"Active" and "Passive" Lava Resurfacing Processes on Io: A Comparative Study of Loki Patera and Prometheus

NASA Technical Reports Server (NTRS)

Davies, A. G.; Matson, D. L.; Leone, G.; Wilson, L.; Keszthelyi, L. P.

2004-01-01

Studies of Galileo Near Infrared Mapping Spectrometer (NIMS) data and ground based data of volcanism at Prometheus and Loki Patera on Io reveal very different mechanisms of lava emplacement at these two volcanoes. Data analyses show that the periodic nature of Loki Patera s volcanism from 1990 to 2001 is strong evidence that Loki s resurfacing over this period resulted from the foundering of a crust on a lava lake. This process is designated passive , as there is no reliance on sub-surface processes: the foundering of the crust is inevitable. Prometheus, on the other hand, displays an episodicity in its activity which we designate active . Like Kilauea, a close analog, Prometheus s effusive volcanism is dominated by pulses of magma through the nearsurface plumbing system. Each system affords views of lava resurfacing processes through modelling.

Summary of Prometheus Radiation Shielding Nuclear Design Analysis

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

J. Stephens

2006-01-13

This report transmits a summary of radiation shielding nuclear design studies performed to support the Prometheus project. Together, the enclosures and references associated with this document describe NRPCT (KAPL & Bettis) shielding nuclear design analyses done for the project.

Saturn's F Ring Core: Calm in the Midst of Chaos

NASA Technical Reports Server (NTRS)

Cuzzi, J. N.; Whizin, A. D.; Hogan, R. C.; Dobrovolskis, A. R.; Dones, L.; Showalter. M. R.; Colwell, J. E.; Scargle, J. D.

2013-01-01

The long-term stability of the narrow F Ring core has been hard to understand. Instead of acting as "shepherds", Prometheus and Pandora together stir the vast preponderance of the region into a chaotic state, consistent with the orbits of newly discovered objects like S/2004S6. We show how a comb of very narrow radial locations of high stability in semimajor axis is embedded within this otherwise chaotic region. The stability of these semimajor axes relies fundamentally on the unusual combination of rapid apse precession and long synodic period which characterizes the region. This situation allows stable "antiresonances" to fall on or very close to traditional Lindblad resonances which, under more common circumstances, are destabilizing. We present numerical integrations of tens of thousands of test particles over tens of thousands of Prometheus orbits that map out the effect. The stable antiresonance zones are most stable in a subset of the region where Prometheus first-order resonances are least cluttered by Pandora resonances. This region of optimum stability is paradoxically closer to Prometheus than a location more representative of "torque balance", helping explain a longstanding paradox. One stable zone corresponds closely to the currently observed semimajor axis of the F Ring core. While the model helps explain the stability of the narrow F Ring core, it does not explain why the F Ring material all shares a common apse longitude; we speculate that collisional damping at the preferred semimajor axis (not included in the current simulations) may provide that final step. Essentially, we find that the F Ring core is not confined by a combination of Prometheus and Pandora, but a combination of Prometheus and precession.

Autonomous Control Capabilities for Space Reactor Power Systems

NASA Astrophysics Data System (ADS)

Wood, Richard T.; Neal, John S.; Brittain, C. Ray; Mullens, James A.

2004-02-01

The National Aeronautics and Space Administration's (NASA's) Project Prometheus, the Nuclear Systems Program, is investigating a possible Jupiter Icy Moons Orbiter (JIMO) mission, which would conduct in-depth studies of three of the moons of Jupiter by using a space reactor power system (SRPS) to provide energy for propulsion and spacecraft power for more than a decade. Terrestrial nuclear power plants rely upon varying degrees of direct human control and interaction for operations and maintenance over a forty to sixty year lifetime. In contrast, an SRPS is intended to provide continuous, remote, unattended operation for up to fifteen years with no maintenance. Uncertainties, rare events, degradation, and communications delays with Earth are challenges that SRPS control must accommodate. Autonomous control is needed to address these challenges and optimize the reactor control design. In this paper, we describe an autonomous control concept for generic SRPS designs. The formulation of an autonomous control concept, which includes identification of high-level functional requirements and generation of a research and development plan for enabling technologies, is among the technical activities that are being conducted under the U.S. Department of Energy's Space Reactor Technology Program in support of the NASA's Project Prometheus. The findings from this program are intended to contribute to the successful realization of the JIMO mission.

Saturnʼs Inner Satellites: Orbits, Masses, and the Chaotic Motion of Atlas from New Cassini Imaging Observations

NASA Astrophysics Data System (ADS)

Cooper, N. J.; Renner, S.; Murray, C. D.; Evans, M. W.

2015-01-01

We present numerically derived orbits and mass estimates for the inner Saturnian satellites, Atlas, Prometheus, Pandora, Janus, and Epimetheus from a fit to 2580 new Cassini Imaging Science Subsystem astrometric observations spanning 2004 February to 2013 August. The observations are provided as machine-readable and Virtual Observatory tables. We estimate G{{M}Atlas} = (0.384 ± 0.001) × 10-3 km3 s-2, a value 13% smaller than the previously published estimate but with an order of magnitude reduction in the uncertainty. We also find G{{M}Prometheus} = (10.677 ± 0.006) × 10-3 km3 s-2, G{{M}Pandora} = (9.133 ± 0.009) × 10-3 km3 s-2, G{{M}Janus} = (126.51 ± 0.03) × 10-3 km3 s-2, and G{{M}Epimetheus} = (35.110 ± 0.009) × 10-3 km3 s-2, consistent with previously published values, but also with significant reductions in uncertainties. We show that Atlas is currently librating in both the 54:53 co-rotation-eccentricity resonance (CER) and the 54:53 inner Lindblad (ILR) resonance with Prometheus, making it the latest example of a coupled CER-ILR system, in common with the Saturnian satellites Anthe, Aegaeon, and Methone, and possibly Neptune's ring arcs. We further demonstrate that Atlas's orbit is chaotic, with a Lyapunov time of ˜10 years, and show that its chaotic behavior is a direct consequence of the coupled resonant interaction with Prometheus, rather than being an indirect effect of the known chaotic interaction between Prometheus and Pandora. We provide an updated analysis of the second-order resonant perturbations involving Prometheus, Pandora, and Epimetheus based on the new observations, showing that these resonant arguments are librating only when Epimetheus is the innermost of the co-orbital pair, Janus and Epimetheus. We also find evidence that the known chaotic changes in the orbits of Prometheus and Pandora are not confined to times of apse anti-alignment.

Galileo Near-Infrared Mapping Spectrometer Detects Active Lava Flows at Prometheus Volcano, Io

NASA Image and Video Library

1999-11-04

The active volcano Prometheus on Jupiter moon Io was imaged by NASA Galileo spacecraft during the close flyby of Io on Oct.10, 1999. The spectrometer can detect active volcanoes on Io by measuring their heat in the near-infrared wavelengths.

NASA's 2004 Hall Thruster Program

NASA Technical Reports Server (NTRS)

Jacobson, David T.; Manzella, David H.; Hofer, Richard R.; Peterson, Peter Y.

2004-01-01

An overview of NASA's Hall thruster research and development tasks conducted during fiscal year 2004 is presented. These tasks focus on: raising the technology readiness level of high power Hall thrusters, developing a moderate-power/ moderate specific impulse Hall thruster, demonstrating high-power/high specific impulse Hall thruster operation, and addressing the fundamental technical challenges of emerging Hall thruster concepts. Programmatic background information, technical accomplishments and out year plans for each program element performed under the sponsorship of the In-Space Transportation Program, Project Prometheus, and the Energetics Project are provided.

Inertial Fusion Energy reactor design studies: Prometheus-L, Prometheus-H. Volume 2, Final report

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

Waganer, L.M.; Driemeyer, D.E.; Lee, V.D.

1992-03-01

This report contains a review of design studies for Inertial Confinement reactor. This second of three volumes discussions is some detail the following: Objectives, requirements, and assumptions; rationale for design option selection; key technical issues and R&D requirements; and conceptual design selection and description.

77 FR 31838 - Notice of Orders Granting Authority to Import and Export Natural Gas and Liquefied Natural Gas...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-30

...: Office of Fossil Energy, Department of Energy (DOE). ACTION: Notice of orders. FE Docket Nos. Prometheus... Resources, Inc 12-42-NG Minnesota Energy Resources Corporation... 12-40-NG SUMMARY: The Office of Fossil... attached appendix and may be found on the FE Web site at http://www.fossil.energy.gov/programs...

Multiple Irradiation Capsule Experiment (MICE)-3B Irradiation Test of Space Fuel Specimens in the Advanced Test Reactor (ATR) - Close Out Documentation for Naval Reactors (NR) Information

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

M. Chen; CM Regan; D. Noe

2006-01-09

Few data exist for UO{sub 2} or UN within the notional design space for the Prometheus-1 reactor (low fission rate, high temperature, long duration). As such, basic testing is required to validate predictions (and in some cases determine) performance aspects of these fuels. Therefore, the MICE-3B test of UO{sub 2} pellets was designed to provide data on gas release, unrestrained swelling, and restrained swelling at the upper range of fission rates expected for a space reactor. These data would be compared with model predictions and used to determine adequacy of a space reactor design basis relative to fission gas releasemore » and swelling of UO{sub 2} fuel and to assess potential pellet-clad interactions. A primary goal of an irradiation test for UN fuel was to assess performance issues currently associated with this fuel type such as gas release, swelling and transient performance. Information learned from this effort may have enabled use of UN fuel for future applications.« less

An Overview of the VHITAL Program: A Two-Stage Bismuth Fed Very High Specific Impulse Thruster with Anode Layer

NASA Technical Reports Server (NTRS)

Sengupta, Anita; Marrese-Reading, Colleen; Capelli, Mark; Scharfe, David; Tverdokhlebov, Sergey; Semenkin, Sasha; Tverdokhlebov, Oleg; Boyd, Ian; Keidar, Michael; Yalin, Azer;

A Forethought and an Afterthought

NASA Image and Video Library

2014-10-27

Befitting moons named for brothers, the moons Prometheus and Epimetheus share a lot in common. Both are small, icy moons that orbit near the main rings of Saturn. But, like most brothers, they also assert their differences: while Epimetheus is relatively round for a small moon, Prometheus is elongated in shape, similar to a lemon. Prometheus (53 miles, or 86 kilometers across) orbits just outside the A ring - seen here upper-middle of the image - while Epimetheus (70 miles, 113 kilometers across) orbits farther out - seen in the upper-left, doing an orbital two-step with its partner, Janus. This view looks toward the sunlit side of the rings from about 28 degrees above the ringplane. The image was taken in visible light with the Cassini spacecraft wide-angle camera on July 9, 2013. The view was obtained at a distance of approximately 557,000 miles (897,000 kilometers) from Saturn and at a Sun-Saturn-spacecraft, or phase, angle of 11 degrees. Image scale is 33 miles (54 kilometers) per pixel. Prometheus and Epimetheus have been brightened by a factor of 2 relative to the rest of the image to enhance their visibility. http://photojournal.jpl.nasa.gov/catalog/PIA18286

Prometheus payment model: application to hip and knee replacement surgery.

PubMed

Rastogi, Amita; Mohr, Beth A; Williams, Jeffery O; Soobader, Mah-Jabeen; de Brantes, Francois

2009-10-01

The Prometheus Payment Model offers a potential solution to the failings of the current fee-for-service system and various forms of capitation. At the core of the Prometheus model are evidence-informed case rates (ECRs), which include a bundle of typical services that are informed by evidence and/or expert opinion as well as empirical data analysis, payment based on the severity of patients, and allowances for potentially avoidable complications (PACs) and other provider-specific variations in payer costs. We outline the methods and findings of the hip and knee arthroplasty ECRs with an emphasis on PACs. Of the 2076 commercially insured patients undergoing hip arthroplasty in our study, PAC costs totaled $7.8 million (14% of total costs; n = 699 index PAC stays). Similarly, PAC costs were $12.7 million (14% of total costs; n = 897 index PAC stays) for 3403 patients undergoing knee arthroplasty. By holding the providers clinically and financially responsible for PACs, and by segmenting and quantifying the type of PACs generated during and after the procedure, the Prometheus model creates an opportunity for providers to focus on the reduction of PACs, including readmissions, making the data actionable and turn the waste related to PAC costs into potential savings.

Efficient Thread Labeling for Monitoring Programs with Nested Parallelism

NASA Astrophysics Data System (ADS)

Ha, Ok-Kyoon; Kim, Sun-Sook; Jun, Yong-Kee

It is difficult and cumbersome to detect data races occurred in an execution of parallel programs. Any on-the-fly race detection techniques using Lamport's happened-before relation needs a thread labeling scheme for generating unique identifiers which maintain logical concurrency information for the parallel threads. NR labeling is an efficient thread labeling scheme for the fork-join program model with nested parallelism, because its efficiency depends only on the nesting depth for every fork and join operation. This paper presents an improved NR labeling, called e-NR labeling, in which every thread generates its label by inheriting the pointer to its ancestor list from the parent threads or by updating the pointer in a constant amount of time and space. This labeling is more efficient than the NR labeling, because its efficiency does not depend on the nesting depth for every fork and join operation. Some experiments were performed with OpenMP programs having nesting depths of three or four and maximum parallelisms varying from 10,000 to 1,000,000. The results show that e-NR is 5 times faster than NR labeling and 4.3 times faster than OS labeling in the average time for creating and maintaining the thread labels. In average space required for labeling, it is 3.5 times smaller than NR labeling and 3 times smaller than OS labeling.

Entity Bases: Large-Scale Knowledgebases for Intelligence Data

DTIC Science & Technology

2009-02-01

declaratively expressed as Datalog rules . The EntityBase supports two query scenarios: • Free-Form Querying: A human analyst or a client program can pose...integration, Prometheus follows the Inverse Rules algo- rithm (Duschka 1997) with additional optimizations (Thakkar et al. 2005). We use the mediator...Discovery and Data Mining (PAKDD󈧈), Sydney, Australia. Crammer , K., Dekel, O., Keshet, J., Shalev-Shwartz, S., and Singer, Y. (2006). Online passive

F Ring Core Stability: Corotation Resonance Plus Antiresonance

NASA Technical Reports Server (NTRS)

Cuzzi, Jeffrey N.; Marouf, Essam; French, Richard; Jacobson, Robert

2014-01-01

The decades-or-longer stability of the narrow F Ring core in a sea of orbital chaos appears to be due to an unusual combination of traditional corotation resonance and a novel kind of "antiresonance". At a series of specific locations in the F Ring region, apse precession between synodic encounters with Prometheus allows semimajor axis perturbations to promptly cancel before significant orbital period changes can occur. This cancellation fails for particles that encounter Prometheus when it is near its apoapse, especially during periods of antialignment of its apse with that of the F Ring. At these times, the strength of the semimajor axis perturbation is large (tens of km) and highly nonsinusoidal in encounter longitude, making it impossible to cancel promptly on a subsequent encounter and leading to chaotic orbital diffusion. Only particles that consistently encounter Prometheus away from its apoapse can use antiresonance to maintain stable orbits, implying that the true mean motion nF of the stable core must be defined by a corotational resonance of the form nF = nP(-kappa)P/m, where (nP, kappaP) are Prometheus' mean motion and epicycle frequency. To test this hypothesis we used the fact that Cassini RSS occultations only sporadically detect a "massive" F Ring core, composed of several-cm-and-larger particles. We regressed the inertial longitudes of 24 Cassini RSS (and VGR) detections and 43 nondetections to a common epoch, using a comb of candidate nP, and then folded them modulo the anticipated m-number of the corotational resonance (Prometheus m = 110 outer CER), to see if clustering appears. We find the "true F Ring core" is actually arranged in a series of short longitudinal arcs separated by nearly empty longitudes, orbiting at a well determined semimajor axis of 140222.4 km (from 2005-2012 at least). Small particles seen by imaging and stellar occultations spread quickly in azimuth and obscure this clumpy structure. Small chaotic variations in the mean motion and/or apse longitude of Prometheus quickly become manifest in the F Ring core, and we suggest that the core must adapt to these changes for the F Ring to maintain stability over timescales of decades and longer

Power Management and Distribution Trades Studies for a Deep-Space Mission Scientific Spacecraft

NASA Technical Reports Server (NTRS)

Kimnach, Greg L.; Soltis, James V.

2004-01-01

As part of NASA's Project Prometheus, the Nuclear Systems Program, NASA GRC performed trade studies on the various Power Management and Distribution (PMAD) options for a deep-space scientific spacecraft which would have a nominal electrical power requirement of 100 kWe. These options included AC (1000Hz and 1500Hz and DC primary distribution at various voltages. The distribution system efficiency, reliability, mass, thermal, corona, space radiation levels and technology readiness of devices and components were considered. The final proposed system consisted of two independent power distribution channels, sourced by two 3-phase, 110 kVA alternators nominally operating at half-rated power. Each alternator nominally supplies 50kWe to one half of the ion thrusters and science modules but is capable of supplying the total power re3quirements in the event of loss of one alternator. This paper is an introduction to the methodology for the trades done to arrive at the proposed PMAD architecture. Any opinions expressed are those of the author(s) and do not necessarily reflect the views of Project Prometheus.

Power Management and Distribution Trades Studies for a Deep-space Mission Scientific Spacecraft

NASA Astrophysics Data System (ADS)

Kimnach, Greg L.; Soltis, James V.

2004-02-01

As part of NASA's Project Prometheus, the Nuclear Systems Program, NASA GRC performed trade studies on the various Power Management and Distribution (PMAD) options for a deep-space scientific spacecraft, which would have a nominal electrical power requirement of 100 kWe. These options included AC (1000Hz and 1500Hz) and DC primary distribution at various voltages. The distribution system efficiency, reliability, mass, thermal, corona, space radiation levels, and technology readiness of devices and components were considered. The final proposed system consisted of two independent power distribution channels, sourced by two 3-phase, 110 kVA alternators nominally operating at half-rated power. Each alternator nominally supplies 50 kWe to one-half of the ion thrusters and science modules, but is capable of supplying the total power requirements in the event of loss of one alternator. This paper is an introduction to the methodology for the trades done to arrive at the proposed PMAD architecture. Any opinions expressed are those of the author(s) and do not necessarily reflect the views of Project Prometheus.

Double Retort System for Materials Compatibility Testing

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

V. Munne; EV Carelli

2006-02-23

With Naval Reactors (NR) approval of the Naval Reactors Prime Contractor Team (NRPCT) recommendation to develop a gas cooled reactor directly coupled to a Brayton power conversion system as the Space Nuclear Power Plant (SNPP) for Project Prometheus (References a and b) there was a need to investigate compatibility between the various materials to be used throughout the SNPP. Of particular interest was the transport of interstitial impurities from the nickel-base superalloys, which were leading candidates for most of the piping and turbine components to the refractory metal alloys planned for use in the reactor core. This kind of contaminationmore » has the potential to affect the lifetime of the core materials. This letter provides technical information regarding the assembly and operation of a double retort materials compatibility testing system and initial experimental results. The use of a double retort system to test materials compatibility through the transfer of impurities from a source to a sink material is described here. The system has independent temperature control for both materials and is far less complex than closed loops. The system is described in detail and the results of three experiments are presented.« less

Tityus: a forgotten myth of liver regeneration.

PubMed

Tiniakos, Dina G; Kandilis, Apostolos; Geller, Stephen A

2010-08-01

The ancient Greek myth of Tityus is related to liver regeneration in the same way as the well known myth of Prometheus is. Depictions of the punishment of Prometheus are frequently used by lecturers on liver regeneration; however, Tityus remains unknown despite the fact that he received the same punishment and his myth could also be used as a paradigm for the organ's extraordinary ability to regenerate. Nevertheless, there is no convincing evidence that ancient Greeks had any specific knowledge about liver regeneration, a concept introduced in the early 19th century. We describe and analyze the myth of Tityus and compare it to the myth of Prometheus. We also explore artistic and literary links and summarize recent scientific data on the mechanisms of liver regeneration. Finally, we highlight links of the legend of Tityus with other sciences. Copyright 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Thrombolytic utilization for ischemic stroke in US hospitals with neurology residency program.

PubMed

Moradiya, Yogesh; Crystal, Howard; Valsamis, Helen; Levine, Steven R

2013-12-03

We aimed to compare the rates of thrombolysis utilization for acute ischemic stroke in hospitals with neurology residency (NR) to those of other teaching (OT) and nonteaching (NT) hospitals. A retrospective serial cross-sectional cohort study of a nationally representative sample of stroke patients was conducted. Accreditation Council for Graduate Medical Education-accredited NR program-affiliated hospitals in the United States were cross-matched to the hospitals in the Nationwide Inpatient Sample from 2000 to 2010. ICD-9-CM codes were used for case ascertainment. A total of 712,433 adult ischemic stroke patients from 6,839 hospital samples were included, of whom 10.1%, 29.1%, and 60.8% were treated in NR, OT, and NT hospitals, respectively. Stroke patients in NR received thrombolysis more frequently (3.74% ± 0.24% [standard error]) than in OT (2.28% ± 0.11%, p < 0.001) and NT hospitals (1.44% ± 0.06%, p < 0.001). The adjusted odds ratios (ORs) of thrombolysis rates in NR vs OT and NR vs NT increased with each decade increment in age. In multivariate analysis, NR was independently predictive of higher thrombolysis rate (adjusted OR 1.51; 95% confidence interval [CI] 1.44-1.59 [NR vs OT], and adjusted OR 1.82; 95% CI 1.73-1.91 [NR vs NT]). Acute stroke care in NR hospitals is associated with an increased thrombolytic utilization. The disparities between the thrombolysis rate in NR and that in OT and NT hospitals are greater among elderly patients.

Mary Wollstonecraft Shelley's Frankenstein, or the modern Prometheus: a psychological study of unrepaired shame.

PubMed

Severino, Sally K; Morrison, Nancy K

2013-01-01

Mary Wollstonecraft Shelley's modern Prometheus shows us the eternal punishment of unrepaired shame--eternal entrapment within the shame triangle of victim, perpetrator and rescuer. This paper describes how Shelley's insight--that lack of love creates a monster living in shame--is being confirmed by neuroscience and how this is exemplified in two characters--the creature and Victor Frankenstein. Additionally, it delineates how pastoral counselors can help those suffering from unrepaired shame

Reducing Potentially Avoidable Complications in Patients with Chronic Diseases: The Prometheus Payment Approach

PubMed Central

de Brantes, Francois; Rastogi, Amita; Painter, Michael

2010-01-01

Objective (or Study Question) To determine whether a new payment model can reduce current incidence of potentially avoidable complications (PACs) in patients with a chronic illness. Data Sources/Study Setting A claims database of 3.5 million commercially insured members under age 65. Study Design We analyzed the database using the Prometheus Payment model's analytical software for six chronic conditions to quantify total costs, proportion spent on PACs, and their variability across the United States. We conducted a literature review to determine the feasibility of reducing PACs. We estimated the financial impact on a prototypical practice if that practice received payments based on the Prometheus Payment model. Principal Findings We find that (1) PACs consume an average of 28.6 percent of costs for the six chronic conditions studied and vary significantly; (2) reducing PACs to the second decile level would save U.S.$116.7 million in this population; (3) current literature suggests that practices in certain settings could decrease PACs; and (4) using the Prometheus model could create a large potential incentive for a prototypical practice to reduce PACs. Conclusions By extrapolating these findings we conclude that costs might be reduced through payment reform efforts. A full extrapolation of these results, while speculative, suggests that total costs associated to the six chronic conditions studied could decrease by 3.8 percent. PMID:20662949

ORIGIN OF THE CHAOTIC MOTION OF THE SATURNIAN SATELLITE ATLAS

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

Renner, S.; Vienne, A.; Cooper, N. J.

2016-05-01

We revisit the dynamics of Atlas. Using Cassini ISS astrometric observations spanning 2004 February to 2013 August, Cooper et al. found evidence that Atlas is currently perturbed by both a 54:53 corotation eccentricity resonance (CER) and a 54:53 Lindblad eccentricity resonance (LER) with Prometheus. They demonstrated that the orbit of Atlas is chaotic, with a Lyapunov time of order 10 years, as a direct consequence of the coupled resonant interaction (CER/LER) with Prometheus. Here we investigate the interactions between the two resonances using the CoraLin analytical model, showing that the chaotic zone fills almost all the corotation sites occupied bymore » the satellite's orbit. Four 70:67 apse-type mean motion resonances with Pandora are also overlapping, but these resonances have a much weaker effect. Frequency analysis allows us to highlight the coupling between the 54:53 resonances, and confirms that a simplified system including the perturbations due to Prometheus and Saturn's oblateness only captures the essential features of the dynamics.« less

Status of a Power Processor for the Prometheus-1 Electric Propulsion System

NASA Technical Reports Server (NTRS)

Pinero, Luis R.; Hill, Gerald M.; Aulisio, Michael; Gerber, Scott; Griebeler, Elmer; Hewitt, Frank; Scina, Joseph

2006-01-01

NASA is developing technologies for nuclear electric propulsion for proposed deep space missions in support of the Exploration initiative under Project Prometheus. Electrical power produced by the combination of a fission-based power source and a Brayton power conversion and distribution system is used by a high specific impulse ion propulsion system to propel the spaceship. The ion propulsion system include the thruster, power processor and propellant feed system. A power processor technology development effort was initiated under Project Prometheus to develop high performance and lightweight power-processing technologies suitable for the application. This effort faces multiple challenges including developing radiation hardened power modules and converters with very high power capability and efficiency to minimize the impact on the power conversion and distribution system as well as the heat rejection system. This paper documents the design and test results of the first version of the beam supply, the design of a second version of the beam supply and the design and test results of the ancillary supplies.

Origin of the Chaotic Motion of the Saturnian Satellite Atlas

NASA Astrophysics Data System (ADS)

Renner, S.; Cooper, N. J.; El Moutamid, M.; Sicardy, B.; Vienne, A.; Murray, C. D.; Saillenfest, M.

2016-05-01

We revisit the dynamics of Atlas. Using Cassini ISS astrometric observations spanning 2004 February to 2013 August, Cooper et al. found evidence that Atlas is currently perturbed by both a 54:53 corotation eccentricity resonance (CER) and a 54:53 Lindblad eccentricity resonance (LER) with Prometheus. They demonstrated that the orbit of Atlas is chaotic, with a Lyapunov time of order 10 years, as a direct consequence of the coupled resonant interaction (CER/LER) with Prometheus. Here we investigate the interactions between the two resonances using the CoraLin analytical model, showing that the chaotic zone fills almost all the corotation sites occupied by the satellite's orbit. Four 70:67 apse-type mean motion resonances with Pandora are also overlapping, but these resonances have a much weaker effect. Frequency analysis allows us to highlight the coupling between the 54:53 resonances, and confirms that a simplified system including the perturbations due to Prometheus and Saturn's oblateness only captures the essential features of the dynamics.

Develop and demonstrate manufacturing processes for fabricating graphite filament reinforced polymide (Gr/PI) composite structural elements

NASA Technical Reports Server (NTRS)

Chase, V. A.; Harrison, E. S.

1985-01-01

A study was conducted to assess the merits of using graphite/polyimide, NR-150B2 resin, for structural applications on advanced space launch vehicles. The program was divided into two phases: (1) Fabrication Process Development; and (2) Demonstration Components. The first phase of the program involved the selection of a graphite fiber, quality assurance of the NR-150B2 polyimide resin, and the quality assurance of the graphite/polyimide prepreg. In the second phase of the program, a limited number of components were fabricated before the NR-150B2 resin system was removed from the market by the supplier, Du Pont. The advancement of the NR-150B2 polyimide resin binder was found to vary significantly based on previous time and temperature history during the prepregging operation. Strength retention at 316C (600F) was found to be 50% that of room temperature strength. However, the composite would retain its initial strength after 200 hours exposure at 316C (600F). Basic chemistry studies are required for determining NR-150B2 resin binder quality assurance parameters. Graphite fibers are available that can withstand high temperature cure and postcure cycles.

A theory-based newsletter nutrition education program reduces nutritional risk and improves dietary intake for congregate meal participants.

PubMed

Francis, Sarah L; MacNab, Lindsay; Shelley, Mack

2014-01-01

At-risk older adults need community-based nutrition programs that improve nutritional status and practices. This 6-month study assessed the impact of the traditional Chef Charles (CC) program (Control) compared to a theory-based CC program (Treatment) on nutritional risk (NR), dietary intakes, self-efficacy (SE), food security (FS), and program satisfaction for congregate meal participants. Participants were mostly educated, single, "food secure" White females. NR change for the treatment group was significantly higher (P = 0.042) than the control group. No differences were noted for SE or FS change and program satisfaction between groups. The overall distribution classification levels of FS changed significantly (P < .001) from pre to post. Over half (n = 46, 76.7%) reported making dietary changes and the majority (n = 52, 86.7%) rated CC as good to excellent. Results suggest the theory-based CC program (treatment) is more effective in reducing NR and dietary practices than the traditional CC program (control).

Space Nuclear Power Plant Pre-Conceptual Design Report, For Information

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

B. Levine

2006-01-27

This letter transmits, for information, the Project Prometheus Space Nuclear Power Plant (SNPP) Pre-Conceptual Design Report completed by the Naval Reactors Prime Contractor Team (NRPCT). This report documents the work pertaining to the Reactor Module, which includes integration of the space nuclear reactor with the reactor radiation shield, energy conversion, and instrumentation and control segments. This document also describes integration of the Reactor Module with the Heat Rejection segment, the Power Conditioning and Distribution subsystem (which comprise the SNPP), and the remainder of the Prometheus spaceship.

Active Volcanic Eruptions on Io

NASA Technical Reports Server (NTRS)

1996-01-01

Six views of the volcanic plume named Prometheus, as seen against Io's disk and near the bright limb (edge) of the satellite by the SSI camera on the Galileo spacecraft during its second (G2) orbit of Jupiter. North is to the top of each frame. To the south-southeast of Prometheus is another bright spot that appears to be an active plume erupting from a feature named Culann Patera. Prometheus was active 17 years ago during both Voyager flybys, but no activity was detected by Voyager at Culann. Both of these plumes were seen to glow in the dark in an eclipse image acquired by the imaging camera during Galileo's first (G1) orbit, and hot spots at these locations were detected by Galileo's Near-Infrared Mapping Spectrometer.

The plumes are thought to be driven by heating sulfur dioxide in Io's subsurface into an expanding fluid or 'geyser'. The long-lived nature of these eruptions requires that a substantial supply of sulfur dioxide must be available in Io's subsurface, similar to groundwater. Sulfur dioxide gas condenses into small particles of 'snow' in the expanding plume, and the small particles scatter light and appear bright at short wavelengths. The images shown here were acquired through the shortest-wavelength filter (violet) of the Galileo camera. Prometheus is about 300 km wide and 75 km high and Culann is about 150 km wide and less than 50 km high. The images were acquired on September 4, 1996 at a range of 2,000,000 km (20 km/pixel resolution). Prometheus is named after the Greek fire god and Culann is named after the Celtic smith god.

The Jet Propulsion Laboratory, Pasadena, CA manages the Galileo mission for NASA's Office of Space Science, Washington, DC. JPL is an operating division of California Institute of Technology (Caltech).

This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov. Background information and educational context for the images can be found at URL http://www.jpl.nasa.gov/galileo/sepo

Appearance of Saturn’s F ring azimuthal channels for the anti-alignment configuration between the ring and Prometheus

NASA Astrophysics Data System (ADS)

Chavez, Carlos E.

2009-09-01

In this article we explore the aspect of the F ring with respect to the anti-alignment configuration between the ring and Prometheus. We focus our attention on the shape of the F ring's azimuthal channels which were first reported by Porco et al. (Porco, C.C., Baker, E., Barbara, J., Beurle, K., Brahic, A., Burns, J.A., Charnoz, S., Cooper, N., Dawson, D.D., Del Genio, A.D., Denk, T., Dones, L., Dyudina, U., Evans, M.W., Giese, B., Grazier, K., Helfenstein, P., Ingersoll, A.P., Jacobson, R.A., Johnson, T.V., McEwen, A., Murray, C.D., Neukum, G., Owen, W.M., Perry, J., Roatsch, T., Spitale, J., Squyres, S., Thomas, P., Tiscareno, M., Turtle, E., Vasavada, A.R., Veverka, J., Wagner, R., West, R. [2005] Science, 307, 1226-1236) and numerically explored by Murray et al. (Murray, C.D., Chavez, C., Beurle, K., Cooper, N., Evans, M.W., Burns, J.A., Porco, C.C. [2005] Nature 437, 1326-1329) who found excellent agreement between Cassini's ISS reprojected images and their numerical model via a direct comparison. We find that for anti-alignment the channels are wider and go deeper inside the ring material. From our numerical model we find a new feature, an island in the middle of the channel. This island is made up of the particles that have been perturbed the most by Prometheus and only appears when this satellite is close to apoapsis. In addition, plots of the anti-alignment configuration for different orbital stages of Prometheus are obtained and discussed here.

Pyroelectric Applications of the VDF-TrFE Copolymer

NASA Technical Reports Server (NTRS)

Simonne, J. J.; Bauer, Ph.; Audaire, L.; Bauer, F.

1995-01-01

VDF/TrFe pyroelectric sensors have now definitely reached the level of a product. Based on a bidimensional staring array, it can be considered as a whole system with a monolithic technology processed on a silicon substrate provided with the integrated read out circuit. The paper will describe the main procedure dealing with the elaboration of a 32 x 32 focal plane array developed, in the context of the PROMETHEUS PROCHIP European Program (EUREKA), as a passive infrared obstacle detection applied to automotive. Additional experimental data suggest that this microsystem could operate in space environment.

