNOS) was detected by Western blotting in control and LPS-treated rats. LC and INDO, but not MELO, were able to inhibit the expression of these enzymes. 6. Therefore, reduction of iNOS and nNOS levels in cerebellum may explain, in part, the anti-inflammatory effect of these NSAIDs and may also have importance in the prevention of NO-mediated neuronal injury.

Health facility challenges to the provision of Option B+ in western Kenya: a qualitative study

PubMed Central

Akama, Eliud; Bukusi, Elizabeth A; Musoke, Pamela; Nalwa, Wafula Z; Odeny, Thomas A; Onono, Maricianah; Spangler, Sydney A; Turan, Janet M; Wanga, Iris; Abuogi, Lisa L

2017-01-01

Current WHO guidelines recommend lifelong antiretroviral therapy (ART) for all HIV-positive individuals, including pregnant and breastfeeding women (Option B+) in settings with generalized HIV epidemics. While Option B+ is scaled-up in Kenya, insufficient adherence and retention to care could undermine the expected positive impact of Option B+. To explore challenges to the provision of Option B+ at the health facility level, we conducted forty individual gender-matched in-depth interviews with HIV-positive pregnant/postpartum women and their male partners, and four focus groups with thirty health care providers at four health facilities in western Kenya between September-November 2014. Transcripts were coded with the Dedoose software using a coding framework based on the literature, topics from interview guides, and emerging themes from transcripts. Excerpts from broad codes were then fine-coded using an inductive approach. Three major themes emerged: 1) Option B+ specific challenges (same-day initiation into treatment, health care providers unconvinced of the benefits of Option B+, insufficient training); 2) facility resource constraints (staff and drug shortages, long queues, space limitations); and 3) lack of client-friendly services (scolding of patients, inconvenient operating hours, lack of integration of services, administrative requirements). This study highlights important challenges at the health facility level related to Option B+ rollout in western Kenya. Addressing these specific challenges may increase linkage, retention and adherence to life-long ART treatment for pregnant HIV-positive women in Kenya, contribute towards elimination of mother-to-child HIV transmission, and improve maternal and child outcomes. PMID:28207061

Health facility challenges to the provision of Option B+ in western Kenya: a qualitative study.

PubMed

Helova, Anna; Akama, Eliud; Bukusi, Elizabeth A; Musoke, Pamela; Nalwa, Wafula Z; Odeny, Thomas A; Onono, Maricianah; Spangler, Sydney A; Turan, Janet M; Wanga, Iris; Abuogi, Lisa L

2017-03-01

Current WHO guidelines recommend lifelong antiretroviral therapy (ART) for all HIV-positive individuals, including pregnant and breastfeeding women (Option B+) in settings with generalized HIV epidemics. While Option B+ is scaled-up in Kenya, insufficient adherence and retention to care could undermine the expected positive impact of Option B+. To explore challenges to the provision of Option B+ at the health facility level, we conducted forty individual gender-matched in-depth interviews with HIV-positive pregnant/postpartum women and their male partners, and four focus groups with thirty health care providers at four health facilities in western Kenya between September-November 2014. Transcripts were coded with the Dedoose software using a coding framework based on the literature, topics from interview guides, and emerging themes from transcripts. Excerpts from broad codes were then fine-coded using an inductive approach. Three major themes emerged: 1) Option B+ specific challenges (same-day initiation into treatment, health care providers unconvinced of the benefits of Option B+, insufficient training); 2) facility resource constraints (staff and drug shortages, long queues, space limitations); and 3) lack of client-friendly services (scolding of patients, inconvenient operating hours, lack of integration of services, administrative requirements). This study highlights important challenges at the health facility level related to Option B+ rollout in western Kenya. Addressing these specific challenges may increase linkage, retention and adherence to life-long ART treatment for pregnant HIV-positive women in Kenya, contribute towards elimination of mother-to-child HIV transmission, and improve maternal and child outcomes.

Expression of human inducible nitric oxide synthase in a tetrahydrobiopterin (H4B)-deficient cell line: H4B promotes assembly of enzyme subunits into an active dimer.

PubMed Central

Tzeng, E; Billiar, T R; Robbins, P D; Loftus, M; Stuehr, D J

1995-01-01

Murine inducible nitric oxide (NO) synthase (iNOS) is catalytically active only in dimeric form. Assembly of its purified subunits into a dimer requires H4B. To understand the structure-activity relationships of human iNOS, we constitutively expressed recombinant human iNOS in NIH 3T3 cells by using a retroviral vector. These cells are deficient in de novo H4B biosynthesis and the role of H4B in the expression and assembly of active iNOS in an intact cell system could be studied. In the absence of added H4B, NO synthesis by the cells was minimal, whereas cells grown with supplemental H4B or the H4B precursor sepiapterin generated NO (74.1 and 63.3 nmol of nitrite per 10(6) cells per 24 h, respectively). NO synthesis correlated with an increase in intracellular H4B but no increase in iNOS protein. Instead, an increased percentage of dimeric iNOS was observed, rising from 20% in cytosols from unsupplemented cells to 66% in H4B-supplemented cell cytosols. In all cases, only dimeric iNOS displayed catalytic activity. Cytosols prepared from H4B-deficient cells exhibited little iNOS activity but acquired activity during a 60- to 120-min incubation with H4B, reaching final activities of 60-72 pmol of citrulline per mg of protein per min. Reconstitution of cytosolic NO synthesis activity was associated with conversion of monomers into dimeric iNOS during the incubation. Thus, human iNOS subunits dimerize to form an active enzyme, and H4B plays a critical role in promoting dimerization in intact cells. This reveals a post-translational mechanism by which intracellular H4B can regulate iNOS expression. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8524846

Artesunate protects pancreatic beta cells against cytokine-induced damage via SIRT1 inhibiting NF-κB activation.

PubMed

Yu, L; Chen, J F; Shuai, X; Xu, Y; Ding, Y; Zhang, J; Yang, W; Liang, X; Su, D; Yan, C

2016-01-01

Artesunate (ART) has been known as the most effective and safe reagents to treat malaria for many years. In this study, we explored whether ART could protect pancreatic beta-cell against cytokine-induced damage. The production of nitrite (NO) was detected with the Griess Assay Kit. SIRT1 and inducible nitric oxide synthase (iNOS) expression were determined with Western blot. The transcriptional activity of NF-κB was evaluated by luciferase reporter assay. The expression of Sirt1 was silenced by RNA interference. Glucose-stimulated insulin secretion (GSIS) and potassium-stimulated insulin secretion (KSIS) assays were performed to measure the effect of ART on pancreatic beta-cells' function. The effect of ART on beta-cells apoptosis was evaluated by using Hochest/PI staining and TUNEL assay. ART enhanced GSIS (KSIS) and reduced apoptosis of pancreatic beta-cells induced by IL-1β. Further study showed that ART inhibited IL-1β-induced increase of NF-κB activity, iNOS expression, and NO production. Moreover, ART up-regulated SIRT1 expression in INS-1 cells and islets exposed to IL-1β. Inhibition of SIRT1 expression could partially abolished the inhibitory effect of ART on NF-κB activity in IL-1β-treated beta-cells. More importantly, the protective effect of ART on cytokine-induced damage was reversed by silencing SIRT1 expression. ART can elicit a protective effect on beta-cells exposed to IL-1β by stimulating SIRT1 expression, which resulted in the decrease of NF-κB activity, iNOS expression, and NO production. Hence, ART might be an effective drug for diabetes.

[Association of Inorganics Accumulation with the Activation of NF-κB Signaling Pathway and the iNOS Expression of Lung Tissue in Xuanwei Lung Cancer Patients].

PubMed

Yang, Jiapeng; Li, Guangjian; Huang, Yunchao; Ye, Lianhua; Zhou, Yongchun; Zhao, Guangqiang; Lei, Yujie; Chen, Xiaobo; Wang, Kun; Chen, Ying; Dai, Chun; Zhang, Yanjun

2016-01-01

Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB (NF-κB)-inducible nitric oxide synthase (iNOS) signaling pathway of lung tissue in Xuanwei lung cancer patients. From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy (TEM) to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-κB-p65 protein and iNOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHdG accumulation in lung cancer tissues and urine was measured. A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon (Si) content was found in inorganic elemental analysis. The serum interleukin (IL)-1β levels (31.50 ± 19.16) pg/mL of Xuanwei lung-cancer patients were remarkably higher than those from other regions (11.33 ± 6.94) pg/mL (P<0.01), with statistically significant difference. The pathological tissues of Xuanwei lung-cancer patients express NF-κB-p65, and iNOS expression were significantly higher than those of patients from non-Xuanwei regions. No significant difference was found between cancerous and normal adjacent tissues. Xuanwei lung-cancer tissues and urine 8-OHdG level (40.124 ± 8

Anti-inflammatory effects of shea butter through inhibition of iNOS, COX-2, and cytokines via the Nf-κB pathway in LPS-activated J774 macrophage cells.

PubMed

Verma, Nandini; Chakrabarti, Rina; Das, Rakha H; Gautam, Hemant K

2012-01-12

Shea butter is traditionally used in Africa for its anti-inflammatory and analgesic effects. In this study we explored the anti-inflammatory activities of the methanolic extract of shea butter (SBE) using lipopolysaccharide (LPS)-induced murine macrophage cell line J774. It was observed that SBE significantly reduced the levels of LPS-induced nitric oxide, Tumor necrosis factor-α (TNF-α), interleukins, 1β (IL-1β), and -12 (IL-12) in the culture supernatants in a dose dependent manner. Expression of pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were also inhibited by SBE. These anti-inflammatory effects were due to an inhibitory action of SBE on LPS-induced iNOS, COX-2, TNF-α, IL-1β, and IL-12 mRNA expressions. Moreover, SBE efficiently suppressed IκB phosphorylation and NF-κB nuclear translocation induced by LPS. These findings explain the molecular bases of shea butter's bioactivity against various inflammatory conditions and substantiate it as a latent source of novel therapeutic agents.

Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina.

PubMed

Musicki, Biljana; Liu, Tongyun; Strong, Travis D; Lagoda, Gwen A; Bivalacqua, Trinity J; Burnett, Arthur L

2010-05-01

Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17beta (15 microg). Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. These results

Involvement of PI3K, Akt, and RhoA in oestradiol regulation of cardiac iNOS expression.

PubMed

Zafirovic, Sonja; Sudar-Milovanovic, Emina; Obradovic, Milan; Djordjevic, Jelena; Jasnic, Nebojsa; Borovic, Milica Labudovic; Isenovic, Esma R

2018-02-12

Oestradiol is an important regulatory factor with several positive effects on the cardiovascular (CV) system. We evaluated the molecular mechanism of the in vivo effects of oestradiol on the regulation of cardiac inducible nitric oxide (NO) synthase (iNOS) expression and activity. Male Wistar rats were treated with oestradiol (40 mg/kg, intraperitoneally) and after 24 h the animals were sacrificed. The concentrations of NO and L-Arginine (L-Arg) were determined spectrophotometrically. For protein expressions of iNOS, p65 subunit of nuclear factor-κB (NFκB-p65), Ras homolog gene family-member A (RhoA), angiotensin II receptor type 1 (AT1R), insulin receptor substrate 1 (IRS-1), p85, p110 and protein kinase B (Akt), Western blot method was used. Co-immunoprecipitation was used for measuring the association of IRS-1 with the p85 subunit of phosphatidylinositol-3-kinase (PI3K). The expression of iNOS messenger ribonucleic acid (mRNA) was measured with the quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of the tissue was used to detect localization and expression of iNOS in heart tissue. Oestradiol treatment reduced L-Arg concentration (p<0.01), iNOS mRNA (p<0.01) and protein (p<0.001) expression, level of RhoA (p<0.05) and AT1R (p<0.001) protein. In contrast, plasma NO (p<0.05), Akt phosphorylation at Thr308 (p<0.05) and protein level of p85 (p<0.001) increased after oestradiol treatment. Our results suggest that oestradiol in vivo regulates cardiac iNOS expression via the PI3K/Akt signaling pathway, through attenuation of RhoA and AT1R. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Requirements Doc for Refurb of JASPER Facility in B131HB

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knittel, Kenn M.

The Joint Actinide Shock Physics Experimental Research (JASPER) Program target fabrication facility is currently located in building 131 (B131) of the Lawrence Livermore National Laboratory (LLNL). A portion of this current facility has been committed to another program as part of a larger effort to consolidate LLNL capabilities into newer facilities. This facility assembles precision targets for scientific studies at the Nevada National Security Site (NNSS). B131 is also going through a modernization project to upgrade the infrastructure and abate asbestos. These activities will interrupt the continuous target fabrication efforts for the JASPER Program. Several options are explored to meetmore » the above conflicting requirements, with the final recommendation to prepare a new facility for JASPER target fabrication operations before modernization efforts begin in the current facility assigned to JASPER. This recommendation fits within all schedule constraints and minimizes the disruption to the JASPER Program. This option is not without risk, as it requires moving an aged, precision coordinate measuring machine, which is essential to the JASPER Program’s success. The selected option balances the risk to the machine with continuity of operations.« less

[Association of Schizophrenia and its Clinical Implications with the NOS1AP Gene in the Colombian Population].

PubMed

Valencia, Jenny García; Duarte, Ana Victoria Valencia; Vila, Ana Lucía Páez; Kremeyer, Bárbara; Montoya, María Patricia Arbeláez; Linares, Andrés Ruiz; Acosta, Carlos Alberto Palacio; Duque, Jorge Ospina; Berrío, Gabriel Bedoya

2012-06-01

The nitric oxide synthase 1 adaptor protein (NOS1AP) gene is possibly implicated in schizophrenia etiopathogenesis. To determine the association of NOS1AP gene variants with schizophrenia and the relationship of variants with the clinical dimensions of the disorder in the Colombian population. It is a case-control study with 255 subjects per group. Markers within the NOS1AP gene were typified as well as other informative material of genetic origin so as to adjust by population stratification. A factorial analysis of the main components for each item in the Scales for Evaluating Negative Symptoms (SENS) together with the Scales for Evaluating Positive Symptoms (SEPS) to determine clinical dimensions. Association between the C/C genotype of the rs945713 marker with schizophrenia (OR = 1.79, 95% CI: 1.13 - 2.84) was found. The C/C genotype of the rs945713 was related to higher scores in the "affective flattening and alogia" dimension; and the A/A genotype of the rs4657181 marker was associated to lower scores in the same dimension. Significant associations of markers inside the NOS1AP gene with schizophrenia and the "affective flattening and alogia" clinical dimension were found. These results are consistent with previous studies and support the possibility that NOS1AP influences schizophrenia susceptibility. Furthermore, NOS1AP might be a modifier of schizophrenia clinical characteristics. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

42 CFR 52b.11 - What are the requirements for acquisition and modernization of existing facilities?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false What are the requirements for acquisition and modernization of existing facilities? 52b.11 Section 52b.11 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.11 What are the...

42 CFR 52b.11 - What are the requirements for acquisition and modernization of existing facilities?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false What are the requirements for acquisition and modernization of existing facilities? 52b.11 Section 52b.11 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.11 What are the...

42 CFR 52b.11 - What are the requirements for acquisition and modernization of existing facilities?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false What are the requirements for acquisition and modernization of existing facilities? 52b.11 Section 52b.11 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.11 What are the...

42 CFR 52b.11 - What are the requirements for acquisition and modernization of existing facilities?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false What are the requirements for acquisition and modernization of existing facilities? 52b.11 Section 52b.11 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.11 What are the...

42 CFR 52b.11 - What are the requirements for acquisition and modernization of existing facilities?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false What are the requirements for acquisition and modernization of existing facilities? 52b.11 Section 52b.11 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.11 What are the...

40 CFR 35.917 - Facilities planning (step 1).

Code of Federal Regulations, 2012 CFR

2012-07-01

... plans. (b) Facilities planning consists of those necessary plans and studies which directly relate to... environmental and social considerations. (See appendix A to this subpart.) (c) EPA requires full compliance with... be initiated before award of a step 1 grant or written approval of a plan of study (see § 35.920-3(a...

1. CONNECTING TUNNEL AT LEFT, CONTROL BUILDING B AT RIGHT, ...

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

1. CONNECTING TUNNEL AT LEFT, CONTROL BUILDING B AT RIGHT, VIEW TOWARDS SOUTHEAST - Glenn L. Martin Company, Titan Missile Test Facilities, Control Building B, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

Withaferin A inhibits iNOS expression and nitric oxide production by Akt inactivation and down-regulating LPS-induced activity of NF-kappaB in RAW 264.7 cells.

PubMed

Oh, Jung Hwa; Lee, Tae-Jin; Park, Jong-Wook; Kwon, Taeg Kyu

2008-12-03

Induction of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production is thought to have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, withaferin A inhibited LPS-induced expression of both iNOS protein and mRNA in a dose-dependent manner. To investigate the mechanism by which withaferin A inhibits iNOS gene expression, we examined activation of mitogen-activated protein kinases (MAPKs) and Akt in Raw 264.7 cells. We did not observe any significant changes in the phosphorylation of p38 MAPK in cells treated with LPS alone or LPS plus withaferin A. However, LPS-induced Akt phosphorylation was markedly inhibited by withaferin A, while the phosphorylation of p42/p44 extracellular signal-regulated kinases (ERKs) was slightly inhibited by withaferin A treatment. Withaferin A prevented IkappaB phosphorylation, blocking the subsequent nuclear translocation of nuclear factor-kappaB (NF-kappaB) and inhibiting its DNA binding activity. LPS-induced p65 phosphorylation, which is mediated by extracellular signal-regulated kinase (ERK) and Akt pathways, was attenuated by withaferin A treatment. Moreover, LPS-induced NO production and NF-kappaB activation were inhibited by SH-6, a specific inhibitor of Akt. Taken together, these results suggest that withaferin A inhibits inflammation through inhibition of NO production and iNOS expression, at least in part, by blocking Akt and subsequently down-regulating NF-kappaB activity.

6-Shogaol suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages.

PubMed

Pan, Min-Hsiung; Hsieh, Min-Chi; Hsu, Ping-Chi; Ho, Sheng-Yow; Lai, Ching-Shu; Wu, Hou; Sang, Shengmin; Ho, Chi-Tang

2008-12-01

Ginger, the rhizome of Zingiber officinale, is a traditional medicine with carminative effect, antinausea, anti-inflammatory, and anticarcinogenic properties. In this study, we investigated the inhibitory effects of 6-shogaol and a related compound, 6-gingerol, on the induction of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with LPS. Western blotting and reverse transcription-PCR analyses demonstrated that 6-shogaol significantly blocked protein and mRNA expression of inducible NOS (iNOS) and COX-2 in LPS-induced macrophages. The in vivo anti-inflammatory activity was evaluated by a topical 12-O-tetradecanoylphorbol 13-acetate (TPA) application to mouse skin. When applied topically onto the shaven backs of mice prior to TPA, 6-shogaol markedly inhibited the expression of iNOS and COX-2 proteins. Treatment with 6-shogaol resulted in the reduction of LPS-induced nuclear translocation of nuclear factor-kappaB (NF kappaB) subunit and the dependent transcriptional activity of NF kappaB by blocking phosphorylation of inhibitor kappaB (I kappaB)alpha and p65 and subsequent degradation of I kappaB alpha. Transient transfection experiments using NF kappaB reporter constructs indicated that 6-shogaol inhibits the transcriptional activity of NF kappaB in LPS-stimulated mouse macrophages. We found that 6-shogaol also inhibited LPS-induced activation of PI3K/Akt and extracellular signal-regulated kinase 1/2, but not p38 mitogen-activated protein kinase (MAPK). Taken together, these results show that 6-shogaol downregulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NF kappaB by interfering with the activation PI3K/Akt/I kappaB kinases IKK and MAPK.

Formononetin attenuates IL-1β-induced apoptosis and NF-κB activation in INS-1 cells.

PubMed

Wang, Yao; Zhu, Yunxia; Gao, Lu; Yin, Han; Xie, Zuoling; Wang, Dong; Zhu, Zhengqiu; Han, Xiao

2012-08-24

Several studies suggest that the inflammation plays a role in the pathogenesis of some glucose disorders in adults. Exposure of pancreatic β-cells to cytokines, such as interleukin-1β (IL-1β), is thought to contribute to β-cell apoptosis. One important event triggered by IL-1β is induction of nitric oxide synthase (iNOS), an enzyme that catalyzes intracellular generation of the cytotoxic free radical NO. Recent work have suggested that formononetin, as an O-methylated isoflavone found in a number of plants and herbs like Astragalus membranaceus, inhibited some pro-inflammatory cytokine production in macrophages. However, the roles of formononetin in pancreatic beta cells have not been fully established. The aim of the present study was to assess possible in vitro effects of formononetin on cell apoptosis induced by IL-1β in the rat insulinoma cell line, INS-1. Our results demonstrate that formononetin significantly prevents IL-1β-increased INS-1 cell death and blocks cytokine-induced apoptotic signaling (the reduction of Bax/Bcl-2 ratio and caspase-3 activity). Formononetin also inhibited the activation of nuclear factor-kappaB (NF-κB), which is a significant transcription factor for iNOS, so as to decease nitric oxide (NO) formation in a dose dependent manner in vitro. Our observations indicated that formononetin could protect against pancreatic β-cell apoptosis caused by IL-1β and therefore could be used in the future as a new drug improving diabetes mellitus.

Facile Aqueous Phase Synthesis of Pd3Cu-B/C Nanocatalyst for Glucose Electrooxidation

NASA Astrophysics Data System (ADS)

Chai, Dan; Lu, Haibin; Wang, Yaqian; Hua, Xiuwen; Ren, Na; Zhang, Xiongwen

2018-01-01

A novel Pd3Cu-B/C nanocatalyst was facilely synthesized through an aqueous phase process. And it was developed for use in the glucose electrooxidation reaction in fuel cells. Cyclic voltammetry shown that the electrochemical surface area of Pd3Cu-B/C is 2.25 times that of Pd/C. Glucose electrooxidation curves revealed that peak current on the Pd3Cu-B/C is actually 1.73 times of the Pd/C. This high performance of Pd3Cu-B/C could be ascribed to the synergistic effect between Pd, Cu and B.

Proposed Facility Modifications to Support Propulsion Systems Testing Under Simulated Space Conditions at Plum Brook Station's Spacecraft Propulsion Research Facility (B-2)

NASA Technical Reports Server (NTRS)

Edwards, Daryl A.

2008-01-01

Preparing NASA's Plum Brook Station's Spacecraft Propulsion Research Facility (B-2) to support NASA's new generation of launch vehicles has raised many challenges for B-2's support staff. The facility provides a unique capability to test chemical propulsion systems/vehicles while simulating space thermal and vacuum environments. Designed and constructed in the early 1960s to support upper stage cryogenic engine/vehicle system development, the Plum Brook Station B-2 facility will require modifications to support the larger, more powerful, and more advanced engine systems for the next generation of vehicles leaving earth's orbit. Engine design improvements over the years have included large area expansion ratio nozzles, greater combustion chamber pressures, and advanced materials. Consequently, it has become necessary to determine what facility changes are required and how the facility can be adapted to support varying customers and their specific test needs. Exhaust system performance, including understanding the present facility capabilities, is the primary focus of this work. A variety of approaches and analytical tools are being employed to gain this understanding. This presentation discusses some of the challenges in applying these tools to this project and expected facility configuration to support the varying customer needs.

Proposed Facility Modifications to Support Propulsion Systems Testing Under Simulated Space Conditions at Plum Brook Station's Spacecraft Propulsion Research Facility (B-2)

NASA Technical Reports Server (NTRS)

Edwards, Daryl A.

2007-01-01

Preparing NASA's Plum Brook Station's Spacecraft Propulsion Research Facility (B-2) to support NASA's new generation of launch vehicles has raised many challenges for B-2 s support staff. The facility provides a unique capability to test chemical propulsion systems/vehicles while simulating space thermal and vacuum environments. Designed and constructed 4 decades ago to support upper stage cryogenic engine/vehicle system development, the Plum Brook Station B-2 facility will require modifications to support the larger, more powerful, and more advanced engine systems for the next generation of vehicles leaving earth's orbit. Engine design improvements over the years have included large area expansion ratio nozzles, greater combustion chamber pressures, and advanced materials. Consequently, it has become necessary to determine what facility changes are required and how the facility can be adapted to support varying customers and their specific test needs. Instrumental in this task is understanding the present facility capabilities and identifying what reasonable changes can be implemented. A variety of approaches and analytical tools are being employed to gain this understanding. This paper discusses some of the challenges in applying these tools to this project and expected facility configuration to support the varying customer needs.

Post-translational Regulation of Endothelial Nitric Oxide Synthase (eNOS) by Estrogens in the Rat Vagina

PubMed Central

Musicki, Biljana; Liu, Tongyun; Strong, Travis D.; Lagoda, Gwen A.; Bivalacqua, Trinity J.; Burnett, Arthur L.

2010-01-01

Introduction Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Aims Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. Methods We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17β (15 μg). Main Outcome Measures Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. Results We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement

Consistency of the Health of the Nation Outcome Scales (HoNOS) at inpatient-to-community transition.