Naval Reactors Prime Contractor Team (NRPCT) Experiences and Considerations With Irradiation Test Performance in an International Environment

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

MH Lane

2006-02-15

This letter forwards a compilation of knowledge gained regarding international interactions and issues associated with Project Prometheus. The following topics are discussed herein: (1) Assessment of international fast reactor capability and availability; (2) Japanese fast reactor (JOYO) contracting strategy; (3) NRPCT/Program Office international contract follow; (4) Completion of the Japan Atomic Energy Agency (JAEA)/Pacific Northwest National Laboratory (PNNL) contract for manufacture of reactor test components; (5) US/Japanese Departmental interactions and required Treaties and Agreements; and (6) Non-technical details--interactions and considerations.

Ion Engine Plume Interaction Calculations for Prototypical Prometheus 1

NASA Technical Reports Server (NTRS)

Mandell, Myron J.; Kuharski, Robert A.; Gardner, Barbara M.; Katz, Ira; Randolph, Tom; Dougherty, Ryan; Ferguson, Dale C.

2005-01-01

Prometheus 1 is a conceptual mission to demonstrate the use of atomic energy for distant space missions. The hypothetical spacecraft design considered in this paper calls for multiple ion thrusters, each with considerably higher beam energy and beam current than have previously flown in space. The engineering challenges posed by such powerful thrusters relate not only to the thrusters themselves, but also to designing the spacecraft to avoid potentially deleterious effects of the thruster plumes. Accommodation of these thrusters requires good prediction of the highest angle portions of the main beam, as well as knowledge of clastically scattered and charge exchange ions, predictions for grid erosion and contamination of surfaces by eroded grid material, and effects of the plasma plume on radio transmissions. Nonlinear interactions of multiple thrusters are also of concern. In this paper we describe two- and three-dimensional calculations for plume structure and effects of conceptual Prometheus 1 ion engines. Many of the techniques used have been validated by application to ground test data for the NSTAR and NEXT ion engines. Predictions for plume structure and possible sputtering and contamination effects will be presented.

BOOK REVIEW: Numerical Recipes in C++: The Art of Scientific Computing (2nd edn)1 Numerical Recipes Example Book (C++) (2nd edn)2 Numerical Recipes Multi-Language Code CD ROM with LINUX or UNIX Single-Screen License Revised Version3Numerical Recipes in C++: The Art of Scientific Computing (2nd edn) Numerical Recipes Example Book (C++) (2nd edn) Numerical Recipes Multi-Language Code CD ROM with LINUX or UNIX Single-Screen License Revised Version

NASA Astrophysics Data System (ADS)

Press, William H.; Teukolsky, Saul A.; Vettering, William T.; Flannery, Brian P.

2003-05-01

The two Numerical Recipes books are marvellous. The principal book, The Art of Scientific Computing, contains program listings for almost every conceivable requirement, and it also contains a well written discussion of the algorithms and the numerical methods involved. The Example Book provides a complete driving program, with helpful notes, for nearly all the routines in the principal book. The first edition of Numerical Recipes: The Art of Scientific Computing was published in 1986 in two versions, one with programs in Fortran, the other with programs in Pascal. There were subsequent versions with programs in BASIC and in C. The second, enlarged edition was published in 1992, again in two versions, one with programs in Fortran (NR(F)), the other with programs in C (NR(C)). In 1996 the authors produced Numerical Recipes in Fortran 90: The Art of Parallel Scientific Computing as a supplement, called Volume 2, with the original (Fortran) version referred to as Volume 1. Numerical Recipes in C++ (NR(C++)) is another version of the 1992 edition. The numerical recipes are also available on a CD ROM: if you want to use any of the recipes, I would strongly advise you to buy the CD ROM. The CD ROM contains the programs in all the languages. When the first edition was published I bought it, and have also bought copies of the other editions as they have appeared. Anyone involved in scientific computing ought to have a copy of at least one version of Numerical Recipes, and there also ought to be copies in every library. If you already have NR(F), should you buy the NR(C++) and, if not, which version should you buy? In the preface to Volume 2 of NR(F), the authors say 'C and C++ programmers have not been far from our minds as we have written this volume, and we think that you will find that time spent in absorbing its principal lessons will be amply repaid in the future as C and C++ eventually develop standard parallel extensions'. In the preface and introduction to NR(C++), the authors point out some of the problems in the use of C++ in scientific computing. I have not found any mention of parallel computing in NR(C++). Fortran has quite a lot going for it. As someone who has used it in most of its versions from Fortran II, I have seen it develop and leave behind other languages promoted by various enthusiasts: who now uses Algol or Pascal? I think it unlikely that C++ will disappear: it was devised as a systems language, and can also be used for other purposes such as scientific computing. It is possible that Fortran will disappear, but Fortran has the strengths that it can develop, that there are extensive Fortran subroutine libraries, and that it has been developed for parallel computing. To argue with programmers as to which is the best language to use is sterile. If you wish to use C++, then buy NR(C++), but you should also look at volume 2 of NR(F). If you are a Fortran programmer, then make sure you have NR(F), volumes 1 and 2. But whichever language you use, make sure you have one version or the other, and the CD ROM. The Example Book provides listings of complete programs to run nearly all the routines in NR, frequently based on cases where an anlytical solution is available. It is helpful when developing a new program incorporating an unfamiliar routine to see that routine actually working, and this is what the programs in the Example Book achieve. I started teaching computational physics before Numerical Recipes was published. If I were starting again, I would make heavy use of both The Art of Scientific Computing and of the Example Book. Every computational physics teaching laboratory should have both volumes: the programs in the Example Book are included on the CD ROM, but the extra commentary in the book itself is of considerable value. P Borcherds

Prometheus: Io's wandering plume.

PubMed

Kieffer, S W; Lopes-Gautier, R; McEwen, A; Smythe, W; Keszthelyi, L; Carlson, R

2000-05-19

Unlike any volcanic behavior ever observed on Earth, the plume from Prometheus on Io has wandered 75 to 95 kilometers west over the last 20 years since it was first discovered by Voyager and more recently observed by Galileo. Despite the source motion, the geometric and optical properties of the plume have remained constant. We propose that this can be explained by vaporization of a sulfur dioxide and/or sulfur "snowfield" over which a lava flow is moving. Eruption of a boundary-layer slurry through a rootless conduit with sonic conditions at the intake of the melted snow can account for the constancy of plume properties.

An Overview of the Jupiter Icy Moons Orbiter (JIMO) Mission, Environments, and Materials Challenges

NASA Technical Reports Server (NTRS)

Edwards, Dave

2012-01-01

Congress authorized NASA's Prometheus Project in February 2003, with the first Prometheus mission slated to explore the icy moons of Jupiter with the following main objectives: (1) Develop a nuclear reactor that would provide unprecedented levels of power and show that it could be processed safely and operated reliably in space for long-duration. (2) Explore the three icy moons of Jupiter -- Callisto, Ganymede, and Europa -- and return science data that would meet the scientific goals as set forth in the Decadal Survey Report of the National Academy of Sciences.

Initial description of primate-specific cystine-knot Prometheus genes and differential gene expansions of D-dopachrome tautomerase genes

PubMed Central

Premzl, Marko

2015-01-01

Using eutherian comparative genomic analysis protocol and public genomic sequence data sets, the present work attempted to update and revise two gene data sets. The most comprehensive third party annotation gene data sets of eutherian adenohypophysis cystine-knot genes (128 complete coding sequences), and d-dopachrome tautomerases and macrophage migration inhibitory factor genes (30 complete coding sequences) were annotated. For example, the present study first described primate-specific cystine-knot Prometheus genes, as well as differential gene expansions of D-dopachrome tautomerase genes. Furthermore, new frameworks of future experiments of two eutherian gene data sets were proposed. PMID:25941635

JOYO-1 Irradiation Test Campaign Technical Close-out, For Information

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

G. Borges

2006-01-31

The JOYO-1 irradiation testing was designed to screen the irradiation performance of candidate cladding, structural and reflector materials in support of space reactor development. The JOYO-1 designation refers to the first of four planned irradiation tests in the JOYO reactor. Limited irradiated material performance data for the candidate materials exists for the expected Prometheus-1 duration, fluences and temperatures. Materials of interest include fuel element cladding and core materials (refractory metal alloys and silicon carbide (Sic)), vessel and plant structural materials (refractory metal alloys and nickel-base superalloys), and control and reflector materials (BeO). Key issues to be evaluated were long termmore » microstructure and material property stability. The JOYO-1 test campaign was initiated to irradiate a matrix of specimens at prototypical temperatures and fluences anticipated for the Prometheus-1 reactor [Reference (1)]. Enclosures 1 through 9 describe the specimen and temperature monitors/dosimetry fabrication efforts, capsule design, disposition of structural material irradiation rigs, and plans for post-irradiation examination. These enclosures provide a detailed overview of Naval Reactors Prime Contractor Team (NRPCT) progress in specific areas; however, efforts were in various states of completion at the termination of NRPCT involvement with and restructuring of Project Prometheus.« less

Chaotic dynamics outside Saturn’s main rings: The case of Atlas

NASA Astrophysics Data System (ADS)

Renner, Stéfan; Cooper, Nicholas J.; El Moutamid, Maryame; Evans, Mike W.; Murray, Carl D.; Sicardy, Bruno

2014-11-01

We revisit in detail the dynamics of Atlas. From a fit to new Cassini ISS astrometric observations spanning February 2004 to August 2013, we estimate GM_Atlas=0.384+/-0.001 x 10^(-3)km^3s^(-2), a value 13% smaller than the previously published estimate but with an order of magnitude reduction in the uncertainty. Our numerically-derived orbit shows that Atlas is currently librating in both a 54:53 corotation eccentricity resonance (CER) and a 54:53 Lindblad eccentricity resonance (LER) with Prometheus. We demonstrate that the orbit of Atlas is chaotic, with a Lyapunov time of order 10 years, as a direct consequence of the coupled resonant interaction (CER/LER) with Prometheus. The interactions between the two resonances is investigated using the CoraLin analytical model (El Moutamid et al., 2014), showing that the chaotic zone fills almost all the corotation site occupied by the satellite’s orbit. Four 70 :67 apse-type mean motion resonances with Pandora are also overlapping, but these resonances have a much weaker effect on Atlas.We estimate the capture probabilities of Atlas into resonances with Prometheus as the orbits expand through tidal effects, and discuss the implications for the orbital evolution.

F Ring Core Stability: Corotation Resonance Plus Antiresonance

NASA Astrophysics Data System (ADS)

Cuzzi, Jeffrey N.; Marouf, Essam; French, Richard; Jacobson, Robert

2014-11-01

The decades-or-longer stability of the narrow F Ring core in a sea of orbital chaos appears to be due to an unusual combination of traditional corotation resonance and a novel kind of “antiresonance”. At a series of specific locations in the F Ring region, apse precession between synodic encounters with Prometheus allows semimajor axis perturbations to promptly cancel before significant orbital period changes can occur (Cuzzi et al. 2014, Icarus 232, 157-175). This cancellation fails for particles that encounter Prometheus when it is near its apoapse, especially during periods of antialignment of its apse with that of the F Ring. At these times, the strength of the semimajor axis perturbation is large (tens of km) and highly nonsinusoidal in encounter longitude, making it impossible to cancel promptly on a subsequent encounter and leading to chaotic orbital diffusion. Only particles that consistently encounter Prometheus away from its apoapse can use antiresonance to maintain stable orbits, implying that the true mean motion nF of the stable core must be defined by a corotational resonance of the form nF = nP-κP/m, where (nP, κP) are Prometheus’ mean motion and epicycle frequency. To test this hypothesis we used the fact that Cassini RSS occultations only sporadically detect a “massive” F Ring core, composed of several-cm-and-larger particles. We regressed the inertial longitudes of 24 Cassini RSS (and VGR) detections and 43 nondetections to a common epoch, using a comb of candidate nP, and then folded them modulo the anticipated m-number of the corotational resonance (Prometheus m=110 outer CER), to see if clustering appears. We find the “true F Ring core” is actually arranged in a series of short longitudinal arcs separated by nearly empty longitudes, orbiting at a well determined semimajor axis of 140222.4km (from 2005-2012 at least). Small particles seen by imaging and stellar occultations spread quickly in azimuth and obscure this clumpy structure. Small chaotic variations in the mean motion and/or apse longitude of Prometheus quickly become manifest in the F Ring core, and we suggest that the core must adapt to these changes for the F Ring to maintain stability over timescales of decades and longer.

Principles of Training in Marine Corps Task Analysis. Training Manual 1

DTIC Science & Technology

1975-12-01

Training Research Programs Psychological Sciences Division Office of Naval Research Contract No. N00014-74-A-0436-0001 NR 151-370 Approved for...and Training Research Programs Psychological Sciences Division Office of Naval Research Contract No. N00014-74-A-0436-0001 NR 151-370 Approved... psychological reward; the trainee loses the connection between performance and the pat on the back that is its consequence. DIMENSIONS OF THE TRAINING

Guidelines for Research Planning and Design in Task Analysis

DTIC Science & Technology

1975-09-01

Personnel and Training Research Programs Psychological Sciences Division Office of Naval Research Contract No. N00014-74-A-0436-0001 NR 151-370...Programs Psychological Sciences Division Office of Naval Research Contract No. N00014-74-A-0436-0001 NR 151-370 Approved for public release...for ways in which the hypothesis can be tested . There are 11 several ways to do this and they are often used jointly. 1* Review of the Literature

Thrombolytic utilization for ischemic stroke in US hospitals with neurology residency program

PubMed Central

Crystal, Howard; Valsamis, Helen; Levine, Steven R.

2013-01-01

Objective: We aimed to compare the rates of thrombolysis utilization for acute ischemic stroke in hospitals with neurology residency (NR) to those of other teaching (OT) and nonteaching (NT) hospitals. Methods: A retrospective serial cross-sectional cohort study of a nationally representative sample of stroke patients was conducted. Accreditation Council for Graduate Medical Education–accredited NR program–affiliated hospitals in the United States were cross-matched to the hospitals in the Nationwide Inpatient Sample from 2000 to 2010. ICD-9-CM codes were used for case ascertainment. Results: A total of 712,433 adult ischemic stroke patients from 6,839 hospital samples were included, of whom 10.1%, 29.1%, and 60.8% were treated in NR, OT, and NT hospitals, respectively. Stroke patients in NR received thrombolysis more frequently (3.74% ± 0.24% [standard error]) than in OT (2.28% ± 0.11%, p < 0.001) and NT hospitals (1.44% ± 0.06%, p < 0.001). The adjusted odds ratios (ORs) of thrombolysis rates in NR vs OT and NR vs NT increased with each decade increment in age. In multivariate analysis, NR was independently predictive of higher thrombolysis rate (adjusted OR 1.51; 95% confidence interval [CI] 1.44–1.59 [NR vs OT], and adjusted OR 1.82; 95% CI 1.73–1.91 [NR vs NT]). Conclusions: Acute stroke care in NR hospitals is associated with an increased thrombolytic utilization. The disparities between the thrombolysis rate in NR and that in OT and NT hospitals are greater among elderly patients. PMID:24186911

Modeling of Fission Gas Release in UO2

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

MH Krohn

2006-01-23

A two-stage gas release model was examined to determine if it could provide a physically realistic and accurate model for fission gas release under Prometheus conditions. The single-stage Booth model [1], which is often used to calculate fission gas release, is considered to be oversimplified and not representative of the mechanisms that occur during fission gas release. Two-stage gas release models require saturation at the grain boundaries before gas is release, leading to a time delay in release of gases generated in the fuel. Two versions of a two-stage model developed by Forsberg and Massih [2] were implemented using Mathcadmore » [3]. The original Forsbers and Massih model [2] and a modified version of the Forsberg and Massih model that is used in a commercially available fuel performance code (FRAPCON-3) [4] were examined. After an examination of these models, it is apparent that without further development and validation neither of these models should be used to calculate fission gas release under Prometheus-type conditions. There is too much uncertainty in the input parameters used in the models. In addition. the data used to tune the modified Forsberg and Massih model (FRAPCON-3) was collected under commercial reactor conditions, which will have higher fission rates relative to Prometheus conditions [4].« less

Prometheus and Pandora

NASA Image and Video Library

2004-04-15

Cassini has sighted Prometheus and Pandora, the two F-ring-shepherding moons whose unpredictable orbits both fascinate scientists and wreak havoc on the F ring. Prometheus (102 kilometers, or 63 miles across) is visible left of center in the image, inside the F ring. Pandora (84 kilometers, or 52 miles across) appears above center, outside the ring. The dark shadow cast by the planet stretches more than halfway across the A ring, the outermost main ring. The mottled pattern appearing in the dark regions of the image is 'noise' in the signal recorded by the camera system, which has subsequently been magnified by the image processing. The F ring is a narrow, ribbon-like structure, with a width seen in this geometry equivalent to a few kilometers. The two small, irregularly shaped moons exert a gravitational influence on particles that make up the F ring, confining it and possibly leading to the formation of clumps, strands and other structures observed there. Pandora prevents the F ring from spreading outward and Prometheus prevents it from spreading inward. However, their interaction with the ring is complex and not fully understood. The shepherds are also known to be responsible for many of the observed structures in Saturn's A ring. The moons, which were discovered in images returned by the Voyager 1 spacecraft in 1980, are in chaotic orbits--their orbits can change unpredictably when the moons get very close to each other. This strange behavior was first noticed in ground-based and Hubble Space Telescope observations in 1995, when the rings were seen nearly edge-on from Earth and the usual glare of the rings was reduced, making the satellites more readily visible than usual. The positions of both satellites at that time were different than expected based on Voyager data. One of the goals for the Cassini-Huygens mission is to derive more precise orbits for Prometheus and Pandora. Seeing how their orbits change over the duration of the mission will help to determine their masses, which in turn will help constrain models of their interiors and provide a more complete understanding of their effect on the rings. This narrow angle camera image was snapped through the broadband green spectral filter, centered at 568 nanometers, on March 10, 2004, when the spacecraft was 55.5 million kilometers (34.5 million miles) from the planet. Image scale is approximately 333 kilometers (207 miles) per pixel. Contrast has been greatly enhanced, and the image has been magnified to aid visibility of the moons as well as structure in the rings. http://photojournal.jpl.nasa.gov/catalog/PIA05387

Reflector and Shield Material Properties for Project Prometheus

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

J. Nash

2005-11-02

This letter provides updated reflector and shield preliminary material property information to support reactor design efforts. The information provided herein supersedes the applicable portions of Revision 1 to the Space Power Program Preliminary Reactor Design Basis (Reference (a)). This letter partially answers the request in Reference (b) to provide unirradiated and irradiated material properties for beryllium, beryllium oxide, isotopically enriched boron carbide ({sup 11}B{sub 4}C) and lithium hydride. With the exception of {sup 11}B{sub 4}C, the information is provided in Attachments 1 and 2. At the time of issuance of this document, {sup 11}B{sub 4}C had not been studied.

Nuclear Thermal Propulsion (NTP) Development Activities at the NASA Marshall Space Flight Center - 2006 Accomplishments

NASA Technical Reports Server (NTRS)

Ballard, Richard O.

2007-01-01

In 2005-06, the Prometheus program funded a number of tasks at the NASA-Marshall Space Flight Center (MSFC) to support development of a Nuclear Thermal Propulsion (NTP) system for future manned exploration missions. These tasks include the following: 1. NTP Design Develop Test & Evaluate (DDT&E) Planning 2. NTP Mission & Systems Analysis / Stage Concepts & Engine Requirements 3. NTP Engine System Trade Space Analysis and Studies 4. NTP Engine Ground Test Facility Assessment 5. Non-Nuclear Environmental Simulator (NTREES) 6. Non-Nuclear Materials Fabrication & Evaluation 7. Multi-Physics TCA Modeling. This presentation is a overview of these tasks and their accomplishments

Epigenetic Regulation of Placental "NR3C1": Mechanism Underlying Prenatal Programming of Infant Neurobehavior by Maternal Smoking?

ERIC Educational Resources Information Center

Stroud, Laura R.; Papandonatos, George D.; Salisbury, Amy L.; Phipps, Maureen G.; Huestis, Marilyn A.; Niaura, Raymond; Padbury, James F.; Marsit, Carmen J.; Lester, Barry M.

2016-01-01

Epigenetic regulation of the placental glucocorticoid receptor gene ("NR3C1") was investigated as a mechanism underlying links between maternal smoking during pregnancy (MSDP) and infant neurobehavior in 45 mother-infant pairs (49% MSDP-exposed; 52% minorities; ages 18-35). The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral…

Two Shepherds

NASA Image and Video Library

2013-10-21

Although their gravitational effects on nearby ring material look quite different, Prometheus and Pan are both shepherd moons, holding back nearby ring edges in this image captured by NASA Cassini spacecraft.

Feed-forward transcriptional programming by nuclear receptors: regulatory principles and therapeutic implications.

PubMed

Sasse, Sarah K; Gerber, Anthony N

2015-01-01

Nuclear receptors (NRs) are widely targeted to treat a range of human diseases. Feed-forward loops are an ancient mechanism through which single cell organisms organize transcriptional programming and modulate gene expression dynamics, but they have not been systematically studied as a regulatory paradigm for NR-mediated transcriptional responses. Here, we provide an overview of the basic properties of feed-forward loops as predicted by mathematical models and validated experimentally in single cell organisms. We review existing evidence implicating feed-forward loops as important in controlling clinically relevant transcriptional responses to estrogens, progestins, and glucocorticoids, among other NR ligands. We propose that feed-forward transcriptional circuits are a major mechanism through which NRs integrate signals, exert temporal control over gene regulation, and compartmentalize client transcriptomes into discrete subunits. Implications for the design and function of novel selective NR ligands are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Accretion in Saturn's F Ring

NASA Astrophysics Data System (ADS)

Meinke, B. K.; Esposito, L. W.; Stewart, G.

2012-12-01

Saturn's F ring is the solar system's principal natural laboratory for direct observation of accretion and disruption processes. The ring resides in the Roche zone, where tidal disruption competes with self-gravity, which allows us to observe the lifecycle of moonlets. Just as nearby moons create structure at the B ring edge (Esposito et al. 2012) and the Keeler gap (Murray 2007), the F ring "shepherding" moons Prometheus and Pandora stir up ring material and create observably changing structures on timescales of days to decades. In fact, Beurle et al (2010) show that Prometheus makes it possible for "distended, yet gravitationally coherent clumps" to form in the F ring, and Barbara and Esposito (2002) predicted a population of ~1 km bodies in the ring. In addition to the observations over the last three decades, the Cassini Ultraviolet Imaging Spectrograph (UVIS) has detected 27 statistically significant features in 101 occultations by Saturn's F ring since July 2004. Seventeen of those 27 features are associated with clumps of ring material. Two features are opaque in occultation, which makes them candidates for solid objects, which we refer to as Moonlets. The 15 other features partially block stellar signal for 22 m to just over 3.7 km along the radial expanse of the occultation. Upon visual inspection of the occultation profile, these features resemble Icicles, thus we will refer to them as such here. The density enhancements responsible for such signal attenuations are likely due to transient clumping of material, evidence that aggregations of material are ubiquitous in the F ring. Our lengthy observing campaign reveals that Icicles are likely transient clumps, while Moonlets are possible solid objects. Optical depth is an indicator of clumping because more-densely aggregated material blocks more light; therefore, it is natural to imagine moonlets as later evolutionary stage of icicle, when looser clumps of material compact to form a feature that appears opaque in occultation. We suggest that Icicles may evolve into Moonlets, which are an order of magnitude less abundant in UVIS observations. Motivated by the observations and previous models, I develop a more rigorous model of the evolution of aggregates in Saturn's F ring via tidally-modified accretion. I apply the model to the F ring for bodies of constant density undergoing binary collisions. Because the locations of the UVIS-observed clump-associated features are weakly correlated to the location of Prometheus (Esposito et al. 2012) and images show material stirred up after Prometheus passage (Murray et al. 2008), we develop an additional production term describing "enhanced growth" beyond sticking of hard spheres in binary collisions. In the scenario we devise, Prometheus creates high-density regions in which larger bodies efficiently sweep up smaller bodies. Including a term for this growth mechanism in the numerical model results in the modeled size distribution evolving to a state consistent with observations. Together, the observations and model tell a story of how moonlets are made. Prometheus may be the agent responsible for moonlet growth, a complicated and rare process in the F ring. This can explain how accretion gets the upper hand in forming F ring aggregates. Growth and destruction may be cyclical on a longer time scale. This research was supported by the Cassini project.

Evaluation of Silicon Nitride for Brayton Turbine Wheel Application

NASA Technical Reports Server (NTRS)

Freedman, Marc R.

2008-01-01

Silicon nitride (Si3N4) is being evaluated as a risk-reduction alternative for a Jupiter Icy Moons Orbiter Brayton turbine wheel in the event that the Prometheus program design requirements exceed the creep strength of the baseline metallic superalloys. Five Si3N4 ceramics, each processed by a different method, were screened based on the Weibull distribution of bend strength at 1700 F (927 C). Three of the Si3N4 ceramics, Honeywell AS800, Kyocera SN282, and Saint-Gobain NT154, had bend strengths in excess of 87 ksi (600 MPa) at 1700 F (927 C). These were chosen for further assessment and consideration for future subcomponent and component fabrication and testing.

Calving traits, milk production, body condition, fertility, and survival of Holstein-Friesian and Norwegian Red dairy cattle on commercial dairy farms over 5 lactations.

PubMed

Ferris, C P; Patterson, D C; Gordon, F J; Watson, S; Kilpatrick, D J

2014-01-01

The objective of this study was to compare calving traits, BCS, milk production, fertility, and survival of Holstein-Friesian (HF) and Norwegian Red (NR) dairy cattle in moderate-concentrate input systems. The experiment was conducted on 19 commercial Northern Ireland dairy farms, and involved 221 HF cows and 221 NR cows. Cows completed 5 lactations during the experiment, unless they died or were culled or sold. Norwegian Red cows had a lower calving difficulty score than HF cows when calving for the first and second time, but not for the third and fourth time. At first calving, the incidence of stillbirths for NR cows was 4%, compared with 13% for HF cows, whereas no difference existed between breeds in the proportion of calves born alive when calving for the second time. When calving for the first time, NR cows had a poorer milking temperament than HF cows, whereas milking temperament was unaffected by breed following the second calving. Holstein-Friesian cows had a higher full-lactation milk yield than NR cows, whereas NR cows produced milk with a higher milk fat and protein content. Full-lactation fat + protein yield was unaffected by genotype. Norwegian Red cows had a lower somatic cell score than HF cows during all lactations. Although NR cattle had a higher BCS than the HF cows during lactations 1 and 2, no evidence existed that the 2 genotypes either lost or gained body condition at different rates. Conception rates to first artificial insemination were higher with the NR cows during lactations 1 to 4 (57.8 vs. 40.9%, respectively), with 28.5% of HF cows and 11.8% of NR cows culled as infertile before lactation 6. A greater percentage of NR cows calved for a sixth time compared with HF cows (27.2 vs. 16.3%, respectively). In general, NR cows outperformed HF cows in traits that have been historically included in the NR breeding program. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Little Tuber Moon

NASA Image and Video Library

2010-01-05

Saturn small moon Prometheus, slightly overexposed in this image taken by NASA Cassini spacecraft, shows off its potato-like shape as it orbits in the Roche Division between the A ring and thin F ring.

Moon Shadow, Planet Shadow

NASA Image and Video Library

2010-05-12

Saturn moon Prometheus casts a narrow shadow on the rings near the much larger shadow cast by the planet in this image taken by NASA Cassini spacecraft about five months after Saturn August 2009 equinox.

Potato Pair

NASA Image and Video Library

2010-01-14

Pandora and Prometheus, the shepherding moons of the F ring, orbit inside and outside the thin ring. The elongated, potato-like shapes of the two moons are both visible in this image taken by NASA Cassini spacecraft.

Brother Moons

NASA Image and Video Library

2013-01-14

Saturn small moons Atlas, Prometheus, and Epimetheus keep each other company in this image from NASA Cassini spacecraft of the planet night side. It seems fitting that they should do so since in Greek mythology, their namesakes were brothers.

The Ring Sculptor

NASA Image and Video Library

2006-09-08

Prometheus zooms across the Cassini spacecraft field of view, attended by faint streamers and deep gores in the F ring. This movie sequence of five images shows the F ring shepherd moon shaping the ring inner edge

Linear structures on the small inner satellites of Saturn

NASA Technical Reports Server (NTRS)

Stooke, Philip J.

1993-01-01

Shape modelling methods developed for non-spherical worlds were applied to four satellites of Saturn: Prometheus, Pandora, Janus, and Epimetheus. This results in the first detailed shaded relief maps of their surfaces. Ridges and valleys are described with their implications for satellite history and asteroid 951 Gaspra. They probably result from fracturing during break-up of parent bodies and/or later large impacts. Prometheus and perhaps Gaspra may be coated with debris from parent body fragmentation as well as more recent regolith. These four satellites are covered by relatively few useful images, so the shapes are imperfectly known and positions of features on maps may be wrong by up to a few tens of degrees in some areas (worst where a feature is seen only near a limb). Nevertheless, these shape models are more useful than the previous triaxial ellipsoid models.

Interior properties of the inner Saturnian moons from space astrometry data

NASA Astrophysics Data System (ADS)

Lainey, Valery; Noyelles, Benoît; Cooper, Nick; Murray, Carl; Park, Ryan; Rambaux, Nicolas

2018-04-01

During thirteen years in orbit around Saturn before its final plunge, the Cassini spacecraft provided more than ten thousand astrometric measurements. Such large amounts of accurate data enable the search for extremely faint signals in the orbital motion of the moons. Among those, the detection of the dynamical feedback of the rotation of the inner moons of Saturn on their respective orbits becomes possible. Using all the currently available astrometric data associated with Atlas, Prometheus, Pandora, Janus and Epimetheus, we provide a detailed analysis of the ISS data, with special emphasis on their statistical behavior and source of biases. Then, we try quantifying the physical librations of Prometheus, Pandora, Epimetheus and Janus from the monitoring of their orbits. Last, we show how introducing measurements directly derived from imaging can provide tighter constraints on these quantities.

Dynamical phenomena at the inner edge of the Keeler gap

NASA Astrophysics Data System (ADS)

Tajeddine, Radwan; Nicholson, Philip D.; Tiscareno, Matthew S.; Hedman, Matthew M.; Burns, Joseph A.; El Moutamid, Maryame

2017-06-01

We analyze several thousand Cassini ISS images in order to study the inner edge of the Keeler gap in Saturn's outer A ring. We find strong evidence for an m = 32 perturbation with a mean amplitude of radial variation of 4.5 km. Phase analysis yields a pattern speed consistent with the mean motion of Prometheus, indicating that this pattern is generated by the 32:31 Inner Lindblad resonance with Prometheus. In addition, we find evidence of 18-lobed and 20-lobed patterns with amplitudes of ∼1.5 km. These patterns, whose rotation rates correspond to resonance locations ∼4 km interior to the gap edge, are believed to be normal modes. The former is probably related to the nearby 18:17 (m = 18) resonance with Pandora. In addition to these resonant and normal mode patterns, we also observe multiple localized features that appear to move at the local keplerian rate and that persist for only a few months. One hypothesis is that different groups of ring particles at the inner edge of the gap may be reacting differently to the resonance with Prometheus, with local variations in the forced eccentricity and/or pericenter; an alternative hypothesis is the existence of several unseen objects embedded at or near the inner edge of the Keeler gap, similar to those suspected to exist at the outer edges of the A and B rings. In either case, observations of the ring edge at opposite ansae demonstrate that the localized features must be on eccentric orbits.

Line grouping using perceptual saliency and structure prediction for car detection in traffic scenes

NASA Astrophysics Data System (ADS)

Denasi, Sandra; Quaglia, Giorgio

1993-08-01

Autonomous and guide assisted vehicles make a heavy use of computer vision techniques to perceive the environment where they move. In this context, the European PROMETHEUS program is carrying on activities in order to develop autonomous vehicle monitoring that assists people to achieve safer driving. Car detection is one of the topics that are faced by the program. Our contribution proposes the development of this task in two stages: the localization of areas of interest and the formulation of object hypotheses. In particular, the present paper proposes a new approach that builds structural descriptions of objects from edge segmentations by using geometrical organization. This approach has been applied to the detection of cars in traffic scenes. We have analyzed images taken from a moving vehicle in order to formulate obstacle hypotheses: preliminary results confirm the efficiency of the method.

Planetary science: Shepherds of Saturn's ring

NASA Astrophysics Data System (ADS)

Crida, Aurélien

2015-09-01

Saturn's F ring is chaperoned on both sides by the tiny moons Prometheus and Pandora. Numerical simulations show that this celestial ballet can result from the collision of two aggregates that evolved out of Saturn's main rings.

Prometheus unbound: A study of the Dallas/Fort Worth Regional Airport. [Socio-economic considerations

NASA Technical Reports Server (NTRS)

Starling, J. D.; Brown, J.; Dominus, M. I.

1975-01-01

The history of the controversies in the development of the Dallas/Fort Worth Regional Airport is detailed. Present technological and organizational management problems are outlined. Maps and illustrations are included.

Io's Sodium Cloud (Green-yellow Filter)

NASA Technical Reports Server (NTRS)

1997-01-01

This image of Jupiter's moon Io and its surrounding sky is shown in false color. North is at the top, and east is to the right. Most of Io's visible surface is in shadow, though one can see part of a white crescent on its western side. This crescent is being illuminated mostly by 'Jupitershine' (i.e. sunlight reflected off Jupiter).

The striking burst of white light near Io's eastern equatorial edge is sunlight being scattered by the plume of the volcano Prometheus. Prometheus lies just beyond the visible edge of the moon on Io's far side. Its plume extends about 100 kilometers above the surface, and is being hit by sunlight just a little east of Io's eastern edge.

Scattered light from Prometheus' plume and Io's lit crescent also contribute to the diffuse yellowish emission which appears throughout much of the sky. However, much of this emission comes from Io's Sodium Cloud: sodium atoms within Io's extensive material halo are scattering sunlight at the yellow wavelength of about 589 nanometers.

This image was taken at 5 hours 30 minutes Universal Time on Nov. 9, 1996 through the green-yellow filter of the solid state imaging (CCD) system aboard NASA's Galileo spacecraft. Galileo was then in Jupiter's shadow, and located about 2.3 million kilometers (about 32 Jovian radii) from both Jupiter and Io.

The Jet Propulsion Laboratory, Pasadena, CA, manages the mission for NASA's Office of Space Science, Washington D.C. This image and other images and data received from Galileo are posted on the World Wide Web Galileo mission home page at: http://galileo.jpl.nasa.gov.

Experimental Design for Evaluation of Co-extruded Refractory Metal/Nickel Base Superalloy Joints

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

ME Petrichek

2005-12-16

Prior to the restructuring of the Prometheus Program, the NRPCT was tasked with delivering a nuclear space reactor. Potential NRPCT nuclear space reactor designs for the Prometheus Project required dissimilar materials to be in contact with each other while operating at extreme temperatures under irradiation. As a result of the high reactor core temperatures, refractory metals were the primary candidates for many of the reactor structural and cladding components. They included the tantalum-base alloys ASTAR-811C and Ta-10W, the niobium-base alloy FS-85, and the molybdenum base alloys Moly 41-47.5 Rhenium. The refractory metals were to be joined to candidate nickel basemore » alloys such as Haynes 230, Alloy 617, or Nimonic PE 16 either within the core if the nickel-base alloys were ultimately selected to form the outer core barrel, or at a location exterior to the core if the nickel-base alloys were limited to components exterior to the core. To support the need for dissimilar metal joints in the Prometheus Project, a co-extrusion experiment was proposed. There are several potential methods for the formation of dissimilar metal joints, including explosive bonding, friction stir welding, plasma spray, inertia welding, HIP, and co-extrusion. Most of these joining methods are not viable options because they result in the immediate formation of brittle intermetallics. Upon cooling, intermetallics form in the weld fusion zone between the joined metals. Because brittle intermetallics do not form during the initial bonding process associated with HIP, co-extrusion, and explosive bonding, these three joining procedures are preferred for forming dissimilar metal joints. In reference to a Westinghouse Astronuclear Laboratory report done under a NASA sponsored program, joints that were fabricated between similar materials via explosive bonding had strengths that were directly affected by the width of the diffusion barrier. It was determined that the diffusion zone should not exceed a critical thickness (0.0005 in.). A diffusion barrier that exceeded this thickness would likely fail. The joint fabrication method must therefore mechanically bond the two materials causing little or no interdiffusion upon formation. Co-extrusion fits this description since it forms a mechanical joint between two materials by using heat and pressure. The two materials to be extruded are first assembled and sealed within a co-extrusion billet which is subsequently heated and then extruded through a die. For a production application, once the joint is formed, it is dejacketed to remove the outer canister. The remaining piece consists of two materials bonded together with a thin diffusion barrier. Therefore, the long-term stability of the joint is determined primarily by the kinetics of interdiffusion reaction between the two materials. An experimental design for co-extrusion of refractory metals and nickel-based superalloys was developed to evaluate this joining process and determine the long-term stability of the joints.« less

Moons Around Saturn

NASA Technical Reports Server (NTRS)

1996-01-01

This series of 10 Hubble Space Telescope images captures several small moons orbiting Saturn. Hubble snapped the five pairs of images while the Earth was just above the ring plane and the Sun below it. The telescope captured a pair of images every 97 minutes as it circled the Earth. Moving out from Saturn, the visible rings are: the broad C Ring, the Cassini Division, and the narrow F Ring.

The first pair of images shows the large, bright moon Dione, near the middle of the frames. Two smaller moons, Pandora (the brighter one closer to Saturn) and Prometheus, appear as if they're touching the F Ring. In the second frame, Mimas emerges from Saturn's shadow and appears to be chasing Prometheus.

In the second image pair, Mimas has moved towards the tip of the F Ring. Rhea, another bright moon, has just emerged from behind Saturn. Prometheus, the closest moon to Saturn, has rounded the F Ring's tip and is approaching the planet. The slightly larger moon Epimetheus has appeared.

The third image pair shows Epimetheus, as a tiny dot just beyond the tip of the F Ring. Prometheus is in the lower right corner. An elongated clump or arc of debris in the F ring is seen as a slight brightening on the far side of this thin ring.

In the fourth image pair, Epimetheus, in the lower right corner, streaks towards Saturn. The long ring arc can be seen in both frames.

The fifth image pair again captures Mimas, beyond the tip of the F Ring. The same ring arc is still visible.

In addition to the satellites, a pair of stars can be seen passing behind the rings, appearing to move towards the lower left due to Saturn's motion across the sky.

The images were taken Nov. 21, 1995 with Wide Field Planetary Camera-2.

The Wide Field/Planetary Camera 2 was developed by the Jet Propulsion Laboratory and managed by the Goddard Spaced Flight Center for NASA's Office of Space Science.

This image and other images and data received from the Hubble Space Telescope are posted on the World Wide Web on the Space Telescope Science Institute home page at URL http://oposite.stsci.edu/pubinfo/

40 CFR 158.220 - Experimental use permit data requirements for product performance.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Note No. Efficacy of antimicrobial agents 91-8 Products for treating water systems NR NR CR NR NR NR NR... reproductive inhibitors R R NR NR NR NR NR R R NR EP 1 95-17 Mammalian predacides R R NR NR NR NR NR R NR NR EP... pesticide product bears a claim to control pest microorganisms that pose a threat to human health and whose...

Identification of mission sensitivities for high-power electric propulsion systems

NASA Technical Reports Server (NTRS)

Frisbee, Robert H.; Moeller, Robert C.

2005-01-01

This paper presents the results of mission analyses that expose various mission performance sensitivities and system advantages of the ALFA technology for a small but representative subset of nuclear electric propulsion (NEP) missions considered under NASA's Project Prometheus.

Molecular Detection and Identification of Rickettsia Species in Ticks (Acari: Ixodidae) Collected From Belize, Central America.

PubMed

Polsomboon, Suppaluck; Hoel, David F; Murphy, Jittawadee R; Linton, Yvonne-Marie; Motoki, Maysa; Robbins, Richard G; Bautista, Kim; Bricen O, Ireneo; Achee, Nicole L; Grieco, John P; Ching, Wei-Mei; Chao, Chien-Chung

2017-11-07

Little is known about tick-borne rickettsial pathogens in Belize, Central America. We tested ixodid ticks for the presence of Rickettsia species in three of the six northern and western Belizean districts. Ticks were collected from domestic animals and tick drags over vegetation in 23 different villages in November 2014, February 2015, and May 2015. A total of 2,506 collected ticks were identified to the following species: Dermacentor nitens Neumann (46.69%), Rhipicephalus sanguineus (Latreille) (19.55%), Rhipicephalus microplus (Canestrini) (19.47%), Amblyomma cajennense complex (9.74%), Amblyomma maculatum Koch (3.47%), Amblyomma ovale Koch (0.68%), Ixodes nr affinis (0.16%), Amblyomma nr maculatum (0.12%), and Amblyomma nr oblongoguttatum (0.12%). Ticks were pooled according to species, life stage (larva, nymph, or adult), and location (n = 509) for DNA extraction and screened for genus Rickettsia by quantitative real-time polymerase chain reaction (qPCR). All 42 positive pools were found to be positive for spotted fever group (SFG) Rickettsia in pools of A. cajennense complex (n = 33), A. maculatum (n = 4), A. nr maculatum (n = 1), A. ovale (n = 1), R. sanguineus (n = 1), and I. nr affinis (n = 2). Rickettsia amblyommatis was identified from A. cajennense complex and A. nr maculatum. Rickettsia parkeri was found in A. maculatum, and Rickettsia sp. endosymbiont was detected in I. nr affinis. The presence of infected ticks suggests a risk of tick-borne rickettsioses to humans and animals in Belize. This knowledge can contribute to an effective tick management and disease control program benefiting residents and travelers. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.

Polymer Nanocomposite Films: Dispersion of Polymer Grafted Nanorods and Optical Properties

NASA Astrophysics Data System (ADS)

Composto, Russell

2013-03-01

The thermodynamic factors that affect the dispersion of polymer-brush grafted gold nanorods (NR) in polymer matrix films have been studied by experiment and theory. When brush and matrix have a favorable interaction, such as poly(ethylene oxide) (PEO)-NR/ poly(methyl methacrylate) (PMMA) and polystyrene (PS)-NR / poly(2,6-dimethyl-p-phenylene oxide) (PPO), nanorods are uniformly dispersed. For PEO-NRs in PMMA, the NRs are regularly spaced and well dispersed, independent of the ratio of the degree of polymerization of the matrix (P) to that of the brush (N), namely P/N. As the NR volume fraction increases, the local orientation of the nanorods increases, whereas the macroscopic orientation remains isotropic. When the brush and matrix are similar (i.e., PS-NR / PS and PEO-NR / PEO), the nanorods randomly disperse for P/N < 2 (i.e., wet brush), but align side-by-side in aggregates for P/N > 2. UV-visible spectroscopy and discrete dipole approximation (DDA) calculations demonstrate that surface plasmon coupling leads to a blue shift in the longitudinal surface plasmon resonance (LSPR) as P/N increases. For P/N > 2, self-consistent field theory (SCFT) calculations and Monte Carlo (MC) simulations indicate that nanorod aggregation is caused by depletion-attraction forces. Starting with a dry brush system, namely, a PS matrix where P/N = 30, these attractive forces can be mediated by adding a compatibilizing agent (e.g., PPO) that drives the NRs to disperse. Finally, dry and wet brush behavior is observed for NR aspect ratios varying from 2.5 to 7. However, compared at the same volume fraction, long rods for the dry case exhibit much better local order than lower aspect ratio nanorods, suggesting that long rods may exhibit nematic-like ordering at higher loadings. NSF Polymer and CEMRI Programs.

Comparison of Fission Product Yields and Their Impact

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

S. Harrison

2006-02-01

This memorandum describes the Naval Reactors Prime Contractor Team (NRPCT) Space Nuclear Power Program (SNPP) interest in determining the expected fission product yields from a Prometheus-type reactor and assessing the impact of these species on materials found in the fuel element and balance of plant. Theoretical yield calculations using ORIGEN-S and RACER computer models are included in graphical and tabular form in Attachment, with focus on the desired fast neutron spectrum data. The known fission product interaction concerns are the corrosive attack of iron- and nickel-based alloys by volatile fission products, such as cesium, tellurium, and iodine, and the radiologicalmore » transmutation of krypton-85 in the coolant to rubidium-85, a potentially corrosive agent to the coolant system metal piping.« less

Qualified and Unqualified (N-R C) mental health nursing staff--minor differences in sources of stress and burnout. A European multi-centre study.

PubMed

Sorgaard, Knut W; Ryan, Peter; Dawson, Ian

2010-06-14

Unqualified/non-registered caregivers (N-R Cs) will continue to play important roles in the mental health services. This study compares levels of burnout and sources of stress among qualified and N-R Cs working in acute mental health care. A total of 196 nursing staff --124 qualified staff (mainly nurses) and 72 N-R Cs with a variety of different educational backgrounds--working in acute wards or community mental teams from 5 European countries filled out the Maslach Burnout Inventory (MBI), the Mental Health Professional Scale (MHPSS) and the Psychosocial Work Environment and Stress Questionnaire (PWSQ). (a) The univariate differences were generally small and restricted to a few variables. Only Social relations (N-R Cs being less satisfied) at Work demands (nurses reporting higher demands) were different at the .05 level. (b) The absolute scores both groups was highest on variables that measured feelings of not being able to influence a work situation characterised by great demands and insufficient resources. Routines and educational programs for dealing with stress should be available on a routine basis. (c) Multivariate analyses identified three extreme groups: (i) a small group dominated by unqualified staff with high depersonalization, (ii) a large group that was low on depersonalisation and high on work demands with a majority of qualified staff, and (iii) a small N-R C-dominated group (low depersonalization, low work demands) with high scores on professional self-doubt. In contrast to (ii) the small and N-R C-dominated groups in (i) and (iii) reflected mainly centre-dependent problems. The differences in burnout and sources of stress between the two groups were generally small. With the exception of high work demands the main differences between the two groups appeared to be centre-dependent. High work demands characterized primarily qualified staff. The main implication of the study is that no special measures addressed towards N-R Cs in general with regard to stress and burnout seem necessary. The results also suggest that centre-specific problems may cause more stress among N-R Cs compared to the qualified staff (e.g. professional self-doubt).

Changing volcanoes on Io

NASA Technical Reports Server (NTRS)

1996-01-01

Volcanoes on Jupiter's moon Io are compared in these images from NASA's Galileo spacecraft (right) taken in early September of this year, and from the Voyager spacecraft (left) taken in 1979. Prometheus (bright ring in upper right) was first seen as an erupting volcano by the Voyager spacecraft and still features an active plume. A smaller active plume was discovered at the volcano Culann Patera (dark feature at lower left) by the Galileo spacecraft.

Prometheus has displayed similar characteristics such as size, shape and brightness to Galileo's cameras as it did to Voyager's. However, several intriguing differences are also apparent. There appears to be a new dark lava flow emanating from the vent of Prometheus, and the plume is now erupting from a position about 75 kilometers (46.5 miles) west from where the hot spot resided in 1979. It is not known if the plume source is the same or if the plume is now emanating from a new source. Overall, scientists studying Galileo images of Io see that a wide variety of surface changes have occurred on Io since 1979. The Galileo image was taken at a range of about 487,000 kilometers (about 302,000 miles) from Io. The Voyager image was taken from about 800,000 kilometers (about 500,000 miles).

The Jet Propulsion Laboratory, Pasadena, CA, manages the mission for NASA's Office of Space Science, Washington, DC. This image and other images and data received from Galileo are posted on the Galileo mission home page on the World Wide Web at http://galileo.jpl.nasa.gov. Background information and educational context for the images can be found at http:// www.jpl.nasa.gov/galileo/sepo

Io's Sodium Cloud (Clear and Green-Yellow Filters)

NASA Technical Reports Server (NTRS)

1997-01-01

The green-yellow filter and clear filter images of Io which were released over the past two days were originally exposed on the same frame. The camera pointed in slightly different directions for the two exposures, placing a clear filter image of Io on the top half of the frame, and a green-yellow filter image of Io on the bottom half of the frame. This picture shows that entire original frame in false color, the most intense emission appearing white.

East is to the right. Most of Io's visible surface is in shadow, though one can see part of an illuminated crescent on its western side. The burst of white light near Io's eastern equatorial edge (most distinctive in the green filter image) is sunlight scattered by the plume of the volcano Prometheus.

There is much more bright light near Io in the clear filter image, since that filter's wider wavelength range admits more scattered light from Prometheus' sunlit plume and Io's illuminated crescent. Thus in the clear filter image especially, Prometheus's plume was bright enough to produce several white spikes which extend radially outward from the center of the plume emission. These spikes are artifacts produced by the optics of the camera. Two of the spikes in the clear filter image appear against Io's shadowed surface, and the lower of these is pointing towards a bright round spot. That spot corresponds to thermal emission from the volcano Pele.

The Jet Propulsion Laboratory, Pasadena, CA manages the mission for NASA's Office of Space Science, Washington, DC.

This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov.

Moon Convention

NASA Image and Video Library

2015-03-23

People with similar jobs or interests hold conventions and meetings, so why shouldn't moons? Pandora, Prometheus, and Pan -- seen here, from right to left -- also appear to be holding some sort of convention in this image. Some moons control the structure of nearby rings via gravitational "tugs." The cumulative effect of the moon's tugs on the ring particles can keep the rings' edges from spreading out as they are naturally inclined to do, much like shepherds control their flock. Pan is a prototypical shepherding moon, shaping and controlling the locations of the inner and outer edges of the Encke gap through a mechanism suggested in 1978 to explain the narrow Uranian rings. However, though Prometheus and Pandora have historically been called "the F ring shepherd moons" due to their close proximity to the ring, it has long been known that the standard shepherding mechanism that works so well for Pan does not apply to these two moons. The mechanism for keeping the F ring narrow, and the roles played -- if at all -- by Prometheus and Pandora in the F ring's configuration are not well understood. This is an ongoing topic for study by Cassini scientists. This view looks toward the sunlit side of the rings from about 29 degrees above the ringplane. The image was taken in visible light with the Cassini spacecraft narrow-angle camera on Jan. 2, 2015. The view was obtained at a distance of approximately 1.6 million miles (2.6 million kilometers) from the rings and at a Sun-ring-spacecraft, or phase, angle of 86 degrees. Image scale is 10 miles (15 kilometers) per pixel. http://photojournal.jpl.nasa.gov/catalog/pia18306

Medical Surveillance Monthly Report (MSMR). Volume 2, Number 11, November 2015

DTIC Science & Technology

2015-11-01

encounters within 2 weeks Typhoid fever 002.0 once per 360 days 1 inpatient Typhus fever 080, 081.x once per lifetime 1 inpatient, 2 outpatient encounters...Tuberculosis 49 18 36.7 3 1 33.3 NR NR NR NR NR NR Tularemia 2 1 50.0 0 0 * 1 1 100.0 0 0 * Typhoid fever 4 0 0.0 0 0 * NR NR NR NR NR NR Typhus fever 2 1 50.0 0...Tularemia 1 1 100.0 0 0 * 1 1 100.0 0 0 * Typhoid fever 3 0 0.0 0 0 * NR NR NR NR NR NR Typhus fever 2 0 0.0 0 0 * 0 0 * 0 0 * Vaccine, adverse event 1

Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities.

PubMed

Melas, Philippe A; Wei, Yabin; Wong, Chloe C Y; Sjöholm, Louise K; Åberg, Elin; Mill, Jonathan; Schalling, Martin; Forsell, Yvonne; Lavebratt, Catharina

2013-08-01

Monoamine oxidase A (MAOA) harbours a polymorphic upstream variable-number tandem repeat (u-VNTR). The MAOA-L allele of the u-VNTR leads to decreased gene expression levels in vitro and has been found to increase the risk of conduct disorder in males with childhood adversities. Early-life adversities have been associated with hypermethylation of the glucocorticoid receptor (NR3C1). In this study, we first performed a genetic association analysis of the MAOA u-VNTR using individuals with depression (n = 392) and controls (n = 1276). Next, DNA methylation analyses of MAOA and NR3C1 were performed using saliva samples of depressed and control subgroups. Adult MAOA-L females with childhood adversities were found to have a higher risk of developing depression (p = 0.006) and overall MAOA methylation levels were decreased in depressed females compared to controls (mean depressed, 42% vs. mean controls, 44%; p = 0.04). One specific childhood adversity [early parental death (EPD)] was associated with hypermethylation of NR3C1 close to an NGFI-A binding site (mean EPD, 19% vs. mean non-EPD, 14%; p = 0.005). Regression analysis indicated that this association may be mediated by the MAOA-L allele (adjusted R² = 0.24, ANOVA: F = 23.48, p < 0.001). Conclusively: (1) depression in females may result from a gene × childhood-adversity interaction and/or a dysregulated epigenetic programming of MAOA; (2) childhood-adversity subtypes may differentially impact DNA methylation at NR3C1; (3) baseline MAOA-genotypic variations may affect the extent of NR3C1 methylation.

Luminescent Photoelectrochemical Cells. 6. Spatial Aspects of the Photoluminescence and Electroluminescence of Cadmium Selenide Electrodes.

DTIC Science & Technology

1981-10-06

STRECKERT, J TONS, A B ELLIS N01478-C5633 UNCLASSI1FIED TRAS NL OFFICE OF NAVAL RESEARCH Contract No. N00014-78’-C-0633 Task No. NR 051-690 TECHNICAL REPORT...of Wisconsin NR 051-690 Madison, Wisconsin 53706 II. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE *Office of Naval Research /Chemistry Program...identify by block number) Samples of single-crystal, n-type CdSe emit when excited with ultraband gap excitation. The emission band (Xmax 񔊐 nm) is

The NR3B subgroup: an ovERRview

PubMed Central

Tremblay, Annie M.; Giguère, Vincent

2007-01-01

Members of the NR3B group of the nuclear receptor superfamily, known as the estrogen-related receptors (ERRs), were the first orphan receptors to be identified two decades ago. Despite the fact that a natural ligand has yet to be associated with the ERRs, considerable knowledge about their mode of action and biological functions has emerged through extensive biochemical, genetic and functional genomics studies. This review describes our current understanding of how the ERRs work as transcription factors and as such, how they control diverse developmental and physiological programs. PMID:18174917

The Cheshire Jet: Harnessing Metamaterials to Achieve an Optical Stealth Capability

DTIC Science & Technology

2010-07-01

Prometheus Books, 2005. Hamilton, Dave. Address. 23rd Annual National Test and Evaluation Conference, Hilton Head Island, SC, 15 March 2007. http...ment 2008: Challenges and Implications for the Future Joint Force. Norfolk, VA: Center for Joint Futures, 25 November 2008. Valentine, Jason , Shuang

Glucocorticoid Receptor (NR3C1) Variants Associate with the Muscle Strength and Size Response to Resistance Training.

PubMed

Ash, Garrett I; Kostek, Matthew A; Lee, Harold; Angelopoulos, Theodore J; Clarkson, Priscilla M; Gordon, Paul M; Moyna, Niall M; Visich, Paul S; Zoeller, Robert F; Price, Thomas B; Devaney, Joseph M; Gordish-Dressman, Heather; Thompson, Paul D; Hoffman, Eric P; Pescatello, Linda S

2016-01-01

Glucocorticoid receptor (NR3C1) polymorphisms associate with obesity, muscle strength, and cortisol sensitivity. We examined associations among four NR3C1 polymorphisms and the muscle response to resistance training (RT). European-American adults (n = 602, 23.8±0.4yr) completed a 12 week unilateral arm RT program. Maximum voluntary contraction (MVC) assessed isometric strength (kg) and MRI assessed biceps size (cm2) pre- and post-resistance training. Subjects were genotyped for NR3C1 -2722G>A, -1887G>A, -1017T>C, and +363A>G. Men carrying the -2722G allele gained less relative MVC (17.3±1.2vs33.5±6.1%) (p = 0.010) than AA homozygotes; men with -1887GG gained greater relative MVC than A allele carriers (19.6±1.4vs13.2±2.3%) (p = 0.016). Women carrying the -1017T allele gained greater relative size (18.7±0.5vs16.1±0.9%) (p = 0.016) than CC homozygotes. We found sex-specific NR3C1 associations with the muscle strength and size response to RT. Future studies should investigate whether these associations are partially explained by cortisol's actions in muscle tissue as they interact with sex differences in cortisol production.

Greek and Roman Myths.

ERIC Educational Resources Information Center

Carr, Fredella; Faggionato, Michael

Designed for use with the text "Greek and Roman Myths," this junior high school learning activity packet introduces students to mythology and examines the influence of myths on contemporary culture. Over 20 exercises, tagged to specific readings in the text, cover identification of the major gods, the Prometheus myth, the Atlas myth,…

Advancements in Curricular Design: Web-Assisted Courseware Applications in Mass Communication.

ERIC Educational Resources Information Center

Reppert, James E.

Interactive courseware applications are becoming more prevalent as instructional tools in the communication classroom. Prometheus, developed by George Washington University, allows instructors to post syllabi, course outlines, lecture notes, and tests online, in addition to giving students access to discussions and chat sessions. Other popular…

The Birth of "Frankenstein"

ERIC Educational Resources Information Center

Howard, Jennifer

2008-01-01

Nobody shouts "It's alive!" in the novel that gave birth to Frankenstein's monster. "Frankenstein, or the Modern Prometheus," does not feature mad scientists messing around with beakers in laboratories, nor does it deliver any bug-eyed assistants named Igor. Hollywood has given people those stock images, but the story of the monster and his maker…

Qualified and Unqualified (N-R C) mental health nursing staff - minor differences in sources of stress and burnout. A European multi-centre study

PubMed Central

2010-01-01

Background Unqualified/non-registered caregivers (N-R Cs) will continue to play important roles in the mental health services. This study compares levels of burnout and sources of stress among qualified and N-R Cs working in acute mental health care. Methods A total of 196 nursing staff - 124 qualified staff (mainly nurses) and 72 N-R Cs with a variety of different educational backgrounds - working in acute wards or community mental teams from 5 European countries filled out the Maslach Burnout Inventory (MBI), the Mental Health Professional Scale (MHPSS) and the Psychosocial Work Environment and Stress Questionnaire (PWSQ). Results (a) The univariate differences were generally small and restricted to a few variables. Only Social relations (N-R Cs being less satisfied) at Work demands (nurses reporting higher demands) were different at the .05 level. (b) The absolute scores both groups was highest on variables that measured feelings of not being able to influence a work situation characterised by great demands and insufficient resources. Routines and educational programs for dealing with stress should be available on a routine basis. (c) Multivariate analyses identified three extreme groups: (i) a small group dominated by unqualified staff with high depersonalization, (ii) a large group that was low on depersonalisation and high on work demands with a majority of qualified staff, and (iii) a small N-R C-dominated group (low depersonalization, low work demands) with high scores on professional self-doubt. In contrast to (ii) the small and N-R C-dominated groups in (i) and (iii) reflected mainly centre-dependent problems. Conclusion The differences in burnout and sources of stress between the two groups were generally small. With the exception of high work demands the main differences between the two groups appeared to be centre-dependent. High work demands characterized primarily qualified staff. The main implication of the study is that no special measures addressed towards N-R Cs in general with regard to stress and burnout seem necessary. The results also suggest that centre-specific problems may cause more stress among N-R Cs compared to the qualified staff (e.g. professional self-doubt). PMID:20546587

40 CFR 158.243 - Experimental use permit data requirements for terrestrial and aquatic nontarget organisms.

Code of Federal Regulations, 2010 CFR

2010-07-01

... toxicity R R R NR NR NR TGAI, TEP 1, 2, 5, 6, 11 850.1010 Acute toxicity freshwater invertebrates R R R NR NR NR TGAI, TEP 1, 2, 6, 7, 11 850.1300 Aquatic invertebrate life cycle (freshwater) NR R R NR NR NR... aquatic organisms. 7. Data are required on one freshwater aquatic invertebrate species. 8. Data are...

Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial.

PubMed

Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

2017-04-01

Our aim was to investigate the effects and prevalence of nonresponders (NR) to high-intensity interval training (HIIT) and resistance training (RT) in women with insulin resistance on cardiometabolic health parameters. Sedentary overweight/obese insulin-resistant women (age = 33.5 ± 6.5 yr; body mass index = 29.9 ± 3.7 kg/m 2 ) were randomly assigned to a triweekly HIIT program (HIIT; n = 18) or resistance training (RT; n = 17). Anthropometry (body mass, fat mass, muscle mass, waist circumference, and skinfold thickness), cardiovascular (blood pressure), metabolic [fasting glucose, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR)], as well as muscle strength, and endurance performance covariables were measured before and after 12 wk in both intervention groups. The interindividual variability to exercise training of the subjects was categorized as responders and NR using as cut points two times the typical error of measurement in mean outcomes. After intervention, significant reduction in waist circumference, skinfold thicknesses, fat mass, blood pressure, fasting glucose, insulin, and HOMA-IR ( P < 0.05) were identified to HIIT and RT group, respectively. Both HIIT and RT groups exhibited a significant decrease in the endurance performance, whereas only RT exhibited increased muscle strength. Significant differences in the NR prevalence between the HIIT and RT groups were identified for a decrease in fat mass (HIIT 33.3% vs. RT 70.5%; P = 0.028), muscle mass (HIIT 100% vs. RT 52.9%; P = 0.001), and tricipital skinfold (HIIT 5.5% vs. RT 29.4%; P < 0.041). For diastolic blood pressure, significant differences were observed in the NR prevalence between the HIIT and RT groups (55.5% vs. 94.1; P = 0.009). However, there were no differences in the NR prevalence between HIIT and RT for decreasing fasting glucose. Twelve weeks of HIIT and RT have similar effects and NR prevalence to improve glucose control variables; however, there is different NR prevalence in other anthropometric, cardiovascular, strength, and endurance performance measurements in insulin-resistant women. These findings were displayed with a similar time investment per week of 114 vs. 108 min, respectively, to HIIT and RT. NEW & NOTEWORTHY The effects and prevalence of nonresponders (NR) to improve glucose control variables have predominately been reported by endurance training. A uniqueness of the present study was to examine the NR prevalence in women with insulin resistance after high-intensity interval (HIIT) and resistance training (RT). This study demonstrates that 12 wk of HIIT and RT have similar effects and NR prevalence to improve glucose control variables. However, significantly different NR prevalence were observed in other anthropometric, cardiovascular, strength, and endurance performance measurements. Copyright © 2017 the American Physiological Society.

Students from Aurora Triumph in Competition of the Mind

Science.gov Websites

fast-paced questions about physics, math, biology, astronomy, chemistry, computers and the earth educational programs to help stimulate young people's interest in science and math. NR-00797

Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts

PubMed Central

Gurtan, Allan M.; Ravi, Arvind; Rahl, Peter B.; Bosson, Andrew D.; JnBaptiste, Courtney K.; Bhutkar, Arjun; Whittaker, Charles A.; Young, Richard A.; Sharp, Phillip A.

2013-01-01

MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to derepression of let-7 targets at levels that exceed 10-fold to 100-fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 (E3.5) and the induction of let-7 upon differentiation at E10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor-suppressive function. PMID:23630078

Modulation of NMDA Receptor Properties and Synaptic Transmission by the NR3A Subunit in Mouse Hippocampal and Cerebrocortical Neurons

PubMed Central

Tong, Gary; Takahashi, Hiroto; Tu, Shichun; Shin, Yeonsook; Talantova, Maria; Zago, Wagner; Xia, Peng; Nie, Zhiguo; Goetz, Thomas; Zhang, Dongxian; Lipton, Stuart A.; Nakanishi, Nobuki

2015-01-01

Expression of the NR3A subunit with NR1/NR2 in Xenopus oocytes or mammalian cell lines leads to a reduction in N-methyl-D-aspartate (NMDA)-induced currents and decreased Mg2+ sensitivity and Ca2+ permeability compared with NR1/NR2 receptors. Consistent with these findings, neurons from NR3A knockout (KO) mice exhibit enhanced NMDA-induced currents. Recombinant NR3A can also form excitatory glycine receptors with NR1 in the absence of NR2. However, the effects of NR3A on channel properties in neurons and synaptic transmission have not been fully elucidated. To study physiological roles of NR3A subunits, we generated NR3A transgenic (Tg) mice. Cultured NR3A Tg neurons exhibited two populations of NMDA receptor (NMDAR) channels, reduced Mg2+ sensitivity, and decreased Ca2+ permeability in response to NMDA/glycine, but glycine alone did not elicit excitatory currents. In addition, NMDAR-mediated excitatory postsynaptic currents (EPSCs) in NR3A Tg hippocampal slices showed reduced Mg2+ sensitivity, consistent with the notion that NR3A subunits incorporated into synaptic NMDARs. To study the function of endogenous NR3A subunits, we compared NMDAR-mediated EPSCs in NR3A KO and WT control mice. In NR3A KO mice, the ratio of the amplitudes of the NMDAR-mediated component to α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptor-mediated component of the EPSC was significantly larger than that seen in WT littermates. This result suggests that NR3A subunits contributed to the NMDAR-mediated component of the EPSC in WT mice. Taken together, these results show that NR3A subunits contribute to NMDAR responses from both synaptic and extra-synaptic receptors, likely composed of NR1, NR2, and NR3 subunits. PMID:18003876

A Practical Approach to Starting Fission Surface Power Development

NASA Technical Reports Server (NTRS)

Mason, Lee S.

2006-01-01

The Prometheus Power and Propulsion Program has been reformulated to address NASA needs relative to lunar and Mars exploration. Emphasis has switched from the Jupiter Icy Moons Orbiter (JIMO) flight system development to more generalized technology development addressing Fission Surface Power (FSP) and Nuclear Thermal Propulsion (NTP). Current NASA budget priorities and the deferred mission need date for nuclear systems prohibit a fully funded reactor Flight Development Program. However, a modestly funded Advanced Technology Program can and should be conducted to reduce the risk and cost of future flight systems. A potential roadmap for FSP technology development leading to possible flight applications could include three elements: 1) Conceptual Design Studies, 2) Advanced Component Technology, and 3) Non-Nuclear System Testing. The Conceptual Design Studies would expand on recent NASA and DOE analyses while increasing the depth of study in areas of greatest uncertainty such as reactor integration and human-rated shielding. The Advanced Component Technology element would address the major technology risks through development and testing of reactor fuels, structural materials, primary loop components, shielding, power conversion, heat rejection, and power management and distribution (PMAD). The Non-Nuclear System Testing would provide a modular, technology testbed to investigate and resolve system integration issues.

The Vu from Mt. Deja (Epimetheus Reports That Prometheus Remains Bound).

ERIC Educational Resources Information Center

Achilles, C. M.

Application of the study of humanities in administrator education is explored in this paper. The argument is made that humanities studies help to conceptualize ideas and generate theory, and to represent and explain what is uniquely human. Effective administrators require problem-solving and critical thinking skills for dealing with people-related…

The Effects of Railroads on the Emergence of Operational Art During the American Civil War, 1861-1865

DTIC Science & Technology

2013-05-23

L&N Railroad in the Civil War: A Vital North–South Link and the Struggle to Control It. Jefferson: McFarland & Company, 2011. Lord, Francis A...Battlefield 1861-1863. Amherst: Prometheus Books, 2008. Reynolds, Paul Davidson. A Primer in Theory Construction. Boston: Allyn and Bacon Classics

Two F Ring Views

NASA Technical Reports Server (NTRS)

2005-01-01

These views, taken two hours apart, demonstrate the dramatic variability in the structure of Saturn's intriguing F ring.

In the image at the left, ringlets in the F ring and Encke Gap display distinctive kinks, and there is a bright patch of material on the F ring's inner edge. Saturn's moon Janus (181 kilometers, or 113 miles across) is shown here, partly illuminated by reflected light from the planet.