PubMed

Luo, Wei; Harvey, Richard; Tran, Truyen; Phung, Dinh; Venkatesh, Svetha; Connor, Jason P

2016-04-27

The Health of the Nation Outcome Scales (HoNOS) are mandated outcome-measures in many mental-health jurisdictions. When HoNOS are used in different care settings, it is important to assess if setting specific bias exists. This article examines the consistency of HoNOS in a sample of psychiatric patients transitioned from acute inpatient care and community centres. A regional mental health service with both acute and community facilities. 111 psychiatric patients were transferred from inpatient care to community care from 2012 to 2014. Their HoNOS scores were extracted from a clinical database; Each inpatient-discharge assessment was followed by a community-intake assessment, with the median period between assessments being 4 days (range 0-14). Assessor experience and professional background were recorded. The difference of HoNOS at inpatient-discharge and community-intake were assessed with Pearson correlation, Cohen's κ and effect size. Inpatient-discharge HoNOS was on average lower than community-intake HoNOS. The average HoNOS was 8.05 at discharge (median 7, range 1-22), and 12.16 at intake (median 12, range 1-25), an average increase of 4.11 (SD 6.97). Pearson correlation between two total scores was 0.073 (95% CI -0.095 to 0.238) and Cohen's κ was 0.02 (95% CI -0.02 to 0.06). Differences did not appear to depend on assessor experience or professional background. Systematic change in the HoNOS occurs at inpatient-to-community transition. Some caution should be exercised in making direct comparisons between inpatient HoNOS and community HoNOS scores. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Recurrent hypoinsulinemic hyperglycemia in neonatal rats increases PARP-1 and NF-κB expression and leads to microglial activation in the cerebral cortex.

PubMed

Gisslen, Tate; Ennis, Kathleen; Bhandari, Vineet; Rao, Raghavendra

2015-11-01

Hyperglycemia is a common metabolic problem in extremely low-birth-weight preterm infants. Neonatal hyperglycemia is associated with increased mortality and brain injury. Glucose-mediated oxidative injury may be responsible. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and cell survival. However, PARP-1 overactivation leads to cell death. NF-κB is coactivated with PARP-1 and regulates microglial activation. The effects of recurrent hyperglycemia on PARP-1/NF-κB expression and microglial activation are not well understood. Rat pups were subjected to recurrent hypoinsulinemic hyperglycemia of 2 h duration twice daily from postnatal (P) day 3-P12 and killed on P13. mRNA and protein expression of PARP-1/NF-κB and their downstream effectors were determined in the cerebral cortex. Microgliosis was determined using CD11 immunohistochemistry. Recurrent hyperglycemia increased PARP-1 expression confined to the nucleus and without causing PARP-1 overactivation and cell death. NF-κB mRNA expression was increased, while IκB mRNA expression was decreased. inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expressions were decreased. Hyperglycemia significantly increased the number of microglia. Recurrent hyperglycemia in neonatal rats is associated with upregulation of PARP-1 and NF-κB expression and subsequent microgliosis but not neuronal cell death in the cerebral cortex.

Noscapinoids bearing silver nanocrystals augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1, mouse melanoma skin cancer cells.

PubMed

Soni, Naina; Jyoti, Kiran; Jain, Upendra Kumar; Katyal, Anju; Chandra, Ramesh; Madan, Jitender

2017-06-01

Noscapine (Nos) and reduced brominated analogue of noscapine (Red-Br-Nos) prevent cellular proliferation and induce apoptosis in cancer cells either alone or in combination with other chemotherapeutic drugs. However, owing to poor physicochemical properties, Nos and Red-Br-Nos have demonstrated their anticancer activity at higher and multiple doses. Therefore, in present investigation, silver nanocrystals of noscapinoids (Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals) were customized to augment drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1 mouse melanoma cancer cells. Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals were prepared separately by precipitation method. The mean particle size of Nos-Ag 2+ nanocrystals was measured to be 25.33±3.52nm, insignificantly (P>0.05) different from 27.43±4.51nm of Red-Br-Nos-Ag 2+ nanocrystals. Furthermore, zeta-potential of Nos-Ag 2+ nanocrystals was determined to be -25.3±3.11mV significantly (P<0.05) different from -15.2±3.33mV of Red-Br-Nos-Ag 2+ nanocrystals. The shape of tailored nanocrystals was slightly spherical and or irregular in shape. The architecture of Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals was crystalline in nature. FT-IR spectroscopy evinced the successful interaction of Ag 2+ nanocrystals with Nos and Red-Br-Nos, respectively. The superior therapeutic efficacy of tailored nanocrystals was measured in terms of enhanced cytotoxicity, apoptosis and cellular uptake. The Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals exhibited an IC 50 of 16.6μM and 6.5μM, significantly (P<0.05) lower than 38.5μM of Nos and 10.3μM of Red-Br-Nos, respectively. Finally, cellular morphological alterations in B16F1 cells upon internalization of Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals provided the evidences for accumulation within membrane-bound cytoplasmic vacuoles and in enlarged lysosomes and thus triggered mitochondria mediated apoptosis via

40 CFR 60.110b - Applicability and designation of affected facility.

Code of Federal Regulations, 2010 CFR

2010-07-01

... an attachment to the notification required by 40 CFR 65.5(b). [52 FR 11429, Apr. 8, 1987, as amended... designation of affected facility. (a) Except as provided in paragraph (b) of this section, the affected..., reconstruction, or modification is commenced after July 23, 1984. (b) This subpart does not apply to storage...

40 CFR 60.110b - Applicability and designation of affected facility.

Code of Federal Regulations, 2013 CFR

2013-07-01

... an attachment to the notification required by 40 CFR 65.5(b). [52 FR 11429, Apr. 8, 1987, as amended... designation of affected facility. (a) Except as provided in paragraph (b) of this section, the affected..., reconstruction, or modification is commenced after July 23, 1984. (b) This subpart does not apply to storage...

40 CFR 60.110b - Applicability and designation of affected facility.

Code of Federal Regulations, 2012 CFR

2012-07-01

... an attachment to the notification required by 40 CFR 65.5(b). [52 FR 11429, Apr. 8, 1987, as amended... designation of affected facility. (a) Except as provided in paragraph (b) of this section, the affected..., reconstruction, or modification is commenced after July 23, 1984. (b) This subpart does not apply to storage...

40 CFR 60.110b - Applicability and designation of affected facility.

Code of Federal Regulations, 2011 CFR

2011-07-01

... an attachment to the notification required by 40 CFR 65.5(b). [52 FR 11429, Apr. 8, 1987, as amended... designation of affected facility. (a) Except as provided in paragraph (b) of this section, the affected..., reconstruction, or modification is commenced after July 23, 1984. (b) This subpart does not apply to storage...

40 CFR 60.110b - Applicability and designation of affected facility.

Code of Federal Regulations, 2014 CFR

2014-07-01

... an attachment to the notification required by 40 CFR 65.5(b). [52 FR 11429, Apr. 8, 1987, as amended... designation of affected facility. (a) Except as provided in paragraph (b) of this section, the affected..., reconstruction, or modification is commenced after July 23, 1984. (b) This subpart does not apply to storage...

42 CFR 52b.8 - How will NIH monitor the use of facilities constructed with federal funds?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false How will NIH monitor the use of facilities constructed with federal funds? 52b.8 Section 52b.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.8 How will NIH...

42 CFR 52b.8 - How will NIH monitor the use of facilities constructed with federal funds?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false How will NIH monitor the use of facilities constructed with federal funds? 52b.8 Section 52b.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.8 How will NIH...

42 CFR 52b.8 - How will NIH monitor the use of facilities constructed with federal funds?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false How will NIH monitor the use of facilities constructed with federal funds? 52b.8 Section 52b.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.8 How will NIH...

42 CFR 52b.8 - How will NIH monitor the use of facilities constructed with federal funds?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false How will NIH monitor the use of facilities constructed with federal funds? 52b.8 Section 52b.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.8 How will NIH...

42 CFR 52b.8 - How will NIH monitor the use of facilities constructed with federal funds?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false How will NIH monitor the use of facilities constructed with federal funds? 52b.8 Section 52b.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.8 How will NIH...

[Influence of hepatocyte growth factor on iNOS, NO and IL-1β in the cerebrum during cerebral ischemia/reperfusion in rats].

PubMed

He, Fang; Ye, Bei; Chen, Jianzhen; Sun, Xiaoyan; Li, Chang

2014-01-01

To explore the effect of hepatocyte growth factor (HGF) on inducible nitric oxide synthase (iNOS), NO and interleukin-1β (IL-1β) in the cerebrum of rats subjected to cerebral ischemia/reperfusion (I/R). Sprague-Dawley rats were randomly divided into 5 groups: a sham group, an I/R group,an HGF1 group, an HGF2 group, and an HGF3 group. The latter 3 groups were respectively injected 15, 30 and 60 μg/kg HGF. The focal cerebral I/R model was established by sutureoccluded method. After 1.5 h ischemia followed by 24 h reperfusion, the iNOS activity and NO content in the ischemic cerebral tissue were assessed. The expression of iNOS mRNA and IL-1β mRNA was detected. The level of iNOS protein and IL-1β content were determined. In addition, cultured cerebral cortical neurons in vitro were exposed to I/R. Then the expression of iNOS and IL-1β protein in the neurons was detected, and NO content was assessed. The iNOS activity and NO content in the ischemic cerebral tissue were increased. The expression of iNOS mRNA and IL-1β mRNA was upregulated. The level of iNOS protein and IL- 1β content were increased. Administration of HGF decreased the iNOS activity and NO content, and downregulated the expression of iNOS mRNA, IL-1β mRNA, iNOS protein and IL-1β content in the ischemic cerebral tissue. HGF decreased the expression of IL-1β, iNOS protein and NO content in the cortical neurons exposed to I/R in vitro. HGF can inhibit the expression of IL-1β and decrease the expression of iNOS and content of NO, which is probably one of the mechanisms mediating the protection of HGF against cerebral ischemia injury.

FACILITY 802B, BEDROOM ADJACENT TO BATHROOM, VIEW FACING NORTH. ...

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

FACILITY 802B, BEDROOM ADJACENT TO BATHROOM, VIEW FACING NORTH. - Schofield Barracks Military Reservation, Bachelor Officers' Quarters Type, Between Grimes & Tidball Streets near Ayres Avenue, Wahiawa, Honolulu County, HI

Overexpression of SIRT1 Protects Pancreatic β-Cells Against Cytokine Toxicity by Suppressing the Nuclear Factor-κB Signaling Pathway

PubMed Central

Lee, Ji-Hyun; Song, Mi-Young; Song, Eun-Kyung; Kim, Eun-Kyung; Moon, Woo Sung; Han, Myung-Kwan; Park, Jin-Woo; Kwon, Kang-Beom; Park, Byung-Hyun

2009-01-01

OBJECTIVE—SIRT1, a class III histone/protein deacetylase, is known to interfere with the nuclear factor-κB (NF-κB) signaling pathway and thereby has an anti-inflammatory function. Because of the central role of NF-κB in cytokine-mediated pancreatic β-cell damage, we postulated that SIRT1 might work in pancreatic β-cell damage models. RESEARCH DESIGN AND METHODS—RINm5F (RIN) cells or isolated rat islets were treated with interleukin-1β and interferon-γ. SIRT1 was activated by resveratrol, a pharmacological activator, or ectopic overexpression. The underlying mechanisms of SIRT1 against cytokine toxicity were further explored. RESULTS—Treatment of RIN cells with cytokines induced cell damage, and this damage was well correlated with the expression of the inducible form of nitric oxide (NO) synthase (iNOS) and NO production. However, SIRT1 overexpression completely prevented cytokine-mediated cytotoxicity, NO production, and iNOS expression. The molecular mechanism by which SIRT1 inhibits iNOS expression appeared to involve the inhibition of the NF-κB signaling pathway through deacetylation of p65. In addition, SIRT1 activation by either resveratrol or adenoviral-directed overexpression of SIRT1 could prevent cytokine toxicity and maintain normal insulin-secreting responses to glucose in isolated rat islets. CONCLUSIONS—This study will provide valuable information not only into the mechanisms underlying β-cell destruction but also into the regulation of SIRT1 as a possible target to attenuate cytokine-induced β-cell damage. PMID:19008341

FACILITY 802B, LIVING ROOM AND ENTRY, VIEW FACING EASTNORTHEAST. ...

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

FACILITY 802B, LIVING ROOM AND ENTRY, VIEW FACING EAST-NORTHEAST. - Schofield Barracks Military Reservation, Bachelor Officers' Quarters Type, Between Grimes & Tidball Streets near Ayres Avenue, Wahiawa, Honolulu County, HI

Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum

PubMed Central

DiGirolamo, G; Farina, M; Riberio, M L; Ogando, D; Aisemberg, J; de los Santos, A R; Martí, M L; Franchi, A M

2003-01-01

The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins. Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions such as Parkinson and Alzheimer disease, and Huntington's chorea. In the present study, the in vivo effect of three NSAIDs (lysine clonixinate (LC), indomethacine (INDO) and meloxicam (MELO)) on NO production and nitric oxide synthase expression in rat cerebellar slices was analysed. Rats were treated with (a) saline, (b) lipopolysaccharide (LPS) (5 mg kg−1, i.p.), (c) saline in combination with different doses of NSAIDs and (d) LPS in combination with different doses of NSAIDs and then killed 6 h after treatment. NO synthesis, evaluated by Bred and Snyder technique, was increased by LPS. This augmentation was inhibited by coadministration of the three NSAIDs assayed. None of the NSAIDs tested was able to modify control NO synthesis. Expression of iNOS and neural NOS (nNOS) was detected by Western blotting in control and LPS-treated rats. LC and INDO, but not MELO, were able to inhibit the expression of these enzymes. Therefore, reduction of iNOS and nNOS levels in cerebellum may explain, in part, the anti-inflammatory effect of these NSAIDs and may also have importance in the prevention of NO-mediated neuronal injury. PMID:12871835

Title I, Part B, Institutionalized Facilities Program, Summer 1982. Annual Evaluation Report.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Office of Educational Evaluation.

This 1982 summer Title I, Part B, Institutionalized Facilities Program provided supplementary career instruction to 188 students residing in facilities for neglected and delinquent children and youth. This report briefly describes the program, providing information on methodology, physical setting, equipment, and supplies; population and class…

Ethyl caffeate suppresses NF-kappaB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE2 in vitro or in mouse skin.

PubMed

Chiang, Yi-Ming; Lo, Chiu-Ping; Chen, Yi-Ping; Wang, Sheng-Yang; Yang, Ning-Sun; Kuo, Yueh-Hsiung; Shyur, Lie-Fen

2005-10-01

Ethyl caffeate, a natural phenolic compound, was isolated from Bidens pilosa, a medicinal plant popularly used for treating certain inflammatory syndromes. The purpose of this study was to investigate the structural activity, and the anti-inflammatory functions and mechanism(s) of ethyl caffeate. Ethyl caffeate was found to markedly suppress the lipopolysaccharide (LPS)-induced nitric oxide (NO) production (IC(50) = 5.5 microg ml(-1)), mRNA and protein expressions of inducible nitric oxide synthase (iNOS), and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Transient gene expression assays using human cox-2 promoter construct revealed that ethyl caffeate exerted an inhibitory effect on cox-2 transcriptional activity in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells. Immunohistochemical studies of mouse skin demonstrated that TPA-induced COX-2 expression was significantly inhibited by ethyl caffeate with a superior effect to that of celecoxib, a nonsteroidal anti-inflammatory drug. The phosphorylation and degradation of inhibitor kappaB (IkappaB) and the translocation of nuclear transcription factor-kappaB (NF-kappaB) into the nucleus, as well as the activation of mitogen-activated protein kinases (MAPKs) induced by LPS in macrophages, were not affected by ethyl caffeate. Ethyl caffeate, however, could inhibit NF-kappaB activation by impairing the binding of NF-kappaB to its cis-acting element. These results suggest that ethyl caffeate suppresses iNOS and COX-2 expressions partly through the inhibition of the NF-kappaB.DNA complex formation. Structure-activity relationship analyses suggested that the catechol moiety and alpha,beta-unsaturated ester group in ethyl caffeate are important and essential structural features for preventing NF-kappaB.DNA complex formation. This study provides an insight into the probable mechanism(s) underlying the anti-inflammatory and therapeutic properties of ethyl caffeate.

Human Parvovirus B19 NS1 Protein Aggravates Liver Injury in NZB/W F1 Mice

PubMed Central

Tsai, Chun-Chou; Chiu, Chun-Ching; Hsu, Jeng-Dong; Hsu, Huai-Sheng; Tzang, Bor-Show; Hsu, Tsai-Ching

2013-01-01

Human parvovirus B19 (B19) has been associated with a variety of diseases. However, the influence of B19 viral proteins on hepatic injury in SLE is still obscure. To elucidate the effects of B19 viral proteins on livers in SLE, recombinant B19 NS1, VP1u or VP2 proteins were injected subcutaneously into NZB/W F1 mice, respectively. Significant expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected in NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Markedly hepatocyte disarray and lymphocyte infiltration were observed in livers from NZB/WF 1 mice receiving B19 NS1 as compared to those mice receiving PBS. Additionally, significant increases of Tumor Necrosis Factor –α (TNF-α), TNF-α receptor, IκB kinase –α (IKK-α), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB) and nuclear factor-kappa B (NF-κB) were detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Accordingly, significant increases of matrix metalloproteinase-9 (MMP9) and U-plasminogen activator (uPA) were also detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Contrarily, no significant variation on livers from NZB/W F1 mice receiving B19 VP1u or VP2 was observed as compared to those mice receiving PBS. These findings firstly demonstrated the aggravated effects of B19 NS1 but not VP1u or VP2 protein on hepatic injury and provide a clue in understanding the role of B19 NS1 on hepatic injury in SLE. PMID:23555760

Association of the ACE, GSTM1, IL-6, NOS3, and CYP1A1 polymorphisms with susceptibility of mycoplasma pneumoniae pneumonia in Chinese children

PubMed Central

Zhao, Jie; Zhang, Wen; Shen, Li; Yang, Xiaomeng; Liu, Yi; Gai, Zhongtao

2017-01-01

Abstract Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) and the clinical presentation of mycoplasma pneumoniae pneumonia (MPP) varies widely. Genetic variability affecting the host response may also influence the susceptibility to MPP. Several studies have investigated the association between single nucleotide polymorphism (SNP) of some genes and the risks of CAP; however, the results were inconsistent. Here, we investigated the association of 5 functional genes and the risks of MPP, including ACE (rs4340), GSTM1 (Ins/del), IL-6 (rs1800795), NOS3 (rs1799983), and CYP1A1 (rs2606345) in a total of 715 subjects (415 cases, 300 controls) by using tetra-primer allele-specific polymerase chain reaction (PCR) and Sanger sequencing. The gene–gene interactions were analyzed using the Multifactor Dimensionality Reduction and cumulative genetic risk score approaches. Our results showed that 3 SNPs of ACE rs4340, IL-6 rs1800795, and NOS3 rs1799983 were significantly associated with the risks of MPP, while no differences were observed in genotype frequencies of GSTM1 (Ins/del) and CYP1A1 rs2606345 between both groups. The combinations of ACE rs4340D/NOS3 rs1799983T/CYP1A1 rs2606345G and ACE rs4340D/NOS3 rs1799983T contribute to the genetic susceptibility of MPP in Chinese children. PMID:28403117

The return of the Scarlet Pimpernel: cobalamin in inflammation II — cobalamins can both selectively promote all three nitric oxide synthases (NOS), particularly iNOS and eNOS, and, as needed, selectively inhibit iNOS and nNOS

PubMed Central

Wheatley, Carmen

2007-01-01

The up-regulation of transcobalamins [hitherto posited as indicating a central need for cobalamin (Cbl) in inflammation], whose expression, like inducible nitric oxide synthase (iNOS), is Sp1- and interferondependent, together with increased intracellular formation of glutathionylcobalamin (GSCbl), adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), may be essential for the timely promotion and later selective inhibition of iNOS and concordant regulation of endothelial and neuronal NOS (eNOS/nNOS.) Cbl may ensure controlled high output of nitric oxide (NO) and its safe deployment, because: (1) Cbl is ultimately responsible for the synthesis or availability of the NOS substrates and cofactors heme, arginine, BH4 flavin adenine dinucleotide/flavin mononucleotide (FAD/FMN) and NADPH, via the far-reaching effects of the two Cbl coenzymes, methionine synthase (MS) and methylmalonyl CoA mutase (MCoAM) in, or on, the folate, glutathione, tricarboxylic acid (TCA) and urea cycles, oxidative phosphorylation, glycolysis and the pentose phosphate pathway. Deficiency of any of theNOS substrates and cofactors results in ‘uncoupled’ NOS reactions, decreasedNO production and increased or excessive O2−, H2O2, ONOO− and other reactive oxygen species (ROS), reactive nitric oxide species (RNIS) leading to pathology. (2) Cbl is also the overlooked ultimate determinant of positive glutathione status, which favours the formation of more benign NO species, s-nitrosothiols, the predominant form in which NO is safely deployed. Cbl status may consequently act as a ‘back-up disc’ that ensures the active status of antioxidant systems, as well as reversing and modulating the effects of nitrosylation in cell signal transduction.New evidence shows that GSCbl can significantly promote iNOS/ eNOS NO synthesis in the early stages of inflammation, thus lowering high levels of tumour necrosis factor-a that normally result in pathology, while existing evidence shows that in extreme

FACILITY 810, CORNER ENTRY TO UNIT B, OBLIQUE VIEW FACING ...

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

FACILITY 810, CORNER ENTRY TO UNIT B, OBLIQUE VIEW FACING SOUTH-SOUTHWEST. - Schofield Barracks Military Reservation, Duplex Housing Type with Corner Entries, Between Hamilton & Tidball Streets near Williston Avenue, Wahiawa, Honolulu County, HI

Neuronal nitric oxide synthase (NOS1) polymorphisms interact with financial hardship to affect depression risk.

PubMed

Sarginson, Jane E; Deakin, J F William; Anderson, Ian M; Downey, Darragh; Thomas, Emma; Elliott, Rebecca; Juhasz, Gabriella

2014-11-01

There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression.

Neuronal Nitric Oxide Synthase (NOS1) Polymorphisms Interact with Financial Hardship to Affect Depression Risk

PubMed Central

Sarginson, Jane E; Deakin, JF William; Anderson, Ian M; Downey, Darragh; Thomas, Emma; Elliott, Rebecca; Juhasz, Gabriella

2014-01-01

There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression. PMID:24917196

Refining the W1 and SE1 Facilities

NASA Technical Reports Server (NTRS)

Chambers, Rodney D.

2004-01-01

The Engine Research Building (ERB) houses more than 60 test rigs that study all aspects of engine development. By working with Mary Gibson in the SE1 and W1A Turbine Facilities, I became aware of her responsibilities and better acquainted with the inner workings of the ERB. The SE1 Supersonic/Subsonic Wind Tunnel Facility contains 2 small wind tunnels. The first tunnel uses an atmospheric inlet, while the second uses treated 40-psig air. Both of the tunnels are capable of subsonic and supersonic operation. An auxiliary air supply and exhaust piping providing both test sections with suction, blowing, and crossfire capabilities. The current configuration of SE1 consists of a curved diffuser that studies the blockage along the endwalls. The W1A Low Speed Compressor Facility provides insight for the complex flow phenomena within its 4-stage axial compressor, sand the data obtained from W 1A is used to develop advanced models for fluid dynamic assessment. W1A is based off of a low speed research compressor developed by GE in the 1950's. This compressor has a removable casing treatment under rotor 1, which allows for various tip treatment studies. The increased size and low speed allows instrumentation to be located in the compressor s complex flow paths. Air enters the facility through a filtered roof vent, conditioned for temperature and turbulence, and then passed through the compressor W1A is described as a dynamic facility with many projects taking place simultaneously. This current environment makes it challenging to follow the various affairs that are taking place within the area. During my first 4 weeks at the NASA Glenn Research Center, I have assisted Mary Gibson in multiple tasks such as facility documents, record keeping, maintenance and upgrades. The facility has lube systems for its gearbox and compressor. These systems are critical in the successful operation of the facility. I was assigned the task of creating a facility estimate list, which included the

Moringa fruit inhibits LPS-induced NO/iNOS expression through suppressing the NF-κ B activation in RAW264.7 cells.

PubMed

Lee, Hyo-Jin; Jeong, Yun-Jeong; Lee, Tae-Sung; Park, Yoon-Yub; Chae, Whi-Gun; Chung, Il-Kyung; Chang, Hyeun-Wook; Kim, Cheorl-Ho; Choi, Yung-Hyun; Kim, Wun-Jae; Moon, Sung-Kwon; Chang, Young-Chae

2013-01-01

In this study, we evaluated the anti-inflammatory effects of moringa (Moringa oleifera Lam.), a natural biologically active substance, by determining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Extracts from different parts of moringa (root, leaf, and fruit) reduced LPS-induced nitric oxide (NO) release in a dose-dependent manner. The moringa fruit extract most effectively inhibited LPS-induced NO production and levels of inducible nitric oxide synthase (iNOS). The moringa fruit extract also was shown to suppress the production of inflammatory cytokines including IL-1β, TNF-α, and IL-6. Furthermore, moringa fruit extract inhibited the cytoplasmic degradation of I κ B -α and the nuclear translocation of p65 proteins, resulting in lower levels of NF -κ B transactivation. Collectively, the results of this study demonstrate that moringa fruit extract reduces the levels of pro-inflammatory mediators including NO , IL-1β, TNF-α, and IL-6 via the inhibition of NF -κ B activation in RAW264.7 cells. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of moringa fruit extract.

MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bi, Rui; Bao, Chunrong; Jiang, Lianyong

Pulmonary artery endothelial dysfunction is associated with pulmonary arterial hypertension (PAH). Based on recent studies showing that microRNA (miR)-27b is aberrantly expressed in PAH, we hypothesized that miR-27b may contribute to pulmonary endothelial dysfunction and vascular remodeling in PAH. The effect of miR-27b on pulmonary endothelial dysfunction and the underlying mechanism were investigated in human pulmonary artery endothelial cells (HPAECs) in vitro and in a monocrotaline (MCT)-induced model of PAH in vivo. miR-27b expression was upregulated in MCT-induced PAH and inversely correlated with the levels of peroxisome proliferator-activated receptor (PPAR)-γ, and miR-27b inhibition attenuated MCT-induced endothelial dysfunction and remodeling and prevented PAHmore » associated right ventricular hypertrophy and systolic pressure in rats. PPARγ was confirmed as a direct target of miR-27b in HPAECs and shown to mediate the effect of miR-27b on the disruption of endothelial nitric oxide synthase (eNOS) coupling to Hsp90 and the suppression of NO production associated with the PAH phenotype. We showed that miR-27b plays a role endothelial function and NO release and elucidated a potential mechanism by which miR-27b regulates Hsp90-eNOS and NO signaling by modulating PPARγ expression, providing potential therapeutic targets for the treatment of PAH. - Highlights: • miR-27b plays a role in endothelial function and NO release. • miR-27b inhibition ameliorates MCT-induced endothelial dysfunction and PAH. • miR-27b targets PPARγ in HPAECs. • miR-27b regulates PPARγ dependent Hsp90-eNOS and NO signaling.« less

Zeb1-Hdac2-eNOS circuitry identifies early cardiovascular precursors in naive mouse embryonic stem cells.

PubMed

Cencioni, Chiara; Spallotta, Francesco; Savoia, Matteo; Kuenne, Carsten; Guenther, Stefan; Re, Agnese; Wingert, Susanne; Rehage, Maike; Sürün, Duran; Siragusa, Mauro; Smith, Jacob G; Schnütgen, Frank; von Melchner, Harald; Rieger, Michael A; Martelli, Fabio; Riccio, Antonella; Fleming, Ingrid; Braun, Thomas; Zeiher, Andreas M; Farsetti, Antonella; Gaetano, Carlo

2018-03-29

Nitric oxide (NO) synthesis is a late event during differentiation of mouse embryonic stem cells (mESC) and occurs after release from serum and leukemia inhibitory factor (LIF). Here we show that after release from pluripotency, a subpopulation of mESC, kept in the naive state by 2i/LIF, expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes NO. This eNOS/NO-positive subpopulation (ESNO+) expresses mesendodermal markers and is more efficient in the generation of cardiovascular precursors than eNOS/NO-negative cells. Mechanistically, production of endogenous NO triggers rapid Hdac2 S-nitrosylation, which reduces association of Hdac2 with the transcriptional repression factor Zeb1, allowing mesendodermal gene expression. In conclusion, our results suggest that the interaction between Zeb1, Hdac2, and eNOS is required for early mesendodermal differentiation of naive mESC.

Nos2 inactivation promotes the development of medulloblastoma in Ptch1(+/-) mice by deregulation of Gap43-dependent granule cell precursor migration.

PubMed

Haag, Daniel; Zipper, Petra; Westrich, Viola; Karra, Daniela; Pfleger, Karin; Toedt, Grischa; Blond, Frederik; Delhomme, Nicolas; Hahn, Meinhard; Reifenberger, Julia; Reifenberger, Guido; Lichter, Peter

2012-01-01

Medulloblastoma is the most common malignant brain tumor in children. A subset of medulloblastoma originates from granule cell precursors (GCPs) of the developing cerebellum and demonstrates aberrant hedgehog signaling, typically due to inactivating mutations in the receptor PTCH1, a pathomechanism recapitulated in Ptch1(+/-) mice. As nitric oxide may regulate GCP proliferation and differentiation, we crossed Ptch1(+/-) mice with mice lacking inducible nitric oxide synthase (Nos2) to investigate a possible influence on tumorigenesis. We observed a two-fold higher medulloblastoma rate in Ptch1(+/-) Nos2(-/-) mice compared to Ptch1(+/-) Nos2(+/+) mice. To identify the molecular mechanisms underlying this finding, we performed gene expression profiling of medulloblastomas from both genotypes, as well as normal cerebellar tissue samples of different developmental stages and genotypes. Downregulation of hedgehog target genes was observed in postnatal cerebellum from Ptch1(+/+) Nos2(-/-) mice but not from Ptch1(+/-) Nos2(-/-) mice. The most consistent effect of Nos2 deficiency was downregulation of growth-associated protein 43 (Gap43). Functional studies in neuronal progenitor cells demonstrated nitric oxide dependence of Gap43 expression and impaired migration upon Gap43 knock-down. Both effects were confirmed in situ by immunofluorescence analyses on tissue sections of the developing cerebellum. Finally, the number of proliferating GCPs at the cerebellar periphery was decreased in Ptch1(+/+) Nos2(-/-) mice but increased in Ptch1(+/-) Nos2(-/) (-) mice relative to Ptch1(+/-) Nos2(+/+) mice. Taken together, these results indicate that Nos2 deficiency promotes medulloblastoma development in Ptch1(+/-) mice through retention of proliferating GCPs in the external granular layer due to reduced Gap43 expression. This study illustrates a new role of nitric oxide signaling in cerebellar development and demonstrates that the localization of pre-neoplastic cells during

eNOS gene Glu298Asp and 4b/a polymorphisms are associated with renal function parameters in Mexican patients with Fabry disease.

PubMed

Marin-Medina, A; Brambila-Tapia, A J L; Picos-Cárdenas, V J; Gallegos-Arreola, M P; Figuera, L E

2016-10-24

Fabry disease (FD) is an inherited X-linked lysosomal disease that causes renal failure in a high percentage of affected individuals. The eNOS gene encodes for endothelial nitric oxide synthase, which plays an important role in glomerular hemodynamics. This gene has two main polymorphisms (Glu298Asp and 4b/a) that have been studied in the context of many different diseases, including those involving cardiovascular and renal alterations. Considering the lack of information regarding eNOS variants and FD, we investigated whether there were associations between eNOS genetic variants and renal function parameters in Mexican patients with FD and renal impairment. In total, 15 FD patients with renal alterations were included in the present study, and associations between eNOS polymorphisms and renal function parameters (urea, creatinine, and GFR) were evaluated. The Asp298 and 4a alleles of the eNOS gene were found to be significantly associated with increased levels of urea and creatinine, and a decreased glomerular filtration rate in FD patients, and this association behaved in a co-dominant fashion. Our results coincide with previous reports showing an association between these polymorphisms and kidney disease, and along with other studies regarding their role in the nitric oxide pathway, suggest that these variants affect the severity of nephropathy in patients with FD.

38. View of DRS 1, 2, and 3 (structure nos. ...

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

38. View of DRS 1, 2, and 3 (structure nos. 735, 736, and 737) console fault locator for beam power status, radio frequency (RF) and intermediate frequency (IF) fault conditions, RF switches status and TR status. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

Role of ERK1/2 kinase in the expression of iNOS by NDMA in human neutrophils.

PubMed

Ratajczak-Wrona, Wioletta; Jablonska, Ewa; Garley, Marzena; Jablonski, Jakub; Radziwon, Piotr

2013-01-01

Potential role of ERK1/2 kinase in conjunction with p38 in the regulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, and superoxide anion generation by human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA) was determined. Increased synthesis of NO due to the involvement of iNOS in neutrophils exposed to NDMA was observed. In addition, intensified activation of ERK1/2 and p38 kinases was determined in these cells. Inhibition of kinase regulated by extracellular signals (ERK1/2) pathway, in contrast to p38 pathway, led to an increased production of NO and expression of iNOS in PMNs. Moreover, as a result of inhibition of ERK1/2 pathway, a decreased activation of p38 kinase was observed in neutrophils, while inhibition of p38 kinase did not affect activation of ERK1/2 pathway in these cells. An increased ability to release superoxide anion by the studied PMNs was observed, which decreased after ERK1/2 pathway inhibition. In conclusion, in human neutrophils, ERK1/2 kinase is not directly involved in the regulation of iNOS and NO production induced by NDMA; however, the kinase participates in superoxide anion production in these cells.

Attenuation of smoke induced neuronal and physiological changes by bacoside rich extract in Wistar rats via down regulation of HO-1 and iNOS.

PubMed

Pandareesh, M D; Anand, T

2014-01-01

Bacopa monniera is well known herbal medicine for its neuropharmacological effects. It alleviates variety of disorders including neuronal and physiological changes. Crackers smoke is a potent risk factor that leads to free radical mediated oxidative stress in vivo. The aim of the current study is to evaluate the protective efficacy of B. monniera extract (BME) against crackers smoke induced neuronal and physiological changes via modulating inducible nitric oxide synthase (iNOS) and hemeoxygenase-1 (HO-1) expression in rats. Rats were exposed to smoke for 1h for a period of 3 weeks and consecutively treated with BME at three different dosages (i.e., 10, 20 and 40 mg/kg b.wt.). Our results elucidate that BME treatment ameliorates histopathalogical changes, reactive oxygen species levels, lipid peroxidation, acetylcholine esterase activity and brain neurotransmitter levels to normal. BME supplementation efficiently inhibited HO-1 expression and nitric oxide generation by down-regulating iNOS expression. Smoke induced depletion of antioxidant enzyme status, monoamine oxidase activity was also replenished by BME supplementation. Thus the present study indicates that BME ameliorates various impairments associated with neuronal and physiological changes in rats exposed to crackers smoke by its potent neuromodulatory, antioxidant and adaptogenic propensity. Copyright © 2013 Elsevier Inc. All rights reserved.

76 FR 59745 - Virginia Electric and Power Company; North Anna Power Station, Unit Nos. 1 and 2; Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-27

... hours. After the high wind conditions pass, wind damage to the plant and surrounding area might preclude... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-338 and 50-339] Virginia Electric and Power Company; North Anna Power Station, Unit Nos. 1 and 2; Exemption 1.0 Background Virginia Electric Power Company...

Annual Data Summary and Climatological Evaluation CERC (Coastal Engineering Research Center) Field Research Facility, 1985. Volume 1. Main Text and Appendixes A and B.

DTIC Science & Technology

1987-09-01

AD-AI6 442 ANNUAL DATA SUMMARY AND CLINATOLOGICAL EVALUATION CEC I/ (COASTAL ENGINEERI.. (U) COASTAL ENGINEERING RESEARCH CENTER VICKSBURG NS H C ...MILLER ET RL. SEP 87 UNL ASSIF IED C RC-TR-87-i-L-1 F/0G/3 Mmsomommosmsss EmhhhmmmmmhEhEshhhhEhBhhE .EhI-EllhhlhhI mll/I/I l/I/u -1 I.I I ’ 22 I 1.8...SUMMARY AND ofEgier CLIMATOLOGICAL EVALUATION CERC FIELD RESEARCH FACILITY, 1985 NVolume I MAIN TEXT AND APPENDIXES A AND B, by ,, U Herman C . Miller

5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and Nrf-2-dependent heme oxygenase-1 induction.

PubMed

Kang, Chang-Hee; Kim, Min Jeong; Seo, Min Jeong; Choi, Yung Hyun; Jo, Wol Soon; Lee, Kyung-Tae; Jeong, Yong Kee; Kim, Gi-Young

2013-07-01

In this study, we found that 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase (iNOS) in BV2 microglia. In addition, 5HHMF blocked LPS-induced phosphorylation of IκB, resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression. Pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity. Thus, we found that 5HHMF enhances heme oxygenase-1 (HO-1) expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation. In addition, cobalt protoporphyrin (CoPP), a specific HO-1 inducer, predominantly suppressed LPS-induced NO production. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, showed a partial suppressive effect of 5HHMF on LPS-induced NO production. Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity. Taken together, our findings indicate that 5HHMF suppresses NO production through modulation of iNOS, consequently suppressing NF-κB activity and induction of Nrf2-dependent HO-1 activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Association of NOS1 gene polymorphisms with cerebral palsy in a Han Chinese population: a case-control study.

PubMed

Yu, Ting; Xia, Lei; Bi, Dan; Wang, Yangong; Shang, Qing; Zhu, Dengna; Song, Juan; Wang, Yong; Wang, Xiaoyang; Zhu, Changlian; Xing, Qinghe

2018-06-25

Cerebral palsy (CP) is the leading cause of motor disability in children; however, its pathogenesis is unknown in most cases. Growing evidence suggests that Nitric oxide synthase 1 (NOS1) is involved in neural development and neurologic diseases. The purpose of this study was to determine whether genetic variants of NOS1 contribute to CP susceptibility in a Han Chinese population. A case-control study involving 652 CP patients and 636 healthy controls was conducted. Six SNPs in the NOS1 gene (rs3782219, rs6490121, rs2293054, rs10774909, rs3741475, and rs2682826) were selected, and the MassARRAY typing technique was applied for genotyping. Data analysis was conducted using SHEsis online software, and multiple test corrections were performed using SNPSpD online software. There were no significant differences in genotype and allele frequencies between patients and controls for the SNPs except rs6490121, which deviated from Hardy-Weinberg equilibrium and was excluded from further analyses. Subgroup analysis revealed differences in genotype frequencies between the CP with neonatal encephalopathy group (CP + NE) and control group for rs10774909, rs3741475, and rs2682826 (after SNPSpD correction, p = 0.004, 0.012, and 0.002, respectively). The T allele of NOS1 SNP rs3782219 was negatively associated with spastic quadriplegia (OR = 0.742, 95% CI = 0.600-0.918, after SNPSpD correction, p = 0.023). There were no differences in allele or genotype frequencies between CP subgroups and controls for the other genetic polymorphisms. NOS1 is associated with CP + NE and spastic quadriplegia, suggesting that NOS1 is likely involved in the pathogenesis of CP and that it is a potential therapeutic target for treatment of cerebral injury.

IL-10 and NOS2 Modulate Antigen-Specific Reactivity and Nerve Infiltration by T Cells in Experimental Leprosy

PubMed Central

Hagge, Deanna A.; Scollard, David M.; Ray, Nashone A.; Marks, Vilma T.; Deming, Angelina T.; Spencer, John S.; Adams, Linda B.

2014-01-01

Background Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions. Methodology/Principal Findings The role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10−/−), as well as mice deficient in both inducible nitric oxide synthase (NOS2−/−) and IL-10 (10NOS2−/−). Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP), inflammation increased from C57Bl/6 (B6)NOS2−/−<10NOS2−/−. While IL-10−/− mice exhibited modest FP induration compared to B6, NOS2−/− and 10NOS2−/− mice developed markedly enlarged FP marking distinct phases: early (1 month), peak (3–4 months), and chronic (8 months). IFN-γ-producing CD4+CD44+ cells responding to M. leprae cell wall, membrane, and cytosol antigens and ML2028 (Ag85B) were significantly increased in the evolved granuloma in NOS2−/− FP compared to B6 and IL-10−/− during early and peak phases. In 10NOS2−/− FP, CD4+CD44+ and especially CD8+CD44+ responses were augmented even further to these antigens as well as to ML0380 (GroES), ML2038 (bacterioferritin), and ML1877 (EF-Tu). Moreover, fragmented nerves containing CD4+ cells were present in 10NOS2−/− FP. Conclusions/Significance The 10NOS2−/− strain offers insight on the regulation of granuloma formation and maintenance by immune modulators in the resistant forms of leprosy and presents a new model for investigating the

Gas-Grain Simulation Facility (GGSF). Volume 1: Stage 1 facility definition studies

NASA Technical Reports Server (NTRS)

Gat, Nahum

1993-01-01

The Gas-Grain Simulation Facility (GGSF) is a facility-type payload to be included in the Space Station Freedom (SSF). The GGSF is a multidisciplinary facility that will accommodate several classes of experiments, including exobiology, planetary science, atmospheric science, and astrophysics. The physical mechanisms envisioned to be investigated include crystal growth, aggregation, nucleation, coagulation, condensation, collisions, fractal growth, cycles of freezing and evaporation, scavenging, longevity of bacteria, and more. TRW performed a Phase A study that included analyses of the science and technical (S&T) requirements, the development of facility functional requirements, and a conceptual design of the facility. The work that was performed under Stage 1 of the Phase A study and the results to date are summarized. In this stage, facility definition studies were conducted in sufficient detail to establish the technical feasibility of the candidate strawman experiments. The studies identified technical difficulties, identified required facility subsystems, surveyed existing technology studies and established preliminary facility weight, volume, power consumption, data systems, interface definition, and crew time requirements. The results of this study served as the basis for Stage 2 of the Phase A study in which a conceptual design and a reference design were performed. The results also served as a basis for a related study for a Gas-Grain Simulation Experiment Module (GGSEM), which is an apparatus intended to perform a subset of the GGSF experiments on board a low-Earth-orbiting platform.

FACILITY 802B, BATHROOM CONVERTED TO LAUNDRY ROOM, VIEW FACING WESTNORTHWEST. ...

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

FACILITY 802B, BATHROOM CONVERTED TO LAUNDRY ROOM, VIEW FACING WEST-NORTHWEST. - Schofield Barracks Military Reservation, Bachelor Officers' Quarters Type, Between Grimes & Tidball Streets near Ayres Avenue, Wahiawa, Honolulu County, HI

Inhibition of endogenous heat shock protein 70 attenuates inducible nitric oxide synthase induction via disruption of heat shock protein 70/Na(+) /H(+) exchanger 1-Ca(2+) -calcium-calmodulin-dependent protein kinase II/transforming growth factor β-activated kinase 1-nuclear factor-κB signals in BV-2 microglia.

PubMed

Huang, Chao; Lu, Xu; Wang, Jia; Tong, Lijuan; Jiang, Bo; Zhang, Wei

2015-08-01

Inducible nitric oxide synthase (iNOS) critically contributes to inflammation and host defense. The inhibition of heat shock protein 70 (Hsp70) prevents iNOS induction in lipopolysaccharide (LPS)-stimulated macrophages. However, the role and mechanism of endogenous Hsp70 in iNOS induction in microglia remains unclear. This study addresses this issue in BV-2 microglia, showing that Hsp70 inhibition or knockdown prevents LPS-induced iNOS protein expression and nitric oxide production. Real-time PCR experiments showed that LPS-induced iNOS mRNA transcription was blocked by Hsp70 inhibition. Further studies revealed that the inhibition of Hsp70 attenuated LPS-stimulated nuclear translocation and phosphorylation of nuclear factor (NF)-κB as well as the degradation of inhibitor of κB (IκB)-α and phosphorylation of IκB kinase β (IKKβ). This prevention effect of Hsp70 inhibition on IKKβ-NF-κB activation was found to be dependent on the Ca(2+) /calcium-calmodulin-dependent protein kinase II (CaMKII)/transforming growth factor β-activated kinase 1 (TAK1) signals based on the following observations: 1) chelation of intracellular Ca(2+) or inhibition of CaMKII reduced LPS-induced increases in TAK1 phosphorylation and 2) Hsp70 inhibition reduced LPS-induced increases in CaMKII/TAK1 phosphorylation, intracellular pH value, [Ca(2+) ]i , and CaMKII/TAK1 association. Mechanistic studies showed that Hsp70 inhibition disrupted the association between Hsp70 and Na(+) /H(+) exchanger 1 (NHE1), which is an important exchanger responsible for Ca(2+) influx in LPS-stimulated cells. These studies demonstrate that the inhibition of endogenous Hsp70 attenuates the induction of iNOS, which likely occurs through the disruption of NHE1/Hsp70-Ca(2+) -CaMKII/TAK1-NF-κB signals in BV-2 microglia, providing further insight into the functions of Hsp70 in the CNS. © 2015 Wiley Periodicals, Inc.

Overall contextual view of Building Nos. 92, 391, and 392, ...

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

Overall contextual view of Building Nos. 92, 391, and 392, taken from pier side, crane rails along bravo piers in foreground, palm tree and street light at right center, view facing east-northeast - U.S. Naval Base, Pearl Harbor, Marine Railway No. 1 Accessories House & Apprentice Welding School, Additions, Intersection of Avenue B & Sixth Street, Pearl City, Honolulu County, HI

FACILITY 802B, HALLWAY, LOOKING TOWARD REAR OF HOUSE, VIEW FACING ...

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

FACILITY 802B, HALLWAY, LOOKING TOWARD REAR OF HOUSE, VIEW FACING SOUTH-SOUTHWEST. - Schofield Barracks Military Reservation, Bachelor Officers' Quarters Type, Between Grimes & Tidball Streets near Ayres Avenue, Wahiawa, Honolulu County, HI

Carica papaya ameliorates allergic asthma via down regulation of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS levels.

PubMed

Inam, Asma; Shahzad, Muhammad; Shabbir, Arham; Shahid, Hira; Shahid, Khadija; Javeed, Aqeel

2017-08-15

Natural products have a prime importance as an essential source for new drug discovery. Carica papaya leaves (CPL) have been used to treat inflammation in traditional system of medicine. Current study evaluates the anti-inflammatory and immunomodulatory effects of CPL extract using mouse model of ovalbumin- (OVA) induced allergic asthma. All the mice were intraperitoneally sensitized and subsequently given intranasal challenge with OVA except the control group. Group-III and -IV were treated for seven consecutive days with CPL extract and methylprednisolone (MP), respectively. At the end of study, histopathological examination of the lungs was performed and inflammatory cell counts were done in blood as well as bronchoalveolar lavage fluid (BALF). The mRNA expression levels of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS were measured using reverse transcription polymerase chain reaction (RT-PCR). Results showed significant attenuation of lung infiltration of inflammatory cells, alveolar thickening, and goblet cell hyperplasia after treatment with CPL extract. We also found significant suppression of total and differential leukocyte counts in both blood and BALF samples of CPL extract treated group. CPL extract also alleviated the expression levels of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS. Similarly, treatment with MP, used as a reference drug, also significantly ameliorated all the pro-inflammatory markers. Current study shows that CPL extract possesses anti-inflammatory effect in mouse model of allergic airway inflammation by down-regulating IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS expression levels. Copyright © 2017 Elsevier GmbH. All rights reserved.

Effects of NOS1AP rs12742393 polymorphism on repaglinide response in Chinese patients with type 2 diabetes mellitus.

PubMed

Wang, Tao; Wang, Yan; Lv, Dong-Mei; Song, Jin-Fang; Lu, Qian; Gao, Xing; Zhang, Fan; Guo, Hao; Li, Wei; Yin, Xiao-Xing

2014-02-01

To investigate the associations of NOS1AP rs12742393 polymorphism with the risk of type 2 diabetes mellitus (T2DM) and repaglinide therapeutic efficacy in Chinese patients with T2DM. Prospective case-control study. Academic medical center. A total of 300 patients with T2DM and 200 healthy volunteers were enrolled to identify NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay. Eighty-four patients with various genotypes were randomly selected to receive oral repaglinide as a single-agent therapy (3 mg/day) for 8 weeks. Anthropometric measurements and fasting plasma glucose (FPG), postprandial plasma glucose, hemoglobin A1c , fasting serum insulin (FINS), postprandial serum insulin, homeostasis model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol tests were obtained before and after repaglinide treatment. The risk C allelic frequency of NOS1AP rs12742393 was higher in patients with T2DM than in healthy volunteers (p<0.001). Patients with T2DM and genotypes AA and AC at NOS1AP rs12742393 had a significant reduction in FPG (mmol/l) compared with those with genotype CC (p<0.01). Patients with CC homozygotes and AC heterozygotes had a greater increase in FINS (mU/l) than those with wild-type AA (p<0.05). In addition, the carriers of genotype CC at NOS1AP rs12742393 had higher differential values of HOMA-IR compared with genotypes AC and AA carriers (p<0.001). The effects of repaglinide treatment on FPG (p<0.01), FINS (p<0.05) and HOMA-IR (p<0.001) were reduced in patients with T2DM carrying the NOS1AP rs12742393 risk C allele compared with the AA genotype carriers. The NOS1AP rs12742393 polymorphism is associated with therapeutic efficacy of repaglinide in Chinese T2DM patients. © 2013 Pharmacotherapy Publications, Inc.

AP-1 Inhibition by SR 11302 Protects Human Hepatoma HepG2 Cells from Bile Acid-Induced Cytotoxicity by Restoring the NOS-3 Expression

PubMed Central

González-Rubio, Sandra; Linares, Clara I.; Aguilar-Melero, Patricia; Rodríguez-Perálvarez, Manuel; Montero-Álvarez, José L.