At the right, Prometheus (102 kilometers, or 63 miles across) orbits ahead of the radial striations in the F ring, called 'drapes' by scientists. The drapes appear to be caused by successive passes of Prometheus as it reaches the greatest distance (apoapse) in its orbit of Saturn. Also in this image, the outermost ringlet visible in the Encke Gap displays distinctive bright patches.

These views were obtained from about three degrees below the ring plane.

The images were taken in visible light with the Cassini spacecraft narrow-angle camera on June 29, 2005, when Cassini was about 1.5 million kilometers (900,000 miles) from Saturn. The image scale is about 9 kilometers (6 miles) per pixel.

Initial Assessment of Environmental Barrier Coatings for the Prometheus Project

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

M. Frederick

2005-12-15

Depending upon final design and materials selections, a variety of engineering solutions may need to be considered to avoid chemical degradation of components in a notional space nuclear power plant (SNPP). Coatings are one engineered approach that was considered. A comprehensive review of protective coating technology for various space-reactor structural materials is presented, including refractory metal alloys [molybdenum (Mo), tungsten (W), rhenium (Re), tantalum (Ta), and niobium (Nb)], nickel (Ni)-base superalloys, and silicon carbide (Sic). A summary description of some common deposition techniques is included. A literature survey identified coatings based on silicides or iridium/rhenium as the primary methods formore » environmental protection of refractory metal alloys. Modified aluminide coatings have been identified for superalloys and multilayer ceramic coatings for protection of Sic. All reviewed research focused on protecting structural materials from extreme temperatures in highly oxidizing conditions. Thermodynamic analyses indicate that some of these coatings may not be protective in the high-temperature, impure-He environment expected in a Prometheus reactor system. Further research is proposed to determine extensibility of these coating materials to less-oxidizing or neutral environments.« less

The molecular physiology of liver regeneration following partial hepatectomy.

PubMed

Mangnall, David; Bird, Nigel C; Majeed, Ali W

2003-04-01

The ability of the liver to regenerate after resection has been known for many years. Two reports from Germany in the late 1800s probably mark the introduction of the phenomenon into the scientific literature, but in the early 1900s the first reviews of this subject had appeared in the English literature. Predating these early scientific reports the legends from the Greek mythology described the fate of Prometheus. As punishment for defying Zeus and revealing the secret of fire to man, Prometheus was chained to a rock and each day had part of his liver ripped out by an eagle which, returning the following day, repeated the torture because his liver regenerated itself overnight. Although the speed of regeneration in the Greek legend is somewhat greater than that observed either clinically or in the laboratory, the myth does serve to emphasise the remarkable ability of the liver to repeatedly regenerate following repeated resections. This review aims to summarise the more recent literature concerning the early molecular events accompanying liver regeneration and to integrate this with the existing knowledge of this subject.

"Chiron": A Proposed Remote Sensing Prompt Gamma Ray Activation Analysis Instrument for a Nuclear Powered Prometheus Mission

NASA Technical Reports Server (NTRS)

Floyd, Samuel R.; Keller, John W.; Dworkin, Jason P.; Mildner, David F. R.

2004-01-01

Prompt Gamma Ray Activation Analysis (PGAA) from neutron capture is an important experimental method that yields information on the elemental abundance of target materials. Gamma ray analysis has been used in planetary exploration missions by taking advantage of the production of neutrons as a result of Galactic Cosmic Ray interaction within the planetary surfaces. The .gamma ray signal that can be obtained from the GCR production of neutrons is very low, so we seek a superior neutron source. NASA s Project Prometheus and the Dept. of Energy aim to develop a nuclear power system for planetary exploration. This provides us with a tremendous opportunity to harness the reactor as a source of neutrons that can be used for PGAA. We envision a narrow stream of neutrons from the reactor directed toward the surface of an asteroid or comet producing the prompt gamma ray signal for analysis. Under ideal conditions of neutron flux and spacecraft orbit, both the signal strength and the spatial resolution will improved by several orders of magnitude over previously missions.

Use of the partial farm budget technique to predict the economic impact of the flock management decision to use B-mode ultrasonographic pregnancy diagnosis.

PubMed

Sprecher, D J; Ley, W B; Whittier, W D; Bowen, J M; Thatcher, C D; Pelzer, K D; Moore, J M

1989-07-15

A computer spreadsheet was developed to predict the economic impact of a management decision to use B-mode ultrasonographic ovine pregnancy diagnosis. The spreadsheet design and spreadsheet cell formulas are provided. The program used the partial farm budget technique to calculate net return (NR) or cash flow changes that resulted from the decision to use ultrasonography. Using the program, either simple pregnancy diagnosis or pregnancy diagnosis with the ability to determine singleton or multiple pregnancies may be compared with no flock ultrasonographic pregnancy diagnosis. A wide range of user-selected regional variables are used to calculate the cash flow changes associated with the ultrasonography decisions. A variable may be altered through a range of values to conduct a sensitivity analysis of predicted NR. Example sensitivity analyses are included for flock conception rate, veterinary ultrasound fee, and the price of corn. Variables that influence the number of cull animals and the cost of ultrasonography have the greatest impact on predicted NR. Because the determination of singleton or multiple pregnancies is more time consuming, its economic practicality in comparison with simple pregnancy diagnosis is questionable. The value of feed saved by identifying and separately feeding ewes with singleton pregnancies is not offset by the increased ultrasonography cost.

Beyond prometheus and Bakasura: Elements of an alternative to nuclear power in India's response to the energy-environment crisis

NASA Astrophysics Data System (ADS)

Mathai, Manu Verghese

In India, as elsewhere, modern energy-society relations and economic development, metaphorically, Prometheus and the insatiable demon Bakasura, respectively, have produced unprecedented economic growth even as they have ushered in the "energy-environment crisis." Government efforts interpret the crisis as insufficiently advanced modernity. Resulting efforts to redress this crisis reaffirm more economic growth through modern energy-society relations and economic development. The civilian nuclear power renaissance in India, amidst rapidly accelerating economic growth and global climate change, is indicative. It presents the prospect of producing "abundant energy" and being "green" at the same time. This confidence in civilian nuclear power is questioned. It is investigated as proceeding from the modern discourse of "Cornucopianism" and its institutionalization as "modern megamachine organization of society." It is found that civilian nuclear power as energy policy is based on a presumption of overabundance as imperative for viable social and economic development; is predisposed to centralization and secrecy; its institutionalization limits deliberation on energy-society relations to technocratic terms; such deliberation is restrained to venues accessible only to the highest political office and technocratic elite; it fails to redress entrenched "energy injustice;" it embodies "modern technique" fostering the "displaced person" while eclipsing the "complete human personality." Overall, despite its green rhetoric, civilian nuclear power reaffirms the "politics of commodification" and refutes social and political arrangements for sustainability and equity. Alternatives are surveyed as strategies for resistance. They include the DEFENDUS approach for energy planning, the "Human Development and Capability Approach" and the "Sustainable Energy Utility." These alternatives and the synergy between them are offered as avenues to resist nuclear power as a response to the energy-environment crisis and to reclaim human-centered imagination and creativity for charting new realities free of the awe inspired by Prometheus and fear of the insatiable Bakasura.

Directional Processing and Noise Reduction in Hearing Aids: Individual and Situational Influences on Preferred Setting.

PubMed

Neher, Tobias; Wagener, Kirsten C; Fischer, Rosa-Linde

2016-09-01

A better understanding of individual differences in hearing aid (HA) outcome is a prerequisite for more personalized HA fittings. Currently, knowledge of how different user factors relate to response to directional processing (DIR) and noise reduction (NR) is sparse. To extend a recent study linking preference for DIR and NR to pure-tone average hearing thresholds (PTA) and cognitive factors by investigating if (1) equivalent links exist for different types of DIR and NR, (2) self-reported noise sensitivity and personality can account for additional variability in preferred DIR and NR settings, and (3) spatial target speech configuration interacts with individual DIR preference. Using a correlational study design, overall preference for different combinations of DIR and NR programmed into a commercial HA was assessed in a complex speech-in-noise situation and related to PTA, cognitive function, and different personality traits. Sixty experienced HA users aged 60-82 yr with controlled variation in PTA and working memory capacity took part in this study. All of them had participated in the earlier study, as part of which they were tested on a measure of "executive control" tapping into cognitive functions such as working memory, mental flexibility, and selective attention. Six HA settings based on unilateral (within-device) or bilateral (across-device) DIR combined with inactive, moderate, or strong single-microphone NR were programmed into a pair of behind-the-ear HAs together with individually prescribed amplification. Overall preference was assessed using a free-field simulation of a busy cafeteria situation with either a single frontal talker or two talkers at ±30° azimuth as the target speech. In addition, two questionnaires targeting noise sensitivity and the "Big Five" personality traits were administered. Data were analyzed using multiple regression analyses and repeated-measures analyses of variance with a focus on potential interactions between the HA settings and user factors. Consistent with the earlier study, preferred HA setting was related to PTA and executive control. However, effects were weaker this time. Noise sensitivity and personality did not interact with HA settings. As expected, spatial target speech configuration influenced preference, with bilateral and unilateral DIR "winning" in the single- and two-talker scenario, respectively. In general, participants with higher PTA tended to more strongly prefer bilateral DIR than participants with lower PTA. Although the current study lends some support to the view that PTA and cognitive factors affect preferred DIR and NR setting, it also indicates that these effects can vary across noise management technologies. To facilitate more personalized HA fittings, future research should investigate the source of this variability. American Academy of Audiology.

Positive feedback of NR2B-containing NMDA receptor activity is the initial step toward visual imprinting: a model for juvenile learning.

PubMed

Nakamori, Tomoharu; Sato, Katsushige; Kinoshita, Masae; Kanamatsu, Tomoyuki; Sakagami, Hiroyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

2015-01-01

Imprinting in chicks is a good model for elucidating the processes underlying neural plasticity changes during juvenile learning. We recently reported that neural activation of a telencephalic region, the core region of the hyperpallium densocellulare (HDCo), was critical for success of visual imprinting, and that N-Methyl-D-aspartic (NMDA) receptors containing the NR2B subunit (NR2B/NR1) in this region were essential for imprinting. Using electrophysiological and multiple-site optical imaging techniques with acute brain slices, we found that long-term potentiation (LTP) and enhancement of NR2B/NR1 currents in HDCo neurons were induced in imprinted chicks. Enhancement of NR2B/NR1 currents as well as an increase in surface NR2B expression occurred even following a brief training that was too weak to induce LTP or imprinting behavior. This means that NR2B/NR1 activation is the initial step of learning, well before the activation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors which induces LTP. We also showed that knockdown of NR2B/NR1 inhibited imprinting, and inversely, increasing the surface NR2B expression by treatment with a casein kinase 2 inhibitor successfully reduced training time required for imprinting. These results suggest that imprinting stimuli activate post-synaptic NR2B/NR1 in HDCo cells, increase NR2B/NR1 signaling through up-regulation of its expression, and induce LTP and memory acquisition. The study investigated the neural mechanism underlying juvenile learning. In the initial stage of chick imprinting, NMDA receptors containing the NMDA receptor subunit 2B (NR2B) are activated, surface expression of NR2B/NR1 (NMDA receptor subunit 1) is up-regulated, and consequently long-term potentiation is induced in the telencephalic neurons. We suggest that the positive feedback in the NR2B/NR1 activation is a unique process of juvenile learning, exhibiting rapid memory acquisition. © 2014 International Society for Neurochemistry.

Management Auditing

DTIC Science & Technology

1975-09-01

Programs Psychological Sciences Division Office of Naval Research Contract No. N00014-74-A-0436-0001 NR 151-370 Approved for public release...Supported By Commandant of the Marine Corps (Code RD) And Monitored By Personnel and Training Research Programs Psychological Sciences Division...balance 6. Test for effectiveness 7. Search for problems 8. Ascertain solutions 9« Determine alternatives 10. Seek out methods for improvement

Status of Low Thrust Work at JSC

NASA Technical Reports Server (NTRS)

Condon, Gerald L.

2004-01-01

High performance low thrust (solar electric, nuclear electric, variable specific impulse magnetoplasma rocket) propulsion offers a significant benefit to NASA missions beyond low Earth orbit. As NASA (e.g., Prometheus Project) endeavors to develop these propulsion systems and associated power supplies, it becomes necessary to develop a refined trajectory design capability that will allow engineers to develop future robotic and human mission designs that take advantage of this new technology. This ongoing work addresses development of a trajectory design and optimization tool for assessing low thrust (and other types) trajectories. This work targets to advance the state of the art, enable future NASA missions, enable science drivers, and enhance education. This presentation provides a summary of the low thrust-related JSC activities under the ISP program and specifically, provides a look at a new release of a multi-gravity, multispacecraft trajectory optimization tool (Copernicus) along with analysis performed using this tool over the past year.

Results of the JIMO Follow-on Destinations Parametric Studies

NASA Technical Reports Server (NTRS)

Noca, Muriel A.; Hack, Kurt J.

2005-01-01

NASA's proposed Jupiter Icy Moon Orbiter (JIMO) mission currently in conceptual development is to be the first one of a series of highly capable Nuclear Electric Propulsion (NEP) science driven missions. To understand the implications of a multi-mission capability requirement on the JIMO vehicle and mission, the NASA Prometheus Program initiated a set of parametric high-level studies to be followed by a series of more in-depth studies. The JIMO potential follow-on destinations identified include a Saturn system tour, a Neptune system tour, a Kuiper Belt Objects rendezvous, an Interstellar Precursor mission, a Multiple Asteroid Sample Return and a Comet Sample Return. This paper shows that the baseline JIMO reactor and design envelop can satisfy five out of six of the follow-on destinations. Flight time to these destinations can significantly be reduced by increasing the launch energy or/and by inserting gravity assists to the heliocentric phase.

Results of a 2000 Hour Wear Tof the NEXIS Ion Engine

NASA Technical Reports Server (NTRS)

Snyder, John Steven; Goebel, Dan M.; Polk, James E.; Schneider, Analyn C; Sengupta, Anita

2005-01-01

The Nuclear Electric Xenon Ion System (NEXIS) ion thruster was developed for potential outer planet robotic missions under NASA's Prometheus program. This engine was designed to operate at power levels ranging from 16 to over 20 kWe at specific impulses of 6000 to 7500 s for burn times of up to 10 years, satisfying the requirements of nuclear electric propulsion systems such as that on the proposed Prometheus 1 mission to explore the icy moons of Jupiter. State-of-the-art performance and life assessment tools were used to design the thruster. Following the successful performance validation of a Laboratory Model thruster, Development Model hardware was fabricated and subjected to vibration and wear testing. The results of a 2000-hour wear test are reported herein. Thruster performance achieved the target requirements and was steady for the duration of the test. Ion optics performance was similarly stable. Discharge loss increases of 6 eV/ion were observed in the first 500 hours of the test and were attributed to primary electron energy decreases due to cathode insert conditioning. Relatively high recycle rates were observed and were identified to be high-voltage-to-ground arcs in the back of the thruster caused by wire insulation outgassing and electron penetration through the plasma screen. Field emission of electrons between the accelerator and screen grids was observed and attributed to evolution of field emitter sites at accelerator grid aperture edges caused by ion bombardment. Preliminary modeling and analysis indicates that the NEXIS engine can meet mission performance requirements over the required lifetime. Finally, successful validation of the NEXIS design methodology, design tools, and technologies with the results of the wear test and companion performance and vibration tests presents significant applicability of the NEXIS development effort to missions of near-term as well as long-term interest for NASA.

Results of a 2000 hour wear test of the NEXIS ion engine

NASA Technical Reports Server (NTRS)

Snyder, John Steven; Goebel, Dan M.; Polk, James E.; Schneider, Analyn C; Sengupta, Anita

2005-01-01

The Nuclear Electric Xenon Ion System (NEXIS) ion thruster was developed for potential outer planet robotic missions under NASA's Prometheus program. This engine was designed to operate at power levels ranging from 16 to over 20 kWe at specific impulses of 6000 to 7500 s for burn times of up to 10 years, satisfying the requirements of nuclear electric propulsion systems such as that on the proposed Prometheus 1 mission to explore the icy moons of Jupiter. State-of-the-art performance and life assessment tools were used to design the thruster. Following the successful performance validation of a Laboratory Model thruster, Development Model hardware was fabricated and subjected to vibration and wear testing. The results of a 2000-hour wear test are reported herein. Thruster performance achieved the target requirements and was steady for the duration of the test. Ion optics performance was similarly stable. Discharge loss increases of 6 eV/ion were observed in the first 500 hours of the test and were attributed to primary electron energy decreases due to cathode insert conditioning. Relatively high recycle rates were observed and were identified to be high-voltage-to-ground arcs in the back of the thruster caused by wire insulation outgassing and electron penetration through the plasma screen. Field emission of electrons between the accelerator and screen grids was observed and attributed to evolution of field emitter sites at accelerator grid aperture edges caused by ion bombardment. Preliminary modeling and analysis indicates that the NEXIS engine can meet mission performance requirements over the required lifetime. Finally, successful validation of the NEXIS design methodology, design tools, and technologies with the results of the wear test and companion performance and vibration tests presents significant applicability of the NEXIS development effort to missions of near-term as well as long-term interest for NASA.

Army Reserve Component Personalized Empowerment Program (ARCPEP)

DTIC Science & Technology

2010-10-01

in U.S. hospitals—2007. Am J Health Syst Pharm 2008; 65:2244-64 2. Hardiker NR, Grant MJ. Barriers and facilitators that affect public engagement with eHealth services. Stud Health Technol Inform 2010; 160:13-7

Development of N-Methyl-D-Aspartate Receptor Subunits in Avian Auditory Brainstem

PubMed Central

TANG, YE-ZHONG; CARR, CATHERINE E.

2012-01-01

N-methyl-D-aspartate (NMDA) receptor subunit-specific probes were used to characterize developmental changes in the distribution of excitatory amino acid receptors in the chicken’s auditory brainstem nuclei. Although NR1 subunit expression does not change greatly during the development of the cochlear nuclei in the chicken (Tang and Carr [2004] Hear. Res 191:79 – 89), there are significant developmental changes in NR2 subunit expression. We used in situ hybridization against NR1, NR2A, NR2B, NR2C, and NR2D to compare NR1 and NR2 expression during development. All five NMDA subunits were expressed in the auditory brainstem before embryonic day (E) 10, when electrical activity and synaptic responses appear in the nucleus magnocellularis (NM) and the nucleus laminaris (NL). At this time, the dominant form of the receptor appeared to contain NR1 and NR2B. NR2A appeared to replace NR2B by E14, a time that coincides with synaptic refinement and evoked auditory responses. NR2C did not change greatly during auditory development, whereas NR2D increased from E10 and remained at fairly high levels into adulthood. Thus changes in NMDA NR2 receptor subunits may contribute to the development of auditory brainstem responses in the chick. PMID:17366608

Computer Program for Calculation of Separated Turbulent Flows on Axisymmetric Afterbodies including Exhaust Plume Effects

DTIC Science & Technology

1979-03-01

automatically extended to match the inviscid grid. 53 AEDC-T R-79-4 XT DXP HLIM CFCI DELTA1 DELSTI UEI DUEDX NR XRP ,RL Axial location of...layer-edge velocity gradient at initial boundary-layer station. Integer number of values of XRP and RL to be input for body shape. If NSHPBL = 0, this...If LSHPBL = 0 and LPROG = 0, skip items 20 and 21 NR XRP ,RL 715 I5 2FI0.0 8FI0.0 5F10.0 2FI0.0 2f10.0 I615 2FI0.0 125 AEDC-TR-79-4

β-Cell deletion of Nr4a1 and Nr4a3 nuclear receptors impedes mitochondrial respiration and insulin secretion.

PubMed

Reynolds, Merrick S; Hancock, Chad R; Ray, Jason D; Kener, Kyle B; Draney, Carrie; Garland, Kevin; Hardman, Jeremy; Bikman, Benjamin T; Tessem, Jeffery S

2016-07-01

β-Cell insulin secretion is dependent on proper mitochondrial function. Various studies have clearly shown that the Nr4a family of orphan nuclear receptors is essential for fuel utilization and mitochondrial function in liver, muscle, and adipose. Previously, we have demonstrated that overexpression of Nr4a1 or Nr4a3 is sufficient to induce proliferation of pancreatic β-cells. In this study, we examined whether Nr4a expression impacts pancreatic β-cell mitochondrial function. Here, we show that β-cell mitochondrial respiration is dependent on the nuclear receptors Nr4a1 and Nr4a3. Mitochondrial respiration in permeabilized cells was significantly decreased in β-cells lacking Nr4a1 or Nr4a3. Furthermore, respiration rates of intact cells deficient for Nr4a1 or Nr4a3 in the presence of 16 mM glucose resulted in decreased glucose mediated oxygen consumption. Consistent with this reduction in respiration, a significant decrease in glucose-stimulated insulin secretion rates is observed with deletion of Nr4a1 or Nr4a3. Interestingly, the changes in respiration and insulin secretion occur without a reduction in mitochondrial content, suggesting decreased mitochondrial function. We establish that knockdown of Nr4a1 and Nr4a3 results in decreased expression of the mitochondrial dehydrogenase subunits Idh3g and Sdhb. We demonstrate that loss of Nr4a1 and Nr4a3 impedes production of ATP and ultimately inhibits glucose-stimulated insulin secretion. These data demonstrate for the first time that the orphan nuclear receptors Nr4a1 and Nr4a3 are critical for β-cell mitochondrial function and insulin secretion. Copyright © 2016 the American Physiological Society.

78 FR 2077 - Implementation of the Local Community Radio Act of 2010; Revision of Service and Eligibility...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-09

... strictly defined circumstances.'' In contrast, Prometheus and others argue that ``[b]eyond a showing of non... the potential benefit of promoting a locally-based non-commercial radio service in potentially... stations as operating with non-directional antennas at their authorized power. 13. We turn now to what...

Differential Roles for "Nr4a1" and "Nr4a2" in Object Location vs. Object Recognition Long-Term Memory

ERIC Educational Resources Information Center

McNulty, Susan E.; Barrett, Ruth M.; Vogel-Ciernia, Annie; Malvaez, Melissa; Hernandez, Nicole; Davatolhagh, M. Felicia; Matheos, Dina P.; Schiffman, Aaron; Wood, Marcelo A.

2012-01-01

"Nr4a1" and "Nr4a2" are transcription factors and immediate early genes belonging to the nuclear receptor Nr4a family. In this study, we examine their role in long-term memory formation for object location and object recognition. Using siRNA to block expression of either "Nr4a1" or "Nr4a2", we found that "Nr4a2" is necessary for both long-term…

The zebrafish orphan nuclear receptor genes nr2e1 and nr2e3 are expressed in developing eye and forebrain.

PubMed

Kitambi, Satish Srinivas; Hauptmann, Giselbert

2007-02-01

Mammalian Nr2e1 (Tailless, Mtll or Tlx) and Nr2e3 (photoreceptor-specific nuclear receptor, Pnr) are highly related orphan nuclear receptors, that are expressed in eye and forebrain-derived structures. In this study, we analyzed the developmental expression patterns of zebrafish nr2e1 and nr2e3. RT-PCR analysis showed that nr2e1 and nr2e3 are both expressed during embryonic and post-embryonic development. To examine the spatial distribution of nr2e1 and nr2e3 during development whole-mount in situ hybridization was performed. At tailbud stage, initial nr2e1 expression was localized to the rostral brain rudiment anterior to pax2.1 and eng2 expression at the prospective midbrain-hindbrain boundary. During subsequent stages, nr2e1 became widely expressed in fore- and midbrain primordia, eye and olfactory placodes. At 24hpf, strong nr2e1 expression was detected in telencephalon, hypothalamus, dorsal thalamus, pretectum, midbrain tectum, and retina. At 2dpf, the initially widespread nr2e1 expression became more restricted to distinct regions within the fore- and midbrain and to the retinal ciliary margin, the germinal zone which gives rise to retina and presumptive iris. Expression of nr2e3 was exclusively found in the developing retina and epiphysis. In both structures, nr2e3 expression was found in photoreceptor cells. The developmental expression profile of zebrafish nr2e1 and nr2e3 is consistent with evolutionary conserved functions in eye and rostral brain structures.

Single-channel activations and concentration jumps: comparison of recombinant NR1a/NR2A and NR1a/NR2D NMDA receptors

PubMed Central

Wyllie, David J A; Béhé, Philippe; Colquhoun, David

1998-01-01

We have expressed recombinant NR1a/NR2A and NR1a/NR2D N-methyl-D-aspartate (NMDA) receptor channels in Xenopus oocytes and made recordings of single-channel and macroscopic currents in outside-out membrane patches. For each receptor type we measured (a) the individual single-channel activations evoked by low glutamate concentrations in steady-state recordings, and (b) the macroscopic responses elicited by brief concentration jumps with high agonist concentrations, and we explore the relationship between these two sorts of observation. Low concentration (5–100 nM) steady-state recordings of NR1a/NR2A and NR1a/NR2D single-channel activity generated shut-time distributions that were best fitted with a mixture of five and six exponential components, respectively. Individual activations of either receptor type were resolved as bursts of openings, which we refer to as ‘super-clusters’. During a single activation, NR1a/NR2A receptors were open for 36 % of the time, but NR1a/NR2D receptors were open for only 4 % of the time. For both, distributions of super-cluster durations were best fitted with a mixture of six exponential components. Their overall mean durations were 35.8 and 1602 ms, respectively. Steady-state super-clusters were aligned on their first openings and averaged. The average was well fitted by a sum of exponentials with time constants taken from fits to super-cluster length distributions. It is shown that this is what would be expected for a channel that shows simple Markovian behaviour. The current through NR1a/NR2A channels following a concentration jump from zero to 1 mM glutamate for 1 ms was well fitted by three exponential components with time constants of 13 ms (rising phase), 70 ms and 350 ms (decaying phase). Similar concentration jumps on NR1a/NR2D channels were well fitted by two exponentials with means of 45 ms (rising phase) and 4408 ms (decaying phase) components. During prolonged exposure to glutamate, NR1a/NR2A channels desensitized with a time constant of 649 ms, while NR1a/NR2D channels exhibited no apparent desensitization. We show that under certain conditions, the time constants for the macroscopic jump response should be the same as those for the distribution of super-cluster lengths, though the resolution of the latter is so much greater that it cannot be expected that all the components will be resolvable in a macroscopic current. Good agreement was found for jumps on NR1a/NR2D receptors, and for some jump experiments on NR1a/NR2A. However, the latter were rather variable and some were slower than predicted. Slow decays were associated with patches that had large currents. PMID:9625862

The selectivity of conantokin-G for ion channel inhibition of NR2B subunit-containing NMDA receptors is regulated by amino acid residues in the S2 region of NR2B

PubMed Central

Sheng, Zhenyu; Liang, Zhong; Geiger, James H.; Prorok, Mary; Castellino, Francis J.

2009-01-01

The conantokins are short, naturally-occurring peptides that inhibit ion flow through N-methyl-D-aspartate receptor (NMDAR) channels. One member of this peptide family, conantokin-G (con-G), specifically antagonizes NR2B-containing NMDAR channels, whereas other known conantokins are less selective inhibitors with regard to the nature of the NR2 subunit of the NMDAR complex. In order to define the molecular determinants of NR2B that govern con-G selectivity, we evaluated the ability of con-G to inhibit NMDAR ion channels expressed in human embryonic kidney (HEK)293 cells transfected with NR1, in combination with various NR2A/2B chimeras and point mutants, by electrophysiology using cells voltage-clamped in the whole cell configuration. We found that a variant of the con-G-insensitive subunit, NR2A, in which the 158 residues comprising the S2 peptide segment (E657-I814) were replaced by the corresponding S2 region of NR2B (E658-I815), results in receptors that are highly sensitive to inhibition by con-G. Of the 22 amino acids that are different between the NR2A-S2 and the NR2B-S2 regions, exchange of one of these, M739 of NR2B for the equivalent K738 of NR2A, was sufficient to completely import the inhibitory activity of con-G into NR1b/NR2A-containing NMDARs. Some reinforcement of this effect was found by substitution of a second amino acid, K755 of NR2B for Y754 of NR2A. The discovery of the molecular determinants of NR2B selectivity with con-G has implications for the design of subunit-selective neurobiological probes and drug therapies, in addition to advancing our understanding of NR2B- versus NR2A-mediated neurological processes. PMID:19427876

Lipid-sensors, enigmatic-orphan and orphan nuclear receptors as therapeutic targets in breast-cancer.

PubMed

Garattini, Enrico; Bolis, Marco; Gianni', Maurizio; Paroni, Gabriela; Fratelli, Maddalena; Terao, Mineko

2016-07-05

Breast-cancer is heterogeneous and consists of various groups with different biological characteristics. Innovative pharmacological approaches accounting for this heterogeneity are needed. The forty eight human Nuclear-Hormone-Receptors are ligand-dependent transcription-factors and are classified into Endocrine-Receptors, Adopted-Orphan-Receptors (Lipid-sensors and Enigmatic-Orphans) and Orphan-receptors. Nuclear-Receptors represent ideal targets for the design/synthesis of pharmacological ligands. We provide an overview of the literature available on the expression and potential role played by Lipid-sensors, Enigmatic-Orphans and Orphan-Receptors in breast-cancer. The data are complemented by an analysis of the expression levels of each selected Nuclear-Receptor in the PAM50 breast-cancer groups, following re-elaboration of the data publicly available. The major aim is to support the idea that some of the Nuclear-Receptors represent largely unexploited therapeutic-targets in breast-cancer treatment/chemo-prevention. On the basis of our analysis, we conclude that the Lipid-Sensors, NR1C3, NR1H2 and NR1H3 are likely to be onco-suppressors in breast-cancer. The Enigmatic-Orphans, NR1F1 NR2A1 and NR3B3 as well as the Orphan-Receptors, NR0B1, NR0B2, NR1D1, NR2F1, NR2F2 and NR4A3 exert a similar action. These Nuclear-Receptors represent candidates for the development of therapeutic strategies aimed at increasing their expression or activating them in tumor cells. The group of Nuclear-Receptors endowed with potential oncogenic properties consists of the Lipid-Sensors, NR1C2 and NR1I2, the Enigmatic-Orphans, NR1F3, NR3B1 and NR5A2, as well as the Orphan-Receptors, NR2E1, NR2E3 and NR6A1. These oncogenic Nuclear-Receptors should be targeted with selective antagonists, reverse-agonists or agents/strategies capable of reducing their expression in breast-cancer cells.

Noise reduction technologies implemented in head-worn preprocessors for improving cochlear implant performance in reverberant noise fields.

PubMed

Chung, King; Nelson, Lance; Teske, Melissa

2012-09-01

The purpose of this study was to investigate whether a multichannel adaptive directional microphone and a modulation-based noise reduction algorithm could enhance cochlear implant performance in reverberant noise fields. A hearing aid was modified to output electrical signals (ePreprocessor) and a cochlear implant speech processor was modified to receive electrical signals (eProcessor). The ePreprocessor was programmed to flat frequency response and linear amplification. Cochlear implant listeners wore the ePreprocessor-eProcessor system in three reverberant noise fields: 1) one noise source with variable locations; 2) three noise sources with variable locations; and 3) eight evenly spaced noise sources from 0° to 360°. Listeners' speech recognition scores were tested when the ePreprocessor was programmed to omnidirectional microphone (OMNI), omnidirectional microphone plus noise reduction algorithm (OMNI + NR), and adaptive directional microphone plus noise reduction algorithm (ADM + NR). They were also tested with their own cochlear implant speech processor (CI_OMNI) in the three noise fields. Additionally, listeners rated overall sound quality preferences on recordings made in the noise fields. Results indicated that ADM+NR produced the highest speech recognition scores and the most preferable rating in all noise fields. Factors requiring attention in the hearing aid-cochlear implant integration process are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Nuclear Receptor Rev-erb Alpha (Nr1d1) Functions in Concert with Nr2e3 to Regulate Transcriptional Networks in the Retina

PubMed Central

Mollema, Nissa J.; Yuan, Yang; Jelcick, Austin S.; Sachs, Andrew J.; von Alpen, Désirée; Schorderet, Daniel; Escher, Pascal; Haider, Neena B.

2011-01-01

The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated by genes such as nuclear hormone receptors. The nuclear hormone receptor gene Rev-erb alpha/Nr1d1 has been widely studied for its role in the circadian cycle and cell metabolism, however its role in the retina is unknown. In order to understand the role of Rev-erb alpha/Nr1d1 in the retina, we evaluated the effects of loss of Nr1d1 to the developing retina and its co-regulation with the photoreceptor-specific nuclear receptor gene Nr2e3 in the developing and mature retina. Knock-down of Nr1d1 expression in the developing retina results in pan-retinal spotting and reduced retinal function by electroretinogram. Our studies show that NR1D1 protein is co-expressed with NR2E3 in the outer neuroblastic layer of the developing mouse retina. In the adult retina, NR1D1 is expressed in the ganglion cell layer and is co-expressed with NR2E3 in the outer nuclear layer, within rods and cones. Several genes co-targeted by NR2E3 and NR1D1 were identified that include: Nr2c1, Recoverin, Rgr, Rarres2, Pde8a, and Nupr1. We examined the cyclic expression of Nr1d1 and Nr2e3 over a twenty-four hour period and observed that both nuclear receptors cycle in a similar manner. Taken together, these studies reveal a novel role for Nr1d1, in conjunction with its cofactor Nr2e3, in regulating transcriptional networks critical for photoreceptor development and function. PMID:21408158

Constitutive expression of nitrate reductase allows normal growth and development of Nicotiana plumbaginifolia plants.