2016-01-01

The harmful effects of bile acid accumulation occurring during cholestatic liver diseases have been associated with oxidative stress increase and endothelial nitric oxide synthase (NOS-3) expression decrease in liver cells. We have previously reported that glycochenodeoxycholic acid (GCDCA) down-regulates gene expression by increasing SP1 binding to the NOS-3 promoter in an oxidative stress dependent manner. In the present study, we aimed to investigate the role of transcription factor (TF) AP-1 on the NOS-3 deregulation during GCDCA-induced cholestasis. The cytotoxic response to GCDCA was characterized by 1) the increased expression and activation of TFs cJun and c-Fos; 2) a higher binding capability of these at position -666 of the NOS-3 promoter; 3) a decrease of the transcriptional activity of the promoter and the expression and activity of NOS-3; and 4) the expression increase of cyclin D1. Specific inhibition of AP-1 by the retinoid SR 11302 counteracted the cytotoxic effects induced by GCDCA while promoting NOS-3 expression recovery and cyclin D1 reduction. NOS activity inhibition by L-NAME inhibited the protective effect of SR 11302. Inducible NOS isoform was no detected in this experimental model of cholestasis. Our data provide direct evidence for the involvement of AP-1 in the NOS-3 expression regulation during cholestasis and define a critical role for NOS-3 in regulating the expression of cyclin D1 during the cell damage induced by bile acids. AP-1 appears as a potential therapeutic target in cholestatic liver diseases given its role as a transcriptional repressor of NOS-3. PMID:27490694

21 CFR 524.1580b - Nitrofurazone ointment.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... (b) Sponsors. See sponsors in § 510.600(c) of this chapter. (1) See Nos. 000010, 000069, 050749, 054925, 058005, and 061623 for use on dogs, cats, or horses. (2) See No. 017135 for use on dogs and horses. (3) See Nos. 017153 and 058829 for use on horses. (c) [Reserved] (d) Conditions of use—(1) Amount...

21 CFR 524.1580b - Nitrofurazone ointment.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... (b) Sponsors. See sponsors in § 510.600(c) of this chapter. (1) See Nos. 000010, 000069, 050749, 054925, 058005, and 061623 for use on dogs, cats, or horses. (2) See No. 017135 for use on dogs and horses. (3) See Nos. 017153 and 058829 for use on horses. (c) [Reserved] (d) Conditions of use—(1) Amount...

21 CFR 524.1580b - Nitrofurazone ointment.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... (b) Sponsors. See sponsors in § 510.600(c) of this chapter. (1) See Nos. 000010, 000069, 050749, 054925, 058005, and 061623 for use on dogs, cats, or horses. (2) See No. 017135 for use on dogs and horses. (3) See Nos. 017153 and 058829 for use on horses. (c) [Reserved] (d) Conditions of use—(1) Amount...

Lipopolysaccharide-induced overproduction of nitric oxide and overexpression of iNOS and interleukin-1β proteins in zinc-deficient rats.

PubMed

Miyazaki, Takashi; Takenaka, Tsuneo; Inoue, Tsutomu; Sato, Makiko; Miyajima, Yuka; Nodera, Makoto; Hanyu, Mayuko; Ohno, Yoichi; Shibazaki, Satomi; Suzuki, Hiromichi

2012-03-01

Zinc deficiency leads to decreased cellular immune responses. The overproduction of nitrogen species derived from inducible nitric oxide synthase (iNOS), its enzyme, and interleukine-1 beta (IL-1β), and inflammatory cytokine have been implicated in immune responses. The goal of this study was to investigate the effects of lipopolysaccharide (LPS)-induced changes in NO metabolites, iNOS, and IL-1β protein expression in the lungs of zinc-deficient rats. Male Sprague-Dawley rats (body weight, 100 g) were divided into two groups and were fed either a zinc-deficient diet (ZnD) or a zinc-containing diet (Cont). After 4 weeks on these diets, rats received a 10-mg/kg dose of LPS injected via the tail vein and were then maintained for an additional 72 h. To determine total NO concentrations in the blood, serum zinc concentration, iNOS protein expression, IL-1β, and iNOS immunohistochemistry, blood and lung samples were obtained at pre-LPS injection, 5, 24, and 72 h after injection. Total NO levels were significantly increased at 5, at 24, and at 72 h after LPS injection compared with pre-LPS injection level in ZnD group; significant changes in total NO levels was elevated at 5 h from at pre-LPS level but not significant changes from basal level at 24 and 72 h in the control group. Based on western blot analyses and immunohistochemistry, clear bands indicating iNOS and IL-1β protein expression and iNOS antibody-stained inflammatory cells were detected at 5 and 24 h in the ZnD group and 5 h in the Cont group, not observed at 24 and 72 h in the control group. These results suggest that zinc deficiency induces overexpression of iNOS and IL-1β proteins from inflammatory cells around the alveolar blood vessels, resulting in overproduction of total NO and persisted inflammatory response in the zinc-deficient rat lung. Taken together, overexpression of LPS-induced iNOS, overproduction of iNOS-derived NO, and overexpression of IL-1β may induce nitrosative and oxidative

26 CFR 1.169-1 - Amortization of pollution control facilities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Amortization of pollution control facilities. 1....169-1 Amortization of pollution control facilities. (a) Allowance of deduction—(1) In general. Under... amortization of the amortizable basis (as defined in § 1.169-3) of any certified pollution control facility (as...

26 CFR 1.169-1 - Amortization of pollution control facilities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Amortization of pollution control facilities. 1....169-1 Amortization of pollution control facilities. (a) Allowance of deduction—(1) In general. Under... amortization of the amortizable basis (as defined in § 1.169-3) of any certified pollution control facility (as...

26 CFR 1.169-1 - Amortization of pollution control facilities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 2 2012-04-01 2012-04-01 false Amortization of pollution control facilities. 1....169-1 Amortization of pollution control facilities. (a) Allowance of deduction—(1) In general. Under... amortization of the amortizable basis (as defined in § 1.169-3) of any certified pollution control facility (as...

26 CFR 1.169-1 - Amortization of pollution control facilities.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Amortization of pollution control facilities. 1....169-1 Amortization of pollution control facilities. (a) Allowance of deduction—(1) In general. Under... amortization of the amortizable basis (as defined in § 1.169-3) of any certified pollution control facility (as...

26 CFR 1.169-1 - Amortization of pollution control facilities.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Amortization of pollution control facilities. 1....169-1 Amortization of pollution control facilities. (a) Allowance of deduction—(1) In general. Under... amortization of the amortizable basis (as defined in § 1.169-3) of any certified pollution control facility (as...

U.S. Naval Base, Pearl Harbor, Operations & Message Center, Behind ...

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

U.S. Naval Base, Pearl Harbor, Operations & Message Center, Behind Facility No. 1, corner of Avenue E & Seventh Street, connected to Facility Nos. 1B & 1D by wooden bridges, Pearl City, Honolulu County, HI

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

PubMed Central

Lee, Chih-Yung Sean; Lu, Tu

2017-01-01

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin. PMID:29111977

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B.

PubMed

Lee, Chih-Yung Sean; Lu, Tu; Seydoux, Geraldine

2017-11-07

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

Centrifuge Facility Conceptual System Study. Volume 1: Facility overview and habitats

NASA Technical Reports Server (NTRS)

Synnestvedt, Robert (Editor)

1990-01-01

The results are presented for a NASA Phase 1 study conducted from mid 1987 through mid 1989 at Ames Research Center. The Centrifuge Facility is the major element of the biological research facility for the implementation of NASA's Life Science Research Program on Space Station Freedom using non-human specimens (such as small primates, rodents, plants, insects, cell tissues). Five systems are described which comprise the Facility: habitats, holding units, centrifuge, glovebox, and service unit. Volume 1 presents a facility overview and describes the habitats - modular units which house living specimens.

Fermented guava leaf extract inhibits LPS-induced COX-2 and iNOS expression in Mouse macrophage cells by inhibition of transcription factor NF-kappaB.

PubMed

Choi, Soo-Youn; Hwang, Joon-Ho; Park, Soo-Young; Jin, Yeong-Jun; Ko, Hee-Chul; Moon, Sang-Wook; Kim, Se-Jae

2008-08-01

The goal of this study was to elucidate the antiinflammatory activities of Psidium guajava L. (guava) leaf. To improve the functionality of guava leaf, it was fermented with Phellinus linteus mycelia, Lactobacillus plantarum and Saccharomyces cerevisiae. The ethanol extract from fermented guava leaf inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production. Western blot analysis showed that fermented guava leaf extract decreased LPS-induced inducible nitric oxide synthase (iNOS) and the cyclooxygenase-2 (COX-2) protein level in RAW 264.7 cells. To investigate the mechanism involved, the study examined the effect of fermented guava leaf extract on LPS-induced nuclear factor-kappaB (NF-kappaB) activation. Fermented guava leaf extract significantly inhibited LPS-induced NF-kappaB transcriptional activity. Immunochemical analysis revealed that fermented guava leaf extract suppressed LPS-induced degradation of I-kappaBalpha. Taken together, the data indicate that fermented guava leaf extract is involved in the inhibition of iNOS and COX-2 via the down-regulation of NF-kappaB pathway, revealing a partial molecular basis for the antiinflammatory properties of fermented guava leaf extract.

40 CFR Appendix B to Subpart I of... - Allowance for Facilities Planning and Design

Code of Federal Regulations, 2013 CFR

2013-07-01

... Design B Appendix B to Subpart I of Part 35 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Pt. 35, Subpt. I, App. B Appendix B to Subpart I of Part 35—Allowance for Facilities Planning and... initial award amount of all prime subagreements for building the project. b. The initial amounts approved...

40 CFR Appendix B to Subpart I of... - Allowance for Facilities Planning and Design

Code of Federal Regulations, 2011 CFR

2011-07-01

... Design B Appendix B to Subpart I of Part 35 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Pt. 35, Subpt. I, App. B Appendix B to Subpart I of Part 35—Allowance for Facilities Planning and... initial award amount of all prime subagreements for building the project. b. The initial amounts approved...

76 FR 1469 - Calvert Cliffs Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-10

... Impact Statement for License Renewal of Nuclear Plants, Calvert Cliffs Nuclear Power Plant (NUREG-1437... Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2 Environmental Assessment... Plant, LLC, the licensee, for operation of the Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

Differential effects of eNOS uncoupling on conduit and small arteries in GTP-cyclohydrolase I-deficient hph-1 mice.

PubMed

d'Uscio, Livius V; Smith, Leslie A; Katusic, Zvonimir S

2011-12-01

In the present study, we used the hph-1 mouse, which displays GTP-cyclohydrolase I (GTPCH I) deficiency, to test the hypothesis that loss of tetrahydrobiopterin (BH(4)) in conduit and small arteries activates compensatory mechanisms designed to protect vascular wall from oxidative stress induced by uncoupling of endothelial nitric oxide synthase (eNOS). Both GTPCH I activity and BH(4) levels were reduced in the aortas and small mesenteric arteries of hph-1 mice. However, the BH(4)-to-7,8-dihydrobiopterin ratio was significantly reduced only in hph-1 aortas. Furthermore, superoxide anion and 3-nitrotyrosine production were significantly enhanced in aortas but not in small mesenteric arteries of hph-1 mice. In contrast to the aorta, protein expression of copper- and zinc-containing superoxide dismutase (CuZnSOD) was significantly increased in small mesenteric arteries of hph-1 mice. Protein expression of catalase was increased in both aortas and small mesenteric arteries of hph-1 mice. Further analysis of endothelial nitric oxide synthase (eNOS)/cyclic guanosine monophosphate (cGMP) signaling demonstrated that protein expression of phosphorylated Ser(1177)-eNOS as well as basal cGMP levels and hydrogen peroxide was increased in hph-1 aortas. Increased production of hydrogen peroxide in hph-1 mice aortas appears to be the most likely mechanism responsible for phosphorylation of eNOS and elevation of cGMP. In contrast, upregulation of CuZnSOD and catalase in resistance arteries is sufficient to protect vascular tissue from increased production of reactive oxygen species generated by uncoupling of eNOS. The results of our study suggest that anatomical origin determines the ability of vessel wall to cope with oxidative stress induced by uncoupling of eNOS.

Ongoing transmission of hepatitis B virus infection among inmates at a state correctional facility.

PubMed

Khan, Amy J; Simard, Edgar P; Bower, William A; Wurtzel, Heather L; Khristova, Marina; Wagner, Karla D; Arnold, Kathryn E; Nainan, Omana V; LaMarre, Madeleine; Bell, Beth P

2005-10-01

We sought to determine hepatitis B virus (HBV) infection prevalence, associated exposures, and incidence among male inmates at a state correctional facility. A cross-sectional serological survey was conducted in June 2000, and susceptible inmates were retested in June 2001. At baseline, 230 inmates (20.5%; 95% confidence interval [CI]=18.2%, 22.9%) exhibited evidence of HBV infection, including 11 acute and 11 chronic infections. Inmates with HBV infection were more likely than susceptible inmates to have injected drugs (38.8% vs 18.0%; adjusted prevalence odds ratio [OR]=3.0; 95% CI=1.9, 4.9), to have had more than 25 female sex partners (27.7% vs 17.5%; adjusted prevalence OR=2.0; 95% CI=1.4, 3.0), and to have been incarcerated for more than 14 years (38.4% vs 17.6%; adjusted prevalence OR=1.7; 95% CI=1.1, 2.6). One year later, 18 (3.6%) showed evidence of new HBV infection. Among 19 individuals with infections, molecular analysis identified 2 clusters involving 10 inmates, each with a unique HBV sequence. We documented ongoing HBV transmission at a state correctional facility. Similar transmission may occur at other US correctional facilities and could be prevented by vaccination of inmates.

75 FR 14639 - Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating Unit Nos. 1, 2, and 3...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-26

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-003, 50-247, and 50-286; NRC-2010-0137] Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating Unit Nos. 1, 2, and 3; Environmental Assessment and Finding of No Significant Impact The U.S. Nuclear Regulatory Commission (NRC) is considering issuance of an exemption, pursuant to Title 10 of...

76 FR 39908 - Calvert Cliffs Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

... Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2; Calvert Cliffs.... DPR-53 and DPR-69, for the Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2 (CCNPP), respectively... (ISFSI), currently held by Calvert Cliffs Nuclear Power Plant, LLC as owner and licensed operator...

15 CFR 712.5 - Annual declaration requirements for facilities engaged in the production of Schedule 1 chemicals...

Code of Federal Regulations, 2013 CFR

2013-01-01

...)(2) of this section if you produced at your facility in excess of 100 grams aggregate of Schedule 1... you will produce at your facility more than 100 grams aggregate of Schedule 1 chemicals in the next... result in production of more than 100 grams aggregate of Schedule 1 chemicals. (b) Declaration forms to...

15 CFR 712.5 - Annual declaration requirements for facilities engaged in the production of Schedule 1 chemicals...

Code of Federal Regulations, 2011 CFR

2011-01-01

...)(2) of this section if you produced at your facility in excess of 100 grams aggregate of Schedule 1... you will produce at your facility more than 100 grams aggregate of Schedule 1 chemicals in the next... result in production of more than 100 grams aggregate of Schedule 1 chemicals. (b) Declaration forms to...

15 CFR 712.5 - Annual declaration requirements for facilities engaged in the production of Schedule 1 chemicals...

Code of Federal Regulations, 2014 CFR

2014-01-01

...)(2) of this section if you produced at your facility in excess of 100 grams aggregate of Schedule 1... you will produce at your facility more than 100 grams aggregate of Schedule 1 chemicals in the next... result in production of more than 100 grams aggregate of Schedule 1 chemicals. (b) Declaration forms to...

4. PART 1 OF 3 PART PANORAMA WITH NOS. CA265J5 ...

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

4. PART 1 OF 3 PART PANORAMA WITH NOS. CA-265-J-5 AND CA-265-J-6 OF FIGUEROA STREET AND LOS ANGELES RIVER VIADUCTS. NOTE TUNNEL NO.1 NORTH PORTAL AT LEFT REAR. LOOKING 268°W. - Arroyo Seco Parkway, Figueroa Street Viaduct, Spanning Los Angeles River, Los Angeles, Los Angeles County, CA

75 FR 66802 - Calvert Cliffs Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-29

... Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2; Notice of Withdrawal of...) has granted the request of Calvert Cliffs Nuclear Power Plant, LLC, the licensee, to withdraw its... for the Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2, located in Calvert County, MD. The...

PPARα induced NOS1 phosphorylation via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in Ca(2+)-regulated exocytosis.

PubMed

Tanaka, Saori; Hosogi, Shigekuni; Sawabe, Yukinori; Shimamoto, Chikao; Matsumura, Hitoshi; Inui, Toshio; Marunaka, Yoshinori; Nakahari, Takashi

2016-01-01

A PPARα (peroxisome proliferation activation receptor α) agonist (GW7647) activates nitric oxide synthase 1 (NOS1) to produce NO leading to cGMP accumulation in antral mucous cells. In this study, we examined how PPARα activates NOS1. The NO production stimulated by GW7647 was suppressed by inhibitors of PI3K (wortmannin) and Akt (AKT 1/2 Kinase Inhibitor, AKT-inh), although it was also suppressed by the inhibitors of PPARα (GW6471) and NOS1 (N-PLA). GW7647 enhanced the ACh (acetylcholine)-stimulated exocytosis (Ca(2+)-regulated exocytosis) mediated via NO, which was abolished by GW6471, N-PLA, wortmannin, and AKT-inh. The Western blotting revealed that GW7647 phosphorylates NOS1 via phosphorylation of PI3K/Akt in antral mucous cells. The immunofluorescence examinations demonstrated that PPARα existing with NOS1 co-localizes with PI3K and Akt in the cytoplasm of antral mucous cells. ACh alone and AACOCF3, an analogue of arachidonic acid (AA), induced the NOS1 phosphorylation via PI3K/Akt to produce NO, which was inhibited by GW6471. Since AA is a natural ligand for PPARα, ACh stimulates PPARα probably via AA. In conclusion, PPARα activates NOS1 via PI3K/Akt phosphorylation to produce NO in antral mucous cells during ACh stimulation.

Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS

PubMed Central

Dabiré, Hubert; Barthélémy, Inès; Blanchard-Gutton, Nicolas; Sambin, Lucien; Sampedrano, Carolina Carlos; Gouni, Vassiliki; Unterfinger, Yves; Aguilar, Pablo; Thibaud, Jean-Laurent; Ghaleh, Bijan; Bizé, Alain; Pouchelon, Jean-Louis; Blot, Stéphane; Berdeaux, Alain; Hittinger, Luc; Chetboul, Valérie; Su, Jin Bo

2012-01-01

Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 μg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin. PMID:22193759

40 CFR Table 1b to Subpart Ec of... - Emissions Limits for Small, Medium, and Large HMIWI at Affected Facilities as Defined in § 60.50c...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Waste Incinerators for Which Construction is Commenced After June 20, 1996 Pt. 60, Subpt. Ec, Table 1B... Facilities as Defined in § 60.50c(a)(3) and (4) Pollutant Units (7 percent oxygen, dry basis) Emissions... matter Milligrams per dry standard cubic meter (grains per dry standard cubic foot) 66 (0.029) 22 (0.0095...

Site overview. Part 1 of 3part panorama with nos. CA27022 ...

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

Site overview. Part 1 of 3-part panorama with nos. CA-2702-2 and CA-2707-3. Southern LTA ship hangar (building 28; hangar no. 2 in distant center of photograph. Seen from roadway leading to northern LTA ship hangar (building 29; hangar no. 1) landing pad. Looking 208 SSW. - Marine Corps Air Station Tustin, East of Red Hill Avenue between Edinger Avenue & Barranca Parkway, Tustin, Orange County, CA

Site overview. Part 1 of 3part panorama with nos. CA27022 ...

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

Site overview. Part 1 of 3-part panorama with nos. CA-2702-2 and CA-2707-3. Southern LTA ship hangar (building 28; hangar no. 2 in distant center of photograph. Seen from roadway leading to northern LTA ship hangar (building 29; hangar no. 1) landing pad. Looking 208 SSW. - Marine Corps Air Station Tustin, Northern Lighter Than Air Ship Hangar, Meffett Avenue & Maxfield Street, Tustin, Orange County, CA

The role of MAP kinases in the induction of iNOS expression in neutrophils exposed to NDMA: the involvement transcription factors.

PubMed

Ratajczak-Wrona, W; Jablonska, E; Garley, M; Jablonski, J; Radziwon, P; Iwaniuk, A

2013-01-01

The role of MAP kinases in the activation of AP-1 (c-Jun, c-Fos) and NF-κB p65 engaged in the regulation of iNOS expression in human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA) was analyzed in the study. The study included a group of 20 healthy individuals. Isolated human PMN were incubated in the presence of NDMA. Selective MAP kinases inhibitors were used. The expression of proteins in the cytoplasmic and nuclear fractions was assessed using Western blot method. The results show that NDMA intensifies iNOS, c-Jun, NF-κB p65 and IκB-α expression in the analyzed PMNs. The blocking of the p38 pathway led to lower iNOS expression, and higher expression of c-Jun and c-Fos in the cytoplasmic fraction, and also lower c-Jun expression in the nuclear fraction of PMNs exposed to NDMA. A decrease in iNOS expression in the cytoplasmic fraction, and also c-Jun in both fractions of the examined cells, was observed as a result of JNK pathway inhibition. The blocking of the ERK5 pathway led to higher iNOS, c-Jun and c-Fos expression in the cytoplasmic fraction, and higher c-Jun expression in the nuclear fraction of PMNs exposed to NDMA. The study also demonstrated that blocking of the p38 and JNK pathways resulted in higher expression of NF-κB p65 and IκB-α in the cytoplasmic fraction and their lower expression in the nuclear fraction of these cells. Our data indicate the role of MAP kinases p38 and JNK in the activation of c-Jun and NF-κB p65 transcription factors engaged in the regulation of iNOS expression in human neutrophils exposed to NDMA. However ERK5 kinase is not involved in the regulation of iNOS and NO production by those cells.

Melatonin influences NO/NOS pathway and reduces oxidative and nitrosative stress in a model of hypoxic-ischemic brain damage.

PubMed

Blanco, Santos; Hernández, Raquel; Franchelli, Gustavo; Ramos-Álvarez, Manuel Miguel; Peinado, María Ángeles

2017-01-30

In this work, using a rat model combining ischemia and hypobaric hypoxia (IH), we evaluate the relationships between the antioxidant melatonin and the cerebral nitric oxide/nitric oxide synthase (NO/NOS) system seeking to ascertain whether melatonin exerts its antioxidant protective action by balancing this key pathway, which is highly involved in the cerebral oxidative and nitrosative damage underlying these pathologies. The application of the IH model increases the expression of the three nitric oxide synthase (NOS) isoforms, as well as nitrogen oxide (NOx) levels and nitrotyrosine (n-Tyr) impacts on the cerebral cortex. However, melatonin administration before IH makes nNOS expression response earlier and stronger, but diminishes iNOS and n-Tyr expression, while both eNOS and NOx remain unchanged. These results were corroborated by nicotine adenine dinucleotide phosphate diaphorase (NADPH-d) staining, as indicative of in situ NOS activity. In addition, the rats previously treated with melatonin exhibited a reduction in the oxidative impact evaluated by thiobarbituric acid reactive substances (TBARS). Finally, IH also intensified glial fibrillary acidic protein (GFAP) expression, reduced hypoxia-inducible factor-1alpha (HIF-1α), but did not change nuclear factor kappa B (NF-κB); meanwhile, melatonin did not significantly affect any of these patterns after the application of the IH model. The antioxidant melatonin acts on the NO/NOS system after IH injury balancing the release of NO, reducing peroxynitrite formation and protecting from nitrosative/oxidative damage. In addition, this paper raises questions concerning the classical role of some controversial molecules such as NO, which are of great consequence in the final fate of hypoxic neurons. We conclude that melatonin protects the brain from hypoxic/ischemic-derived damage in the first steps of the ischemic cascade, influencing the NO/NOS pathway and reducing oxidative and nitrosative stress. Copyright �

Dietary Blue Pigments Derived from Genipin, Attenuate Inflammation by Inhibiting LPS-Induced iNOS and COX-2 Expression via the NF-κB Inactivation

PubMed Central

Wang, Qiang-Song; Xiang, Yaozu; Cui, Yuan-Lu; Lin, Ke-Ming; Zhang, Xin-Fang

2012-01-01

Background and Purpose The edible blue pigments produced by gardenia fruits have been used as value-added colorants for foods in East Asia for 20 years. However, the biological activity of the blue pigments derived from genipin has not been reported. Methodology/Principal Findings The anti-inflammatory effect of blue pigments was studied in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage in vitro. The secretions of nitric oxide (NO) and prostaglandin E2 (PGE2) were inhibited in concentration-dependent manner by blue pigments. Real-time reverse-transcription polymerase chain reaction (Real-time RT-PCR) analyses demonstrated that the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) was inhibited, moreover, ELISA results showed that the productions of IL-6 and TNF-α were inhibited. Cell-based ELISA revealed the COX-2 protein expression was inhibited. The proteome profiler array showed that 12 cytokines and chemokines involved in the inflammatory process were down-regulated by blue pigments. Blue pigments inhibited the nuclear transcription factor kappa-B (NF-κB) activation induced by LPS, and this was associated with decreasing the DNA-binding activity of p65 and p50. Furthermore, blue pigments suppressed the degradation of inhibitor of κB (IκB) α, Inhibitor of NF-κB Kinase (IKK) α, IKK-β, and phosphorylation of IκB-α. The anti-inflammatory effect of blue pigments in vivo was studied in carrageenan-induced paw edema and LPS-injecting ICR mice. Finally, blue pigments significantly inhibited paw swelling and reduced plasma TNF-α and IL-6 production in vivo. Conclusions and Implications These results suggest that the anti-inflammatory properties of blue pigments might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1β, and TNF-α expression through the down-regulation of NF-κB activation, which will provide strong scientific evidence for the

Effect of Flooding and the nosZ Gene in Bradyrhizobia on Bradyrhizobial Community Structure in the Soil.

PubMed

Saeki, Yuichi; Nakamura, Misato; Mason, Maria Luisa T; Yano, Tsubasa; Shiro, Sokichi; Sameshima-Saito, Reiko; Itakura, Manabu; Minamisawa, Kiwamu; Yamamoto, Akihiro

2017-06-24

We investigated the effects of the water status (flooded or non-flooded) and presence of the nosZ gene in bradyrhizobia on the bradyrhizobial community structure in a factorial experiment that examined three temperature levels (20°C, 25°C, and 30°C) and two soil types (andosol and gray lowland soil) using microcosm incubations. All microcosms were inoculated with Bradyrhizobium japonicum USDA6 T , B. japonicum USDA123, and B. elkanii USDA76 T , which do not possess the nosZ gene, and then half received B. diazoefficiens USDA110 T wt (wt for the wild-type) and the other half received B. diazoefficiens USDA110ΔnosZ. USDA110 T wt possesses the nosZ gene, which encodes N 2 O reductase; 110ΔnosZ, a mutant variant, does not. Changes in the community structure after 30- and 60-d incubations were investigated by denaturing-gradient gel electrophoresis and an image analysis. USDA6 T and 76 T strains slightly increased in non-flooded soil regardless of which USDA110 T strain was present. In flooded microcosms with the USDA110 T wt strain, USDA110 T wt became dominant, whereas in microcosms with the USDA110ΔnosZ, a similar change in the community structure occurred to that in non-flooded microcosms. These results suggest that possession of the nosZ gene confers a competitive advantage to B. diazoefficiens USDA110 T in flooded soil. We herein demonstrated that the dominance of B. diazoefficiens USDA110 T wt within the soil bradyrhizobial population may be enhanced by periods of flooding or waterlogging systems such as paddy-soybean rotations because it appears to have the ability to thrive in moderately anaerobic soil.

Repeated B cell depletion in treatment of refractory systemic lupus erythematosus

PubMed Central

Ng, K P; Leandro, M J; Edwards, J C; Ehrenstein, M R; Cambridge, G; Isenberg, D A

2006-01-01

Objectives To report the clinical outcome and safety profile of repeated B cell depletion in seven patients with refractory systemic lupus erythematosus (SLE). Methods Since June 2000, seven patients with refractory SLE had repeated cycles of B cell depletion (18 cycles in total, up to three cycles per patient) because of disease relapse. The clinical response (assessed by the British Isles Lupus Activity Guide (BILAG) activity index), duration of B cell depletion, and adverse events in these patients was reviewed. Results Four patients (Nos 1, 2, 3, 6) had three cycles of treatment and three (Nos 4, 5, 7) had two cycles. Four of the seven patients (Nos 1, 3, 5, 6) improved. The mean global BILAG scores dropped from 15 to 6 at 5–7 months. The median duration of clinical response and B cell depletion was 13 months and 6 months, respectively. After the third cycle, 2/4 patients (Nos 1 and 2) improved. The median duration of clinical benefit was 12 months. Most patients tolerate re‐treatment very well. Conclusion Re‐treatment with B cell depletion of patients with severe SLE is safe and may be effective for 6–12 months on average. PMID:16269424

NNSA B-Roll: MOX Facility

ScienceCinema

None

2017-12-09

In 1999, the National Nuclear Security Administration (NNSA) signed a contract with a consortium, now called Shaw AREVA MOX Services, LLC to design, build, and operate a Mixed Oxide (MOX) Fuel Fabrication Facility. This facility will be a major component in the United States program to dispose of surplus weapon-grade plutonium. The facility will take surplus weapon-grade plutonium, remove impurities, and mix it with uranium oxide to form MOX fuel pellets for reactor fuel assemblies. These assemblies will be irradiated in commercial nuclear power reactors.

NNSA B-Roll: MOX Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2010-05-21

In 1999, the National Nuclear Security Administration (NNSA) signed a contract with a consortium, now called Shaw AREVA MOX Services, LLC to design, build, and operate a Mixed Oxide (MOX) Fuel Fabrication Facility. This facility will be a major component in the United States program to dispose of surplus weapon-grade plutonium. The facility will take surplus weapon-grade plutonium, remove impurities, and mix it with uranium oxide to form MOX fuel pellets for reactor fuel assemblies. These assemblies will be irradiated in commercial nuclear power reactors.

CXCL14 and NOS1 expression in specimens from patients with stage I-IIIA nonsmall cell lung cancer after curative resection.

PubMed

Ji, Xiaoqin; Shen, Zetian; Zhao, Benxin; Yuan, Xi; Zhu, Xixu

2018-03-01

Many studies show that CXC chemokine ligand 14 (CXCL14) is highly expressed in tumor-associated stromal cells, promoting tumor cell growth, and invasion. Because of its unclear receptors, CXCL14-initiated intracellular signal cascades remain largely unknown. However, CXCL14 can regulate nitric oxide synthase 1 (NOS1) as its intracellular molecular target. In this paper, we investigated the expression of CXCL14 and NOS1 in specimens from patients with stage I-IIIA nonsmall cell lung cancer (NSCLC) after curative resection, and evaluated the prognostic significance of this gene expression in stromal fibroblasts and cancer cells.Immunohistochemistry was used to detect the expression of CXCL14 and NOS1 in 106 formalin fixed, paraffin-embedded specimens from patients with stage I-IIIA NSCLC. The chi-square test was performed to examine the correlation of CXCL14 and NOS1 expression level with clinicopathological features. The effects of the expression of CXCL14 or NOS1 on progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier and Cox hazard proportional model.The percentages of high CXCL14 expression in stromal fibroblasts and that in cancer cells were 46.2% (49/106) and 23.6% (25/106), respectively. The positive expression rates of NOS1 in cancer cells were 42.5% (45/106). The result indicated that there was a significant positive correlation between CXCL14 expression level in stromal fibroblasts and that in cancer cells (χ = 4.158, P = .041). In addition, the expression of CXCL14 in stromal fibroblasts was significantly correlated with NOS1 expression in cancer cells (χ = 16.156, P < .001). The 5-year PFS rates with low and high CXCL14 expression in stromal fibroblasts were 66.7% and 14.3% (χ = 44.008, P < .001), respectively, and the 5-year OS rates with those were 87.1% and 43.5% (χ = 21.531, P < .001), respectively. The 5-year PFS rates with negative and positive expression of NOS1 in cancer

Hypervelocity Impact (HVI). Volume 8; Tile Small Targets A-1, Ag-1, B-1, and Bg-1

NASA Technical Reports Server (NTRS)

Gorman, Michael R.; Ziola, Steven M.

2007-01-01

During 2003 and 2004, the Johnson Space Center's White Sands Testing Facility in Las Cruces, New Mexico conducted hypervelocity impact tests on the space shuttle wing leading edge. Hypervelocity impact tests were conducted to determine if Micro-Meteoroid/Orbital Debris impacts could be reliably detected and located using simple passive ultrasonic methods. The objective of Targets A-1, Ag-1, B-1, and Bg-1 was to study hypervelocity impacts on the reinforced Shuttle Heat Shield Tiles of the Wing. Impact damage was detected using lightweight, low power instrumentation capable of being used in flight.

75 FR 6223 - PSEG Nuclear LLC; Hope Creek Generating Station and Salem Nuclear Generating Station, Unit Nos. 1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-272, 50-311 and 50-354; NRC-2010-0043] PSEG Nuclear LLC; Hope Creek Generating Station and Salem Nuclear Generating Station, Unit Nos. 1 and 2; Environmental Assessment and Finding of No Significant Impact The U.S. Nuclear Regulatory Commission (NRC) is considering issuance of an Exemption, pursuant...

Effects of AAV-mediated knockdown of nNOS and GPx-1 gene expression in rat hippocampus after traumatic brain injury.

PubMed

Boone, Deborah R; Leek, Jeanna M; Falduto, Michael T; Torres, Karen E O; Sell, Stacy L; Parsley, Margaret A; Cowart, Jeremy C; Uchida, Tatsuo; Micci, Maria-Adelaide; DeWitt, Douglas S; Prough, Donald S; Hellmich, Helen L

2017-01-01

Virally mediated RNA interference (RNAi) to knock down injury-induced genes could improve functional outcome after traumatic brain injury (TBI); however, little is known about the consequences of gene knockdown on downstream cell signaling pathways and how RNAi influences neurodegeneration and behavior. Here, we assessed the effects of adeno-associated virus (AAV) siRNA vectors that target two genes with opposing roles in TBI pathogenesis: the allegedly detrimental neuronal nitric oxide synthase (nNOS) and the potentially protective glutathione peroxidase 1 (GPx-1). In rat hippocampal progenitor cells, three siRNAs that target different regions of each gene (nNOS, GPx-1) effectively knocked down gene expression. However, in vivo, in our rat model of fluid percussion brain injury, the consequences of AAV-siRNA were variable. One nNOS siRNA vector significantly reduced the number of degenerating hippocampal neurons and showed a tendency to improve working memory. GPx-1 siRNA treatment did not alter TBI-induced neurodegeneration or working memory deficits. Nevertheless, microarray analysis of laser captured, virus-infected neurons showed that knockdown of nNOS or GPx-1 was specific and had broad effects on downstream genes. Since nNOS knockdown only modestly ameliorated TBI-induced working memory deficits, despite widespread genomic changes, manipulating expression levels of single genes may not be sufficient to alter functional outcome after TBI.

Regulation of iNOS function and cellular redox state by macrophage Gch1 reveals specific requirements for tetrahydrobiopterin in NRF2 activation

PubMed Central

McNeill, Eileen; Crabtree, Mark J.; Sahgal, Natasha; Patel, Jyoti; Chuaiphichai, Surawee; Iqbal, Asif J.; Hale, Ashley B.; Greaves, David R.; Channon, Keith M.

2015-01-01

Inducible nitric oxide synthase (iNOS) is a key enzyme in the macrophage inflammatory response, which is the source of nitric oxide (NO) that is potently induced in response to proinflammatory stimuli. However, the specific role of NO production, as distinct from iNOS induction, in macrophage inflammatory responses remains unproven. We have generated a novel mouse model with conditional deletion of Gch1, encoding GTP cyclohydrolase 1 (GTPCH), an essential enzyme in the biosynthesis of tetrahydrobiopterin (BH4) that is a required cofactor for iNOS NO production. Mice with a floxed Gch1 allele (Gch1fl/fl) were crossed with Tie2cre transgenic mice, causing Gch1 deletion in leukocytes (Gch1fl/flTie2cre). Macrophages from Gch1fl/flTie2cre mice lacked GTPCH protein and de novo biopterin biosynthesis. When activated with LPS and IFNγ, macrophages from Gch1fl/flTie2cre mice induced iNOS protein in a manner indistinguishable from wild-type controls, but produced no detectable NO, as judged by L-citrulline production, EPR spin trapping of NO, and by nitrite accumulation. Incubation of Gch1fl/flTie2cre macrophages with dihydroethidium revealed significantly increased production of superoxide in the presence of iNOS expression, and an iNOS-independent, BH4-dependent increase in other ROS species. Normal BH4 levels, nitric oxide production, and cellular redox state were restored by sepiapterin, a precursor of BH4 production by the salvage pathway, demonstrating that the effects of BH4 deficiency were reversible. Gch1fl/flTie2cre macrophages showed only minor alterations in cytokine production and normal cell migration, and minimal changes in basal gene expression. However, gene expression analysis after iNOS induction identified 78 genes that were altered between wild-type and Gch1fl/flTie2cre macrophages. Pathway analysis identified decreased NRF2 activation, with reduced induction of archetypal NRF2 genes (gclm, prdx1, gsta3, nqo1, and catalase) in BH4-deficient Gch1fl

Rerouting the Pathway for the Biosynthesis of the Side Ring System of Nosiheptide: The Roles of NosI, NosJ, and NosK

PubMed Central

2017-01-01

Nosiheptide (NOS) is a highly modified thiopeptide antibiotic that displays formidable in vitro activity against a variety of Gram-positive bacteria. In addition to a central hydroxypyridine ring, NOS contains several other modifications, including multiple thiazole rings, dehydro-amino acids, and a 3,4-dimethylindolic acid (DMIA) moiety. The DMIA moiety is required for NOS efficacy and is synthesized from l-tryptophan in a series of reactions that have not been fully elucidated. Herein, we describe the role of NosJ, the product of an unannotated gene in the biosynthetic operon for NOS, as an acyl carrier protein that delivers 3-methylindolic acid (MIA) to NosK. We also reassign the role of NosI as the enzyme responsible for catalyzing the ATP-dependent activation of MIA and MIA’s attachment to the phosphopantetheine moiety of NosJ. Lastly, NosK catalyzes the transfer of the MIA group from NosJ-MIA to a conserved serine residue (Ser102) on NosK. The X-ray crystal structure of NosK, solved to 2.3 Å resolution, reveals that the protein is an α/β-fold hydrolase. Ser102 interacts with Glu210 and His234 to form a catalytic triad located at the bottom of an open cleft that is large enough to accommodate the thiopeptide framework. PMID:28343381

Los Angeles County Poor Farm, Patient Ward Nos. 210 & ...

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

Los Angeles County Poor Farm, Patient Ward Nos. 210 & 211 - Type B Plan, 7601 Imperial Highway; bounded by Esperanza Street, Laurel Street, Flores Street, and Descanso Street, Downey, Los Angeles County, CA

40 CFR 35.925-1 - Facilities planning.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Facilities planning. 35.925-1 Section... Facilities planning. That, if the award is for step 2, step 3, or step 2=3 grant assistance, the facilities planning requirements in § 35.917 et seq. have been met. ...

CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Ki Chan; Hyun Joo, So; Shin, Chan Young, E-mail: chanyshin@kku.ac.kr

2011-06-17

Highlights: {yields} Expression and phosphorylation of CPEB1 is increased by LPS stimulation in rat primary astrocytes. {yields} JNK regulates expression and phosphorylation of CPEB1 in reactive astrocytes. {yields} Down-regulation of CPEB1 using siRNA inhibits oxidative stress and iNOS induction by LPS stimulation. {yields} CPEB1 may play an important role in regulating inflammatory responses in reactive astrocytes induced by LPS. -- Abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury,more » yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.« less

Endothelial AMPK Activation Induces Mitochondrial Biogenesis and Stress Adaptation via eNOS-Dependent mTORC1 Signaling

PubMed Central

Li, Chunying; Reif, Michaella M; Craige, Siobhan; Kant, Shashi; Keaney, John F.

2016-01-01

Metabolic stress sensors like AMP-activated protein kinase (AMPK) are known to confer stress adaptation and promote longevity in lower organisms. This study demonstrates that activating the metabolic stress sensor AMP-activated protein kinase (AMPK) in endothelial cells helps maintain normal cellular function by promoting mitochondrial biogenesis and stress adaptation. To better define the mechanisms whereby AMPK promotes endothelial stress resistance, we used 5-aminoimidazole-4-carboxamide riboside (AICAR) to chronically activate AMPK and observed stimulation of mitochondrial biogenesis in wild type mouse endothelium, but not in endothelium from endothelial nitric oxide synthase knockout (eNOS-null) mice. Interestingly, AICAR-enhanced mitochondrial biogenesis was blocked by pretreatment with the mammalian target of rapamycin complex 1 (mTORC1) inhibitor, rapamycin. Further, AICAR stimulated mTORC1 as determined by phosphorylation of its known downstream effectors in wild type, but not eNOS-null, endothelial cells. Together these data indicate that eNOS is needed to couple AMPK activation to mTORC1 and thus promote mitochondrial biogenesis and stress adaptation in the endothelium. These data suggest a novel mechanism for mTORC1 activation that is significant for investigations in vascular dysfunction. PMID:26989010

Acute hepatitis B outbreaks in 2 skilled nursing facilities and possible sources of transmission: North Carolina, 2009-2010.

PubMed

Seña, Arlene C; Moorman, Anne; Njord, Levi; Williams, Roxanne E; Colborn, James; Khudyakov, Yury; Drobenuic, Jan; Xia, Guo-Liang; Wood, Hattie; Moore, Zack

2013-07-01

Acute hepatitis B virus (HBV) infections have been reported in long-term care facilities (LTCFs), primarily associated with infection control breaks during assisted blood glucose monitoring. We investigated HBV outbreaks that occurred in separate skilled nursing facilities (SNFs) to determine factors associated with transmission. Outbreak investigation with case-control studies. Two SNFs (facilities A and B) in Durham, North Carolina, during 2009-2010. Residents with acute HBV infection and controls randomly selected from HBV-susceptible residents during the outbreak period. After initial cases were identified, screening was offered to all residents, with repeat testing 3 months later for HBV-susceptible residents. Molecular testing was performed to assess viral relatedness. Infection control practices were observed. Case-control studies were conducted to evaluate associations between exposures and acute HBV infection in each facility. Six acute HBV cases were identified in each SNF. Viral phylogenetic analysis revealed a high degree of HBV relatedness within, but not between, facilities. No evaluated exposures were significantly associated with acute HBV infection in facility A; those associated with infection in facility B (all odds ratios >20) included injections, hospital or emergency room visits, and daily blood glucose monitoring. Observations revealed absence of trained infection control staff at facility A and suboptimal hand hygiene practices during blood glucose monitoring and insulin injections at facility B. These outbreaks underscore the vulnerability of LTCF residents to acute HBV infection, the importance of surveillance and prompt investigation of incident cases, and the need for improved infection control education to prevent transmission.

Multiple Independent Genetic Factors at NOS1AP Modulate the QT Interval in a Multi-Ethnic Population

PubMed Central

Arking, Dan E.; Khera, Amit; Xing, Chao; Kao, W. H. Linda; Post, Wendy; Boerwinkle, Eric; Chakravarti, Aravinda

2009-01-01

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6×10−5) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP × sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63×10−8), as well as the sex-interaction with rs16847548 (P = 8.68×10−6). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval. PMID:19180230

Investigation of gene expression and serum levels of PIN1 and eNOS with high blood pressure in patients with Alzheimer disease.

PubMed

Azimi, Mina; Nikanfar, Masoud; Khakikhatibi, Fatemeh; Rahbarghazi, Reza; Nourazarian, Seyed Manuchehr; Biray Avci, Cigir; Nourazarian, Alireza

2017-09-01

According to evidence, Alzheimer's disease is known as one of the most serious neurodegenerative diseases, for which hypertension has been observed to be a key risk factor. Therefore, this study aims to examine the relationship between the PIN1 and eNOS genes expression, as well as serum levels and hypertension in Alzheimer's disease sufferers. Blood samples were obtained from subjects who were divided into four groups: the control group, normotensive Alzheimer's patients, the Alzheimer's sufferers group with hypertension, and the healthy group with only hypertension, considering the inhibition of confounding factors. Thereafter, eNOS and PIN1 genes expression along with serum levels were studied. Based on the obtained results, a statistically significant correlation didn't exist between serum level of PIN1 and the systolic and diastolic blood pressure, between serum level of eNOS and diastolic blood pressure in the norm tension Alzheimer's disease patients, between serum levels of PIN1, eNOS and systolic blood pressure, and between serum eNOS and systolic and diastolic blood pressure in the patients with hypertension (p<0.05). According to the results obtained from this study, measuring the serum levels of eNOS and Pin1 may contribute to the prognosis, prevention, and monitoring of hypertension and also to the reduction of death rates from cardiovascular diseases in Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Technicians Manufacture a Nozzle for the Kiwi B-1-B Engine

NASA Image and Video Library

1964-05-21

Technicians manufacture a nozzle for the Kiwi B-1-B nuclear rocket engine in the Fabrication Shop’s vacuum oven at the National Aeronautics and Space Administration (NASA) Lewis Research Center. The Nuclear Engine for Rocket Vehicle Applications (NERVA) was a joint NASA and Atomic Energy Commission (AEC) endeavor to develop a nuclear-powered rocket for both long-range missions to Mars and as a possible upper-stage for the Apollo Program. The early portion of the program consisted of basic reactor and fuel system research. This was followed by a series of Kiwi reactors built to test basic nuclear rocket principles in a non-flying nuclear engine. The next phase, NERVA, would create an entire flyable engine. The final phase of the program, called Reactor-In-Flight-Test, would be an actual launch test. The AEC was responsible for designing the nuclear reactor and overall engine. NASA Lewis was responsible for developing the liquid-hydrogen fuel system. The turbopump, which pumped the fuels from the storage tanks to the engine, was the primary tool for restarting the engine. The NERVA had to be able to restart in space on its own using a safe preprogrammed startup system. Lewis researchers endeavored to design and test this system. This non-nuclear Kiwi engine, seen here, was being prepared for tests at Lewis’ High Energy Rocket Engine Research Facility (B-1) located at Plum Brook Station. The tests were designed to start an unfueled Kiwi B-1-B reactor and its Aerojet Mark IX turbopump without any external power.

Eupatolide inhibits lipopolysaccharide-induced COX-2 and iNOS expression in RAW264.7 cells by inducing proteasomal degradation of TRAF6.

PubMed

Lee, Jongkyu; Tae, Nara; Lee, Jung Joon; Kim, Taeho; Lee, Jeong-Hyung

2010-06-25

Inula britannica is a traditional medicinal plant used to treat bronchitis, digestive disorders, and inflammation in Eastern Asia. Here, we identified eupatolide, a sesquiterpene lactone from I. britannica, as an inhibitor of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Eupatolide inhibited the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) as well as iNOS and COX-2 protein expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Eupatolide dose-dependently decreased the mRNA levels and the promoter activities of COX-2 and iNOS in LPS-stimulated RAW264.7 cells. Moreover, eupatolide significantly suppressed the LPS-induced expression of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) reporter genes. Pretreatment of eupatolide inhibited LPS-induced phosphorylation and degradation of I kappaB alpha, and phosphorylation of RelA/p65 on Ser-536 as well as the activation of mitogen-activated protein kinases (MAPKs) and Akt in LPS-stimulated RAW264.7 cells. Eupatolide induced proteasomal degradation of tumor necrosis factor receptor-associated factor-6 (TRAF6), and subsequently inhibited LPS-induced TRAF6 polyubiquitination. These results suggest that eupatolide blocks LPS-induced COX-2 and iNOS expression at the transcriptional level through inhibiting the signaling pathways such as NF-kappaB and MAPKs via proteasomal degradation of TRAF6. Taken together, eupatolide may be a novel anti-inflammatory agent that induces proteasomal degradation of TRAF6, and a valuable compound for modulating inflammatory conditions. (c) 2010 Elsevier B.V. All rights reserved.

cAMP inhibits inducible nitric oxide synthase expression and NF-kappaB-binding activity in cultured rat hepatocytes.

PubMed

Harbrecht, B G; Taylor, B S; Xu, Z; Ramalakshmi, S; Ganster, R W; Geller, D A

2001-08-01

The inducible nitric oxide synthase (iNOS) is strongly expressed following inflammatory stimuli. Adenosine 3',5'-cyclic monophosphate (cAMP) increases iNOS expression and activity in a number of cell types but decreases cytokine-stimulated iNOS expression in hepatocytes. The mechanisms for this effect are unknown. Rat hepatocytes were stimulated with cytokines to induce iNOS and cultured with cAMP agonists dibutyryl-cAMP (dbcAMP), 8-bromo-cAMP, and forskolin (FSK). Nitric oxide synthesis was assessed by supernatant nitrite levels and iNOS expression was measured by Northern and Western blot analyses. Nuclear factor kappaB binding was assessed by electromobility shift assay. Cyclic AMP dose dependently decreased NO synthesis in response to a combination of proinflammatory cytokines or interleukin-1beta (IL-1beta) alone. The adenylate cyclase inhibitor SQ 22,536 increased cytokine- or IL-1beta-stimulated NO synthesis. dbcAMP decreased iNOS mRNA expression and iNOS protein expression. Both dbcAMP and glucagon decreased iNOS promoter activity in rat hepatocytes transfected with the murine iNOS promoter and decreased DNA binding of the transcription factor NF-kappaB. These data suggest that cAMP is important in hepatocyte iNOS expression and agents that alter cAMP levels may profoundly alter the response of hepatocytes to inflammatory stimuli through effects onthe iNOS promoter region and NF-kappaB. Copyright 2001 Academic Press.

75 FR 13318 - Virginia Electric and Power Company; Surry Power Station, Unit Nos. 1 and 2 (Surry 1 and 2...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-19

... notice. SUMMARY: This document corrects a notice appearing in the Federal Register on March 3, 2010 (75... Power Company; Surry Power Station, Unit Nos. 1 and 2 (Surry 1 and 2); Correction to Environmental... Surry 1 and 2, respectively.'' This action is necessary to add an implementation date for Surry Unit 2...

Zinc chelation decreases IFN-β-induced STAT1 upregulation and iNOS expression in RAW 264.7 macrophages.

PubMed

Reiber, Cathleen; Brieger, Anne; Engelhardt, Gabriela; Hebel, Silke; Rink, Lothar; Haase, Hajo

2017-12-01

One consequence of lipopolysaccharide (LPS)-induced stimulation of macrophages is the release of Interferon (IFN)-β, and subsequently the activation of the JAK-STAT1 pathway, resulting in the expression of inducible nitric oxide synthase (iNOS). Free intracellular zinc ions (Zn 2+ ) have a profound impact as a second messenger in LPS-dependent gene expression. Previous work had indicated a Zn 2+ -dependent upregulation of STAT1 mRNA in response to LPS and IFN-β, potentially affecting STAT1-dependent downstream signaling upon pre-incubation with these agents. The aim of the present study was to investigate the long-term influence of Zn 2+ chelation on cellular STAT1 levels and their effect on protein levels and activity of iNOS. The LPS- and IFN-β-mediated increase of STAT1 mRNA and protein levels was abrogated by chelation of Zn 2+ with the membrane permeable chelator N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) in RAW 264.7 macrophages. After 48h pre-incubation together with IFN-β, TPEN also led to reduced nitric monoxide formation in response to a second stimulation with LPS. Nonetheless, the latter was observed regardless of any pre-incubation with IFN-β, suggesting that the effect of treatment with TPEN negatively affects iNOS induction independently from cellular STAT1 levels. In conclusion, long term Zn 2+ chelation does affect STAT1 protein expression, but interferes with NO production by a different, yet unknown pathway not involving STAT1. However, as there are many additional STAT1-dependent genes, there might still be effects on targets other than iNOS. Copyright © 2017 Elsevier GmbH. All rights reserved.