PubMed Central

Vincentz, M; Caboche, M

1991-01-01

A nitrate reductase (NR) deficient mutant of Nicotiana plumbaginifolia totally impaired in the production of NR transcript and protein was restored for NR activity by transformation with a chimaeric NR gene. This gene was composed of a full-length tobacco NR cDNA fused to the CaMV 35S promoter and to termination signals from the tobacco NR gene. The transgenic plants we obtained were viable and fertile and expressed from one-fifth to three times the wild-type NR activity in their leaves. The analysis of chimeric NR gene expression in these plants showed, by comparison with wild-type plants, that the regulation of NR gene expression by light, nitrate and circadian rhythm takes place at the transcriptional level. However, unlike nitrate, light was required for the accumulation of NR protein in transgenic plants, suggesting that NR expression is also controlled at the translational and/or post-translational level. Images PMID:2022181

Reactive nitrogen impacts on ecosystem services

EPA Science Inventory

The Ecosystem Services Research Program (ESRP) is a new, multi-year research initiative under development by the Environmental Protection Agency (EPA). As one of its components, ESRP has chosen to focus on reactive Nitrogen (Nr) for stressor-specific ecosystem research through a...

Private Prometheus: Private Higher Education and Development in the 21st Century. Contributions to the Study of Education, Number 77.

ERIC Educational Resources Information Center

Altbach, Philip G., Ed.

This document addresses changes and trends in private higher education, with particular emphasis on Latin America. It focuses on specific issues facing private higher education, which has developed significantly worldwide. A variety of factors have brought private higher education to the forefront. There has been a shift in several countries from…

MOBLAB: a mobile laboratory for testing real-time vision-based systems in path monitoring

NASA Astrophysics Data System (ADS)

Cumani, Aldo; Denasi, Sandra; Grattoni, Paolo; Guiducci, Antonio; Pettiti, Giuseppe; Quaglia, Giorgio

1995-01-01

In the framework of the EUREKA PROMETHEUS European Project, a Mobile Laboratory (MOBLAB) has been equipped for studying, implementing and testing real-time algorithms which monitor the path of a vehicle moving on roads. Its goal is the evaluation of systems suitable to map the position of the vehicle within the environment where it moves, to detect obstacles, to estimate motion, to plan the path and to warn the driver about unsafe conditions. MOBLAB has been built with the financial support of the National Research Council and will be shared with teams working in the PROMETHEUS Project. It consists of a van equipped with an autonomous power supply, a real-time image processing system, workstations and PCs, B/W and color TV cameras, and TV equipment. This paper describes the laboratory outline and presents the computer vision system and the strategies that have been studied and are being developed at I.E.N. `Galileo Ferraris'. The system is based on several tasks that cooperate to integrate information gathered from different processes and sources of knowledge. Some preliminary results are presented showing the performances of the system.

On the tidal environment of an outwardly migrating F ring

NASA Astrophysics Data System (ADS)

Sutton, Phil J.

2018-07-01

Saturn's F ring is a unique narrow ring that lies (radially) close to the tidally disruptive Roche limit of water ice for Saturn. Significant work has been done that shows it to be one of the most dynamic places in the Solar system. Aggregates that are fortunate enough to form constantly battle against the strong tidal forces of Saturn and the nearby moons Prometheus and Pandora, which act to gravitationally stir up ring material. Planetary rings are also known to radially spread. Therefore, as the F ring lies at the edge of the main rings, we investigate the effect of an outwardly migrated F ring and its interaction with Prometheus. An increase in the maximum number density of particles at the channel edges is observed with decreasing local tidal environment. Radial velocity dispersions are also observed to fall below the typical escape velocity of a 150 m icy moonlet (<10 cm s^{-1}) where density is enhanced, and are gravitationally unstable with Toomre parameters Q < 2. Additionally, in locations of the ring where Q < 2 is observed, more particles are seen to fall below or close to the critical Toomre parameter as the radial location of the ring increases.

An Approach to Model Based Testing of Multiagent Systems

PubMed Central

Nadeem, Aamer

2015-01-01

Autonomous agents perform on behalf of the user to achieve defined goals or objectives. They are situated in dynamic environment and are able to operate autonomously to achieve their goals. In a multiagent system, agents cooperate with each other to achieve a common goal. Testing of multiagent systems is a challenging task due to the autonomous and proactive behavior of agents. However, testing is required to build confidence into the working of a multiagent system. Prometheus methodology is a commonly used approach to design multiagents systems. Systematic and thorough testing of each interaction is necessary. This paper proposes a novel approach to testing of multiagent systems based on Prometheus design artifacts. In the proposed approach, different interactions between the agent and actors are considered to test the multiagent system. These interactions include percepts and actions along with messages between the agents which can be modeled in a protocol diagram. The protocol diagram is converted into a protocol graph, on which different coverage criteria are applied to generate test paths that cover interactions between the agents. A prototype tool has been developed to generate test paths from protocol graph according to the specified coverage criterion. PMID:25874263

Differential functions of NR2A and NR2B in short-term and long-term memory in rats.

PubMed

Jung, Ye-Ha; Suh, Yoo-Hun

2010-08-23

N-methyl-D-aspartate receptors (NMDARs) are glutamate receptors implicated in synaptic plasticity and memory function. The specific functions of NMDA receptor subunits NR2A and NR2B have not yet been fully determined in the different types of memory. Nine Wistar rats (8-weeks-old) were subjected to the Morris water maze task to evaluate the memory behaviorally. Quantitative analysis of NR1, NR2A, and NR2B levels in the right and left forebrain of rats was performed and subunit associations with different types of memory were investigated using the Morris water maze task. Right forebrain NR2A expression was significantly increased and correlated with faster escape time onto a hidden platform, indicating involvement of short-term memory, because of the training time interval. Right forebrain NR2B expression was positively associated with long-term memory lasting 24-h (h). In the left forebrain, NR2B expression was positively related to 72-h long-term memory. In conclusion, the functions of NR2A and NR2B receptors were differentially specialized in short-term and long-term memory, depending on the right or left forebrain.

NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes.

PubMed

Deutsch, Alexander J A; Rinner, Beate; Pichler, Martin; Prochazka, Katharina; Pansy, Katrin; Bischof, Marco; Fechter, Karoline; Hatzl, Stefan; Feichtinger, Julia; Wenzl, Kerstin; Frisch, Marie-Therese; Stiegelbauer, Verena; Prokesch, Andreas; Krogsdam, Anne; Sill, Heinz; Thallinger, Gerhard G; Greinix, Hildegard T; Wang, Chenguang; Beham-Schmid, Christine; Neumeister, Peter

2017-05-01

Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared with vector control and uninduced cells that formed massive tumors. Transcript analysis of four different aggressive lymphoma cell lines overexpressing either NR4A3 or NR4A1 revealed that apoptosis was driven similarly by induction of BAK, Puma, BIK, BIM, BID, and Trail. Overall, our results showed that NR4A3 possesses robust tumor suppressor functions of similar impact to NR4A1 in aggressive lymphomas. Cancer Res; 77(9); 2375-86. ©2017 AACR . ©2017 American Association for Cancer Research.

Drug targeting of NR4A nuclear receptors for treatment of acute myeloid leukemia.

PubMed

Boudreaux, Seth P; Duren, Ryan P; Call, Steven G; Nguyen, Loc; Freire, Pablo R; Narayanan, Padmini; Redell, Michele S; Conneely, Orla M

2018-06-08

NR4As are AML tumor suppressors that are frequently silenced in human acute myeloid leukemia (AML). Despite their potential as novel targets for therapeutic intervention, mechanisms of NR4A silencing and strategies for their reactivation remain poorly defined. Here we show that NR4A silencing in AML occurs through blockade of transcriptional elongation rather than epigenetic promoter silencing. By intersection of NR4A-regulated gene signatures captured upon acute, exogenous expression of NR4As in human AML cells with in silico chemical genomics screening, we identify several FDA-approved drugs including dihydroergotamine (DHE) that reactivate NR4A expression and regulate NR4A-dependent gene signatures. We show that DHE induces NR4A expression via recruitment of the super elongation complex to enable elongation of NR4A promoter paused RNA polymerase II. Finally, DHE exhibits AML selective NR4A-dependent anti-leukemic activity in cytogenetically distinct human AML cells in vitro and delays AML progression in mice revealing its potential as a novel therapeutic agent in AML.

When Helping Babies Breathe Is Not Enough: Designing a Novel, Mid-Level Neonatal Resuscitation Algorithm for Médecins Sans Frontières Field Teams Working in Low-Resource Hospital Settings.

PubMed

Umphrey, Lisa; Breindahl, Morten; Brown, Alexandra; Saugstad, Ola Didrik; Thio, Marta; Trevisanuto, Daniele; Roehrg, Charles Christoph; Blennow, Mats

2018-05-25

Neonatal resuscitation (NR) combines a set of life-saving interventions in order to stabilize compromised newborns at birth or when critically ill. Médecins Sans Frontières/Doctors Without Borders (MSF), as an international medical-humanitarian organization working particularly in low-resource settings (LRS), assisted over 250,000 births in obstetric and newborn care aid projects in 2016 and provides thousands of newborn resuscitations annually. The Helping Babies Breathe (HBB) program has been used as formal guidance for basic resuscitation since 2012. However, in some MSF projects with the capacity to provide more advanced NR interventions but a lack of adapted guidance, staff have felt prompted to create their own advanced algorithms, which runs counter to the organization's aim for standardized protocols in all aspects of its care. The aim is to close a significant gap in neonatal care provision in LRS by establishing consensus on a protocol that would guide MSF field teams in their practice of more advanced NR. An independent committee of international experts was formed and met regularly from June 2016 to agree on the content and design of a new NR algorithm. Consensus was reached on a novel, mid-level NR algorithm in April 2017. The algorithm was accepted for use by MSF Operational Center Paris. This paper contributes to the literature on decision-making in the development of cognitive aids. The authors also highlight how critical gaps in healthcare delivery in LRS can be addressed, even when there is limited evidence to guide the process. © 2018 The Author(s) Published by S. Karger AG, Basel.

Teamwork in Task Analysis. Training Manual V

DTIC Science & Technology

1975-11-01

Research Programs Psychological Sciences Division Office of Naval Research Contract No. N00014-74-A-0436-0001 NR 151-370 Approved for public...Corps (Code RD) And Monitored By Personnel and Training Research Programs Psychological Sciences Division Office of Naval Research Contract No...survival in the hidden warfare of the destructive psychological win-lose game. Win-lose behavior stems from individual attitudes and manage- ment climate

In Situ Reductive Synthesis of Structural Supported Gold Nanorods in Porous Silicon Particles for Multifunctional Nanovectors.

PubMed

Zhu, Guixian; Liu, Jen-Tsai; Wang, Yuzhen; Zhang, Dechen; Guo, Yi; Tasciotti, Ennio; Hu, Zhongbo; Liu, Xuewu

2016-05-11

Porous silicon nanodisks (PSD) were fabricated by the combination of photolithography and electrochemical etching of silicon. By using PSD as a reducing agent, gold nanorods (AuNR) were in situ synthesized in the nanopores of PSD, forming PSD-supported-AuNR (PSD/AuNR) hybrid particles. The formation mechanism of AuNR in porous silicon (pSi) was revealed by exploring the role of pSi reducibility and each chemical in the reaction. With the PSD support, AuNR exhibited a stable morphology without toxic surface ligands (CTAB). The PSD/AuNR hybrid particles showed enhanced plasmonic property compared to free AuNR. Because high-density "hot spots" can be generated by controlling the distribution of AuNR supported in PSD, surface-enhanced raman scattering (SERS) using PSD/AuNR as particle substrates was demonstrated. A multifunctional vector, PSD/AuNR/DOX, composed of doxorubicin (DOX)-loaded PSD/AuNR capped with agarose (agar), was developed for highly efficient, combinatorial cancer treatment. Their therapeutic efficacy was examined using two pancreatic cancer cell lines, PANC-1 and MIA PaCa-2. PSD/AuNR/DOX (20 μg Au and 1.25 μg DOX/mL) effectively destroyed these cells under near-IR laser irradiation (810 nm, 15 J·cm(-2) power, 90 s). Overall, we envision that PSD/AuNR may be a promising injectable, multifunctional nanovector for biomedical application.

Centennial-scale analysis of the creation and fate of reactive nitrogen in China (1910–2010)

PubMed Central

Cui, Shenghui; Shi, Yalan; Groffman, Peter M.; Schlesinger, William H.; Zhu, Yong-Guan

2013-01-01

Human mobilization and use of reactive nitrogen (Nr) has been one of the major aspects of global change over the past century. Nowhere has that change been more dramatic than in China, where annual net Nr creation increased from 9.2 to 56 Tg from 1910 to 2010. Since 1956, anthropogenic Nr creation exceeded natural Nr creation, contributing over 80% of total Nr until 2010. There is great interest and uncertainty in the fate and effects of this Nr in China. Here, a comprehensive inventory of Nr in China shows that Nr (including recycled Nr) has continuously and increasingly accumulated on land (from 17 to 45 Tg), accompanied by increasing transfers to the atmosphere (before deposition; from 7.6 to 20 Tg), inland waters (from 2.7 to 9.6 Tg), and coastal waters (from 4.5 to 7.7 Tg) over the past 30 y. If current trends continue, Nr creation from human activities will increase to 63 Tg by 2050, raising concerns about deleterious environmental consequences for land, air, and water at regional and global scales. Tremendous amounts of Nr have accumulated in plants, soils, and waters in China over the past 30 y, but the retention capacity of the terrestrial landscape seems to be declining. There is a possibility that the negative environmental effects of excessive Nr may accelerate in coming decades, increasing the urgency to alter the trajectory of increasing Nr imbalance. Here, a conceptual framework of the relationships between human drivers and Nr cycling in China is oriented and well-targeted to Chinese abatement strategies for Nr environmental impact. PMID:23341613

Seagrass Control Project: Containment Boom Evaluation. A Method to Protect Seawater Intakes from Seagrass Accumulation.

DTIC Science & Technology

1983-10-01

12 FEB 83 2942* NR 4 SM PUMP DRAWS EXCESSIVE CURRENT 26 FEB 83 2973 NR 3 SWPUMIPINOP 08 MAR 83 3021* NR 1 SM PUMP PRESSURE SWITCH FAILED 29 MIAR 83...VLV FAILED 16 JUN 83 PHM 2 0392 NR 2 S PUMP LOW PRESSURE SWITCH INOP M1 MAR 83 2/18/83 0452 ALL SW PUMPS HAVE INACCESSIBLE ZINCS 27 MAR 83 0462 NR 2 SW...PUMP LOW PRESSURE SWITCH INOP 29 MAR 83 0512 NR 3 SW PUMP CHECK ,1V FAILED 28 APR 83 06 NR 2 SW PUMP SEAL FAILED 30 JUN 83 P-- 93 675* NR S1 S PUMP

Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation.

PubMed

Savic, Daniel; Ramaker, Ryne C; Roberts, Brian S; Dean, Emma C; Burwell, Todd C; Meadows, Sarah K; Cooper, Sara J; Garabedian, Michael J; Gertz, Jason; Myers, Richard M

2016-07-11

The liver X receptors (LXRs, NR1H2 and NR1H3) and peroxisome proliferator-activated receptor gamma (PPARG, NR1C3) nuclear receptor transcription factors (TFs) are master regulators of energy homeostasis. Intriguingly, recent studies suggest that these metabolic regulators also impact tumor cell proliferation. However, a comprehensive temporal molecular characterization of the LXR and PPARG gene regulatory responses in tumor cells is still lacking. To better define the underlying molecular processes governing the genetic control of cellular growth in response to extracellular metabolic signals, we performed a comprehensive, genome-wide characterization of the temporal regulatory cascades mediated by LXR and PPARG signaling in HT29 colorectal cancer cells. For this analysis, we applied a multi-tiered approach that incorporated cellular phenotypic assays, gene expression profiles, chromatin state dynamics, and nuclear receptor binding patterns. Our results illustrate that the activation of both nuclear receptors inhibited cell proliferation and further decreased glutathione levels, consistent with increased cellular oxidative stress. Despite a common metabolic reprogramming, the gene regulatory network programs initiated by these nuclear receptors were widely distinct. PPARG generated a rapid and short-term response while maintaining a gene activator role. By contrast, LXR signaling was prolonged, with initial, predominantly activating functions that transitioned to repressive gene regulatory activities at late time points. Through the use of a multi-tiered strategy that integrated various genomic datasets, our data illustrate that distinct gene regulatory programs elicit common phenotypic effects, highlighting the complexity of the genome. These results further provide a detailed molecular map of metabolic reprogramming in cancer cells through LXR and PPARG activation. As ligand-inducible TFs, these nuclear receptors can potentially serve as attractive therapeutic targets for the treatment of various cancers.

The shed ectodomain of Nr-CAM stimulates cell proliferation and motility, and confers cell transformation.

PubMed

Conacci-Sorrell, Maralice; Kaplan, Anna; Raveh, Shani; Gavert, Nancy; Sakurai, Takeshi; Ben-Ze'ev, Avri

2005-12-15

Nr-CAM, a cell-cell adhesion molecule of the immunoglobulin-like cell adhesion molecule family, known for its function in neuronal outgrowth and guidance, was recently identified as a target gene of beta-catenin signaling in human melanoma and colon carcinoma cells and tissue. Retrovirally mediated transduction of Nr-CAM into fibroblasts induces cell motility and tumorigenesis. We investigated the mechanisms by which Nr-CAM can confer properties related to tumor cell behavior and found that Nr-CAM expression in NIH3T3 cells protects cells from apoptosis in the absence of serum by constitutively activating the extracellular signal-regulated kinase and AKT signaling pathways. We detected a metalloprotease-mediated shedding of Nr-CAM into the culture medium of cells transfected with Nr-CAM, and of endogenous Nr-CAM in B16 melanoma cells. Conditioned medium and purified Nr-CAM-Fc fusion protein both enhanced cell motility, proliferation, and extracellular signal-regulated kinase and AKT activation. Moreover, Nr-CAM was found in complex with alpha4beta1 integrins in melanoma cells, indicating that it can mediate, in addition to homophilic cell-cell adhesion, heterophilic adhesion with extracellular matrix receptors. Suppression of Nr-CAM levels by small interfering RNA in B16 melanoma inhibited the adhesive and tumorigenic capacities of these cells. Stable expression of the Nr-CAM ectodomain in NIH3T3 cells conferred cell transformation and tumorigenesis in mice, suggesting that the metalloprotease-mediated shedding of Nr-CAM is a principal route for promoting oncogenesis by Nr-CAM.

Evidence for a plasma-membrane-bound nitrate reductase involved in nitrate uptake of Chlorella sorokiniana

NASA Technical Reports Server (NTRS)

Tischner, R.; Ward, M. R.; Huffaker, R. C.

1989-01-01

Anti-nitrate-reductase (NR) immunoglobulin-G (IgG) fragments inhibited nitrate uptake into Chlorella cells but had no affect on nitrate uptake. Intact anti-NR serum and preimmune IgG fragments had no affect on nitrate uptake. Membrane-associated NR was detected in plasma-membrane (PM) fractions isolated by aqueous two-phase partitioning. The PM-associated NR was not removed by sonicating PM vesicles in 500 mM NaCl and 1 mM ethylenediaminetetraacetic acid and represented up to 0.8% of the total Chlorella NR activity. The PM NR was solubilized by Triton X-100 and inactivated by Chlorella NR antiserum. Plasma-membrane NR was present in ammonium-grown Chlorella cells that completely lacked soluble NR activity. The subunit sizes of the PM and soluble NRs were 60 and 95 kDa, respectively, as determined by sodium-dodecyl-sulfate electrophoresis and western blotting.

Green natural rubber-g-modified starch for controlling urea release.

PubMed

Riyajan, Sa-Ad; Sasithornsonti, Yodsathorn; Phinyocheep, Pranee

2012-06-05

The hydrophilicity of natural rubber (NR) was improved by grafting with modified cassava starch (ST) (NR-g-ST) by using potassium persulfate (K2S2O8) as a catalyst. The modified ST was added to NR latex in the presence of Terric16A16 as a non-ionic surfactant at 60 °C for 3 h and cast film on a glass plate to obtain NR-g-ST. The chemical structure of NR-g-ST was confirmed by FTIR. The swelling ratio of NR-g-ST was investigated in water and results showed that the swelling ratio of the modified NR decreased as function of ST. In addition, the tensile strength of the modified NR in the presence of modified ST at 50 phr was the highest value. Also, the thermal stability modified NR-g-ST was higher than of NR/ST blend confirmed by TGA. Finally, the NR-g-ST was used a polymer membrane for controlling urea fertilizer and it easily degraded in soil. This product with good controlled-release and water-retention could be especially useful in agricultural and horticultural applications. Published by Elsevier Ltd.

Control over position, orientation, and spacing of arrays of gold nanorods using chemically nanopatterned surfaces and tailored particle-particle-surface interactions.

PubMed

Nepal, Dhriti; Onses, M Serdar; Park, Kyoungweon; Jespersen, Michael; Thode, Christopher J; Nealey, Paul F; Vaia, Richard A

2012-06-26

The synergy of self- and directed-assembly processes and lithography provides intriguing avenues to fabricate translationally ordered nanoparticle arrangements, but currently lacks the robustness necessary to deliver complex spatial organization. Here, we demonstrate that interparticle spacing and local orientation of gold nanorods (AuNR) can be tuned by controlling the Debye length of AuNR in solution and the dimensions of a chemical contrast pattern. Electrostatic and hydrophobic selectivity for AuNR to absorb to patterned regions of poly(2-vinylpyridine) (P2VP) and polystyrene brushes and mats was demonstrated for AuNR functionalized with mercaptopropane sulfonate (MS) and poly(ethylene glycol), respectively. For P2VP patterns of stripes with widths comparable to the length of the AuNR, single- and double-column arrangements of AuNR oriented parallel and perpendicular to the P2VP line were obtained for MS-AuNR. Furthermore, the spacing of the assembled AuNR was uniform along the stripe and related to the ionic strength of the AuNR dispersion. The different AuNR arrangements are consistent with predictions based on maximization of packing of AuNR within the confined strip.

N‐methyl‐D‐aspartate receptor antibody production from germinal center reactions: Therapeutic implications

PubMed Central

Makuch, Mateusz; Wilson, Robert; Al‐Diwani, Adam; Varley, James; Kienzler, Anne‐Kathrin; Taylor, Jennifer; Berretta, Antonio; Fowler, Darren; Lennox, Belinda; Leite, M. Isabel; Waters, Patrick

2018-01-01

Introduction N‐methyl‐D‐aspartate receptor (NMDAR) antibody encephalitis is mediated by immunoglobulin G (IgG) autoantibodies directed against the NR1 subunit of the NMDAR. Around 20% of patients have an underlying ovarian teratoma, and the condition responds to early immunotherapies and ovarian teratoma removal. However, despite clear therapeutic relevance, mechanisms of NR1‐IgG production and the contribution of germinal center B cells to NR1‐IgG levels are unknown. Methods Clinical data and longitudinal paired serum NR1‐reactive IgM and IgG levels from 10 patients with NMDAR‐antibody encephalitis were determined. Peripheral blood mononuclear cells from these 10 patients, and two available ovarian teratomas, were stimulated with combinations of immune factors and tested for secretion of total IgG and NR1‐specific antibodies. Results In addition to disease‐defining NR1‐IgG, serum NR1‐IgM was found in 6 of 10 patients. NR1‐IgM levels were typically highest around disease onset and detected for several months into the disease course. Moreover, circulating patient B cells were differentiated into CD19+CD27++CD38++ antibody‐secreting cells in vitro and, from 90% of patients, secreted NR1‐IgM and NR1‐IgG. Secreted levels of NR1‐IgG correlated with serum NR1‐IgG (p < 0.0001), and this was observed across the varying disease durations, suggestive of an ongoing process. Furthermore, ovarian teratoma tissue contained infiltrating lymphocytes which produced NR1‐IgG in culture. Interpretation Serum NR1‐IgM and NR1‐IgG, alongside the consistent production of NR1‐IgG from circulating B cells and from ovarian teratomas suggest that ongoing germinal center reactions may account for the peripheral cell populations which secrete NR1‐IgG. Cells participating in germinal center reactions might be a therapeutic target for the treatment of NMDAR‐antibody encephalitis. Ann Neurol 2018;83:553–561 PMID:29406578

Prometheus the impostor.

PubMed Central

Laor, N

1985-01-01

The problem of scientific fraud has been used to indict the whole system of science. The response of the scientific community has been understandably heated but insufficient. The discussion seems to have reached an impasse as both parties in the dispute share mistaken views. A switch is needed to a framework in which the democratic foundation of the scientific society and the free spirit of scientific inquiry can be preserved. PMID:3918715

Immunization delivery in the second year of life in Ghana: the need for a multi-faceted approach

PubMed Central

Nyaku, Mawuli; Wardle, Melissa; Eng, Jodi Vanden; Ametewee, Lynnette; Bonsu, George; Larbi Opare, Joseph Kwadwo; Conklin, Laura

2017-01-01

Introduction in 2012, pneumococcal conjugate vaccine (PCV), rotavirus vaccine and a second dose of measles-containing vaccine (MCV2) were introduced into the Expanded Program on Immunization (EPI) in Ghana. According to Ghana’s EPI schedule, PCV and rotavirus vaccine are given in the first year of life and MCV2 in the second year of life (2YL) at 18 months. Although coverage with the last doses of PCV and rotavirus vaccine reached almost 90% coverage within four years of introduction, MCV2 coverage did not rise above 70%. The World Health Organization Global Measles and Rubella Strategic Plan established a 2020 milestone to achieve at least 95% coverage with the first and second doses of measles-containing vaccine in each district and nationally. We developed a project to address challenges to delivery of immunizations and other child health services at the 18-month visit and throughout the 2YL. Methods from March to April 2016, we conducted a cluster survey of households (HHs) with children 24-35 months of age in three regions in Ghana to assess knowledge, attitudes and beliefs among caregivers about immunization during the 2YL and to collect childhood vaccination history data using vaccination cards. Three independent samples were selected from the Northern (NR), Volta (VR), and Greater Accra (GAR) regions. A survey and direct observations were performed a ta representative sample of health facilities (HFs) providing immunization services in the same regions to further characterize barriers to immunization access, utilization and delivery in the 2YL. Results data on a total of 464 children ages 24-35 months were collected in the HH survey: 211 in NR, 153 in VR, and 100 in GAR (response rate > 99%). First dose of measles-containing vaccine (MCV1) coverage was (NR: 87%, VR: 96%, GAR: 99%); however, MCV2 coverage was lower (NR: 60%, VR: 83%, GAR: 70%). MCV1 to MCV2 dropout was 32% in NR, 14% in VR, and 31% in GAR. Caregiver awareness of immunization against measles was 69% in NR, 75% in VR, and 68% in GAR yet less than half knew the recommended ages for receiving the vaccine, (NR: 4%, VR: 9%, GAR: 44%). Among 160 HFs participating in the survey (>50 in each region), most lacked a defaulter tracing system (NR: 94%,VR: 76%,GAR: 85%). A varying proportion of HCWs correctly indicated how to record a catch-up first dose of MCV administered to an 18-month-old child in the 12-23 month immunization register (NR: 38%, VR: 55%, GAR: 67%) and on the vaccination card (NR: 54%, VR: 53%, GAR: 76%). Although more than half of caregivers would accept text messages, (NR: 57%, VR: 78%, GAR: 96%) including reminders, related to their child’s immunizations, < 10% HFs were utilizing this practice. Conclusion challenges encountered with the establishment of an immunization visit beyond the first year of life included knowledge gaps among caregivers, high dropout rates between MCV1 and MCV2 in all study regions, and a lack of defaulter tracing systems in most healthcare facilities providing childhood immunizations. Targeted strategies that promote behavioral, cultural, and policy changes are needed to strengthen 2YL child health service delivery and improve vaccination coverage. PMID:29296139

Immunization delivery in the second year of life in Ghana: the need for a multi-faceted approach.

PubMed

Nyaku, Mawuli; Wardle, Melissa; Eng, Jodi Vanden; Ametewee, Lynnette; Bonsu, George; Larbi Opare, Joseph Kwadwo; Conklin, Laura

2017-01-01

in 2012, pneumococcal conjugate vaccine (PCV), rotavirus vaccine and a second dose of measles-containing vaccine (MCV2) were introduced into the Expanded Program on Immunization (EPI) in Ghana. According to Ghana's EPI schedule, PCV and rotavirus vaccine are given in the first year of life and MCV2 in the second year of life (2YL) at 18 months. Although coverage with the last doses of PCV and rotavirus vaccine reached almost 90% coverage within four years of introduction, MCV2 coverage did not rise above 70%. The World Health Organization Global Measles and Rubella Strategic Plan established a 2020 milestone to achieve at least 95% coverage with the first and second doses of measles-containing vaccine in each district and nationally. We developed a project to address challenges to delivery of immunizations and other child health services at the 18-month visit and throughout the 2YL. from March to April 2016, we conducted a cluster survey of households (HHs) with children 24-35 months of age in three regions in Ghana to assess knowledge, attitudes and beliefs among caregivers about immunization during the 2YL and to collect childhood vaccination history data using vaccination cards. Three independent samples were selected from the Northern (NR), Volta (VR), and Greater Accra (GAR) regions. A survey and direct observations were performed a ta representative sample of health facilities (HFs) providing immunization services in the same regions to further characterize barriers to immunization access, utilization and delivery in the 2YL. data on a total of 464 children ages 24-35 months were collected in the HH survey: 211 in NR, 153 in VR, and 100 in GAR (response rate > 99%). First dose of measles-containing vaccine (MCV1) coverage was (NR: 87%, VR: 96%, GAR: 99%); however, MCV2 coverage was lower (NR: 60%, VR: 83%, GAR: 70%). MCV1 to MCV2 dropout was 32% in NR, 14% in VR, and 31% in GAR. Caregiver awareness of immunization against measles was 69% in NR, 75% in VR, and 68% in GAR yet less than half knew the recommended ages for receiving the vaccine, (NR: 4%, VR: 9%, GAR: 44%). Among 160 HFs participating in the survey (>50 in each region), most lacked a defaulter tracing system (NR: 94%,VR: 76%,GAR: 85%). A varying proportion of HCWs correctly indicated how to record a catch-up first dose of MCV administered to an 18-month-old child in the 12-23 month immunization register (NR: 38%, VR: 55%, GAR: 67%) and on the vaccination card (NR: 54%, VR: 53%, GAR: 76%). Although more than half of caregivers would accept text messages, (NR: 57%, VR: 78%, GAR: 96%) including reminders, related to their child's immunizations, < 10% HFs were utilizing this practice. challenges encountered with the establishment of an immunization visit beyond the first year of life included knowledge gaps among caregivers, high dropout rates between MCV1 and MCV2 in all study regions, and a lack of defaulter tracing systems in most healthcare facilities providing childhood immunizations. Targeted strategies that promote behavioral, cultural, and policy changes are needed to strengthen 2YL child health service delivery and improve vaccination coverage.

Io in the near infrared: Near-Infrared Mapping Spectrometer (NIMS) results from the Galileo flybys in 1999 and 2000

USGS Publications Warehouse

Lopes, R.M.C.; Kamp, L.W.; Doute, S.; Smythe, W.D.; Carlson, R.W.; McEwen, A.S.; Geissler, P.E.; Kieffer, S.W.; Leader, F.E.; Davies, A.G.; Barbinis, E.; Mehlman, R.; Segura, M.; Shirley, J.; Soderblom, L.A.

2001-01-01

Galileo's Near-Infrared Mapping Spectrometer (NIMS) observed Io during the spacecraft's three flybys in October 1999, November 1999, and February 2000. The observations, which are summarized here, were used to map the detailed thermal structure of active volcanic regions and the surface distribution of SO2 and to investigate the origin of a yet unidentified compound showing an absorption feature at ???1 ??m. We present a summary of the observations and results, focusing on the distribution of thermal emission and of SO2 deposits. We find high eruption temperatures, consistent with ultramafic volcanism, at Pele. Such temperatures may be present at other hot spots, but the hottest areas may be too small for those temperatures to be detected at the spatial resolution of our observations. Loki is the site of frequent eruptions, and the low thermal emission may represent lavas cooling on the caldera's surface or the cooling crust of a lava lake. High-resolution spectral observations of Emakong caldera show thermal emission and SO2 within the same pixels, implying that patches of SO2 frost and patches of cooling lavas or sulfur flows are present within a few kilometers from one another. Thermal maps of Prometheus and Amirani show that these two hot spots are characterized by long lava flows. The thermal profiles of flows at both locations are consistent with insulated flows, with the Amirani flow field having more breakouts of fresh lava along its length. Prometheus and Amirani each show a white ring at visible wavelengths, while SO2 distribution maps show that the highest concentration of SO2 in both ring deposits lies outside the white portion. Visible measurements at high phase angles show that the white deposit around Prometheus extends into the SO2 ring. This suggests that the deposits are thin and that compositional or grain size variations may occur in the radial direction. SO2 mapping of the Chaac region shows that the interior of a caldera adjacent to Chaac has almost pure SO2. The deposit appears to be topographically controlled, suggesting a possible origin by liquid flow. Copyright 2001 by the American Geophysical Union.

Profiling of 3696 Nuclear Receptor-Coregulator Interactions: A Resource for Biological and Clinical Discovery.

PubMed

Broekema, Marjoleine F; Hollman, Danielle A A; Koppen, Arjen; van den Ham, Henk-Jan; Melchers, Diana; Pijnenburg, Dirk; Ruijtenbeek, Rob; van Mil, Saskia W C; Houtman, René; Kalkhoven, Eric

2018-06-01

Nuclear receptors (NRs) are ligand-inducible transcription factors that play critical roles in metazoan development, reproduction, and physiology and therefore are implicated in a broad range of pathologies. The transcriptional activity of NRs critically depends on their interaction(s) with transcriptional coregulator proteins, including coactivators and corepressors. Short leucine-rich peptide motifs in these proteins (LxxLL in coactivators and LxxxIxxxL in corepressors) are essential and sufficient for NR binding. With 350 different coregulator proteins identified to date and with many coregulators containing multiple interaction motifs, an enormous combinatorial potential is present for selective NR-mediated gene regulation. However, NR-coregulator interactions have often been determined experimentally on a one-to-one basis across diverse experimental conditions. In addition, NR-coregulator interactions are difficult to predict because the molecular determinants that govern specificity are not well established. Therefore, many biologically and clinically relevant NR-coregulator interactions may remain to be discovered. Here, we present a comprehensive overview of 3696 NR-coregulator interactions by systematically characterizing the binding of 24 nuclear receptors with 154 coregulator peptides. We identified unique ligand-dependent NR-coregulator interaction profiles for each NR, confirming many well-established NR-coregulator interactions. Hierarchical clustering based on the NR-coregulator interaction profiles largely recapitulates the classification of NR subfamilies based on the primary amino acid sequences of the ligand-binding domains, indicating that amino acid sequence is an important, although not the only, molecular determinant in directing and fine-tuning NR-coregulator interactions. This NR-coregulator peptide interactome provides an open data resource for future biological and clinical discovery as well as NR-based drug design.