Heat Shock Protein-70 Inducers and iNOS Inhibitors as Therapeutics to Ameliorate Hemorrhagic Shock

DTIC Science & Technology

2004-09-01

downregulation of iNOS can limit tissue injury caused by ischemia / reperfusion or hemorrhage/resuscitation. In our laboratory, geldanamycin, a member of... ischemia / reperfusion [Charier 1999]. Mice deficient in inducible NO synthase (iNOS) also demonstrate limited hemorrhage/resuscitation-induced injury ...tissues and leukotriene B4 (LTB4) generation increases. In a hemorrhage/resuscitation-induced injury model, iNOS, cyclooxygenase- 2 , and CD14 are all

Regional Transmission Planning: A review of practices following FERC Order Nos. 890 and 1000

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eto, Joseph H.; Gallo, Guilia

Federal Energy Regulatory Commission (FERC) Order Nos. 890 and 10001 established requirements that transmission planning regions must follow in regional transmission planning and allocating the costs of new transmission facilities. Order No. 890, issued in 2007, outlined general requirements for local as well as regional transmission planning practices and procedures. Order No. 1000, issued in 2011, laid out specific requirements for: (1) regional transmission planning; (2) consideration of transmission needs driven by public policy requirements; (3) non-incumbent transmission development; (4) interregional transmission coordination; and (5) cost allocation for transmission facilities that have been selected in a regional transmission plan formore » purposes of cost allocation. This report reviews how these FERC orders are being implemented by the 12 transmission planning regions recognized by FERC.« less

Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock: Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression

PubMed Central

Sampaio, André L. F.; Dalli, Jesmond; Brancaleone, Vincenzo; D'Acquisto, Fulvio; Perretti, Mauro; Wheatley, Carmen

2013-01-01

Background. NOS/•NO inhibitors are potential therapeutics for sepsis, yet they increase clinical mortality. However, there has been no in vivo investigation of the (in vitro) •NO scavenger, cobalamin's (Cbl) endogenous effects on NOS/•NO/inflammatory mediators during the immune response to sepsis. Methods. We used quantitative polymerase chain reaction (qPCR), ELISA, Western blot, and NOS Griess assays, in a C57BL/6 mouse, acute endotoxaemia model. Results. During the immune response, pro-inflammatory phase, parenteral hydroxocobalamin (HOCbl) treatment partially inhibits hepatic, but not lung, iNOS mRNA and promotes lung eNOS mRNA, but attenuates the LPS hepatic rise in eNOS mRNA, whilst paradoxically promoting high iNOS/eNOS protein translation, but relatively moderate •NO production. HOCbl/NOS/•NO regulation is reciprocally associated with lower 4 h expression of TNF-α, IL-1β, COX-2, and lower circulating TNF-α, but not IL-6. In resolution, 24 h after LPS, HOCbl completely abrogates a major late mediator of sepsis mortality, high mobility group box 1 (HMGB1) mRNA, inhibits iNOS mRNA, and attenuates LPS-induced hepatic inhibition of eNOS mRNA, whilst showing increased, but still moderate, NOS activity, relative to LPS only. experiments (LPS+D-Galactosamine) HOCbl afforded significant, dose-dependent protection in mice Conclusions. HOCbl produces a complex, time- and organ-dependent, selective regulation of NOS/•NO during endotoxaemia, corollary regulation of downstream inflammatory mediators, and increased survival. This merits clinical evaluation. PMID:23781123

The influence of authentic scientific research experiences on teachers' conceptions of the nature of science (NOS) and their NOS teaching practices

NASA Astrophysics Data System (ADS)

Moriarty, Meghan A.

This study explored the influence of teachers' authentic scientific research experiences (ASREs) on teachers' conceptions of the nature of science (NOS) and teachers' NOS instruction. Twelve high school biology teachers participated in this study. Six of the participants had authentic scientific research experience (ASRE) and six had not participated in authentic scientific research. Data included background surveys, modified Views of the Nature of Science (VNOS) questionnaires, interviews, and teaching observations. Data was coded based on the eight NOS understandings outlined in 2013 in the Next Generation Science Standards (NGSS). Evidence from this study indicates participating in authentic scientific research as a member of a scientific community has dual benefits of enabling high school science teachers with informed understandings of the NOS and positioning them to teach with the NOS. However, these benefits do not always result from an ASRE. If the nature of the ASRE is limited, then it may limit teachers' NOS understandings and their NOS teaching practices. The results of this study suggest that participation in ASREs may be one way to improve teachers' NOS understandings and teaching practices if the experiences themselves offer a comprehensive view of the NOS. Because ASREs and other science learning experiences do not always offer such experiences, pre-service teacher education and professional development opportunities may engage science teachers in two ways: (1) becoming part of a scientific community may enable them to teach with NOS and (2) being reflective about what being a scientist means may improve teachers' NOS understandings and better position them to teach about NOS.. Keywords: nature of science, authentic scientific research experiences, Next Generation Science Standards, teaching about NOS, teaching with NOS.

Effect of sildenafil citrate on interleukin-1β-induced nitric oxide synthesis and iNOS expression in SW982 cells

PubMed Central

Kim, Kyung-Ok; Park, Shin-Young; Han, Chang-Woo; Chung, Hyun Kee; Ryu, Dae-Hyun

2008-01-01

The purpose of this study was to identify the effect of sildenafil citrate on IL-1β-induced nitric oxide (NO) synthesis and iNOS expression in human synovial sarcoma SW982 cells. IL-1β stimulated the cells to generate NO in both dose- and time-dependent manners. The IL-1β-induced NO synthesis was inhibited by guanylate cyclase (GC) inhibitor, LY83583. When the cells were treated with 8-bromo-cGMP, a hydrolyzable analog of cGMP, NO synthesis was increased upto 5-fold without IL-1β treatment suggesting that cGMP is an essential component for increasing the NO synthesis. Synoviocytes and chondrocytes contain strong cGMP phosphodiesterase (PDE) activity, which has biochemical features of PDE5. When SW982 cells were pretreated with sildenafil citrate (Viagra), a PDE5 specific inhibitor, sildenafil citrate significantly inhibited IL-1β-induced NO synthesis and iNOS expressions. From this result, we noticed that PDE5 activity is required for IL-1β-induced NO synthesis and iNOS expressions in human synovial sarcoma cells, and sildenafil citrate may be able to suppress an inflammatory reaction of synovium through inhibition of NO synthesis and iNOS expression by cytokines. PMID:18587266

NOS3 genotype-dependent correlation between blood pressure and physical activity.

PubMed

Kimura, Tomomi; Yokoyama, Tetsuji; Matsumura, Yasuhiro; Yoshiike, Nobuo; Date, Chigusa; Muramatsu, Masaaki; Tanaka, Heizo

2003-02-01

Endothelium-dependent vasorelaxation plays an important role in reduction of blood pressure and is mediated through release of nitric oxide (NO), which is generated by constitutively expressed endothelial nitric oxide synthase (NOS3). Exercise also augments NO release and has been recommended for primary prevention and improvement of hypertension, but individual responses are highly variable. We therefore postulated that genetic polymorphisms of NOS3 might interact with physical activity level to differentially influence blood pressure level. We genotyped 832 healthy Japanese (mean age of 54.4+/-8.6 years, 372 men and 460 women) for a polymorphism of NOS3 in intron 4 (ecNOS4a/b), using the polymerase chain reaction method, and scored their habitual physical activity level by using the rate of energy expenditure per resting metabolic rate through an interview according to a semiquantitative assessment method. Only in the subjects who had the rarer a allele (aa+ba type), systolic blood pressure was found to be inversely correlated with physical activity level (P for linear trend=0.0496, for interaction=0.0071). Eventually, this polymorphism was significantly associated with the prevalence of systolic hypertension only in the subjects who were in the lowest tertile of physical activity level (OR=2.4, 95% CI, 1.1 to 5.6, P for interaction=0.0474). In the present study, we found a significant interaction between the genotype and physical activity level on systolic blood pressure. These results might allow a better understanding of the mechanism to improve hypertension by exercise and to thereby reduce the risk of cardiovascular disease.

A NOS3 polymorphism determines endothelial response to folate in children with type 1 diabetes or obesity.

PubMed

Wiltshire, Esko J; Peña, Alexia S; MacKenzie, Karen; Bose-Sundernathan, Tulika; Gent, Roger; Couper, Jennifer J

2015-02-01

To determine the effect of polymorphisms in NOS3 and folate pathway enzymes on vascular function and folate status and endothelial response to folate in children with diabetes or obesity. A total of 244 subjects (age 13.8 ± 2.8 years, 125 males) were studied for NOS3 and/or folate pathway polymorphisms using polymerase chain reaction/restriction fragment length polymorphism, including at baseline: 139 with type 1 diabetes; 58 with obesity; and 47 controls. The effect of NOS3 genotype on endothelial response to folate (5 mg) was assessed in 85 subjects with diabetes and 28 obese subjects who received active treatment during intervention trials. Vascular function (flow-mediated dilatation [FMD] and glyceryl trinitrate-mediated dilatation), clinical, and biochemical measurements were assessed at baseline and 8 weeks in folate intervention studies. Folate pathway enzyme and NOS3 polymorphisms did not significantly affect baseline vascular function. The polymorphism in intron 4 of endothelial nitric oxide synthase altered endothelial response to folate significantly: in subjects with diabetes FMD improved by 6.4 ± 5% (insertion carriers) vs 2.3 ± 6.6% (deletion carriers), P = .01; in obese subjects FMD improved by 1.8 ± 5.4% (insertion carriers) and deteriorated by -3.2 ± 7.2% (deletion carriers), P = .05. More subjects carrying the insertion normalized FMD after folate supplementation (insertion 64% vs deletion 28%, χ(2) = 10.14, P = .001). A NOS3 polymorphism predicts endothelial response to folate in children with diabetes or obesity, with implications for vascular risk and folate intervention studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-Inflammatory Activity of Butein and Luteolin Through Suppression of NFκB Activation and Induction of Heme Oxygenase-1.

PubMed

Sung, Jeehye; Lee, Junsoo

2015-05-01

Butein and luteolin are members of the flavonoid family, which displays a variety of biological activities. In this study, we demonstrated that butein and luteolin exert anti-inflammatory activities in RAW264.7 macrophages by inducing heme oxygenase-1 (HO-1) expression. Butein and luteolin dose-dependently attenuated inducible nitric oxide synthase (iNOS) expression, leading to the suppression of iNOS-derived nitric oxide (NO) production. The inhibitory effect of butein on NO production was greater than that of luteolin. Consistent with this finding, butein also showed higher inhibitory effects on lipopolysaccharide (LPS)-induced translocation of nuclear factor κB (NFκB) and NFκB reporter gene activity in macrophages than luteolin. Furthermore, the expression of HO-1 was dose-dependently induced by butein and luteolin treatments in macrophages. Additionally, the anti-inflammatory activities of butein and luteolin involved the induction of HO-1 expression, as confirmed by the zinc protoporphyrin (ZnPP) treatment (HO-1 selective inhibitor) and HO-1 small interfering (si)RNA system. ZnPP-mediated downregulation and siRNA-mediated knockdown of HO-1 significantly abolished the inhibitory effects of butein and luteolin on the production of NO in LPS-induced macrophages. Consequently, butein and luteolin were shown to be effective HO-1 inducers capable of inhibiting macrophage-derived proinflammatory mechanisms. These findings indicate that butein and luteolin are potential therapeutic agents for the treatment of inflammatory diseases.

Melatonin Enhances the Anti-Tumor Effect of Fisetin by Inhibiting COX-2/iNOS and NF-κB/p300 Signaling Pathways

PubMed Central

Yu, Zhenlong; Xiao, Yao; Wang, Jingshu; Qiu, Huijuan; Yu, Wendan; Tang, Ranran; Yuan, Yuhui; Guo, Wei; Deng, Wuguo

2014-01-01

Melatonin is a hormone identified in plants and pineal glands of mammals and possesses diverse physiological functions. Fisetin is a bio-flavonoid widely found in plants and exerts antitumor activity in several types of human cancers. However, the combinational effect of melatonin and fisetin on antitumor activity, especially in melanoma treatment, remains unclear. Here, we tested the hypothesis that melatonin could enhance the antitumor activity of fisetin in melanoma cells and identified the underlying molecular mechanisms. The combinational treatment of melanoma cells with fisetin and melatonin significantly enhanced the inhibitions of cell viability, cell migration and clone formation, and the induction of apoptosis when compared with the treatment of fisetin alone. Moreover, such enhancement of antitumor effect by melatonin was found to be mediated through the modulation of the multiply signaling pathways in melanoma cells. The combinational treatment of fisetin with melatonin increased the cleavage of PARP proteins, triggered more release of cytochrome-c from the mitochondrial inter-membrane, enhanced the inhibition of COX-2 and iNOS expression, repressed the nuclear localization of p300 and NF-κB proteins, and abrogated the binding of NF-κB on COX-2 promoter. Thus, these results demonstrated that melatonin potentiated the anti-tumor effect of fisetin in melanoma cells by activating cytochrome-c-dependent apoptotic pathway and inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways, and our study suggests the potential of such a combinational treatment of natural products in melanoma therapy. PMID:25000190

Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS

PubMed Central

Trettin, Arne; Böhmer, Anke; Suchy, Maria-Theresia; Probst, Irmelin; Staerk, Ulrich; Stichtenoth, Dirk O.; Frölich, Jürgen C.

2014-01-01

Paracetamol (acetaminophen) is a widely used analgesic drug. It interacts with various enzyme families including cytochrome P450 (CYP), cyclooxygenase (COX), and nitric oxide synthase (NOS), and this interplay may produce reactive oxygen species (ROS). We investigated the effects of paracetamol on prostacyclin, thromboxane, nitric oxide (NO), and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol. Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1α, respectively. Endothelial NO synthesis was assessed by measuring nitrite in plasma. Urinary 15(S)-8-iso-prostaglanding F2α was measured to assess oxidative stress. Plasma oleic acid oxide (cis-EpOA) was measured as a marker of cytochrome P450 activity. Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged. Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation. This effect may be antagonized by increasing endothelial NO synthesis. High-dosed paracetamol did not increase oxidative stress. At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes. We conclude that paracetamol does not increase oxidative stress in humans. PMID:24799980

Gentiolactone, a Secoiridoid Dilactone from Gentiana triflora, Inhibits TNF-α, iNOS and Cox-2 mRNA Expression and Blocks NF-κB Promoter Activity in Murine Macrophages

PubMed Central

Yamada, Hidetoshi; Kikuchi, Sayaka; Inui, Tomoki; Takahashi, Hideyuki; Kimura, Ken-ichi

2014-01-01

Background Gentian roots have been used as a herbal medicine because of their anti-inflammatory activities. However, the molecular mechanisms of these anti-inflammatory effects remain to be completely explained. Methods and Findings Here, we investigated anti-inflammatory effects of gentian roots and showed that root extracts from Gentiana triflora inhibited lipopolysaccharide (LPS)-induced expression of TNF-α in RAW264.7 cells. The extracts also contained swertiamarin and gentiopicroside, which are the major active compounds of gentian roots; however, neither compound had any effect on LPS-induced TNF-α production in our test system. We isolated gentiolactone as an inhibitor of TNF-α production from the extracts. Gentiolactone also inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) expression at the mRNA level. Moreover, gentiolactone suppressed NF-κB transcriptional activity without inhibition of IκB degradation or NF-κB nuclear transport. Conclusions Our results indicate that inhibition of TNF-α, iNOS and Cox-2 expression by gentiolactone is one of the mechanisms of the anti-inflammatory properties of gentian roots. PMID:25423092

47 CFR 36.341 - Cable and wire facilities expenses-Account 6410 (Class B telephone companies); Accounts 6411...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cable and wire facilities expenses-Account 6410... Operating Expenses and Taxes Cable and Wire Facilities Expenses § 36.341 Cable and wire facilities expenses... network cable, aerial wire, and conduit systems. (b) The general method of separating cable and wire...

47 CFR 36.341 - Cable and wire facilities expenses-Account 6410 (Class B telephone companies); Accounts 6411...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Cable and wire facilities expenses-Account 6410... Operating Expenses and Taxes Cable and Wire Facilities Expenses § 36.341 Cable and wire facilities expenses... network cable, aerial wire, and conduit systems. (b) The general method of separating cable and wire...

iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat

PubMed Central

Fujii, Naoto; Meade, Robert D.; Alexander, Lacy M.; Akbari, Pegah; Foudil-bey, Imane; Louie, Jeffrey C.; Boulay, Pierre

2015-01-01

Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilation during exercise in younger adults. We hypothesized that endothelial NOS (eNOS) and neuronal NOS (nNOS) mediate NOS-dependent sweating, whereas eNOS induces NOS-dependent cutaneous vasodilation in younger adults exercising in the heat. Further, aging may upregulate inducible NOS (iNOS), which may attenuate sweating and cutaneous vasodilator responses. We hypothesized that iNOS inhibition would augment sweating and cutaneous vasodilation in exercising older adults. Physically active younger (n = 12, 23 ± 4 yr) and older (n = 12, 60 ± 6 yr) adults performed two 30-min bouts of cycling at a fixed rate of metabolic heat production (400 W) in the heat (35°C). Sweat rate and cutaneous vascular conductance (CVC) were evaluated at four intradermal microdialysis sites with: 1) lactated Ringer (control), 2) nNOS inhibitor (nNOS-I, NPLA), 3) iNOS inhibitor (iNOS-I, 1400W), or 4) eNOS inhibitor (eNOS-I, LNAA). In younger adults during both exercise bouts, all inhibitors decreased sweating relative to control, albeit a lower sweat rate was observed at iNOS-I compared with eNOS-I and nNOS-I sites (all P < 0.05). CVC at the eNOS-I site was lower than control in younger adults throughout the intermittent exercise protocol (all P < 0.05). In older adults, there were no differences between control and iNOS-I sites for sweating and CVC during both exercise bouts (all P > 0.05). We show that iNOS and eNOS are the main contributors to NOS-dependent sweating and cutaneous vasodilation, respectively, in physically active younger adults exercising in the heat, and that iNOS inhibition does not alter sweating or cutaneous vasodilation in exercising physically active older adults. PMID:26586908

iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat.

PubMed

Fujii, Naoto; Meade, Robert D; Alexander, Lacy M; Akbari, Pegah; Foudil-Bey, Imane; Louie, Jeffrey C; Boulay, Pierre; Kenny, Glen P

2016-02-01

Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilation during exercise in younger adults. We hypothesized that endothelial NOS (eNOS) and neuronal NOS (nNOS) mediate NOS-dependent sweating, whereas eNOS induces NOS-dependent cutaneous vasodilation in younger adults exercising in the heat. Further, aging may upregulate inducible NOS (iNOS), which may attenuate sweating and cutaneous vasodilator responses. We hypothesized that iNOS inhibition would augment sweating and cutaneous vasodilation in exercising older adults. Physically active younger (n = 12, 23 ± 4 yr) and older (n = 12, 60 ± 6 yr) adults performed two 30-min bouts of cycling at a fixed rate of metabolic heat production (400 W) in the heat (35°C). Sweat rate and cutaneous vascular conductance (CVC) were evaluated at four intradermal microdialysis sites with: 1) lactated Ringer (control), 2) nNOS inhibitor (nNOS-I, NPLA), 3) iNOS inhibitor (iNOS-I, 1400W), or 4) eNOS inhibitor (eNOS-I, LNAA). In younger adults during both exercise bouts, all inhibitors decreased sweating relative to control, albeit a lower sweat rate was observed at iNOS-I compared with eNOS-I and nNOS-I sites (all P < 0.05). CVC at the eNOS-I site was lower than control in younger adults throughout the intermittent exercise protocol (all P < 0.05). In older adults, there were no differences between control and iNOS-I sites for sweating and CVC during both exercise bouts (all P > 0.05). We show that iNOS and eNOS are the main contributors to NOS-dependent sweating and cutaneous vasodilation, respectively, in physically active younger adults exercising in the heat, and that iNOS inhibition does not alter sweating or cutaneous vasodilation in exercising physically active older adults. Copyright © 2016 the American Physiological Society.

/B(E2) values from low-energy Coulomb excitation at an ISOL facility: the /N=80,82 Te isotopes

NASA Astrophysics Data System (ADS)

Barton, C. J.; Caprio, M. A.; Shapira, D.; Zamfir, N. V.; Brenner, D. S.; Gill, R. L.; Lewis, T. A.; Cooper, J. R.; Casten, R. F.; Beausang, C. W.; Krücken, R.; Novak, J. R.

2003-01-01

B(E2;0+1→2+1) values for the unstable, neutron-rich nuclei 132,134Te were determined through Coulomb excitation, in inverse kinematics, of accelerated beams of these nuclei. The systematics of measured B(E2) values from the ground state to the first excited state have been extended to the N=82 shell closure in the Te nuclei and have been compared with the predictions of different theories. The measurements were performed at the Holifield Radioactive Ion Beam Facility (HRIBF) using the GRAFIK detector. The success of this approach, which couples a 5.7% efficient through-well NaI(Tl) γ-ray detector with thin foil microchannel plate beam detectors, also demonstrates the feasibility for Coulomb excitation studies of neutron-rich nuclei even further from the valley of beta stability, both at present-generation ISOL facilities and at the proposed Rare Isotope Accelerator.

Post-transcriptional regulation of inducible nitric oxide synthase in chronic lymphocytic leukemia B cells in pro- and antiapoptotic culture conditions.

PubMed

Tiscornia, A C; Cayota, A; Landoni, A I; Brito, C; Oppezzo, P; Vuillier, F; Robello, C; Dighiero, G; Gabús, R; Pritsch, O

2004-01-01

Functional inducible NOS (iNOS) may be involved in the prolonged lifespan of chronic lymphocytic leukemia cells (B-CLL), although the exact mechanisms implicated remain elusive as yet. In this work, we have examined iNOS expression in normal B lymphocytes and B-CLL cells in pro- and antiapoptotic conditions. Our results demonstrate: (1) The existence of a new splice variant characterized by a complete deletion of exon 14 (iNOS 13-16(14del)), which was preferentially detected in normal B lymphocytes and may represent an isoform that could play a role in the regulation of enzyme activity. (2) The existence of another alternatively spliced iNOS mRNA transcript involving a partial deletion of the flavodoxin region (iNOS 13-16(neg)) was correlated to a decreased B-CLL cell viability. The 9-beta-D-arabinofuranosyl-2-fluoradenine or fludarabine (F-ara) treatment induced iNOS 13-16(neg) transcript variants, whereas IL-4 enhanced both the transcription of variants, including these exons (iNOS 13-16(pos)), and the expression of a 122 kDa iNOS protein. These results suggest that in B-CLL, a regulation process involving nitric oxide (.- NO) levels could occur by a post-transcriptional mechanism mediated by soluble factors. Our results also provide an insight into a new complementary proapoptotic action of F-ara in B-CLL by the induction of particular iNOS splice variants, leading to the activation of a caspase-3-dependent apoptotic pathway.

Characteristics of colonic migrating motor complexes in neuronal NOS (nNOS) knockout mice.

PubMed

Spencer, Nick J

2013-01-01

It is well established that the intrinsic pacemaker mechanism that generates cyclical colonic migrating motor complexes (CMMCs) does not require endogenous nitric oxide (NO). However, pharmacological blockade of endogenous NO production potently increases the frequency of CMMCs, suggesting that endogenous NO acts normally to inhibit the CMMC pacemaker mechanism. In this study, we investigated whether mice with a life long genetic deletion of the neuronal nitric oxide synthase (nNOS) gene would show similar CMMC characteristics as wild type mice that have endogenous NO production acutely inhibited. Intracellular electrophysiological and mechanical recordings were made from circular muscle cells of isolated whole mouse colon in wild type and nNOS knockout (KO) mice at 35°C. In wild type mice, the NOS inhibitor, L-NA (100 μM) caused a significant increase in CMMC frequency and a significant depolarization of the CM layer. However, unexpectedly, the frequency of CMMCs in nNOS KO mice was not significantly different from control mice. Also, the resting membrane potential of CM cells in nNOS KO mice was not depolarized compared to controls; and the amplitude of the slow depolarization phase underlying MCs was of similar amplitude between KO and wild type offspring. These findings show that in nNOS KO mice, the major characteristics of CMMCs and their electrical correlates are, at least in adult mice, indistinguishable from wild type control offspring. One possibility why the major characteristics of CMMCs were no different between both types of mice is that nNOS KO mice may compensate for their life long deletion of the nNOS gene, and their permanent loss of neuronal NO production. In this regard, we suggest caution should be exercised when assuming that data obtained from adult nNOS KO mice can be directly extrapolated to wild type mice, that have been acutely exposed to an inhibitor of NOS.

Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia-reperfusion injury through iNOS inhibition in hyperthyroid rats.

PubMed

Zaman, Jalal; Jeddi, Sajad; Daneshpour, Maryam Sadat; Zarkesh, Maryam; Daneshian, Zahra; Ghasemi, Asghar

2015-10-10

Ischemic postconditioning (IPost) is a strategy to provide protection against ischemia-reperfusion (IR) injury. The cardioprotective effects of IPost in cases of ischemic heart disease along with co-morbidities like hyperthyroidism remain unknown. The aim of this study was to investigate the effects of IPost on expression of eNOS, iNOS, Bax, and Bcl-2 genes in hyperthyroid male rats, subjected to myocardial IR. Hyperthyroidism was induced by adding thyroxine to drinking water for a period of 21 days. Using the Langendorff device hearts were perfused, then subjected to a 30-minute global ischemia which was followed by 120 min of reperfusion; subsequently IPost was induced immediately after ischemia. Results indicated that following IR, expression of eNOS and Bcl-2 decreased, whereas expression of iNOS and Bax increased in both the control and hyperthyroid groups. In hyperthyroid animals, IPost significantly increased expression of eNOS by 3.19 fold and Bcl-2 by 3.66 fold; it also decreased expression of Bax by 51%, and reduced IR-induced DNA laddering pattern and infarct size (45.7 ± 1.82% vs. 59.3 ± 1.83%, p<0.05) in the presence of aminoguanidine (AG), a selective iNOS inhibitor. In conclusion, IPost per se could not provide cardioprotection against myocardial ischemia in hyperthyroid rats, a loss of which however was restored by the combination of IPost and iNOS inhibition that acts by a decrease in Bax and an increase in both eNOS and Bcl-2 expression. Copyright © 2015 Elsevier B.V. All rights reserved.

9 CFR 3.51 - Facilities, indoor.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Facilities, indoor. 3.51 Section 3.51... Facilities and Operating Standards § 3.51 Facilities, indoor. (a) Heating. Indoor housing facilities for rabbits need not be heated. (b) Ventilation. Indoor housing facilities for rabbits shall be adequately...

mNos2 deletion and human NOS2 replacement in Alzheimer disease models.

PubMed

Colton, Carol A; Wilson, Joan G; Everhart, Angela; Wilcock, Donna M; Puoliväli, Jukka; Heikkinen, Taneli; Oksman, Juho; Jääskeläinen, Olli; Lehtimäki, Kimmo; Laitinen, Teemu; Vartiainen, Nina; Vitek, Michael P

2014-08-01

Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that demonstrates a full spectrum of characteristic Alzheimer disease-like pathologies. This model demonstrates an altered immune redox state reminiscent of the human disease and capitalizes on data indicating critical differences between human and mouse immune responses, particularly in nitric oxide levels produced by immune activation of the NOS2 gene. Using the APPSwDI(+)/(+)mNos2(-/-) (CVN-AD) mouse strain, we show a sequence of pathologic events leading to neurodegeneration,which include pathologically hyperphosphorylated tau in the perforant pathway at 6 weeks of age progressing to insoluble tau, early appearance of β-amyloid peptides in perivascular deposits around blood vessels in brain regions known to be vulnerable to Alzheimer disease, and progression to damage and overt loss in select vulnerable neuronal populations in these regions. The role of species differences between hNOS2 and mNos2 was supported by generating mice in which the human NOS2 gene replaced mNos2. When crossed with CVN-AD mice, pathologic characteristics of this new strain (APPSwDI(+)/(-)/HuNOS2(tg+)/(+)/mNos2(-/-)) mimicked the pathologic phenotypes found in the CVN-AD strain.

Ubiad1 Is an Antioxidant Enzyme that Regulates eNOS Activity by CoQ10 Synthesis

PubMed Central

Mugoni, Vera; Postel, Ruben; Catanzaro, Valeria; De Luca, Elisa; Turco, Emilia; Digilio, Giuseppe; Silengo, Lorenzo; Murphy, Michael P.; Medana, Claudio; Stainier, Didier Y.R.; Bakkers, Jeroen; Santoro, Massimo M.

2013-01-01

Summary Protection against oxidative damage caused by excessive reactive oxygen species (ROS) by an antioxidant network is essential for the health of tissues, especially in the cardiovascular system. Here, we identified a gene with important antioxidant features by analyzing a null allele of zebrafish ubiad1, called barolo (bar). bar mutants show specific cardiovascular failure due to oxidative stress and ROS-mediated cellular damage. Human UBIAD1 is a nonmitochondrial prenyltransferase that synthesizes CoQ10 in the Golgi membrane compartment. Loss of UBIAD1 reduces the cytosolic pool of the antioxidant CoQ10 and leads to ROS-mediated lipid peroxidation in vascular cells. Surprisingly, inhibition of eNOS prevents Ubiad1-dependent cardiovascular oxidative damage, suggesting a crucial role for this enzyme and nonmitochondrial CoQ10 in NO signaling. These findings identify UBIAD1 as a nonmitochondrial CoQ10-forming enzyme with specific cardiovascular protective function via the modulation of eNOS activity. PMID:23374346

30 CFR 75.1712-1 - Availability of surface bathing facilities; change rooms; and sanitary facilities.

Code of Federal Regulations, 2012 CFR

2012-07-01

...; change rooms; and sanitary facilities. 75.1712-1 Section 75.1712-1 Mineral Resources MINE SAFETY AND...-UNDERGROUND COAL MINES Miscellaneous § 75.1712-1 Availability of surface bathing facilities; change rooms; and sanitary facilities. Except where a waiver has been granted pursuant to the provisions of § 75.1712-4, each...

30 CFR 75.1712-1 - Availability of surface bathing facilities; change rooms; and sanitary facilities.

Code of Federal Regulations, 2011 CFR

2011-07-01

...; change rooms; and sanitary facilities. 75.1712-1 Section 75.1712-1 Mineral Resources MINE SAFETY AND...-UNDERGROUND COAL MINES Miscellaneous § 75.1712-1 Availability of surface bathing facilities; change rooms; and sanitary facilities. Except where a waiver has been granted pursuant to the provisions of § 75.1712-4, each...

30 CFR 75.1712-1 - Availability of surface bathing facilities; change rooms; and sanitary facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

...; change rooms; and sanitary facilities. 75.1712-1 Section 75.1712-1 Mineral Resources MINE SAFETY AND...-UNDERGROUND COAL MINES Miscellaneous § 75.1712-1 Availability of surface bathing facilities; change rooms; and sanitary facilities. Except where a waiver has been granted pursuant to the provisions of § 75.1712-4, each...

30 CFR 75.1712-1 - Availability of surface bathing facilities; change rooms; and sanitary facilities.

Code of Federal Regulations, 2014 CFR

2014-07-01

...; change rooms; and sanitary facilities. 75.1712-1 Section 75.1712-1 Mineral Resources MINE SAFETY AND...-UNDERGROUND COAL MINES Miscellaneous § 75.1712-1 Availability of surface bathing facilities; change rooms; and sanitary facilities. Except where a waiver has been granted pursuant to the provisions of § 75.1712-4, each...

30 CFR 75.1712-1 - Availability of surface bathing facilities; change rooms; and sanitary facilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

...; change rooms; and sanitary facilities. 75.1712-1 Section 75.1712-1 Mineral Resources MINE SAFETY AND...-UNDERGROUND COAL MINES Miscellaneous § 75.1712-1 Availability of surface bathing facilities; change rooms; and sanitary facilities. Except where a waiver has been granted pursuant to the provisions of § 75.1712-4, each...

Profile of hepatitis B and C virus infection in prisoners in Lubuk Pakam correctional facilities

NASA Astrophysics Data System (ADS)

Rey, I.; Saragih, R. H.; Effendi-YS, R.; Sembiring, J.; Siregar, G. A.; Zain, L. H.

2018-03-01

Prisoners in correctional facilities are predisposed to chronic viral infections because of their high-risk behaviors or unsafe lifestyle. The economic and public health burden of chronic hepatitis B and C and its sequelae need to be addressed, such as by finding the risk factors and therefore reducing the spread of HCV and HBV infection in prisons. This study aimed to see the profile of Hepatitis B and C Virus Infection in prisoners in Lubuk Pakam Correctional Facilities. This cross-sectional study was in Lubuk Pakam Correctional Facilities in 2016. From 1114 prisoners in Lubuk Pakam correctional facility, we randomly examined 120 prisoners for HBV and HCV serology markers. From 120 prisoners, six prisoners were HBV positive, 21 prisoners were HCV positive and one prisoner positive for both HCV and HBV infection. The most common risk factors for prisoners getting HBV infection are tattoos and free sex (36.4% and 36.4%, respectively). The most common risk factors for HCV infection in prisoners are tattoos and free sex (40% and 35%, respectively).

Flavonoids inhibit iNOS production via mitogen activated proteins in lipoteichoic acid stimulated cardiomyoblasts.

PubMed

Gutiérrez-Venegas, Gloria; Ventura-Arroyo, Jairo Agustín; Arreguín-Cano, Juan Antonio; Ostoa-Pérez, María Fernanda

2014-08-01

Infective endocarditis is caused by oral commensal bacteria which are important etiologic agents in this disease and can induce release of nitric oxide (NO), promoting an inflammatory response in the endocardium. In this study, we investigated the properties of kaempherol, epigallocatechin, apigenin, and naringin in embryonic mouse heart cells (H9c2) treated with lipoteichoic acid (LTA) obtained from Streptococcus sanguinis. NO production was measured with the Griess method. Expression of inducible nitric oxide synthase (iNOS) was detected by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, western blot assays and immunofluorescence staining were used to assess translocation of nuclear factor kappa beta (NF-κB), degradation of IκB, and activity of the mitogen activated protein (MAP) kinases extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun N-terminal kinase (JNK). And the effects of these flavonoids on cell viability were also assessed. Our results showed that flavonoids blocked activation of ERK, JNK, and p38 in cardiomyocytes treated with LTA. Moreover, the flavonoids showed no cytotoxic effects and blocked NF-κB translocation and IκB degradation and inhibited LTA-induced NF-κB promoter activity, iNOS expression and NO production. In conclusion these effects are consistent with some of the observed anti-inflammatory properties of other flavonoids. Copyright © 2014 Elsevier B.V. All rights reserved.

Experimental Fuels Facility Re-categorization Based on Facility Segmentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiss, Troy P.; Andrus, Jason

The Experimental Fuels Facility (EFF) (MFC-794) at the Materials and Fuels Complex (MFC) located on the Idaho National Laboratory (INL) Site was originally constructed to provide controlled-access, indoor storage for radiological contaminated equipment. Use of the facility was expanded to provide a controlled environment for repairing contaminated equipment and characterizing, repackaging, and treating waste. The EFF facility is also used for research and development services, including fuel fabrication. EFF was originally categorized as a LTHC-3 radiological facility based on facility operations and facility radiological inventories. Newly planned program activities identified the need to receive quantities of fissionable materials in excessmore » of the single parameter subcritical limit in ANSI/ANS-8.1, “Nuclear Criticality Safety in Operations with Fissionable Materials Outside Reactors” (identified as “criticality list” quantities in DOE-STD-1027-92, “Hazard Categorization and Accident Analysis Techniques for Compliance with DOE Order 5480.23, Nuclear Safety Analysis Reports,” Attachment 1, Table A.1). Since the proposed inventory of fissionable materials inside EFF may be greater than the single parameter sub-critical limit of 700 g of U-235 equivalent, the initial re-categorization is Hazard Category (HC) 2 based upon a potential criticality hazard. This paper details the facility hazard categorization performed for the EFF. The categorization was necessary to determine (a) the need for further safety analysis in accordance with LWP-10802, “INL Facility Categorization,” and (b) compliance with 10 Code of Federal Regulations (CFR) 830, Subpart B, “Safety Basis Requirements.” Based on the segmentation argument presented in this paper, the final hazard categorization for the facility is LTHC-3. Department of Energy Idaho (DOE-ID) approval of the final hazard categorization determined by this hazard assessment document (HAD) was required

Deficiency of iNOS-derived NO accelerates lipid accumulation-independent liver fibrosis in non-alcoholic steatohepatitis mouse model.

PubMed

Nozaki, Yuichi; Fujita, Koji; Wada, Koichiro; Yoneda, Masato; Kessoku, Takaomi; Shinohara, Yoshiyasu; Imajo, Kento; Ogawa, Yuji; Nakamuta, Makoto; Saito, Satoru; Masaki, Naohiko; Nagashima, Yoji; Terauchi, Yasuo; Nakajima, Atsushi

2015-04-01

Although many of the factors and molecules closely associated with non-alcoholic steatohepatitis (NASH) have been reported, the role of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) on the progression of NASH remains unclear. We therefore investigated the role of iNOS-derived NO in NASH pathogenesis with a long-term follow-up study using systemic iNOS-knockout mice under high-fat diet (HFD) conditions. iNOS-knockout and wild-type mice were fed a basal or HFD for 10 or 48 weeks. Lipid accumulation, fibrosis, and inflammation were evaluated, and various factors and molecules closely associated with NASH were analyzed. Marked fibrosis and inflammation (indicators of NASH) were observed in the livers of iNOS-knockout mice compared to wild-type mice after 48 weeks of a HFD; however, lipid accumulation in iNOS-knockout mice livers was less than in the wild-type. Increased expressions of various cytokines that are transcriptionally controlled by NF-kB in iNOS-deficient mice livers were observed during HFD conditions. iNOS-derived NO may play a protective role against the progression to NASH during an HFD by preventing fibrosis and inflammation, which are mediated by NF-kB activation in Kupffer cells. A lack of iNOS-derived NO accelerates progression to NASH without excessive lipid accumulation.

Nuclear Interaction between ADR-Induced p65 and p53 Mediates Cardiac Injury in iNOS (−/−) Mice

PubMed Central

Cole, Marsha P.; Tangpong, Jitbanjong; Oberley, Terry D.; Chaiswing, Luksana; Kiningham, Kinsley K.; St. Clair, Daret K.

2014-01-01

Adriamycin (ADR) treatment causes an imbalance in the levels of nitric oxide (•NO) and superoxide (O2 •−) production leading to cardiac injury. Previously we demonstrated that mice lacking inducible nitric oxide synthase (iNOS) have increased oxidative stress and mitochondrial injury. The molecular events leading to increased mitochondrial injury in iNOS deficient mice is unknown. ADR in the absence of iNOS preferentially activates a proapoptotic pathway without a concurrent increase in prosurvival pathways. Treatment with ADR leads to an increase in DNA binding activity of nuclear factor kappa B (NFκB) and p53 in wildtype mice. Following ADR treatment, p53, but not NFκB DNA binding activity, as well as the level of Bax, a p53 target gene, was increased in iNOS (−/−) mice. This apoptotic signaling effect in iNOS (−/−) is alleviated by overexpression of manganese superoxide dismutase (MnSOD). Increases in NFκB and p53 in ADR-treated wildtype mice did not lead to increases in target genes such as MnSOD, bcl-xL, or Bax. Moreover, co-immunoprecipitation analysis revealed that p65, a prominent member of the NFκB family, interacts with p53 in the nucleus. These results suggest that NFκB and p53 may counter act one another's actions in ADR-treated wildtype (WT) mice. Further, these results identify a novel mechanism by which oxidative stress may regulate transcription of proapoptotic genes. PMID:24586632

Design, synthesis, and biological evaluation of 3,4-dihydroquinolin-2(1H)-one and 1,2,3,4-tetrahydroquinoline-based selective human neuronal nitric oxide synthase (nNOS) inhibitors.

PubMed

Ramnauth, Jailall; Speed, Joanne; Maddaford, Shawn P; Dove, Peter; Annedi, Subhash C; Renton, Paul; Rakhit, Suman; Andrews, John; Silverman, Sarah; Mladenova, Gabriela; Zinghini, Salvatore; Nair, Sheela; Catalano, Concettina; Lee, David K H; De Felice, Milena; Porreca, Frank

2011-08-11

Neuronal nitric oxide synthase (nNOS) inhibitors are effective in preclinical models of many neurological disorders. In this study, two related series of compounds, 3,4-dihydroquinolin-2(1H)-one and 1,2,3,4-tetrahydroquinoline, containing a 6-substituted thiophene amidine group were synthesized and evaluated as inhibitors of human nitric oxide synthase (NOS). A structure-activity relationship (SAR) study led to the identification of a number of potent and selective nNOS inhibitors. Furthermore, a few representative compounds were shown to possess druglike properties, features that are often difficult to achieve when designing nNOS inhibitors. Compound (S)-35, with excellent potency and selectivity for nNOS, was shown to fully reverse thermal hyperalgesia when given to rats at a dose of 30 mg/kg intraperitonieally (ip) in the L5/L6 spinal nerve ligation model of neuropathic pain (Chung model). In addition, this compound reduced tactile hyperesthesia (allodynia) after oral administration (30 mg/kg) in a rat model of dural inflammation relevant to migraine pain.

Mechanism of salutary effects of melatonin-mediated liver protection after trauma-hemorrhage: p38 MAPK-dependent iNOS/HIF-1α pathway.

PubMed

Hsu, Jun-Te; Le, Puo-Hsien; Lin, Chun-Jung; Chen, Tsung-Hsing; Kuo, Chia-Jung; Chiang, Kun-Chun; Yeh, Ta-Sen

2017-05-01

Although melatonin attenuates the increases in inflammatory mediators and reduces organ injury during trauma-hemorrhage, the mechanisms remain unclear. This study explored whether melatonin prevents liver injury after trauma-hemorrhage through the p38 mitogen-activated protein kinase (MAPK)-dependent, inducible nitrite oxide (iNOS)/hypoxia-inducible factor (HIF)-1α pathway. After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure ~40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, melatonin (2 mg/kg), melatonin plus p38 MAPK inhibitor SB203580 (2 mg/kg), or melatonin plus the melatonin receptor antagonist luzindole (2.5 mg/kg). At 2 h after trauma-hemorrhage, histopathology score of liver injury, liver tissue myeloperoxidase activity, malondialdehyde, adenosine triphosphate, serum alanine aminotransferase, and asparate aminotransferase levels were significantly increased compared with sham-operated control. Trauma-hemorrhage resulted in a significant decrease in the p38 MAPK activation compared with that in the sham-treated animals. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression and attenuated cleaved caspase 3 and receptor interacting protein kinase-1 levels. Coadministration of SB203580 or luzindole abolished the melatonin-mediated attenuation of the trauma-hemorrhage-induced increase of iNOS/HIF-1α protein expression and liver injury markers. Taken together, our results suggest that melatonin prevents trauma-hemorrhage-induced liver injury in rats, at least in part, through melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway. NEW & NOTEWORTHY Trauma-hemorrhage resulted in a significant decrease in liver p38 MAPK activation and increase in nitrite oxide synthase (iNOS) and hypoxia-inducible factor (HIF)-1α expression. Administration of melatonin after trauma

30 CFR 57.20008 - Toilet facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Toilet facilities. 57.20008 Section 57.20008....20008 Toilet facilities. (a) Toilet facilities shall be provided at locations that are compatible with the mine operations and that are readily accessible to mine personnel. (b) The facilities shall be...

77 FR 14441 - Facility Operating License Amendment From Southern Nuclear Operating, Inc., Joseph M. Farley...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-348 AND 50-364; NRC-2012-0053] Facility Operating License Amendment From Southern Nuclear Operating, Inc., Joseph M. Farley Nuclear Plant, Units 1 and 2...-0053. You may submit comments by the following methods: Federal Rulemaking Web site: Go to http://www...

Aldo-keto Reductase 1B15 (AKR1B15)

PubMed Central

Weber, Susanne; Salabei, Joshua K.; Möller, Gabriele; Kremmer, Elisabeth; Bhatnagar, Aruni; Adamski, Jerzy; Barski, Oleg A.

2015-01-01

Aldo-keto reductases (AKRs) comprise a superfamily of proteins involved in the reduction and oxidation of biogenic and xenobiotic carbonyls. In humans, at least 15 AKR superfamily members have been identified so far. One of these is a newly identified gene locus, AKR1B15, which clusters on chromosome 7 with the other human AKR1B subfamily members (i.e. AKR1B1 and AKR1B10). We show that alternative splicing of the AKR1B15 gene transcript gives rise to two protein isoforms with different N termini: AKR1B15.1 is a 316-amino acid protein with 91% amino acid identity to AKR1B10; AKR1B15.2 has a prolonged N terminus and consists of 344 amino acid residues. The two gene products differ in their expression level, subcellular localization, and activity. In contrast with other AKR enzymes, which are mostly cytosolic, AKR1B15.1 co-localizes with the mitochondria. Kinetic studies show that AKR1B15.1 is predominantly a reductive enzyme that catalyzes the reduction of androgens and estrogens with high positional selectivity (17β-hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoA conjugates and exhibits strong cofactor selectivity toward NADP(H). In accordance with its substrate spectrum, the enzyme is expressed at the highest levels in steroid-sensitive tissues, namely placenta, testis, and adipose tissue. Placental and adipose expression could be reproduced in the BeWo and SGBS cell lines, respectively. In contrast, AKR1B15.2 localizes to the cytosol and displays no enzymatic activity with the substrates tested. Collectively, these results demonstrate the existence of a novel catalytically active AKR, which is associated with mitochondria and expressed mainly in steroid-sensitive tissues. PMID:25577493

30 CFR 56.20008 - Toilet facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Toilet facilities. 56.20008 Section 56.20008... Toilet facilities. (a) Toilet facilities shall be provided at locations that are compatible with the mine operations and that are readily accessible to mine personnel. (b) The facilities shall be kept clean and...

9 CFR 314.1 - Disposition of condemned products at official establishments having tanking facilities; sealing...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Disposition of condemned products at official establishments having tanking facilities; sealing of tanks. 314.1 Section 314.1 Animals and Animal... § 314.3 before leaving such establishment. (b) The seals of tanks shall be broken only by a Program...

9 CFR 314.1 - Disposition of condemned products at official establishments having tanking facilities; sealing...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Disposition of condemned products at official establishments having tanking facilities; sealing of tanks. 314.1 Section 314.1 Animals and Animal... § 314.3 before leaving such establishment. (b) The seals of tanks shall be broken only by a Program...

Posttranscriptional regulation of human iNOS by the NO/cGMP pathway.

PubMed

Pérez-Sala, D; Cernuda-Morollón, E; Díaz-Cazorla, M; Rodríguez-Pascual, F; Lamas, S

2001-03-01

Nitric oxide (NO) and cGMP may exert positive or negative effects on inducible NO synthase (iNOS) expression. We have explored the influence of the NO/cGMP pathway on iNOS levels in human mesangial cells. Inhibition of NOS activity during an 8-h stimulation with IL-1beta plus tumor necrosis factor (TNF)-alpha reduced iNOS levels, while NO donors amplified iNOS induction threefold. However, time-course studies revealed a subsequent inhibitory effect of NO donors on iNOS protein and mRNA levels. This suggests that NO may contribute both to iNOS induction and downregulation. Soluble guanylyl cyclase (sGC) activation may be involved in these effects. Inhibition of sGC attenuated IL-1beta/TNF-alpha-elicited iNOS induction and reduced NO-driven amplification. Interestingly, cGMP analogs also modulated iNOS protein and mRNA levels in a biphasic manner. Inhibition of transcription unveiled a negative posttranscriptional modulation of the iNOS transcript by NO and cGMP at late times of induction. Supplementation with 8-bromo-cGMP (8-BrcGMP) reduced iNOS mRNA stability by 50%. These observations evidence a complex feedback regulation of iNOS expression, in which posttranscriptional mechanisms may play an important role.

β-Adrenergic induced SR Ca2+ leak is mediated by an Epac-NOS pathway.

PubMed

Pereira, Laëtitia; Bare, Dan J; Galice, Samuel; Shannon, Thomas R; Bers, Donald M

2017-07-01

Cardiac β-adrenergic receptors (β-AR) and Ca 2+ -Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca 2+ signaling. Elevated diastolic Ca 2+ leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activation is known to increase SR Ca 2+ leak via CaMKII-dependent phosphorylation of the ryanodine receptor. Two independent and reportedly parallel pathways have been implicated in this β-AR-CaMKII cascade, one involving exchange protein directly activated by cAMP (Epac2) and another involving nitric oxide synthase 1 (NOS1). Here we tested whether Epac and NOS function in a single series pathway to increase β-AR induced and CaMKII-dependent SR Ca 2+ leak. Leak was measured as both Ca 2+ spark frequency and tetracaine-induced shifts in SR Ca 2+ , in mouse and rabbit ventricular myocytes. Direct Epac activation by 8-CPT (8-(4-chlorophenylthio)-2'-O-methyl-cAMP) mimicked β-AR-induced SR Ca 2+ leak, and both were blocked by NOS inhibition. The same was true for myocyte CaMKII activation (assessed via a FRET-based reporter) and ryanodine receptor phosphorylation. Inhibitor and phosphorylation studies also implicated phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) downstream of Epac and above NOS activation in this pathway. We conclude that these two independently characterized parallel pathways function mainly via a single series arrangement (β-AR-cAMP-Epac-PI3K-Akt-NOS1-CaMKII) to mediate increased SR Ca 2+ leak. Thus, for β-AR activation the cAMP-PKA branch effects inotropy and lusitropy (by effects on Ca 2+ current and SR Ca 2+ -ATPase), this cAMP-Epac-NOS pathway increases pathological diastolic SR Ca 2+ leak. This pathway distinction may allow novel SR Ca 2+ leak therapeutic targeting in treatment of arrhythmias in heart failure that spare the inotropic and lusitropic effects of the PKA branch. Copyright © 2017 Elsevier Ltd. All

Notes from the field: deaths from acute hepatitis B virus infection associated with assisted blood glucose monitoring in an assisted-living facility--North Carolina, August-October 2010.