40 CFR 158.2174 - Experimental use permit microbial pesticides nontarget organisms and environmental fate data...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Freshwater invertebrate toxicity/pathogenicity NR R R R NR NR NR NR TGAI 1, 2, 3 885.4300 Nontarget... exposure. Freshwater invertebrates are preferred for invertebrate testing. 3. Required when there will be significant exposure to aquatic organisms (fish and invertebrates). 4. Required if the microbial pesticide is...

Future Opportunities for Dynamic Power Systems for NASA Missions

NASA Technical Reports Server (NTRS)

Shaltens, Richard K.

2007-01-01

Dynamic power systems have the potential to be used in Radioisotope Power Systems (RPS) and Fission Surface Power Systems (FSPS) to provide high efficiency, reliable and long life power generation for future NASA applications and missions. Dynamic power systems have been developed by NASA over the decades, but none have ever operated in space. Advanced Stirling convertors are currently being developed at the NASA Glenn Research Center. These systems have demonstrated high efficiencies to enable high system specific power (>8 W(sub e)/kg) for 100 W(sub e) class Advanced Stirling Radioisotope Generators (ASRG). The ASRG could enable significant extended and expanded operation on the Mars surface and on long-life deep space missions. In addition, advanced high power Stirling convertors (>150 W(sub e)/kg), for use with surface fission power systems, could provide power ranging from 30 to 50 kWe, and would be enabling for both lunar and Mars exploration. This paper will discuss the status of various energy conversion options currently under development by NASA Glenn for the Radioisotope Power System Program for NASA s Science Mission Directorate (SMD) and the Prometheus Program for the Exploration Systems Mission Directorate (ESMD).

Immunolocalization of NR1, NR2A, and PSD-95 in rat hippocampal subregions during postnatal development.

PubMed

Ling, Wei; Chang, Lirong; Song, Yizhi; Lu, Tao; Jiang, Yuhua; Li, Youxiang; Wu, Yan

2012-05-01

Although the expression of NMDARs and synaptic-associated proteins has been widely studied, the temporospatial distribution of NMDAR subunits and synaptic proteins in different hippocampal subregions during postnatal development still lacks detailed information, and the relationship between NR1 or NR2 subunits and PSD-95 family proteins is controversial. In this study, we used immunofluorescent staining to assess NR1 or NR2A and PSD-95 expressions and the relationship between them in CA1, CA3, and DG of rat hippocampus on postnatal (P) days: P0, P4, P7, P10, P14, P21, P28, P56. The results showed that from P0 to P56, NR1, NR2A, and PSD-95 expressions increased gradually, and the time points of their expression peak differed in CA1, CA3, and DG during postnatal development. Interestingly, although the expression of PSD-95 was positively correlated to both NR1 and NR2A, the NR1 and PSD-95 coexpressed puncta were greatest in CA3, while NR2A and PSD-95 coexpressed puncta were greatest in CA1, compared to other subregions. Surprisingly, at P21, among different strata of CA1, the area of highest expression of NR2A was dramatically changed from stratum pyramidale to stratum polymorphum and stratum moleculare, and returned to stratum pyramidale gradually on the later observed days again, indicating that P21 may be one critical timepoint during postnatal development in CA1. The specific temporospatial distribution pattern of NR1, NR2A, and PSD-95 might be related to the different physiological functions during postnatal development. Discovering the alteration of the relationship between PSD-95 and NMDAR subunits expression may be helpful for understanding mechanisms and therapy of neurodegenerative diseases. Copyright © 2011 Elsevier GmbH. All rights reserved.

Overexpression of Nitrate Reductase in Tobacco Delays Drought-Induced Decreases in Nitrate Reductase Activity and mRNA1

PubMed Central

Ferrario-Méry, Sylvie; Valadier, Marie-Hélène; Foyer, Christine H.

1998-01-01

Transformed (cauliflower mosaic virus 35S promoter [35S]) tobacco (Nicotiana plumbaginifolia L.) plants constitutively expressing nitrate reductase (NR) and untransformed controls were subjected to drought for 5 d. Drought-induced changes in biomass accumulation and photosynthesis were comparable in both lines of plants. After 4 d of water deprivation, a large increase in the ratio of shoot dry weight to fresh weight was observed, together with a decrease in the rate of photosynthetic CO2 assimilation. Foliar sucrose increased in both lines during water stress, but hexoses increased only in leaves from untransformed controls. Foliar NO3− decreased rapidly in both lines and was halved within 2 d of the onset of water deprivation. Total foliar amino acids decreased in leaves of both lines following water deprivation. After 4 d of water deprivation no NR activity could be detected in leaves of untransformed plants, whereas about 50% of the original activity remained in the leaves of the 35S-NR transformants. NR mRNA was much more stable than NR activity. NR mRNA abundance increased in the leaves of the 35S-NR plants and remained constant in controls for the first 3 d of drought. On the 4th d, however, NR mRNA suddenly decreased in both lines. Rehydration at d 3 caused rapid recovery (within 24 h) of 35S-NR transcripts, but no recovery was observed in the controls. The phosphorylation state of the protein was unchanged by long-term drought. There was a strong correlation between maximal extractable NR activity and ambient photosynthesis in both lines. We conclude that drought first causes increased NR protein turnover and then accelerates NR mRNA turnover. Constitutive NR expression temporarily delayed drought-induced losses in NR activity. 35S-NR expression may therefore allow more rapid recovery of N assimilation following short-term water deficit. PMID:9576799

Acute Oral Toxicity of Diethyleneglycol Dinitrate (DEGDN) in Rats

DTIC Science & Technology

1989-03-01

85D00470 Live - Hydronephrosis 37669 85D00471 Live - Not remarkable (NR) 37670 85D00484 Live - NR 37671 85D00496 Live - NR 37672 85D00497 Live - NR...Live - NR 376538 85D00481 Dead - hydronephrosis , pale liver 37781 85D00502 Live - NR 37783 85D00504 Live - NR 37663 85D00506 Dead - severe autolysis...0 0 0 Hydronephrosis 1 0 0 1 0 0 Missing ear tag 0 1 0 0 1 1 Red nasal material 0 0 1 0 0 0 Autolysis 0 0 0 1 0 0 Epididymal focus 0 0 0 0 0 1 Liver

The NMDA receptor NR2A subunit regulates proliferation of MKN45 human gastric cancer cells

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

Watanabe, Kanako; Department of Anesthesiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501; Kanno, Takeshi

2008-03-07

The present study investigated proliferation of MKN28 and MKN45 human gastric cancer cells regulated by the N-methyl-D-aspartate (NMDA) receptor subunit. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5) inhibited proliferation of MKN45 cells, but not MKN28 cells. Of the NMDA subunits such as NR1, NR2 (2A, 2B, 2C, and 2D), and NR3 (3A and 3B), all the NMDA subunit mRNAs except for the NR2B subunit mRNA were expressed in both MKN28 and MKN45 cells. MKN45 cells were characterized by higher expression of the NR2A subunit mRNA and lower expression of the NR1 subunit mRNA, but MKN28 otherwise by higher expression ofmore » the NR1 subunit mRNA and lower expression of the NR2A subunit mRNA. MKN45 cell proliferation was also inhibited by silencing the NR2A subunit-targeted gene. For MKN45 cells, AP5 or knocking-down the NR2A subunit increased the proportion of cells in the G{sub 1} phase of cell cycling and decreased the proportion in the S/G{sub 2} phase. The results of the present study, thus, suggest that blockage of NMDA receptors including the NR2A subunit suppresses MKN45 cell proliferation due to cell cycle arrest at the G{sub 1} phase; in other words, the NR2A subunit promotes MKN45 cell proliferation by accelerating cell cycling.« less

Inhibition of nitrate transport by anti-nitrate reductase IgG fragments and the identification of plasma membrane associated nitrate reductase in roots of barley seedlings

NASA Technical Reports Server (NTRS)

Ward, M. R.; Tischner, R.; Huffaker, R. C.

1988-01-01

Membrane associated nitrate reductase (NR) was detected in plasma membrane (PM) fractions isolated by aqueous two-phase partitioning from barley (Hordeum vulgare L. var CM 72) roots. The PM associated NR was not removed by washing vesicles with 500 millimolar NaCl and 1 millimolar EDTA and represented up to 4% of the total root NR activity. PM associated NR was stimulated up to 20-fold by Triton X-100 whereas soluble NR was only increased 1.7-fold. The latency was a function of the solubilization of NR from the membrane. NR, solubilized from the PM fraction by Triton X-100 was inactivated by antiserum to Chlorella sorokiniana NR. Anti-NR immunoglobulin G fragments purified from the anti-NR serum inhibited NO3- uptake by more than 90% but had no effect on NO2- uptake. The inhibitory effect was only partially reversible; uptake recovered to 50% of the control after thorough rinsing of roots. Preimmune serum immunoglobulin G fragments inhibited NO3- uptake 36% but the effect was completely reversible by rinsing. Intact NR antiserum had no effect on NO3- uptake. The results present the possibility that NO3- uptake and NO3- reduction in the PM of barley roots may be related.

EOARC - Burns |

Science.gov Websites

Skip to Main Content Area Oregon State University USDA Agricultural Research Service | Donate | College of Agricultural Sciences EOARC - Burns banner image Resources Extn Agr Sci and NR Program Ag Agricultural Research Center! Front entrance located on Hwy 205 Front entrance located on Hwy 205 Main office

NR2C in the thalamic reticular nucleus; effects of the NR2C knockout.

PubMed

Zhang, Yuchun; Buonanno, Andres; Vertes, Robert P; Hoover, Walter B; Lisman, John E

2012-01-01

NMDAR antagonists can evoke delta frequency bursting in the nucleus reticularis of the thalamus (nRT). The mechanism of this oscillation was determined; antagonist blocks an NR2C-like conductance that has low Mg block at resting potential and thus can contribute a resting inward current in response to ambient glutamate. Block of this current hyperpolarizes the cell, deinactivating T-type Ca channels and thus triggering delta frequency bursting. The basis for assuming a NR2C-like conductance was that (1) transcripts for NR2C are abundant in the thalamus and (2) the current-voltage curve of the synaptically evoked NMDAR current has the low rectification characteristic of NR2C. In the current study, we have sought to determine whether the channels that generate the NMDAR current are NR2C-like or are actually comprised of receptors containing NR2C. We studied the current-voltage curve of synaptically evoked NMDAR current in the nRT of NR2C knockout mice. In wild-type mice, the current was weakly voltage dependent, as previously observed in rats. This weak rectification was absent in NR2C KO mice. In contrast, NR2C KO had no effect on the strongly rectifying NMDAR current in pyramidal cells of the prefrontal cortex. These results demonstrate that the low rectification normally observed in the nRT is due to NR2C.

Purification and Kinetics of Higher Plant NADH:Nitrate Reductase.

PubMed

Campbell, W H; Smarrelli, J

1978-04-01

Squash cotyledon (Cucurbita pepo L.) NADH:nitrate reductase (NR) was purified 150-fold with 50% recovery by a single step procedure based on the affinity of the NR for blue-Sepharose. Blue-Sepharose, which is prepared by direct coupling of Cibacron blue to Sepharose, appears to bind squash NR at the NADH site. The NR can be purified in 2 to 3 hours to a specific activity of 2 mumol of NADH oxidized/minute * milligram of protein. Corn (Zea mays L.) leaf NR was also purified to a specific activity of 6.9 mumol of NADH oxidized/minute * milligram of protein using a blue-Sepharose affinity step. The blue-Sepharose method offers the advantages of a rapid purification of plant NR to a high specific activity with reasonable recovery of total activity.The kinetic mechanism of higher plant NR was investigated using these highly purified squash and corn NR preparations. Based on initial velocity and product inhibition studies utilizing both enzymes, a two-site ping-pong mechanism is proposed for NR. This kinetic mechanism incorporates the concept of the reduced NR transferring electrons from the NADH site to a physically separated nitrate site.

A Deep Denoising Autoencoder Approach to Improving the Intelligibility of Vocoded Speech in Cochlear Implant Simulation.

PubMed

Lai, Ying-Hui; Chen, Fei; Wang, Syu-Siang; Lu, Xugang; Tsao, Yu; Lee, Chin-Hui

2017-07-01

In a cochlear implant (CI) speech processor, noise reduction (NR) is a critical component for enabling CI users to attain improved speech perception under noisy conditions. Identifying an effective NR approach has long been a key topic in CI research. Recently, a deep denoising autoencoder (DDAE) based NR approach was proposed and shown to be effective in restoring clean speech from noisy observations. It was also shown that DDAE could provide better performance than several existing NR methods in standardized objective evaluations. Following this success with normal speech, this paper further investigated the performance of DDAE-based NR to improve the intelligibility of envelope-based vocoded speech, which simulates speech signal processing in existing CI devices. We compared the performance of speech intelligibility between DDAE-based NR and conventional single-microphone NR approaches using the noise vocoder simulation. The results of both objective evaluations and listening test showed that, under the conditions of nonstationary noise distortion, DDAE-based NR yielded higher intelligibility scores than conventional NR approaches. This study confirmed that DDAE-based NR could potentially be integrated into a CI processor to provide more benefits to CI users under noisy conditions.

Subunit- and pathway-specific localization of NMDA receptors and scaffolding proteins at ganglion cell synapses in rat retina

PubMed Central

Zhang, Jun; Diamond, Jeffrey S.

2014-01-01

Retinal ganglion cells (RGCs) receive excitatory glutamatergic input from ON and OFF bipolar cells in distinct sublaminae of the inner plexiform layer (IPL). AMPA and NMDA receptors (AMPARs and NMDARs) mediate excitatory inputs in both synaptic layers, but specific roles for NMDARs at RGC synapses remain unclear. NMDARs comprise NR1 and NR2 subunits and are anchored by membrane associated guanylate kinases (MAGUKs), but it is unknown whether particular NR2 subunits associate preferentially with particular NR1 splice variants and MAGUKs. Here, we used postembedding immunogold electron microscopy (EM) techniques to examine the subsynaptic localization of NMDAR subunits and MAGUKs at ON and OFF synapses onto rat RGCs. We found that the NR2A subunit, the NR1C2‘ splice variant and MAGUKs PSD-95 and PSD-93 are localized to the postsynaptic density (PSD), preferentially at OFF synapses, whereas the NR2B subunit, the NR1C2 splice variant and the MAGUK SAP102 are localized perisynaptically, with NR2B exhibiting a preference for ON synapses. Consistent with these anatomical data, spontaneous EPSCs (sEPSCs) recorded from OFF cells exhibited an NMDAR component that was insensitive to the NR2B antagonist Ro 25-6981. In ON cells, sEPSCs expressed an NMDAR component, partially sensitive to Ro 25-6981, only when glutamate transport was inhibited, indicating perisynaptic expression of NR2B NMDARs. These results provide the first evidence for preferential association of particular NR1 splice variants, NR2 subunits and MAGUKs at central synapses and suggest that different NMDAR subtypes may play specific roles at functionally distinct synapses in the retinal circuitry. PMID:19339621

The nuclear receptor NR2E1/TLX controls senescence.

PubMed

O'Loghlen, Ana; Martin, Nadine; Krusche, Benjamin; Pemberton, Helen; Alonso, Marta M; Chandler, Hollie; Brookes, Sharon; Parrinello, Simona; Peters, Gordon; Gil, Jesús

2015-07-30

The nuclear receptor NR2E1 (also known as TLX or tailless) controls the self-renewal of neural stem cells (NSCs) and has been implied as an oncogene which initiates brain tumors including glioblastomas. Despite NR2E1 regulating targets like p21(CIP1) or PTEN we still lack a full explanation for its role in NSC self-renewal and tumorigenesis. We know that polycomb repressive complexes also control stem cell self-renewal and tumorigenesis, but so far, no formal connection has been established between NR2E1 and PRCs. In a screen for transcription factors regulating the expression of the polycomb protein CBX7, we identified NR2E1 as one of its more prominent regulators. NR2E1 binds at the CBX7 promoter, inducing its expression. Notably CBX7 represses NR2E1 as part of a regulatory loop. Ectopic NR2E1 expression inhibits cellular senescence, extending cellular lifespan in fibroblasts via CBX7-mediated regulation of p16(INK4a) and direct repression of p21(CIP1). In addition NR2E1 expression also counteracts oncogene-induced senescence. The importance of NR2E1 to restrain senescence is highlighted through the process of knocking down its expression, which causes premature senescence in human fibroblasts and epithelial cells. We also confirmed that NR2E1 regulates CBX7 and restrains senescence in NSCs. Finally, we observed that the expression of NR2E1 directly correlates with that of CBX7 in human glioblastoma multiforme. Overall we identified control of senescence and regulation of polycomb action as two possible mechanisms that can join those so far invoked to explain the role of NR2E1 in control of NSC self-renewal and cancer.

An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers.

PubMed

Airhart, Sophia E; Shireman, Laura M; Risler, Linda J; Anderson, Gail D; Nagana Gowda, G A; Raftery, Daniel; Tian, Rong; Shen, Danny D; O'Brien, Kevin D

2017-01-01

The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR), improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials. In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed. Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss) were observed for both NR (p = 0.03) and NAD+ (p = 0.001); the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008). Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.

Altered emotionality, hippocampus-dependent performance and expression of NMDA receptor subunit mRNAs in chronically stressed mice.

PubMed

Costa-Nunes, João; Zubareva, Olga; Araújo-Correia, Margarida; Valença, Andreia; Schroeter, Careen A; Pawluski, Jodi L; Vignisse, Julie; Steinbusch, Hellen; Hermes, Denise; Phillipines, Marjan; Steinbusch, Harry M W; Strekalova, Tatyana

2014-01-01

N-Methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission in the hippocampus is implicated in cognitive and emotional disturbances during stress-related disorders. Here, using quantitative RT-PCR, we investigated the hippocampal expression of NR2A, NR2B and NR1 subunit mRNAs in a mouse stress paradigm that mimics clinically relevant conditions of simultaneously affected emotionality and hippocampus-dependent functions. A 2-week stress procedure, which comprised ethologically valid stressors, exposure to a rat and social defeat, was applied to male C57BL/6J mice. For predation stress, mice were introduced into transparent containers that were placed in a rat home cage during the night; social defeat was applied during the daytime using aggressive CD1 mice. This treatment impaired hippocampus-dependent performance during contextual fear conditioning. A correlation between this behavior and food displacement performance was demonstrated, suggesting that burrowing behavior is affected by the stress procedure and is hippocampus-dependent. Stressed mice (n = 22) showed behavioral invigoration and anomalous anxiolytic-like profiles in the O-maze and brightly illuminated open field, unaltered short-term memory in the step-down avoidance task and enhanced aggressive traits, as compared to non-stressed mice (n = 10). Stressed mice showed increased basal serum corticosterone concentrations, hippocampal mRNA expression for the NR2A subunit of the NMDAR and in the NR2A/NR2B ratio; mRNA expression of NR2B and NR1 was unchanged. Thus, stress-induced aberrations in both hippocampal-dependent performance and emotional abnormalities are associated with alterations in hippocampal mRNA NR2A levels and the NR2A/NR2B ratio and not with mRNA expression of NR2B or NR1.

An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers

PubMed Central

Airhart, Sophia E.; Shireman, Laura M.; Risler, Linda J.; Anderson, Gail D.; Nagana Gowda, G. A.; Raftery, Daniel; Tian, Rong; Shen, Danny D.; O’Brien, Kevin D.

2017-01-01

Objectives The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. Background Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR), improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials. Methods In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed. Results Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss) were observed for both NR (p = 0.03) and NAD+ (p = 0.001); the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008). Conclusions Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases. PMID:29211728

NASA Project Constellation Systems Engineering Approach

NASA Technical Reports Server (NTRS)

Dumbacher, Daniel L.

2005-01-01

NASA's Office of Exploration Systems (OExS) is organized to empower the Vision for Space Exploration with transportation systems that result in achievable, affordable, and sustainable human and robotic journeys to the Moon, Mars, and beyond. In the process of delivering these capabilities, the systems engineering function is key to implementing policies, managing mission requirements, and ensuring technical integration and verification of hardware and support systems in a timely, cost-effective manner. The OExS Development Programs Division includes three main areas: (1) human and robotic technology, (2) Project Prometheus for nuclear propulsion development, and (3) Constellation Systems for space transportation systems development, including a Crew Exploration Vehicle (CEV). Constellation Systems include Earth-to-orbit, in-space, and surface transportation systems; maintenance and science instrumentation; and robotic investigators and assistants. In parallel with development of the CEV, robotic explorers will serve as trailblazers to reduce the risk and costs of future human operations on the Moon, as well as missions to other destinations, including Mars. Additional information is included in the original extended abstract.

Improvement of Immediate Performance in Neonatal Resuscitation Through Rapid Cycle Deliberate Practice Training.

PubMed

Magee, Maclain J; Farkouh-Karoleski, Christiana; Rosen, Tove S

2018-04-01

Simulation training is an effective method to teach neonatal resuscitation (NR), yet many pediatrics residents do not feel comfortable with NR. Rapid cycle deliberate practice (RCDP) allows the facilitator to provide debriefing throughout the session. In RCDP, participants work through the scenario multiple times, eventually reaching more complex tasks once basic elements have been mastered. We determined if pediatrics residents have improved observed abilities, confidence level, and recall in NR after receiving RCDP training compared to the traditional simulation debriefing method. Thirty-eight pediatrics interns from a large academic training program were randomized to a teaching simulation session using RCDP or simulation debriefing methods. The primary outcome was the intern's cumulative score on the initial Megacode Assessment Form (MCAF). Secondary outcome measures included surveys of confidence level, recall MCAF scores at 4 months, and time to perform critical interventions. Thirty-four interns were included in analysis. Interns in the RCDP group had higher initial MCAF scores (89% versus 84%, P  < .026), initiated positive pressure ventilation within 1 minute (100% versus 71%, P  < .05), and administered epinephrine earlier (152 s versus 180 s, P  < .039). Recall MCAF scores were not different between the 2 groups. Immediately following RCDP interns had improved observed abilities and decreased time to perform critical interventions in NR simulation as compared to those trained with the simulation debriefing. RCDP was not superior in improving confidence level or retention.

Ontogeny and nutritional programming of adiposity in sheep: potential role of glucocorticoid action and uncoupling protein-2.

PubMed

Gnanalingham, Muhuntha G; Mostyn, Alison; Symonds, Michael E; Stephenson, Terence

2005-11-01

Increased glucocorticoid action and adipose tissue inflammation contribute to excess adiposity. These adaptations may be enhanced in offspring exposed to nutrient restriction (NR) in utero, thereby increasing their susceptibility to later obesity. We therefore determined the developmental ontogeny of glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenase (11betaHSD) types 1 and 2, and uncoupling protein (UCP)-2 mRNA in perirenal adipose tissue between late gestation and 6 mo after birth in the sheep, as well as the effect of maternal NR targeted between early to mid (28-80 days, term approximately 147 days)- or late (110-147 days) gestation. GR and 11betaHSD1 mRNA increased with fat mass and were all maximal within the 6-mo observation period. 11betaHSD2 mRNA abundance demonstrated a converse decline, whereas UCP2 peaked at 30 days. GR and 11betaHSD1 mRNA abundance were strongly correlated with total and relative perirenal adipose tissue weight, and UCP2 was strongly correlated with GR and 11betaHSD1 mRNA. Early- to midgestational NR increased GR, 11betaHSD1, and UCP2 mRNA, but decreased 11betaHSD2 mRNA abundance, an adaptation reversed with late-gestational NR. We conclude that the continual rise in glucocorticoid action and fat mass after birth may underlie the development of later obesity. The magnitude of this adaptation is partly dependent on maternal food intake through pregnancy.

Post-translational control of nitrate reductase activity responding to light and photosynthesis evolved already in the early vascular plants.

PubMed

Nemie-Feyissa, Dugassa; Królicka, Adriana; Førland, Nina; Hansen, Margarita; Heidari, Behzad; Lillo, Cathrine

2013-05-01

Regulation of nitrate reductase (NR) by reversible phosphorylation at a conserved motif is well established in higher plants, and enables regulation of NR in response to rapid fluctuations in light intensity. This regulation is not conserved in algae NR, and we wished to test the evolutionary origin of the regulatory mechanism by physiological examination of ancient land plants. Especially a member of the lycophytes is of interest since their NR is candidate for regulation by reversible phosphorylation based on sequence analysis. We compared Selaginella kraussiana, a member of the lycophytes and earliest vascular plants, with the angiosperm Arabidopsis thaliana, and also tested the moss Physcomitrella patens. Interestingly, optimization of assay conditions revealed that S. kraussiana NR used NADH as an electron donor like A. thaliana, whereas P. patens NR activity depended on NADPH. Examination of light/darkness effects showed that S. kraussiana NR was rapidly regulated similar to A. thaliana NR when a differential (Mg(2+) contra EDTA) assay was used to reveal activity state of NR. This implies that already existing NR enzyme was post-translationally activated by light in both species. Light had a positive effect also on de novo synthesis of NR in S. kraussiana, which could be shown after the plants had been exposed to a prolonged dark period (7 days). Daily variations in NR activity were mainly caused by post-translational modifications. As for angiosperms, the post-translational light activation of NR in S. kraussiana was inhibited by 3-(3,4-dichlorophenyl)-1*1-dimethylurea (DCMU), an inhibitor of photosynthesis and stomata opening. Evolutionary, a post-translational control mechanism for NR have occurred before or in parallel with development of vascular tissue in land plants, and appears to be part of a complex mechanisms for coordination of CO2 and nitrogen metabolism in these plants. Copyright © 2013 Elsevier GmbH. All rights reserved.

Non-genomic effects of the NR4A1/Nur77/TR3/NGFIB orphan nuclear receptor.

PubMed

Pawlak, Alicja; Strzadala, Leon; Kalas, Wojciech

2015-03-01

The orphan nuclear receptor NR4A1/Nur77/TR3/NGFIB acts primarily as a transcription factor to regulate the expression of multiple genes. However, increasing research attention has recently been given to non-genomic activities of NR4A1. The first description of a non-genomic action of NR4A1 referred to the conversion of anti-apoptotic Bcl-2 into a pro-apoptotic protein by direct interaction with NR4A1. In response to certain apoptotic stimuli, NR4A1 translocates from the nucleus to the mitochondrial outer membrane (MOM) where it associates with Bcl-2 and thereby causes apoptosis. Afterwards, it appeared that NR4A1 could also bind and convert other anti-apoptotic Bcl-2 family members. The latest studies indicate a significant role of NR4A1 in the process of autophagy. For example, a new NR4A1-mediated pathway specific for melanoma cells has been described where NR4A1 interacts with the adenine nucleotide translocase 1 (ANT1) on the mitochondrial inner membrane (MIM) leading to induction of the autophagy pathway. Moreover, NR4A1 interaction with cytoplasmic p53 may also contribute to the induction of autophagy. In addition to mitochondria, NR4A1 could be translocated to the outer membrane of the endoplasmic reticulum (ER) and associate with Bcl-2 or translocon-associated protein subunit γ (TRAPγ) causing ER stress-induced apoptosis. NR4A1 also contributes to the proteasomal degradation of β-catenin in colon cancer cells in vitro and in vivo, as well as to the stabilization of hypoxia-inducible factor-1α (HIF-1α) under non-hypoxic conditions. This review summarizes research findings on non-genomic effects of NR4A1 in normal and cancer cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhanced growth and nodulation of pigeon pea by co-inoculation of Bacillus strains with Rhizobium spp.

PubMed

Rajendran, Geetha; Sing, Falguni; Desai, Anjana J; Archana, G

2008-07-01

Endophytic bacteria which are known to reside in plant tissues have often been shown to promote plant growth. Present study deals with the isolation of putative endophytes from the surface sterilized root nodules of pigeon pea (Cajanus cajan) designated as non-rhizobial (NR) isolates. Three of these non-rhizobial isolates called NR2, NR4 and NR6 showed plant growth promotion with respect to increase in plant fresh weight, chlorophyll content, nodule number and nodule fresh weight when co-inoculated with the rhizobial bioinoculant strain IC3123. The three isolates were neither able to nodulate C. cajan nor did they show significant plant growth promotion when inoculated alone without Rhizobium spp. IC3123. All the three isolates were gram positive rods with NR2 and NR4 showing endospore formation and formed one single cluster in Amplified Ribosomal DNA Restriction Analysis (ARDRA). Partial sequences of 16S rRNA genes of NR4 and NR6 showed 97% similarity to Bacillus megaterium. The Bacillus strains NR4 and NR6 were able to produce siderophores which the rhizobial bioinoculant IC3123 was able to cross-utilize. Under iron starved conditions IC3123 showed enhanced growth in the presence of the Bacillus isolates indicating that siderophore mediated interactions may be underlying mechanism of beneficial effect of the NR isolates on nodulation by IC3123.

Regulation of nitrate reductase by nitric oxide in Chinese cabbage pakchoi (Brassica chinensis L.).

PubMed

Du, Shaoting; Zhang, Yongsong; Lin, Xianyong; Wang, Yue; Tang, Caixian

2008-02-01

Nitrate reductase (NR), a committed enzyme in nitrate assimilation, involves generation of nitric oxide (NO) in plants. Here we show that the NR activity was significantly enhanced by the addition of NO donors sodium nitroprusside (SNP) and NONOate (diethylamine NONOate sodium) to the culturing solution, whereas it was decreased by NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO). Interestingly, both NO gas and SNP directly enhanced but cPTIO inhibited the NR activities of crude enzyme extracts and purified NR enzyme. The cPTIO terminated the interaction between NR-generated NO and the NR itself. Furthermore, the NR protein content was not affected by the SNP treatment. The investigation of the partial reactions catalysed by purified NR using various electron donors and acceptors indicated that the haem and molybdenum centres in NR were the two sites activated by NO. The results suggest that the activation of NR activity by NO is regulated at the post-translational level, probably via a direct interaction mechanism. Accordingly, the concentration of nitrate both in leaves and roots was decreased after 2 weeks of cultivation with SNP. The present study identifies a new mechanism of NR regulation and nitrate assimilation, which provides important new insights into the complex regulation of N-metabolism in plants.

Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk.

PubMed

Trammell, Samuel Aj; Yu, Liping; Redpath, Philip; Migaud, Marie E; Brenner, Charles

2016-05-01

Nicotinamide riboside (NR) is a recently discovered NAD(+) precursor vitamin with a unique biosynthetic pathway. Although the presence of NR in cow milk has been known for more than a decade, the concentration of NR with respect to the other NAD(+) precursors was unknown. We aimed to determine NAD(+) precursor vitamin concentration in raw samples of milk from individual cows and from commercially available cow milk. LC tandem mass spectrometry and isotope dilution technologies were used to quantify NAD(+) precursor vitamin concentration and to measure NR stability in raw and commercial milk. Nuclear magnetic resonance (NMR) spectroscopy was used to test for NR binding to substances in milk. Cow milk typically contained ∼12 μmol NAD(+) precursor vitamins/L, of which 60% was present as nicotinamide and 40% was present as NR. Nicotinic acid and other NAD(+) metabolites were below the limits of detection. Milk from samples testing positive for Staphylococcus aureus contained lower concentrations of NR (Spearman ρ = -0.58, P = 0.014), and NR was degraded by S. aureus Conventional milk contained more NR than milk sold as organic. Nonetheless, NR was stable in organic milk and exhibited an NMR spectrum consistent with association with a protein fraction in skim milk. NR is a major NAD(+) precursor vitamin in cow milk. Control of S. aureus may be important to preserve the NAD(+) precursor vitamin concentration of milk. © 2016 American Society for Nutrition.

Orphan nuclear receptor NR4A2 inhibits hepatic stellate cell proliferation through MAPK pathway in liver fibrosis.

PubMed

Chen, Pengguo; Li, Jie; Huo, Yan; Lu, Jin; Wan, Lili; Li, Bin; Gan, Run; Guo, Cheng

2015-01-01

Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis, which is a pathological process characterized by extracellular matrix accumulation. NR4A2 is a nuclear receptor belonging to the NR4A subfamily and vital in regulating cell growth, metabolism, inflammation and other biological functions. However, its role in HSCs is unclear. We analyzed NR4A2 expression in fibrotic liver and stimulated HSCs compared with control group and studied the influence on cell proliferation, cell cycle, cell apoptosis and MAPK pathway after NR4A2 knockdown. NR4A2 expression was examined by real-time polymerase chain reaction, Western blotting, immunohistochemistry and immunofluorescence analyses. NR4A2 expression was significantly lower in fibrotic liver tissues and PDGF BB or TGF-β stimulated HSCs compared with control group. After NR4A2 knockdown α-smooth muscle actin and Col1 expression increased. In addition, NR4A2 silencing led to the promotion of cell proliferation, increase of cell percentage in S phase and reduced phosphorylation of ERK1/2, P38 and JNK in HSCs. These results indicate that NR4A2 can inhibit HSC proliferation through MAPK pathway and decrease extracellular matrix in liver fibrogenesis. NR4A2 may be a promising therapeutic target for liver fibrosis.