PubMed

2011-02-18

Sharing of blood glucose monitoring equipment in assisted-living facilities has resulted in at least 16 outbreaks of hepatitis B virus (HBV) infection in the United States since 2004. On October 12, 2010, the North Carolina Division of Public Health (NCDPH) and the Wayne County Health Department were notified by a local hospital of four residents of a single assisted-living facility with suspected acute HBV infection. NCDPH requested HBV testing of all persons who had resided in the facility during January 1-October 13, 2010, and defined an outbreak-associated case as either 1) positive hepatitis B surface antigen and core immunoglobulin M (IgM) results or 2) clinical evidence of acute hepatitis (jaundice or serum aminotransferase levels twice the upper limit of normal) with onset ≥6 weeks after admission to the facility. Records were reviewed for potential health-care-associated exposures and HBV-related risk factors. Infection control practices were assessed through observations and interviews with facility staff.

Control of an H1N1 outbreak in a correctional facility in central Taiwan.

PubMed

Chao, Wen-Cheng; Liu, Po-Yu; Wu, Chieh-Liang

2017-04-01

Controlling the outbreak of H1N1 in correctional facilities is difficult due to the inevitable close and prolonged contact between inmates. The current study reports an H1N1 outbreak in a correction facility and investigates the effectiveness of oseltamivir to control the spread of H1N1. All 2690 inmates at the prison received medical service from a single hospital. A list of patients with a diagnosis of influenza was compiled based on medical diagnoses with respiratory symptoms during the outbreak period. The outbreak was then investigated using both chart review and questionnaires. In the 4-week outbreak period, 24.6% (663/2690) of inmates experienced influenza-associated symptoms, 50.5% (335/663) fulfilled the criteria for influenza-like illness (ILI) with fever, and the overall attack rate of ILI was 12.8%. Twelve inmates were admitted for complicated influenza, and three of them experienced respiratory failure. Oseltamivir was provided at the end of the 2nd week, and the effectiveness of oseltamivir in the 1004 inmates from seven major sections in the prison was analyzed. The ILI incidence rate reduced from 12.6 ± 4.1% between the 1st and 2nd weeks to 4.8 ± 2.4% between the 3rd and 4th weeks (p = 0.018) after the oseltamivir intervention. In the 878 uninfected inmates 47.0% (413/878) of inmates received prophylactic oseltamivir at the end of the 2nd week, the incidence of ILI was lower than those without prophylaxis (6.2% versus 2.4%; p = 0.013). H1N1 influenza spread rapidly in the correctional facility. The use of oseltamivir may be a practical intervention to control an H1N1 outbreak an enclosed environment such as this. Copyright © 2015. Published by Elsevier B.V.

Aucubin protects against pressure overload-induced cardiac remodelling via the β3 -adrenoceptor-neuronal NOS cascades.

PubMed

Wu, Qing-Qing; Xiao, Yang; Duan, Ming-Xia; Yuan, Yuan; Jiang, Xiao-Han; Yang, Zheng; Liao, Hai-Han; Deng, Wei; Tang, Qi-Zhu

2018-05-01

Aucubin, the predominant component of Eucommia ulmoides Oliv., has been shown to have profound effects on oxidative stress. As oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of aucubin on cardiac remodelling and heart failure. Initially, H9c2 cardiomyocytes and neonatal rat cardiomyocytes pretreated with aucubin (1, 3, 10, 25 and 50 μM) were challenged with phenylephrine. Secondly, the transverse aorta was constricted in C57/B6 and neuronal NOS (nNOS)-knockout mice, then aucubin (1 or 5 mg·kg -1 body weight day -1 ) was injected i.p. for 25 days. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histological analyses and hypertrophic markers. Oxidative stress was evaluated by examining ROS generation, oxidase activity and NO generation. NOS expression was determined by Western blotting. Aucubin effectively suppressed cardiac remodelling; in mice, aucubin substantially inhibited pressure overload-induced cardiac hypertrophy, fibrosis and inflammation, whereas knocking out nNOS abolished these cardioprotective effects of aucubin. Blocking or knocking down the β 3 -adrenoceptor abolished the protective effects of aucubin in vitro. Furthermore, aucubin enhanced the protective effects of a β 3 -adrenoceptor agonist in vitro by increasing cellular cAMP levels, whereas treatment with an adenylate cyclase (AC) inhibitor abolished the cardioprotective effects of aucubin. Aucubin suppresses oxidative stress during cardiac remodelling by increasing the expression of nNOS in a process that requires activation of the β 3 -adrenoceptor/AC/cAMP pathway. These findings suggest that aucubin could have potential as a treatment for cardiac remodelling and heart failure. © 2018 The British Pharmacological Society.

High risk of adrenal toxicity of N1-desoxy quinoxaline 1,4-dioxide derivatives and the protection of oligomeric proanthocyanidins (OPC) in the inhibition of the expression of aldosterone synthetase in H295R cells.

PubMed

Wang, Xu; Yang, Chunhui; Ihsan, Awais; Luo, Xun; Guo, Pu; Cheng, Guyue; Dai, Menghong; Chen, Dongmei; Liu, Zhenli; Yuan, Zonghui

2016-02-03

Quinoxaline 1,4-dioxide derivatives (QdNOs) with a wide range of biological activities are used in animal husbandry worldwide. It was found that QdNOs significantly inhibited the gene expression of CYP11B1 and CYP11B2, the key aldosterone synthases, and thus reduced aldosterone levels. However, whether the metabolites of QdNOs have potential adrenal toxicity and the role of oxidative stress in the adrenal toxicity of QdNOs remains unclear. The relatively new QdNOs, cyadox (CYA), mequindox (MEQ), quinocetone (QCT) and their metabolites, were selected for elucidation of their toxic mechanisms in H295R cells. Interestingly, the results showed that the main toxic metabolites of QCT, MEQ, and CYA were their N1-desoxy metabolites, which were more harmful than other metabolites and evoked dose and time-dependent cell damage on adrenal cells and inhibited aldosterone production. Gene and protein expression of CYP11B1 and CYP11B2 and mRNA expression of transcription factors, such as NURR1, NGFIB, CREB, SF-1, and ATF-1, were down regulated by N1-desoxy QdNOs. The natural inhibitors of oxidant stress, oligomeric proanthocyanidins (OPC), could upregulate the expression of diverse transcription factors, including CYP11B1 and CYP11B2, and elevated aldosterone levels to reduce adrenal toxicity. This study demonstrated for the first time that N1-desoxy QdNOs have the potential to be the major toxic metabolites in adrenal toxicity, which may shed new light on the adrenal toxicity of these fascinating compounds and help to provide a basic foundation for the formulation of safety controls for animal products and the design of new QdNOs with less harmful effects. Copyright © 2016. Published by Elsevier Ireland Ltd.

Comparison of chromospheric and photospheric magnetic fields in two solar flares of X1.1/4N and X17.2/4B importance

NASA Astrophysics Data System (ADS)

Lozitsky, V.; Lozitska, N.

2017-12-01

We compare the specral-polarized obsevations of magnetic fields in two powerful solar flares of October 28, 2003 (of X17.2 / 4B class) and July 17, 2004 (of X1.1 / 2N class) using FeI and D1 NaI lines. We found that in both flares the effective magnetic field Beff was stronger in the chromosphere than in the photosphere. The strongest magnetic field (4600 Gs) was measured at the chromospheric level of a weaker flare, and this field was 1.6 times stronger than the magnetic field in the nearest sunspot. Comparing the obtained results with similar data by Lozitska et al [8] for flares of 1981 and 1989 (i.e., for cycles Nos. 21 and 22), we can see a significant difference. In both flares of 2003 and 2004, which relate to 23rd cycle of solar activity, we have Beff (FeI) < Beff(D1) for splitting of emission peaks, whereas for flares of cycles Nos. 21 and 22, the inverse in equality Beff (FeI)>Beff(D1) istrue. This result is still unclear and requires additional scrutiny on a base of new observational data.

B-1 phagocytes: the myeloid face of B-1 cells.

PubMed

Popi, Ana Flavia

2015-12-01

The relationship between malignant B cells and macrophages has long been established. Furthermore, evolutionary studies have demonstrated that B cells from early vertebrates have both phagocytic and antibody production capabilities. In addition to their lymphoid nature, B-1 cells retain several myeloid characteristics. Various reports have demonstrated that B-1 cells can differentiate into phagocytes. However, descriptions of B-1 cells as a novel phagocyte cell member are rarely found in the literature. This review aims to present the available data regarding B-1 cell-derived phagocytes and also discusses how their existence might be relevant to hematopoiesis and immune responses. © 2015 New York Academy of Sciences.

75 FR 16664 - Airworthiness Directives; Turbomeca ARRIEL 1B, 1D, 1D1, 2B, and 2B1 Turboshaft Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-02

... limited to, Eurocopter AS 350 B, AS 350 BA, AS 350 B1, AS 350 B2, AS 350 B3, and EC 130 B4 helicopters... an aviation product. The MCAI describes the unsafe condition as: During production of Arriel 1 and... by Turbom[eacute]ca. Potentially non-conforming PT blades have been traced as having been installed...

Differences in immunolocalization of Kim-1, RPA-1, and RPA-2 in kidneys of gentamicin-, cisplatin-, and valproic acid-treated rats: potential role of iNOS and nitrotyrosine.

PubMed

Zhang, Jun; Goering, Peter L; Espandiari, Parvaneh; Shaw, Martin; Bonventre, Joseph V; Vaidya, Vishal S; Brown, Ronald P; Keenan, Joe; Kilty, Cormac G; Sadrieh, Nakissa; Hanig, Joseph P

2009-08-01

The present study compared the immunolocalization of Kim-1, renal papillary antigen (RPA)-1, and RPA-2 with that of inducible nitric oxide synthase (iNOS) and nitrotyrosine in kidneys of gentamicin sulfate (Gen)- and cisplatin (Cis)-treated rats. The specificity of acute kidney injury (AKI) biomarkers, iNOS, and nitrotyrosine was evaluated by dosing rats with valproic acid (VPA). Sprague-Dawley (SD) rats were injected subcutaneously (sc) with 100 mg/kg/day of Gen for six or fourteen days; a single intraperitoneal (ip) dose of 1, 3, or 6 mg/kg of Cis; or 650 mg/kg/day of VPA (ip) for four days. In Gen-treated rats, Kim-1 was expressed in the epithelial cells, mainly in the S1/S2 segments but less so in the S3 segment, and RPA-1 was increased in the epithelial cells of collecting ducts (CD) in the cortex. Spatial expression of iNOS or nitrotyrosine with Kim-1 or RPA-1 was detected. In Cis-treated rats, Kim-1 was expressed only in the S3 segment cells, and RPA-1 and RPA-2 were increased in the epithelial cells of medullary CD or medullary loop of Henle (LH), respectively. Spatial expression of iNOS or nitrotyrosine with RPA-1 or RPA-2 was also identified. These findings suggest that peroxynitrite formation may be involved in the pathogenesis of Gen and Cis nephrotoxicity and that Kim-1, RPA-1, and RPA-2 have the potential to serve as site-specific biomarkers for Gen or Cis AKI.

[Prevalence of dyslipidemia in middle-aged adults with NOS3 gene polymorphism and low cardiorespiratory fitness].

PubMed

Malagrino, Pamella A; Sponton, Carlos H G; Esposti, Rodrigo D; Franco-Penteado, Carla F; Fernandes, Romulo A; Bezerra, Marcos André C; Albuquerque, Dulcinéia M; Rodovalho, Cynara M; Bacci, Maurício; Zanesco, Angelina

2013-02-01

To evaluate the influence of the interaction between endothelial nitric oxide synthase gene (NOS3) polymorphisms at positions -786T>C, Glu298Asp and intron 4b/a, and cardiorespiratory fitness on plasma nitrite/nitrate levels, blood pressure, lipid profile, and prevalence of cardiometabolic disorders. Ninety-two volunteers were genotyped for NOS3 polymorphisms at positions (-786T>C and Glu298Asp) and (intron 4b/a) and divided according to the genotype: non-polymorphic (NP) and polymorphic (P). After that, they were subdivided according to the cardiorespiratory fitness associated with genotype: high (HNP and HP) and low (LNP and LP). The subjects with polymorphism for the interactions at positions Glu298Asp + intron 4b/a, and Glu298Asp+-786T>C showed the highest values in total cholesterol, as well as dyslipidemia. Our findings show that NOS3 gene polymorphisms at positions -786T>C, Glu298Asp, and intron 4b/a exert negative effects on the lipid profile compared with those who do not carry polymorphisms.

75 FR 14634 - Dominion Nuclear Connecticut, Inc.; Millstone Power Station, Unit Nos. 1, 2, and 3; Environmental...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-26

... Power Station, Unit Nos. 1, 2, and 3 (MPS1, MPS2, and MPS3, respectively), located in New London County.... Environmental Assessment Identification of the Proposed Action The proposed action would exempt MPS1, MPS2, and... part 73. Specifically, MPS1, MPS2, and MPS3 would be granted an exemption from being in full compliance...

Imidacloprid exposure cause the histopathological changes, activation of TNF-α, iNOS, 8-OHdG biomarkers, and alteration of caspase 3, iNOS, CYP1A, MT1 gene expression levels in common carp (Cyprinus carpio L.).

PubMed

Özdemir, Selçuk; Altun, Serdar; Arslan, Harun

2018-01-01

Imidacloprid (IMI) is a neonicotinoid that is widely used for the protection of crops and carnivores from insects and parasites, respectively. It is well known that imidacloprid exposure has a harmful effect on several organisms. However, there is little information about imidacloprid toxicity in aquatic animals, particularly fish. Thus, in the current study, we assessed the histopathological changes; activation of iNOS, 8-OHdG and TNF-α; and expression levels of caspase 3, iNOS, CYP1A and MT1 genes in the common carp exposed to imidacloprid. For this purpose, fish were exposed to either a low dose (140 mg/L) or a high dose (280 mg/L) of imidacloprid for 24 h, 48 h, 72 h and 96 h. After IMI exposure, we detected hyperplasia of secondary lamellar cells and mucous cell hyperplasia in the gills, as well as hydropic degeneration in hepatocytes and necrosis in the liver. Moreover, 8-OHdG, iNOS and TNF-α activation was found particularly in the gills and liver but also moderately in the brain. Transcriptional analysis showed that caspase 3 expression was altered low dose and high doses of IMI for 72 h and 96 h exposure ( p <  0.05), iNOS expression was up-regulated with both low and high doses of IMI and in a time-dependent manner ( p <  0.05, p <  0.01, p <  0.001), CYP1A expression was not significantly changed regardless of the dose of IMI and exposure time ( p >  0.05) except with low and high doses of IMI for 96 h ( p <  0.05), and lastly, MT1 gene expression was up-regulated only in the brain with low doses of IMI for 96 h and high doses of IMI for 48 h, 72 h and 96 h exposure ( p <  0.05, p <  0.01). Our results indicated that acute IMI exposure moderately induce apoptosis in the brain but caused severe histopathological lesions, inflammation, and oxidative stress in the gills, liver, and brain of the common carp.

9 CFR 307.1 - Facilities for Program employees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... INSPECTION AND CERTIFICATION FACILITIES FOR INSPECTION § 307.1 Facilities for Program employees. Office space... employees assigned thereto. The space set aside for this purpose shall meet with approval of the circuit... facilities exist in a nearby convenient location. Laundry service for inspectors' outer work clothing shall...

Science Facilities for Mississippi Schools, Grades 1-12.

ERIC Educational Resources Information Center

Mississippi State Dept. of Education, Jackson. Div. of Instruction.

Prepared to assist those planning the construction of new science facilities on the elementary, intermediate, or secondary school level. Standards are outlined and specifications detailed. A statement of fifteen general pricniples for planning science facilities in secondary schools precedes a discussion of--(1) special facilities for different…

Heme oxygenase-1 induction by (S)-enantiomer of YS-51 (YS-51S), a synthetic isoquinoline alkaloid, inhibits nitric oxide production and nuclear factor-kappaB translocation in ROS 17/2.8 cells activated with inflammatory stimulants.

PubMed

Chaea, Han-Jung; Kim, Hyung-Ryong; Kang, Young Jin; Hyun, Kwang Chul; Kim, Hye Jung; Seo, Han Geuk; Lee, Jae Heun; Yun-Choi, Hye Sook; Chang, Ki Churl

2007-12-05

Activation of the inducible nitric oxide synthase (iNOS) pathway contributes to inflammation-induced osteoporosis by suppressing bone formation and causing osteoblast apoptosis. We investigated the mechanism of action by which YS-51S, a synthetic isoquinoline alkaloid, inhibits iNOS expression and nitric oxide (NO) production in ROS 17/28 osteoblast cells activated with the mixture of TNF-alpha, IFN-gamma and LPS (MIX). YS-51S, concentration- and time-dependently, increased heme oxygenase (HO-1) expression. Treatment with YS-51S 1 h prior to MIX significantly reduced MIX-induced NO production and iNOS expression with the IC50 to NO production of 47+/-3.3 microM. Electrophoretic mobility shift assay (EMSA) and western blot analysis showed that YS-51S inhibited MIX-mediated activation and translocation of NF-kappaB to nucleus by suppressing the degradation of its inhibitory protein IkappaBalpha in cytoplasm. YS-51S also reduced NF-kappaB-luciferase activity. In addition, an HO-1 inhibitor ZnPPIX, antagonized the inhibitory effect of YS-51S on iNOS expression and DNA strand break induced by MIX, indicating prevention of NO production by YS-51S is associated with HO-1 activity. Moreover, YS-51S inhibited the oxidation of cytochrome c(2+) by peroxynitrite (PN). Our results indicated that YS-51S may be beneficial in NO-mediated inflammatory conditions such as rheumatoid arthritis by alleviating iNOS expression and NO-mediated cell death of osteoblast with 1) inducing HO-1 expression, 2) interfering the activation of NF-kappaB and 3) quenching of PN.

Pedagogical Reflections by Secondary Science Teachers at Different NOS Implementation Levels

NASA Astrophysics Data System (ADS)

Herman, Benjamin C.; Clough, Michael P.; Olson, Joanne K.

2017-02-01

This study investigated what 13 secondary science teachers at various nature of science (NOS) instruction implementation levels talked about when they reflected on their teaching. We then determined if differences exist in the quality of those reflections between high, medium, and low NOS implementers. This study sought to answer the following questions: (1) What do teachers talk about when asked general questions about their pedagogy and NOS pedagogy and (2) what qualitative differences, if any, exist within variables across teachers of varying NOS implementation levels? Evidence derived from these teachers' reflections indicated that self-efficacy and perceptions of general importance for NOS instruction were poor indicators of NOS implementation. However, several factors were associated with the extent that these teachers implemented NOS instruction, including the utility value they hold for NOS teaching, considerations of how people learn, understanding of NOS pedagogy, and their ability to accurately and deeply self-reflect about teaching. Notably, those teachers who effectively implemented the NOS at higher levels value NOS instruction for reasons that transcend immediate instructional objectives. That is, they value teaching NOS for achieving compelling ends realized long after formal schooling (e.g., lifelong socioscientific decision-making for civic reasons), and they deeply reflect about how to teach NOS by drawing from research about how people learn. Low NOS implementers' simplistic notions and reflections about teaching and learning appeared to be impeding factors to accurate and consistent NOS implementation. This study has implications for science teacher education efforts that promote NOS instruction.

Findings from a hepatitis B birth dose assessment in health facilities in the Philippines: opportunities to engage the private sector.

PubMed

Patel, Minal K; Capeding, Rosario Z; Ducusin, Joyce U; de Quiroz Castro, Maricel; Garcia, Luzviminda C; Hennessey, Karen

2014-09-03

Hepatitis B vaccination in the Philippines was introduced in 1992 to reduce the high burden of chronic hepatitis B virus (HBV) infection in the population; in 2007, a birth dose (HepB-BD) was introduced to decrease perinatal HBV transmission. Timely HepB-BD coverage, defined as doses given within 24h of birth, was 40% nationally in 2011. A first step in improving timely HepB-BD coverage is to ensure that all newborns born in health facilities are vaccinated. In order to assess ways of improving the Philippines' HepB-BD program, we evaluated knowledge, attitudes, and practices surrounding HepB-BD administration in health facilities. Teams visited selected government clinics, government hospitals, and private hospitals in regions with low reported HepB-BD coverage and interviewed immunization and maternity staff. HepB-BD coverage was calculated in each facility for a 3-month period in 2011. Of the 142 health facilities visited, 12 (8%) did not provide HepB-BD; seven were private hospitals and five were government hospitals. Median timely HepB-BD coverage was 90% (IQR 80%-100%) among government clinics, 87% (IQR 50%-97%) among government hospitals, and 50% (IQR 0%-90%) among private hospitals (p=0.02). The private hospitals were least likely to receive supervision (53% vs. 6%-31%, p=0.0005) and to report vaccination data to the national Expanded Programme on Immunization (36% vs. 96%-100%, p<0.0001). Private sector hospitals in the Philippines, which deliver 18% of newborns, had the lowest timely HepB-BD coverage. Multiple avenues exist to engage the private sector in hepatitis B prevention including through existing laws, newborn health initiatives, hospital accreditation processes, and raising awareness of the government's free vaccine program. Copyright © 2013 World Health Organization (WHO). Published by Elsevier Ltd.. All rights reserved.

Oleuropein inhibits the IL-1β-induced expression of inflammatory mediators by suppressing the activation of NF-κB and MAPKs in human osteoarthritis chondrocytes.

PubMed

Feng, Zhenhua; Li, Xiaobin; Lin, Jian; Zheng, Wenhao; Hu, Zhichao; Xuan, Jiangwei; Ni, Wenfei; Pan, Xiaoyun

2017-10-18

Osteoarthritis (OA) is the most common form of joint disease and is widespread in the elderly population and is characterized by erosion of articular cartilage, subchondral bone sclerosis and synovitis. Oleuropein (OL), a secoiridoid, is considered as the most prevalent phenolic component in olive leaves and seeds, pulp and peel of unripe olives and has been shown to have potent anti-inflammatory effects. However, its effects on OA have not been clearly elucidated. This study aimed to assess the effect of OL on human OA chondrocytes. Human OA chondrocytes were pretreated with OL (10, 50 and 100 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. The production of NO, PGE2, MMP-1, MMP-13, and ADAMTS-5 was evaluated by the Griess reaction and ELISA assays. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP13, ADAMTS-5, aggrecan, and collagen-II was measured by using real-time PCR. The protein expressions of COX-2, iNOS, p65, IκB-α, JNK, p-JNK, ERK, p-ERK, p38, and p-p38 were tested by using western blot. We found that OL significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-13, and ADAMTS-5; and degradation of aggrecan and collagen-II. Furthermore, OL dramatically suppressed IL-1β-stimulated NF-κB and MAPK activation. Immunofluorescence staining demonstrated that OL could suppress IL-1β-induced phosphorylation of p65 nuclear translocation. These results indicate that the therapeutic effect of OL on OA is accomplished through the inhibition of both NF-κB and MAPK signaling pathways. Altogether, our findings provide the evidence to develop OL as a potential therapeutic agent for patients with OA.

Redox-sensitive induction of Src/PI3-kinase/Akt and MAPKs pathways activate eNOS in response to EPA:DHA 6:1.

PubMed

Zgheel, Faraj; Alhosin, Mahmoud; Rashid, Sherzad; Burban, Mélanie; Auger, Cyril; Schini-Kerth, Valérie B

2014-01-01

Omega-3 fatty acid products containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have vasoprotective effects, in part, by stimulating the endothelial formation of nitric oxide (NO). This study determined the role of the EPA:DHA ratio and amount, and characterized the mechanism leading to endothelial NO synthase (eNOS) activation. EPA:DHA 6∶1 and 9∶1 caused significantly greater endothelium-dependent relaxations in porcine coronary artery rings than EPA:DHA 3∶1, 1∶1, 1∶3, 1∶6, 1∶9, EPA and DHA alone, and EPA:DHA 6∶1 with a reduced EPA + DHA amount, which were inhibited by an eNOS inhibitor. Relaxations to EPA:DHA 6∶1 were insensitive to cyclooxygenase inhibition, and reduced by inhibitors of either oxidative stress, Src kinase, PI3-kinase, p38 MAPK, MEK, or JNK. EPA:DHA 6∶1 induced phosphorylation of Src, Akt, p38 MAPK, ERK, JNK and eNOS; these effects were inhibited by MnTMPyP. EPA:DHA 6∶1 induced the endothelial formation of ROS in coronary artery sections as assessed by dihydroethidium, and of superoxide anions and hydrogen peroxide in cultured endothelial cells as assessed by electron spin resonance with the spin probe CMH, and the Amplex Red based assay, respectively. Omega-3 fatty acids cause endothelium-dependent NO-mediated relaxations in coronary artery rings, which are dependent on the EPA:DHA ratio and amount, and involve an intracellular activation of the redox-sensitive PI3-kinase/Akt and MAPKs pathways to activate eNOS.

Phased Demolition of an Occupied Facility