Properties of natural rubber/attapulgite composites prepared by latex compounding method: Effect of filler loading

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

Muttalib, Siti Nadzirah Abdul, E-mail: sitinadzirah.amn@gmail.com; Othman, Nadras, E-mail: srnadras@usm.my; Ismail, Hanafi, E-mail: ihanafi@usm.my

This paper reports on the effect of filler loading on properties of natural rubber (NR)/attapulgite (ATP) composites. The NR/ATP composites were prepared by latex compounding method. It is called as masterbatch. The masterbatch was subsequently added to the NR through melt mixing process. The vulcanized NR/ATP composites were subjected to mechanical, swelling and morphological tests. All the results were compared with NR/ATP composites prepared by conventional system. The composites from masterbatch method showed better results compared to composites prepared by conventional method. They have higher tensile properties, elongation at break and tear strength. The images captured through scanning electron microscopymore » test revealed the improvement of tensile strength in masterbatch NR/ATP composites. It can be seen clearly that masterbatch NR/ATP have better filler dispersion compared to conventional method NR/ATP composites.« less

Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.

PubMed

Trammell, Samuel A J; Schmidt, Mark S; Weidemann, Benjamin J; Redpath, Philip; Jaksch, Frank; Dellinger, Ryan W; Li, Zhonggang; Abel, E Dale; Migaud, Marie E; Brenner, Charles

2016-10-10

Nicotinamide riboside (NR) is in wide use as an NAD + precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD + metabolism in humans. We report that human blood NAD + can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD + with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD + metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD + , is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD + repletion.

An alternative model of free fall

NASA Astrophysics Data System (ADS)

Lattery, Mark

2018-03-01

In Two World Systems (Galileo 1632/1661 Dialogues Concerning Two New Sciences (New York: Prometheus)), Galileo attempted to unify terrestrial and celestial motions using the Aristotelian principle of circularity. The result was a model of free fall that correctly predicts the linear increase of the velocity of an object released from rest near the surface of the Earth. This historical episode provides an opportunity to communicate the nature of science to students.

Alkali Metal Heat Pipe Life Issues

NASA Technical Reports Server (NTRS)

Reid, Robert S.

2004-01-01

One approach to space fission power system design is predicated on the use of alkali metal heat pipes, either as radiator elements, thermal management components, or as part of the core primary heat-transfer system. This synopsis characterizes long-life core heat pipes. References are included where more detailed information can be found. Specifics shown here are for demonstrational purposes and do not necessarily reflect current Project Prometheus point designs.

Warlords and Democratization

DTIC Science & Technology

2003-06-06

3 In order for the liberal agenda to manifest itself, Immanuel Kant identifies two crucial requirements for individual freedom within a state. First...War and Peace, eds. Michael E. Brown et al. (Cambridge, Mass.: The MIT Press, 2000), 143- 144. 3 Ibid., 144. 4 Immanuel Kant , Critique of Pure Reason...John Hopkins University Press, 1999. Kant , Immanuel . Critique of Pure Reason. Translated by J.M.D. Meiklejohn. Amherst, N.Y.: Prometheus Books, 1990

Dynamics and Evolution of SO2 Gas Condensation Around Prometheus-like Volcanic Plumes on Io as Seen by the Near Infrared Mapping Spectrometer

NASA Technical Reports Server (NTRS)

Doute, S.; Lopes-Gautier, R.; Smythe, W. D.; Kamp, L. W.; Carlson, R.

2001-01-01

Near Infrared Mapping Spectrometer data acquired during the I24, 25, and 27 Io's Fly-bys by Galileo are analyzed to map the SO2 frost abundance and granularity. This allows a better understanding of the dynamics and evolution of gas condensation around volcanic plumes. Additional information is contained in the original extended abstract.

NASA atomic hydrogen standards program: An update

NASA Technical Reports Server (NTRS)

Reinhardt, V. S.; Kaufmann, D. C.; Adams, W. A.; Deluca, J. J.; Soucy, J. L.

1976-01-01

Comparisons are made between the NP series and the NX series of hydrogen masers. A field operable hydrogen maser (NR series) is also described. Atomic hydrogen primary frequency standards are in development stages. Standards are being developed for a hydrogen beam frequency standard and for a concertina hydrogen maser.

77 FR 46961 - Approval and Promulgation of Implementation Plans; Wisconsin; Volatile Organic Compound Emission...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-07

... holidays. We recommend that you telephone Steven Rosenthal, Environmental Engineer, at (312) 886-6052... Engineer, Attainment Planning and Maintenance Section, Air Programs Branch (AR-18J), Environmental... January 2012, No. 673, effective February 1, 2012. (D) NR 419.045 Industrial wastewater operations, as...

The Odd Trio

NASA Image and Video Library

2014-09-22

The Cassini spacecraft captures a rare family photo of three of Saturn's moons that couldn't be more different from each other! As the largest of the three, Tethys (image center) is round and has a variety of terrains across its surface. Meanwhile, Hyperion (to the upper-left of Tethys) is the "wild one" with a chaotic spin and Prometheus (lower-left) is a tiny moon that busies itself sculpting the F ring. To learn more about the surface of Tethys (660 miles, or 1,062 kilometers across), see PIA17164 More on the chaotic spin of Hyperion (168 miles, or 270 kilometers across) can be found at PIA07683 And discover more about the role of Prometheus (53 miles, or 86 kilometers across) in shaping the F ring in PIA12786. This view looks toward the sunlit side of the rings from about 1 degree above the ringplane. The image was taken in visible light with the Cassini spacecraft narrow-angle camera on July 14, 2014. The view was acquired at a distance of approximately 1.2 million miles (1.9 million kilometers) from Tethys and at a Sun-Tethys-spacecraft, or phase, angle of 22 degrees. Image scale is 7 miles (11 kilometers) per pixel. http://photojournal.jpl.nasa.gov/catalog/PIA18283

Assessing the Effects of Radiation Damage on Ni-base Alloys for the Prometheus Space Reactor System

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

T. Angeliu

2006-01-19

Ni-base alloys were considered for the Prometheus space reactor pressure vessel with operational parameters of {approx}900 K for 15 years and fluences up to 160 x 10{sup 20} n/cm{sup 2} (E > 0.1 MeV). This paper reviews the effects of irradiation on the behavior of Ni-base alloys and shows that radiation-induced swelling and creep are minor considerations compared to significant embrittlement with neutron ,exposure. While the mechanism responsible for radiation-induced embrittlement is not fully understood, it is likely a combination of helium embrittlement and solute segregation that can be highly dependent on the alloy composition and exposure conditions. Transmutation calculationsmore » show that detrimental helium levels would be expected at the end of life for the inner safety rod vessel (thimble) and possibly the outer pressure vessel, primarily from high energy (E > 1 MeV) n,{alpha} reactions with {sup 58}Ni. Helium from {sup 10}B is significant only for the outer vessel due to the proximity of the outer vessel to the Be0 control elements. Recommendations for further assessments of the material behavior and methods to minimize the effects of radiation damage through alloy design are provided.« less

NR2A-Containing NMDARs in the Prefrontal Cortex Are Required for Working Memory and Associated with Age-Related Cognitive Decline.

PubMed

McQuail, Joseph A; Beas, B Sofia; Kelly, Kyle B; Simpson, Kailey L; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L

2016-12-14

Working memory, the ability to temporarily maintain representational knowledge, is a foundational cognitive process that can become compromised in aging and neuropsychiatric disease. NMDA receptor (NMDAR) activation in prefrontal cortex (PFC) is necessary for the pyramidal neuron activity believed to enable working memory; however, the distinct biophysical properties and localization of NMDARs containing NR2A and NR2B subunits suggest unique roles for NMDAR subtypes in PFC neural activity and working memory. Experiments herein show that working memory depends on NR2A- but not NR2B-NMDARs in PFC of rats and that NR2A-NMDARs mediate the majority of evoked NMDAR currents on layer 2/3 PFC pyramidal neurons. Moreover, attenuated expression of the NR2A but not the NR2B subunit in PFC associates with naturally occurring working memory impairment in aged rats. Finally, NMDAR currents and working memory are enhanced in aged rats by promoting activation of the NR2A-enriched synaptic pool of PFC NMDARs. These results implicate NR2A-NMDARs in normal working memory and suggest novel treatment strategies for improving working memory in cognitive disorders. Working memory, the ability to hold information "in mind," requires persistent activity of pyramidal neurons in prefrontal cortex (PFC) mediated by NMDA receptor (NMDAR) activation. NMDAR loss in PFC may account for working memory impairments in aging and psychiatric disease. Our studies demonstrate that NMDARs containing the NR2A subunit, but not the NR2B subunit, are required for working memory and that loss of NR2A predicts severity of age-related working memory impairment. The importance of NR2A to working memory is likely due its abundant contribution to pyramidal neuron activity and location at synaptic sites in PFC. This information is useful in designing new therapies to treat working memory impairments by enhancing the function of NR2A-containing NMDARs. Copyright © 2016 the authors 0270-6474/16/3612537-12$15.00/0.

Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development.

PubMed

Nissim, Sahar; Weeks, Olivia; Talbot, Jared C; Hedgepeth, John W; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E; Amacher, Sharon L; Goessling, Wolfram

2016-10-01

The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic vs. pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Reversible Reduction of Nitroxides to Hydroxylamines: the Roles for Ascorbate and Glutathione

PubMed Central

Bobko, Andrey A.; Kirilyuk, Igor A.; Grigor'ev, Igor A.; Zweier, Jay L.; Khramtsov, Valery V.

2007-01-01

Biological applications of stable nitroxyl radicals, NR, include their use as contrast agents for magnetic resonance imaging, spin labels, superoxide dismutase mimics, and antioxidants. The rapid reduction of NR in biological samples into hydroxylamines, HA, significantly limits their application. In its turn, reoxidation of HA back to the NR has been used for detection of reactive oxygen species, ROS. In this work comparative studies of the reduction of pyrrolidine, imidazoline and imidazolidine NR by ascorbate were performed taking advantage of recently synthesized tetraethyl substituted NR with much higher stability towards reduction both in vitro and in vivo. Surprisingly, these NR kept 10-50% of initial intensity of electron paramagnetic resonance signal for about 1 h in the presence of hundred fold excess of ascorbate. To explain this data, reoxidation of the corresponding HA by ascorbate radical and dehydroascorbic acid back to the NR was proposed. This hypothesis was supported by direct measurement of the NR appearance from the HA upon ascorbate radical generation by ascorbate oxidase, or in the presence of the dehydroascorbic acid. The reversible reaction between NR and ascorbate was observed for the various types of the NR, and the rate constants for direct and reverse reactions were determined. The equilibrium constants for one-electron reduction of the tetraethyl substituted NR by ascorbate were found to be in the range from 2.65×10−6 to 10−5 which is significantly lower than corresponding values for the tetramethyl substituted NR (less or about 10−4). This explains an establishment of EPR-detectable quasi-equilibrium level of tetraethyl substituted NR in the presence of excess of ascorbate. The redox reactions of the NR-HA couple in ascorbate containing medium was found to be significantly affected by glutathione, GSH. This effect was attributed to the reduction of ascorbate radical by GSH, and the rate constant of this reaction was found to be equal to 10 M−1s−1. In summary, the data provide new insight into the redox chemistry of NR and HA, and significantly affect interpretation and strategy of their use as redox- and ROS-sensitive probes, or as antioxidants. PMID:17210453

Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development

PubMed Central

Nissim, Sahar; Weeks, Olivia; Talbot, Jared C.; Hedgepeth, John W.; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E.; Amacher, Sharon L.; Goessling, Wolfram

2016-01-01

The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic versus pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. PMID:27474396

BMP-induced reprogramming of the neural retina into retinal pigment epithelium requires Wnt signalling

PubMed Central

Steinfeld, Jörg; Steinfeld, Ichie; Bausch, Alexander; Coronato, Nicola; Hampel, Meggi-Lee; Depner, Heike; Layer, Paul G.

2017-01-01

ABSTRACT In vertebrates, the retinal pigment epithelium (RPE) and photoreceptors of the neural retina (NR) comprise a functional unit required for vision. During vertebrate eye development, a conversion of the RPE into NR can be induced by growth factors in vivo at optic cup stages, but the reverse process, the conversion of NR tissue into RPE, has not been reported. Here, we show that bone morphogenetic protein (BMP) signalling can reprogram the NR into RPE at optic cup stages in chick. Shortly after BMP application, expression of Microphthalmia-associated transcription factor (Mitf) is induced in the NR and selective cell death on the basal side of the NR induces an RPE-like morphology. The newly induced RPE differentiates and expresses Melanosomalmatrix protein 115 (Mmp115) and RPE65. BMP-induced Wnt2b expression is observed in regions of the NR that become pigmented. Loss of function studies show that conversion of the NR into RPE requires both BMP and Wnt signalling. Simultaneous to the appearance of ectopic RPE tissue, BMP application reprogrammed the proximal RPE into multi-layered retinal tissue. The newly induced NR expresses visual segment homeobox-containing gene (Vsx2), and the ganglion and photoreceptor cell markers Brn3α and Visinin are detected. Our results show that high BMP concentrations are required to induce the conversion of NR into RPE, while low BMP concentrations can still induce transdifferentiation of the RPE into NR. This knowledge may contribute to the development of efficient standardized protocols for RPE and NR generation for cell replacement therapies. PMID:28546339

Overexpression of the NR2A subunit in the forebrain impairs long-term social recognition and non-social olfactory memory.

PubMed

Jacobs, S A; Tsien, J Z

2014-04-01

Animals must recognize and remember conspecifics and potential mates, and distinguish these animals from potential heterospecific competitors and predators. Despite its necessity, aged animals are known to exhibit impaired social recognition memory. As the brain ages, the ratio of NR2A:NR2B in the brain increases over time and has been postulated to underlie the cognitive decline observed during the aging process. Here, we test the hypothesis that an increased NR2A:NR2B subunit ratio underlies long-term social recognition memory. Using transgenic overexpression of NR2A in the forebrain regions, we investigated the ability of these mice to learn and remember male and female conspecifics, mice of another strain and animals of another rodent species, the rat. Furthermore, due to the importance of olfaction in social recognition, we tested the olfactory memory in the NR2A transgenic mice. Our series of behavioral experiments revealed significant impairments in the NR2A transgenic mice in long-term social memory of both male and female conspecifics. Additionally, the NR2A transgenic mice are unable to recognize mice of another strain or rats. The NR2A transgenic mice also exhibited long-term memory impairments in the olfactory recognition task. Taken together, our results provide evidence that an increased NR2A:NR2B ratio in the forebrain leads to reduced long-term memory function, including the ethologically important memories such as social recognition and olfactory memory.

Cognitive Evaluation Theory: An Experimental Test of Processes and Outcomes.

DTIC Science & Technology

1981-06-26

ICONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE Organizational Effectiveness Research Program June 26, 1981 Office of Naval Research (Code 452) 13. NUMBER...frame- work for explaining the detrimental effects of performance contingent rewards on intrinsically motivated behaviors. A review of the literature...part by the Organizational Effectiveness RMzarch Program, Office of Naval Research (Code 452), under Contract No. N0014-79-C-O750i NR 170-892 with Dr

YCL047C/POF1 Is a Novel Nicotinamide Mononucleotide Adenylyltransferase (NMNAT) in Saccharomyces cerevisiae*

PubMed Central

Kato, Michiko; Lin, Su-Ju

2014-01-01

NAD+ is an essential metabolic cofactor involved in various cellular biochemical processes. Nicotinamide riboside (NR) is an endogenously produced key pyridine metabolite that plays important roles in the maintenance of NAD+ pool. Using a NR-specific cell-based screen, we identified mutants that exhibit altered NR release phenotype. Yeast cells lacking the ORF YCL047C/POF1 release considerably more NR compared with wild type, suggesting that POF1 plays an important role in NR/NAD+ metabolism. The amino acid sequence of Pof1 indicates that it is a putative nicotinamide mononucleotide adenylyltransferase (NMNAT). Unlike other yeast NMNATs, Pof1 exhibits NMN-specific adenylyltransferase activity. Deletion of POF1 significantly lowers NAD+ levels and decreases the efficiency of NR utilization, resistance to oxidative stress, and NR-induced life span extension. We also show that NR is constantly produced by multiple nucleotidases and that the intracellular NR pools are likely to be compartmentalized, which contributes to the regulation of NAD+ homeostasis. Our findings may contribute to the understanding of the molecular basis and regulation of NAD+ metabolism in higher eukaryotes. PMID:24759102

40 CFR 158.260 - Experimental use permit data requirements for environmental fate.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Leaching and adsorption/desorption R NR NR NR R NR TGAI or PAIRA 3 (d) Test notes. The following test notes... cranberry bogs and rice paddies. 3. Adsorption and desorption using a batch equilibrium method is preferred...

40 CFR 158.260 - Experimental use permit data requirements for environmental fate.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Leaching and adsorption/desorption R NR NR NR R NR TGAI or PAIRA 3 (d) Test notes. The following test notes... cranberry bogs and rice paddies. 3. Adsorption and desorption using a batch equilibrium method is preferred...

40 CFR 158.260 - Experimental use permit data requirements for environmental fate.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Leaching and adsorption/desorption R NR NR NR R NR TGAI or PAIRA 3 (d) Test notes. The following test notes... cranberry bogs and rice paddies. 3. Adsorption and desorption using a batch equilibrium method is preferred...

40 CFR 158.260 - Experimental use permit data requirements for environmental fate.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Leaching and adsorption/desorption R NR NR NR R NR TGAI or PAIRA 3 (d) Test notes. The following test notes... cranberry bogs and rice paddies. 3. Adsorption and desorption using a batch equilibrium method is preferred...

Acute Dermal Toxicity of Diethyleneglycol Dinitrate in Rabbits

DTIC Science & Technology

1988-09-01

ACC# ANtAL ID SNc DLW21OSIS 38260 85F157 Mile Not remarkable (NR) 38261 85F158 Mile Purulent otitis media , bilateral 38262 85F159 Mle NR 38263 85F160...Mle NR 38264 85F161 Male Purulent otitis media , left ear 38263 85F164 Female MR 38266 85F166 Female NR 38267 85F167 Female NR 38268 85F168 Female t

Large Scale Solution Assembly of Quantum Dot - Gold Nanorod Architectures with Plasmon Enhanced Fluorescence (Postprint)

DTIC Science & Technology

2013-09-01

around the AuNR. This is illustrated in Figure 3, which compi!res brightfield,scanningTEM ( STEM ), and 3D tomographic reconstruction of QD,/AuNR. The...distribution unlimited ... Cll u 1𔃺 Q. II) QDn/AuNR 1-5 6-10 11-15 16-20 >20 ~ 60 c ~ "’ 40 ..Q ·~ u; c 20 k 2 3 >4 QDn/AuNR Figure 2...showing three-dimensional arrangement of the QOs around the AuNR. (e-i) Elemental mapping from STEM image of silica coated QD·AuNR architecture (e)(scale

Products of Submarine Fountains and Bubble-burst Eruptive Activity at 1200 m on West Mata Volcano, Lau Basin

NASA Astrophysics Data System (ADS)

Clague, D. A.; Rubin, K. H.; Keller, N. S.

2009-12-01

An eruption was observed and sampled at West Mata Volcano using ROV JASON II for 5 days in May 2009 during the NSF-NOAA eruption response cruise to this region of suspected volcanic activity. Activity was focused near the summit at the Prometheus and Hades vents. Prometheus erupted almost exclusively as low-level fountains. Activity at Hades cycled between vigorous degassing, low fountains, and bubble-bursts, building up and partially collapsing a small spatter/scoria cone and feeding short sheet-like and pillow flows. Fire fountains at Prometheus produced mostly small primary pyroclasts that include Pele's hair and fluidal fragments of highly vesicular volcanic glass. These fragments have mostly shattered and broken surfaces, although smooth spatter-like surfaces also occur. As activity wanes, glow in the vent fades, and denser, sometimes altered volcanic clasts are incorporated into the eruption. The latter are likely from the conduit walls and/or vent-rim ejecta, drawn back into the vent by inrushing seawater that replaces water entrained in the rising volcanic plume. Repeated recycling of previously erupted materials eventually produces rounded clasts resembling beach cobbles and pitted surfaces on broken phenocrysts of pyroxene and olivine. We estimate that roughly 33% of near vent ejecta are recycled. Our best sample of this ejecta type was deposited in the drawer of the JASON II ROV during a particularly large explosion that occurred during plume sampling immediately above the vent. Elemental sulfur spherules up to 5 mm in diameter are common in ejecta from both vents and occur inside some of the lava fragments Hades activity included dramatic bubble-bursts unlike anything previously observed under water. The lava bubbles, sometimes occurring in rapid-fire sequence, collapsed in the water-column, producing fragments that are quenched in less than a second to form Pele's hair, limu o Pele, spatter-like lava blobs, and scoria. All are highly vesicular, including the hairs and limu, unlike similar fragments from Loihi Seamount, Axial Seamount, and mid-ocean ridges that have <10% vesicles. The lava bubbles were observed to reach about 1 m in diameter, sometimes appearing to separate from the lava surface, suggesting that they are fed by gasses rising directly from the conduit. Slow-motion video analysis shows that the lava skin stretches to form thin regions that then separate, exposing still incandescent gas within. Bubbles collapse as the lava skin disrupts (usually at the top of the bubble), producing a shower of convex spatter-like lava fragments. Sheet-like lava flows are associated with collapse of the spatter cone and change to pillow lobe extrusion about 5 m from the vent orifice. One pillow lobe sample collected molten contains ~60% vesicles. We suggest that the erupting melt contains large coalesced slugs of magmatic gas and abundant small expanding vesicles that have yet to be incorporated into the large gas slugs. The contrast with Prometheus suggests highly localized conditions of magma devolatilization at W. Mata.

Microbial communities in natural rubber coagula during maturation: impacts on technological properties of dry natural rubber.

PubMed

Salomez, M; Subileau, M; Vallaeys, T; Santoni, S; Bonfils, F; Sainte-Beuve, J; Intapun, J; Granet, F; Vaysse, L; Dubreucq, É

2018-02-01

To characterize microbial communities present in natural rubber (NR) coagula from Hevea brasiliensis latex during maturation and identify microbial taxa (bacteria and fungi) having an impact on dry NR properties. Microbial community dynamics in NR coagula maturated under controlled conditions were compared and related with the evolution of dry NR properties. The pyrosequencing of 16S (119 837 effective reads) and 18S (131 879 effective reads) rRNA gene regions was performed on 21 samples covering different maturation times and two aeration conditions. Results showed a relatively high bacterial richness (Chao1 estimates of 200-1000) associated with significant bacterial dynamics. Lactic acid bacteria (LAB) were dominant in the first days of maturation. Then, in aerobic conditions, development of Actinobacteria represented by the family Microbacteriaceae was associated with alkalinization of the samples and a higher sensitivity of NR to thermo-oxidation as evaluated by its plasticity retention index (PRI). In anaerobiosis, the reduced development of bacteria, mostly LAB present, was associated with improved NR properties (higher initial plasticity P 0 and PRI). The involvement of micro-organisms in the evolution of dry NR properties during the maturation of NR coagula was confirmed. The importance of the structure and dynamics of microbial communities is specifically highlighted. Natural rubber is a key elastomer for the tyre industry and for a variety of other applications. The majority of raw NR is obtained by natural coagulation of H. brasiliensis latex under the activity of micro-organisms. An improved understanding of the microbial communities involved in the maturation of NR coagula may lead to an improvement in the production process of raw NR to provide a better consistency in NR quality. © 2017 The Society for Applied Microbiology.

Measuring Binding Affinity of Protein-Ligand Interaction Using Spectrophotometry: Binding of Neutral Red to Riboflavin-Binding Protein

ERIC Educational Resources Information Center

Chenprakhon, Pirom; Sucharitakul, Jeerus; Panijpan, Bhinyo; Chaiyen, Pimchai

2010-01-01

The dissociation constant, K[subscript d], of the binding of riboflavin-binding protein (RP) with neutral red (NR) can be determined by titrating RP to a fixed concentration of NR. Upon adding RP to the NR solution, the maximum absorption peak of NR shifts to 545 nm from 450 nm for the free NR. The change of the absorption can be used to determine…

Development and testing of cabin sidewall acoustic resonators for the reduction of cabin tone levels in propfan-powered aircraft

NASA Technical Reports Server (NTRS)

Kuntz, H. L.; Gatineau, R. J.; Prydz, R. A.; Balena, F. J.

1991-01-01

The use of Helmholtz resonators to increase the sidewall transmission loss (TL) in aircraft cabin sidewalls is evaluated. Development, construction, and test of an aircraft cabin acoustic enclosure, built in support of the Propfan Test Assessment (PTA) program, is described. Laboratory and flight test results are discussed. Resonators (448) were located between the enclosure trim panels and the fuselage shell. In addition, 152 resonators were placed between the enclosure and aircraft floors. The 600 resonators were each tuned to a propfan fundamental blade passage frequency (235 Hz). After flight testing on the PTA aircraft, noise reduction (NR) tests were performed with the enclosure in the Kelly Johnson Research and Development Center Acoustics Laboratory. Broadband and tonal excitations were used in the laboratory. Tonal excitation simulated the propfan flight test excitation. The resonators increase the NR of the cabin walls around the resonance frequency of the resonator array. Increases in NR of up to 11 dB were measured. The effects of flanking, sidewall absorption, cabin absorption, resonator loading of trim panels, and panel vibrations are presented. Resonator and sidewall panel design and test are discussed.

Wind noise in hearing aids: I. Effect of wide dynamic range compression and modulation-based noise reduction.

PubMed

Chung, King

2012-01-01

The objectives of this study were: (1) to examine the effect of wide dynamic range compression (WDRC) and modulation-based noise reduction (NR) algorithms on wind noise levels at the hearing aid output; and (2) to derive effective strategies for clinicians and engineers to reduce wind noise in hearing aids. Three digital hearing aids were fitted to KEMAR. The noise output was recorded at flow velocities of 0, 4.5, 9.0, and 13.5 m/s in a wind tunnel as the KEMAR head was turned from 0° to 360°. Flow noise levels were compared between the 1:1 linear and 3:1 WDRC conditions, and between NR-activated and NR-deactivated conditions when the hearing aid was programmed to the directional and omnidirectional modes. The results showed that: (1) WDRC increased low-level noise and reduced high-level noise; and (2) different noise reduction algorithms provided different amounts of wind noise reduction in different microphone modes, frequency regions, flow velocities, and head angles. Wind noise can be reduced by decreasing the gain for low-level inputs, increasing the compression ratio for high-level inputs, and activating modulation-based noise reduction algorithms.

Laboratory test and acoustic analysis of cabin treatment for propfan test assessment aircraft

NASA Technical Reports Server (NTRS)

Kuntz, H. L.; Gatineau, R. J.

1991-01-01

An aircraft cabin acoustic enclosure, built in support of the Propfan Test Assessment (PTA) program, is described. Helmholtz resonators were attached to the cabin trim panels to increase the sidewall transmission loss (TL). Resonators (448) were located between the trim panels and fuselage shell. In addition, 152 resonators were placed between the enclosure and aircraft floors. The 600 resonators were each tuned to a 235 Hz resonance frequency. After flight testing on the PTA aircraft, the enclosure was tested in the Kelly Johnson R and D Center Acoustics Lab. Laboratory noise reduction (NR) test results are discussed. The enclosure was placed in a Gulfstream 2 fuselage section. Broadband (138 dB overall SPL) and tonal (149 dB overall SPL) excitations were used in the lab. Tonal excitation simulated the propfan flight test excitation. The fundamental tone was stepped in 2 Hz intervals from 225 through 245 Hz. The resonators increase the NR of the cabin walls around the resonance frequency of the resonator array. The effects of flanking, sidewall absorption, cabin adsorption, resonator loading of trim panels, and panel vibrations are presented. Increases in NR of up to 11 dB were measured.

Friction characteristics of 20 x 4.4, type 7, aircraft tires constructed with different tread rubber compounds

NASA Technical Reports Server (NTRS)

Dreher, R. C.; Yager, T. J.

1976-01-01

A test program was conducted at the Langley aircraft landing loads and traction facility to evaluate the friction characteristics of 20 x 4.4, type, aircraft tires constructed with experimental cut-resistant, tread rubber compounds. These compounds consisted of different blends of natural rubber (NR) and an alfin catalyzed styrene-butadiene copolymer rubber (SBR). One tire having a blend of 30 SBR and 70 NR and another having a blend of 60 SBR and 40 NR in the tread were tested together with a standard production tire with no SBR content in the tread rubber. The results of this investigation indicated that the test tires constructed with the special cut-resistant tread rubber compositions did not suffer any significant degradation in tire friction capability when compared with the standard tire. In general, tire friction capability decreased with increasing speed and surface wetness condition. As yaw angle increased, tire braking capability decreased while tire cornering capability increased. Tread-wear data based on number of brake cycles, however, suggested that the tires with alfin SBR blends experienced significantly greater wear than the standard production tire.

Bisphenol-A rapidly enhanced passive avoidance memory and phosphorylation of NMDA receptor subunits in hippocampus of young rats

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

Xu Xiaohong, E-mail: xuxh63@zjnu.cn; Li Tao; Luo Qingqing

Bisphenol-A (BPA), an endocrine disruptor, is found to influence development of brain and behaviors in rodents. The previous study indicated that perinatal exposure to BPA impaired learning-memory and inhibited N-methyl-D-aspartate receptor (NMDAR) subunits expressions in hippocampus during the postnatal development in rats; and in cultured hippocampal neurons, BPA rapidly promotes dynamic changes in dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDAR subunit NR2B. In the present study, we examined the rapid effect of BPA on passive avoidance memory and NMDAR in the developing hippocampus of Sprague-Dawley rats at the age of postnatal day 18. The results showedmore » that BPA or estradiol benzoate (EB) rapidly extended the latency to step down from the platform 1 h after footshock and increased the phosphorylation levels of NR1, NR2B, and mitogen-activated extracellular signal-regulated kinase (ERK) in hippocampus within 1 h. While 24 h after BPA or EB treatment, the improved memory and the increased phosphorylation levels of NR1, NR2B, ERK disappeared. Furthermore, pre-treatment with an estrogen receptors (ERs) antagonist, ICI182,780, or an ERK-activating kinase inhibitor, U0126, significantly attenuated EB- or BPA-induced phosphorylations of NR1, NR2B, and ERK within 1 h. These data suggest that BPA rapidly enhanced short-term passive avoidance memory in the developing rats. A non-genomic effect via ERs may mediate the modulation of the phosphorylation of NMDAR subunits NR1 and NR2B through ERK signaling pathway. - Highlights: > BPA rapidly extended the latency to step down from platform 1 h after footshock. > BPA rapidly increased pNR1, pNR2B, and pERK in hippocampus within 1 h. > ERs antagonist or MEK inhibitor attenuated BPA-induced pNR1, pNR2B, and pERK.« less

Expression and Functional Pathway Analysis of Nuclear Receptor NR2F2 in Ovarian Cancer

PubMed Central

Hawkins, Shannon M.; Loomans, Holli A.; Wan, Ying-Wooi; Ghosh-Choudhury, Triparna; Coffey, Donna; Xiao, Weimin; Liu, Zhandong; Sangi-Haghpeykar, Haleh

2013-01-01

Context: Recent evidence implicates the orphan nuclear receptor, nuclear receptor subfamily 2, group F, member 2 (NR2F2; chicken ovalbumin upstream promoter-transcription factor II) as both a master regulator of angiogenesis and an oncogene in prostate and other human cancers. Objective: The objective of the study was to determine whether NR2F2 plays a role in ovarian cancer and dissect its potential mechanisms of action. Design, Setting, and Patients: We examined NR2F2 expression in healthy ovary and ovarian cancers using quantitative PCR and immunohistochemistry. NR2F2 expression was targeted in established ovarian cancer cell lines to assess the impact of dysregulated NR2F2 expression in the epithelial compartment of ovarian cancers. Results: Our results indicate that NR2F2 is robustly expressed in the stroma of healthy ovary with little or no expression in epithelia lining the ovarian surface, clefts, or crypts. This pattern of NR2F2 expression was markedly disrupted in ovarian cancers, in which decreased levels of stromal expression and ectopic epithelial expression were frequently observed. Ovarian cancers with the most disrupted patterns of NR2F2 were associated with significantly shorter disease-free interval by Kaplan-Meier analysis. Targeting NR2F2 expression in established ovarian cancer cell lines enhanced apoptosis and increased proliferation. In addition, we found that NR2F2 regulates the expression of NEK2, RAI14, and multiple other genes involved in the cell cycle, suggesting potential pathways by which dysregulated expression of NR2F2 impacts ovarian cancer. Conclusions: These results uncover novel roles for NR2F2 in ovarian cancer and point to a unique scenario in which a single nuclear receptor plays potentially distinct roles in the stromal and epithelial compartments of the same tissue. PMID:23690307

Relating hearing loss and executive functions to hearing aid users' preference for, and speech recognition with, different combinations of binaural noise reduction and microphone directionality

PubMed Central

Neher, Tobias

2014-01-01

Knowledge of how executive functions relate to preferred hearing aid (HA) processing is sparse and seemingly inconsistent with related knowledge for speech recognition outcomes. This study thus aimed to find out if (1) performance on a measure of reading span (RS) is related to preferred binaural noise reduction (NR) strength, (2) similar relations exist for two different, non-verbal measures of executive function, (3) pure-tone average hearing loss (PTA), signal-to-noise ratio (SNR), and microphone directionality (DIR) also influence preferred NR strength, and (4) preference and speech recognition outcomes are similar. Sixty elderly HA users took part. Six HA conditions consisting of omnidirectional or cardioid microphones followed by inactive, moderate, or strong binaural NR as well as linear amplification were tested. Outcome was assessed at fixed SNRs using headphone simulations of a frontal target talker in a busy cafeteria. Analyses showed positive effects of active NR and DIR on preference, and negative and positive effects of, respectively, strong NR and DIR on speech recognition. Also, while moderate NR was the most preferred NR setting overall, preference for strong NR increased with SNR. No relation between RS and preference was found. However, larger PTA was related to weaker preference for inactive NR and stronger preference for strong NR for both microphone modes. Equivalent (but weaker) relations between worse performance on one non-verbal measure of executive function and the HA conditions without DIR were found. For speech recognition, there were relations between HA condition, PTA, and RS, but their pattern differed from that for preference. Altogether, these results indicate that, while moderate NR works well in general, a notable proportion of HA users prefer stronger NR. Furthermore, PTA and executive functions can account for some of the variability in preference for, and speech recognition with, different binaural NR and DIR settings. PMID:25538547

A Nitrogen Inventory of Major Water Regions Across the USA as a Benchmark for Future Progress in Mitigating Nitrogen Pollution

NASA Astrophysics Data System (ADS)

Boyer, E. W.; Galloway, J. N.; Alexander, R. B.

2012-12-01

We present a contemporary inventory of reactive nitrogen (Nr) inputs and, air, and surface waters throughout major water regions in the United States. Inputs of Nr to the nation and the world have been increasing, largely due to human activities associated with food production and energy consumption via the combustion of fossil fuels and biofuels. Despite the obvious essential benefits of a plentiful supply of food and energy, the adverse consequences associated with the accumulation of Nr in the environment are large. Most of the Nr created by anthropogenic activities is released to the environment, often with unintended negative consequences. The greater the inputs of Nr to the landscape, the greater the potential for negative effects, caused by greenhouse gas production, ground level ozone, acid deposition, and Nr overload that can contribute to climate change, degradation of soils and vegetation, acidification of surface waters, coastal eutrophication, hypoxia and habitat loss. Here, we present a consistent accounting method for quantifying Nr sources and transport that was used in our inventory, and discuss associated data needs for tallying Nr inputs at regional scales. The inventory is a necessary tool for exploring the role of Nr contributed to the environment from various sources (e.g., from fertilizers, manure, biological fixation, human waste, atmospheric deposition) and from various industrial sectors (e.g., from agriculture, transportation, electricity generation). Agriculture and use of fertilizers to produce food, feed, and fiber (including bioenergy and biological nitrogen fixation) and combustion of fossil fuels are the largest sources of Nr released into the environment in the USA. Our inventory can be used as a benchmark of the current Nr situation against which future progress can be assessed in varying regions of the country, amidst changing Nr inputs and implementation of policy and management strategies to mitigate Nr pollution.

A contemporary national nitrogen inventory as a benchmark for future progress in mitigating nitrogen pollution in the USA

NASA Astrophysics Data System (ADS)

Boyer, E. W.; Galloway, J. N.; Theis, T.; Alexander, R. B.

2011-12-01

We present a contemporary inventory of reactive nitrogen (Nr) inputs to land, air, and water in the United States. Inputs of Nr to the nation and the world have been increasing, largely due to human activities associated with food production and energy consumption via the combustion of fossil fuels and biofuels. Despite the obvious essential benefits of a plentiful supply of food and energy, the adverse consequences associated with the accumulation of Nr in the environment are large. Most of the Nr created by anthropogenic activities is released to the environment, often with unintended negative consequences. The greater the inputs of Nr to the landscape, the greater the potential for negative effects, caused by greenhouse gas production, ground level ozone, acid deposition, and Nr overload that can contribute to climate change, degradation of soils and vegetation, acidification of surface waters, coastal eutrophication, hypoxia and habitat loss. Here, we present a consistent accounting method for quantifying Nr sources and transport that was used in our inventory, and discuss associated data needs for tallying Nr inputs at regional scales. The inventory is a necessary tool for exploring the role of Nr contributed to the environment from various sources (e.g., from fertilizers, manure, biological fixation, human waste, atmospheric deposition) and from various industrial sectors (e.g., from agriculture, transportation, electricity generation). Agriculture and use of fertilizers to produce food, feed, and fiber (including bioenergy and biological nitrogen fixation) and combustion of fossil fuels are the largest sources of Nr released into the environment in the USA. Our inventory is currently being used by the U.S. Environmental Protection Agency as a benchmark of the current Nr situation against which future progress can be assessed -- amidst changing Nr inputs and implementation of policy and management strategies to mitigate Nr pollution.

Screening and Familial Characterization of Copy-Number Variations in NR5A1 in 46,XY Disorders of Sex Development and Premature Ovarian Failure

PubMed Central

Harrison, Steven M.; Campbell, Ian M.; Keays, Melise; Granberg, Candace F.; Villanueva, Carlos; Tannin, Grace; Zinn, Andrew R.; Castrillon, Diego H.; Shaw, Chad A.; Stankiewicz, Paweł; Baker, Linda A.

2013-01-01

The NR5A1 gene encodes for steroidogenic factor 1, a nuclear receptor that regulates proper adrenal and gonadal development and function. Mutations identified by NR5A1 sequencing have been associated with disorders of sex development (DSD), ranging from sex reversal to severe hypospadias in 46,XY patients and premature ovarian failure (POF) in 46,XX patients. Previous reports have identified four families with a history of both 46,XY DSD and 46,XX POF carrying segregating NR5A1 sequence mutations. Recently, three 46,XY DSD sporadic cases with NR5A1 microdeletions have been reported. Here, we identify the first NR5A1 microdeletion transmitted in a pedigree with both 46,XY DSD and 46,XX POF. A 46,XY individual with DSD due to gonadal dysgenesis was born to a young mother who developed POF. Array CGH analysis revealed a maternally inherited 0.23 Mb microdeletion of chromosome 9q33.3, including the NR5A1 gene. Based on this finding, we screened patients with unexplained 46,XY DSD (n=11), proximal hypospadias (n=21) and 46,XX POF (n=36) for possible NR5A1 copy-number variations (CNVs) via multiplex ligation-dependent probe amplification (MLPA), but did not identify any additional CNVs involving NR5A1. These data suggest that NR5A1 CNVs are an infrequent cause of these disorders but that array CGH and MLPA are useful genomic screening tools to uncover the genetic basis of such unexplained cases. This case is the first report of a familial NR5A1 CNV transmitting in a pedigree, causing both the male and female phenotypes associated with NR5A1 mutations, and the first report of a NR5A1 CNV associated with POF. PMID:23918653

The partial replacement of palm kernel shell by carbon black and halloysite nanotubes as fillers in natural rubber composites

NASA Astrophysics Data System (ADS)

Daud, Shuhairiah; Ismail, Hanafi; Bakar, Azhar Abu

2017-07-01

The effect of partial replacement of palm kernel shell powder by carbon black (CB) and halloysite nanotube (HNT) on the tensile properties, rubber-filler interaction, thermal properties and morphological studies of natural rubber (NR) composites were investigated. Four different compositions of NR/PKS/CB and NR/PKS/HNT composites i.e 20/0, 15/5, 10/10,5/15 and 0/20 parts per hundred rubber (phr) were prepared on a two roll mill. The results showed that the tensile strength and modulus at 100% elongation (M100) and 300% elongation (M300) were higher for NR/PKS/CB compared to NR/PKS/HNT composites. NR/PKS/CB composites had the lowest elongation at break (Eb). The effect of commercial fillers in NR/PKS composites on tensile properties was confirmed by the rubber-filler interaction and scanning electron microscopy (SEM) study. The thermal stability of PKS filled NR composites with partially replaced by commercial fillers also determined by Thermo gravimetric Analysis (TGA).

Spinal serum-inducible and glucocorticoid-inducible kinase 1 mediates neuropathic pain via kalirin and downstream PSD-95-dependent NR2B phosphorylation in rats.

PubMed

Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuan; Hsieh, Ming-Chun; Lin, Tzer-Bin

2013-03-20

The coupling of the spinal postsynaptic density-95 (PSD-95) with the glutamatergic N-methyl-d-aspartate receptor NR2B subunit and the subsequent NR2B phosphorylation contribute to pain-related plasticity. Increasing evidence reveals that kalirin, a Rho-guanine nucleotide exchange factor, modulates PSD-95-NR2B-dependent neuroplasticity. Our laboratory recently demonstrated that serum-inducible and glucocorticoid-inducible kinase 1 (SGK1) participates in inflammation-associated pain hypersensitivity by modulating spinal glutamatergic neurotransmission. Because kalirin is one of the proteins in PSD that is highly phosphorylated by various kinases, we tested whether kalirin could be a downstream target of spinal SGK1 that participates in neuropathic pain development via regulation of the PSD-95-NR2B coupling-dependent phosphorylation of NR2B. We observed that spinal nerve ligation (SNL, L5) in male Sprague Dawley rats resulted in behavioral allodynia, which was associated with phosphorylated SGK1 (pSGK1), kalirin, and phosphorylated NR2B (pNR2B) expression and an increase in pSGK1-kalirin-PSD-95-pNR2B coprecipitation in the ipsilateral dorsal horn (L4-L5). SNL-enhanced kalirin immunofluorescence was coincident with pSGK1, PSD-95, and pNR2B immunoreactivity. Small-interfering RNA (siRNA) that targeted spinal kalirin mRNA expression (10 μg, 10 μl; i.t.) reduced SNL-induced allodynia, kalirin and pNR2B expression, as well as kalirin-PSD-95 and PSD-95-pNR2B coupling and costaining without affecting SGK1 phosphorylation. Daily administration of GSK-650394 (an SGK1 antagonist; 100 nm, 10 μl, i.t.) not only exhibited effects similar to the kalirin mRNA-targeting siRNA but also attenuated pSGK1-kalirin costaining and SGK1-kalirin coupling. We suggest that nerve injury could induce spinal SGK1 phosphorylation that subsequently interacts with and upregulates kalirin to participate in neuropathic pain development via PSD-95-NR2B coupling-dependent NR2B phosphorylation.

Intrathecal injection of the peptide myr-NR2B9c attenuates bone cancer pain via perturbing N-methyl-D-aspartate receptor-PSD-95 protein interactions in mice.

PubMed

Liu, Yue; Cui, Xinlong; Sun, Yu-E; Yang, Xuli; Ni, Kun; Zhou, Yu; Ma, Zhengliang; Gu, Xiaoping

2014-06-01

N-methyl-D-aspartate receptor (NMDARs)-dependent central sensitization plays an important role in cancer pain. Binding of NMDAR subunit 2B (NR2B) by postsynaptic density protein-95 (PSD-95) can couple NMDAR activity to intracellular enzymes, such as neuronal nitric oxide synthase (nNOS), facilitate downstream signaling pathways, and modulate NMDAR stability, contributing to synaptic plasticity. In this study, we investigated whether perturbing the specific interaction between spinal NR2B-containing NMDAR and PSD-95, using a peptide-mimetic strategy, could attenuate bone cancer-related pain behaviors. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer-related pain behaviors. Western blotting was applied to examine the expression of spinal phospho-Tyr1472 NR2B, nNOS, and PSD-95. We further investigated the effects of intrathecal injection of the mimetic peptide Myr-NR2B9c, which competitively disrupts the interaction between PSD-95 and NR2B, on nociceptive behaviors and on the upregulation of phospho-Tyr1472 NR2B, nNOS, and PSD-95 associated with bone cancer pain in the spinal cord. Inoculation of osteosarcoma cells induced progressive bone cancer pain and resulted in a significant upregulation of phospho-Tyr1472 NR2B, nNOS, and PSD-95. Intrathecal administration of Myr-NR2B9c attenuated bone cancer-evoked mechanical allodynia, thermal hyperalgesia, and reduced spinal phospho-Tyr1472 NR2B, nNOS, and PSD-95 expression. Intrathecal administration of Myr-NR2B9c reduced bone cancer pain. Internalization of spinal NR2B and dissociation NR2B-containing NMDARs activation from downstream nNOS signaling may contribute to the analgesic effects of Myr-NR2B9c. This approach may circumvent the negative consequences associated with blocking NMDARs, and may be a novel strategy for the treatment of bone cancer pain.

iNR-PhysChem: A Sequence-Based Predictor for Identifying Nuclear Receptors and Their Subfamilies via Physical-Chemical Property Matrix

PubMed Central

Xiao, Xuan; Wang, Pu; Chou, Kuo-Chen

2012-01-01

Nuclear receptors (NRs) form a family of ligand-activated transcription factors that regulate a wide variety of biological processes, such as homeostasis, reproduction, development, and metabolism. Human genome contains 48 genes encoding NRs. These receptors have become one of the most important targets for therapeutic drug development. According to their different action mechanisms or functions, NRs have been classified into seven subfamilies. With the avalanche of protein sequences generated in the postgenomic age, we are facing the following challenging problems. Given an uncharacterized protein sequence, how can we identify whether it is a nuclear receptor? If it is, what subfamily it belongs to? To address these problems, we developed a predictor called iNR-PhysChem in which the protein samples were expressed by a novel mode of pseudo amino acid composition (PseAAC) whose components were derived from a physical-chemical matrix via a series of auto-covariance and cross-covariance transformations. It was observed that the overall success rate achieved by iNR-PhysChem was over 98% in identifying NRs or non-NRs, and over 92% in identifying NRs among the following seven subfamilies: NR1thyroid hormone like, NR2HNF4-like, NR3estrogen like, NR4nerve growth factor IB-like, NR5fushi tarazu-F1 like, NR6germ cell nuclear factor like, and NR0knirps like. These rates were derived by the jackknife tests on a stringent benchmark dataset in which none of protein sequences included has pairwise sequence identity to any other in a same subset. As a user-friendly web-server, iNR-PhysChem is freely accessible to the public at either http://www.jci-bioinfo.cn/iNR-PhysChem or http://icpr.jci.edu.cn/bioinfo/iNR-PhysChem. Also a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated mathematics involved in developing the predictor. It is anticipated that iNR-PhysChem may become a useful high throughput tool for both basic research and drug design. PMID:22363503

Synthesis and degradation of nitrate reductase during the cell cycle of Chlorella sorokiniana

NASA Technical Reports Server (NTRS)

Velasco, P. J.; Tischner, R.; Huffaker, R. C.; Whitaker, J. R.

1989-01-01

Studies on the diurnal variations of nitrate reductase (NR) activity during the life cycle of synchronized Chlorella sorokiniana cells grown with a 7:5 light-dark cycle showed that the NADH:NR activity, as well as the NR partial activities NADH:cytochrome c reductase and reduced methyl viologen:NR, closely paralleled the appearance and disappearance of NR protein as shown by sodium dodecyl sulfate gel electrophoresis and immunoblots. Results of pulse-labeling experiments with [35S]methionine further confirmed that diurnal variations of the enzyme activities can be entirely accounted for by the concomitant synthesis and degradation of the NR protein.

Iodinated natural rubber latex: preparation, characterisation & antibacterial activity assessment.

PubMed

Tyagi, M; Singh, S; Singh, H

2000-11-01

Natural Rubber (NR) in both its latex and dried form was treated with iodine to make it antibacterial in nature. The NR latex was dried and washed, dissolved in toluene, iodinated and cast into films. In a different approach, NR in its latex form (emulsion) was blended with aqueous solution of povidone-iodine complex (PVP-I) and films were cast. Phase separation of PVP-I was observed in the films prepared using NR latex; whereas the film prepared using NR solution in toluene and molecular iodine were homogeneous, transparent light brown. Solubility assessment of the films revealed that unlike pure NR, the iodinated NR failed to go into solution completely. The films obtained from both the approaches were evaluated for release of iodide ions. On immersion in water, PVP-I blended latex did not retain iodine while sustained release of iodide ion was observed in case of dried NR dissolved in toluene and treated with iodine. The FT-IR spectra of the iodinated films revealed that iodine attaches covalently to the double bonds in the isoprene units of NR. The films were also evaluated for their antibacterial properties and it was observed that the films prepared from both the approaches, acquired antimicrobial properties.

YCL047C/POF1 is a novel nicotinamide mononucleotide adenylyltransferase (NMNAT) in Saccharomyces cerevisiae.

PubMed

Kato, Michiko; Lin, Su-Ju

2014-05-30

NAD(+) is an essential metabolic cofactor involved in various cellular biochemical processes. Nicotinamide riboside (NR) is an endogenously produced key pyridine metabolite that plays important roles in the maintenance of NAD(+) pool. Using a NR-specific cell-based screen, we identified mutants that exhibit altered NR release phenotype. Yeast cells lacking the ORF YCL047C/POF1 release considerably more NR compared with wild type, suggesting that POF1 plays an important role in NR/NAD(+) metabolism. The amino acid sequence of Pof1 indicates that it is a putative nicotinamide mononucleotide adenylyltransferase (NMNAT). Unlike other yeast NMNATs, Pof1 exhibits NMN-specific adenylyltransferase activity. Deletion of POF1 significantly lowers NAD(+) levels and decreases the efficiency of NR utilization, resistance to oxidative stress, and NR-induced life span extension. We also show that NR is constantly produced by multiple nucleotidases and that the intracellular NR pools are likely to be compartmentalized, which contributes to the regulation of NAD(+) homeostasis. Our findings may contribute to the understanding of the molecular basis and regulation of NAD(+) metabolism in higher eukaryotes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Amygdala Infusions of an NR2B-Selective or an NR2A-Preferring NMDA Receptor Antagonist Differentially Influence Fear Conditioning and Expression in the Fear-Potentiated Startle Test

ERIC Educational Resources Information Center

Walker, David L.; Davis, Michael

2008-01-01

Within the amygdala, most N-methyl-D-aspartic acid (NMDA) receptors consist of NR1 subunits in combination with either NR2A or NR2B subunits. Because the particular subunit composition greatly influences the receptors' properties, we investigated the contribution of both subtypes to fear conditioning and expression. To do so, we infused the…

A dual system formed by the ARC and NR molybdoenzymes mediates nitrite-dependent NO production in Chlamydomonas.

PubMed

Chamizo-Ampudia, Alejandro; Sanz-Luque, Emanuel; Llamas, Ángel; Ocaña-Calahorro, Francisco; Mariscal, Vicente; Carreras, Alfonso; Barroso, Juan B; Galván, Aurora; Fernández, Emilio

2016-10-01

Nitric oxide (NO) is a relevant signal molecule involved in many plant processes. However, the mechanisms and proteins responsible for its synthesis are scarcely known. In most photosynthetic organisms NO synthases have not been identified, and Nitrate Reductase (NR) has been proposed as the main enzymatic NO source, a process that in vitro is also catalysed by other molybdoenzymes. By studying transcriptional regulation, enzyme approaches, activity assays with in vitro purified proteins and in vivo and in vitro NO determinations, we have addressed the role of NR and Amidoxime Reducing Component (ARC) in the NO synthesis process. N\\R and ARC were intimately related both at transcriptional and activity level. Thus, arc mutants showed high NIA1 (NR gene) expression and NR activity. Conversely, mutants without active NR displayed an increased ARC expression in nitrite medium. Our results with nia1 and arc mutants and with purified enzymes support that ARC catalyses the NO production from nitrite taking electrons from NR and not from Cytb5-1/Cytb5-Reductase, the component partners previously described for ARC (proposed as NOFNiR, Nitric Oxide-Forming Nitrite Reductase). This NR-ARC dual system would be able to produce NO in the presence of nitrate, condition under which NR is unable to do it. © 2016 John Wiley & Sons Ltd.

Integrated reactive nitrogen budgets and future trends in China

PubMed Central

Gu, Baojing; Ju, Xiaotang; Chang, Jie; Ge, Ying; Vitousek, Peter M.

2015-01-01

Reactive nitrogen (Nr) plays a central role in food production, and at the same time it can be an important pollutant with substantial effects on air and water quality, biological diversity, and human health. China now creates far more Nr than any other country. We developed a budget for Nr in China in 1980 and 2010, in which we evaluated the natural and anthropogenic creation of Nr, losses of Nr, and transfers among 14 subsystems within China. Our analyses demonstrated that a tripling of anthropogenic Nr creation was associated with an even more rapid increase in Nr fluxes to the atmosphere and hydrosphere, contributing to intense and increasing threats to human health, the sustainability of croplands, and the environment of China and its environs. Under a business as usual scenario, anthropogenic Nr creation in 2050 would more than double compared with 2010 levels, whereas a scenario that combined reasonable changes in diet, N use efficiency, and N recycling could reduce N losses and anthropogenic Nr creation in 2050 to 52% and 64% of 2010 levels, respectively. Achieving reductions in Nr creation (while simultaneously increasing food production and offsetting imports of animal feed) will require much more in addition to good science, but it is useful to know that there are pathways by which both food security and health/environmental protection could be enhanced simultaneously. PMID:26124118

Integrated reactive nitrogen budgets and future trends in China.

PubMed

Gu, Baojing; Ju, Xiaotang; Chang, Jie; Ge, Ying; Vitousek, Peter M

2015-07-14

Reactive nitrogen (Nr) plays a central role in food production, and at the same time it can be an important pollutant with substantial effects on air and water quality, biological diversity, and human health. China now creates far more Nr than any other country. We developed a budget for Nr in China in 1980 and 2010, in which we evaluated the natural and anthropogenic creation of Nr, losses of Nr, and transfers among 14 subsystems within China. Our analyses demonstrated that a tripling of anthropogenic Nr creation was associated with an even more rapid increase in Nr fluxes to the atmosphere and hydrosphere, contributing to intense and increasing threats to human health, the sustainability of croplands, and the environment of China and its environs. Under a business as usual scenario, anthropogenic Nr creation in 2050 would more than double compared with 2010 levels, whereas a scenario that combined reasonable changes in diet, N use efficiency, and N recycling could reduce N losses and anthropogenic Nr creation in 2050 to 52% and 64% of 2010 levels, respectively. Achieving reductions in Nr creation (while simultaneously increasing food production and offsetting imports of animal feed) will require much more in addition to good science, but it is useful to know that there are pathways by which both food security and health/environmental protection could be enhanced simultaneously.

Tyrosine Phosphorylation of NR2B Contributes to Chronic Migraines via Increased Expression of CGRP in Rats

PubMed Central

Liang, Xiping; Wang, Sha; Qin, Guangcheng; Xie, Jingmei; Tan, Ge; Zhou, Jiying; McBride, Devin W.

2017-01-01

Tyrosine phosphorylation of NR2B (NR2B-pTyr), a subunit of the N-methyl-D-aspartate (NMDA) receptor, has been reported to develop central sensitization and persistent pain in the spine, but its effect in chronic migraines has not been examined. We hypothesized that tyrosine phosphorylation of NR2B contributes to chronic migraines (CM) through calcitonin gene-related peptide (CGRP) in rats. Ninety-four male Sprague-Dawley rats were subjected to seven inflammatory soup (IS) injections. In a subset of animals, the time course and location of NR2B tyrosine phosphorylation were detected by western blot and immunofluorescence double staining. Another set of animals were given either genistein, vehicle, or genistein and recombinant CGRP. The mechanical threshold was measured, the expressions of NR2B-pTyr, NR2B, and CGRP were quantified using western blot, and nitric oxide (NO) was measured with the nitric acid reductase method. NR2B-pTyr expression, in neurons, peaked at 24 hours after CM. Genistein improved the mechanical threshold and reduced migraine attacks 24 and 72 hours after CM. Tyrosine phosphorylation of NR2B decreased the mechanical threshold and increased migraine attacks via upregulated CGRP expression in the rat model of CM. Thus, tyrosine phosphorylation of NR2B may be a potential therapeutic target for treatment of CM. PMID:28393079

Tyrosine Phosphorylation of NR2B Contributes to Chronic Migraines via Increased Expression of CGRP in Rats.

PubMed

Liang, Xiping; Wang, Sha; Qin, Guangcheng; Xie, Jingmei; Tan, Ge; Zhou, Jiying; McBride, Devin W; Chen, Lixue

2017-01-01

Tyrosine phosphorylation of NR2B (NR2B-pTyr), a subunit of the N-methyl-D-aspartate (NMDA) receptor, has been reported to develop central sensitization and persistent pain in the spine, but its effect in chronic migraines has not been examined. We hypothesized that tyrosine phosphorylation of NR2B contributes to chronic migraines (CM) through calcitonin gene-related peptide (CGRP) in rats. Ninety-four male Sprague-Dawley rats were subjected to seven inflammatory soup (IS) injections. In a subset of animals, the time course and location of NR2B tyrosine phosphorylation were detected by western blot and immunofluorescence double staining. Another set of animals were given either genistein, vehicle, or genistein and recombinant CGRP. The mechanical threshold was measured, the expressions of NR2B-pTyr, NR2B, and CGRP were quantified using western blot, and nitric oxide (NO) was measured with the nitric acid reductase method. NR2B-pTyr expression, in neurons, peaked at 24 hours after CM. Genistein improved the mechanical threshold and reduced migraine attacks 24 and 72 hours after CM. Tyrosine phosphorylation of NR2B decreased the mechanical threshold and increased migraine attacks via upregulated CGRP expression in the rat model of CM. Thus, tyrosine phosphorylation of NR2B may be a potential therapeutic target for treatment of CM.

nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation.

PubMed

Chen, Sijie; Zhang, Hefei; Wang, Fenghua; Zhang, Wei; Peng, Gang

2016-09-15

Sex determinations are diverse in vertebrates. Although many sex-determining genes and pathways are conserved, the mechanistic roles of these genes and pathways in the genetic sex determination are not well understood. DAX1 (encoded by the NR0B1 gene) is a vertebrate specific orphan nuclear receptor that regulates gonadal development and sexual determination. In human, duplication of the NR0B1 gene leads to male-to-female sex reversal. In mice, Nr0b1 shows both pro-testis and anti-testis functions. We generated inheritable nr0b1 mutation in the zebrafish and found the nr0b1 mutation caused homozygous mutants to develop as fertile males due to female-to-male sex reversal. The nr0b1 mutation did not increase Caspase-3 labeling nor tp53 expression in the developing gonads. Introduction of a tp53 mutation into the nr0b1 mutant did not rescue the sex-reversal phenotype. Further examination revealed reduction in cell proliferation and abnormal somatic cell differentiation in the nr0b1 mutant gonads at the undifferentiated and bi-potential ovary stages. Together, our results suggest nr0b1 regulates somatic cell differentiation and cell proliferation to ensure normal sex development in the zebrafish. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

H-Ras Modulates N-Methyl-d-aspartate Receptor Function via Inhibition of Src Tyrosine Kinase Activity*

PubMed Central

Thornton, Claire; Yaka, Rami; Dinh, Son; Ron, Dorit

2005-01-01

Tyrosine phosphorylation of the NR2A and NR2B subunits of the N-methyl-d-aspartate (NMDA) receptor by Src protein-tyrosine kinases modulates receptor channel activity and is necessary for the induction of long term potentiation (LTP). Deletion of H-Ras increases both NR2 tyrosine phosphorylation and NMDA receptor-mediated hippocampal LTP. Here we investigated whether H-Ras regulates phosphorylation and function of the NMDA receptor via Src family protein-tyrosine kinases. We identified Src as a novel H-Ras binding partner. H-Ras bound to Src but not Fyn both in vitro and in brain via the Src kinase domain. Cotransfection of H-Ras and Src inhibited Src activity and decreased NR2A tyrosine phosphorylation. Treatment of rat brain slices with Tat-H-Ras depleted NR2A from the synaptic membrane, decreased endogenous Src activity and NR2A phosphorylation, and decreased the magnitude of hip-pocampal LTP. No change was observed for NR2B. We suggest that H-Ras negatively regulates Src phosphorylation of NR2A and retention of NR2A into the synaptic membrane leading to inhibition of NMDA receptor function. This mechanism is specific for Src and NR2A and has implications for studies in which regulation of NMDA receptor-mediated LTP is important, such as synaptic plasticity, learning, and memory and addiction. PMID:12695509

Regulation of NR4A by nutritional status, gender, postnatal development and hormonal deficiency

PubMed Central

Pérez-Sieira, S.; López, M.; Nogueiras, R.; Tovar, S.

2014-01-01

The NR4A is a subfamily of the orphan nuclear receptors (NR) superfamily constituted by three well characterized members: Nur77 (NR4A1), Nurr1 (NR4A2) and Nor 1 (NR4A3). They are implicated in numerous biological processes as DNA repair, arteriosclerosis, cell apoptosis, carcinogenesis and metabolism. Several studies have demonstrated the role of this subfamily on glucose metabolism, insulin sensitivity and energy balance. These studies have focused mainly in liver and skeletal muscle. However, its potential role in white adipose tissue (WAT), one of the most important tissues involved in the regulation of energy homeostasis, is not well-studied. The aim of this work was to elucidate the regulation of NR4A in WAT under different physiological and pathophysiological settings involved in energy balance such as fasting, postnatal development, gender, hormonal deficiency and pregnancy. We compared NR4A mRNA expression of Nur77, Nurr1 and Nor 1 and found a clear regulation by nutritional status, since the expression of the 3 isoforms is increased after fasting in a leptin-independent manner and sex steroid hormones also modulate NR4A expression in males and females. Our findings indicate that NR4A are regulated by different physiological and pathophysiological settings known to be associated with marked alterations in glucose metabolism and energy status. PMID:24584059

Molecular cloning, expression analysis and transcript localization of testicular orphan nuclear receptor 2 in the male catfish, Clarias batrachus.

PubMed

Murugananthkumar, R; Akhila, M V; Rajakumar, A; Mamta, S K; Sudhakumari, C C; Senthilkumaran, B

2016-12-01

Testicular receptor 2 (TR2; also known as Nr2c1) is one of the first orphan nuclear receptors identified and known to regulate various physiological process with or without any ligand. In this study, we report the cloning of full length nr2c1 and its expression analysis during gonadal development, seasonal testicular cycle and after human chorionic gonadotropin (hCG) induction. In addition, in situ hybridization (ISH) was performed to localize nr2c1 transcripts in adult testis and whole catfish (1day post hatch). Tissue distribution and gonadal ontogeny studies revealed high expression of nr2c1 in developing and adult testis. Early embryonic stage-wise expression of nr2c1 seems to emphasize its importance in cellular differentiation and development. Substantial expression of nr2c1 during pre-spawning phase and localization of nr2c1 transcripts in sperm/spermatids were observed. Significant upregulation after hCG induction indicate that nr2c1 is under the regulation of gonadotropins. Whole mount ISH analysis displayed nr2c1 expression in notochord indicating its role in normal vertebrate development. Taken together, our findings suggest that nr2c1 may have a plausible role in the testicular and embryonic development of catfish. Copyright © 2015. Published by Elsevier Inc.

6-Mercaptopurine augments glucose transport activity in skeletal muscle cells in part via a mechanism dependent upon orphan nuclear receptor NR4A3

PubMed Central

Zhu, Xiaolin; Xu, Lusheng; Fu, Yuchang; Garvey, W. Timothy

2013-01-01

The purine anti-metabolite 6-mercaptopurine (6-MP) is widely used for the treatment of leukemia and inflammatory diseases. The cellular effects of 6-MP on metabolism remain unknown; however, 6-MP was recently found to activate the orphan nuclear receptor NR4A3 in skeletal muscle cell lines. We have reported previously that NR4A3 (also known as NOR-1, MINOR) is a positive regulator of insulin sensitivity in adipocytes. To further explore the role of NR4A3 activation in insulin action, we explored whether 6-MP activation of NR4A3 could modulate glucose transport system activity in L6 skeletal muscle cells. We found that 6-MP increased both NR4A3 expression and NR4A3 transcriptional activity and enhanced glucose transport activity via increasing GLUT4 translocation in both basal and insulin-stimulated L6 cells in an NR4A3-dependent manner. Furthermore, 6-MP increased levels of phospho-AS160, although this effect was not modulated by NR4A3 overexpression or knockdown. These primary findings provide a novel proof of principle that 6-MP, a small molecule NR4A3 agonist, can augment glucose uptake in insulin target cells, although this occurs via both NR4A3-dependent and -independent actions; the latter is related to an increase in phospho-AS160. These results establish a novel target for development of new treatments for insulin resistance. PMID:24022864

6-Mercaptopurine augments glucose transport activity in skeletal muscle cells in part via a mechanism dependent upon orphan nuclear receptor NR4A3.

PubMed

Liu, Qinglan; Zhu, Xiaolin; Xu, Lusheng; Fu, Yuchang; Garvey, W Timothy

2013-11-01

The purine anti-metabolite 6-mercaptopurine (6-MP) is widely used for the treatment of leukemia and inflammatory diseases. The cellular effects of 6-MP on metabolism remain unknown; however, 6-MP was recently found to activate the orphan nuclear receptor NR4A3 in skeletal muscle cell lines. We have reported previously that NR4A3 (also known as NOR-1, MINOR) is a positive regulator of insulin sensitivity in adipocytes. To further explore the role of NR4A3 activation in insulin action, we explored whether 6-MP activation of NR4A3 could modulate glucose transport system activity in L6 skeletal muscle cells. We found that 6-MP increased both NR4A3 expression and NR4A3 transcriptional activity and enhanced glucose transport activity via increasing GLUT4 translocation in both basal and insulin-stimulated L6 cells in an NR4A3-dependent manner. Furthermore, 6-MP increased levels of phospho-AS160, although this effect was not modulated by NR4A3 overexpression or knockdown. These primary findings provide a novel proof of principle that 6-MP, a small molecule NR4A3 agonist, can augment glucose uptake in insulin target cells, although this occurs via both NR4A3-dependent and -independent actions; the latter is related to an increase in phospho-AS160. These results establish a novel target for development of new treatments for insulin resistance.

Negative refraction in metamaterials based on dielectric spherical particles

NASA Astrophysics Data System (ADS)

Huang, T. C.; Wang, B. X.; Zhao, C. Y.

2018-07-01

Negative refraction (NR) metamaterials are featured with unique physical properties and potential to realize full control of electromagnetic waves, which have attracted much attention since the last decade. However, few researches focus on the realization of three-dimensional dielectric NR metamaterials in optic frequency, and the current design methods need further development. In this paper, a three-dimensional all-dielectric NR metamaterial with two NR bands has been realized based on proper excitation of electric and magnetic multipoles. It is also predicted that the coupling of magnetic dipole and electric dipole can lead to the NR bands in near-infrared frequencies, and NR in the visible frequencies can be achieved by the coupling of magnetic quadrupole and electric dipole. Band structures and equal-frequency surfaces of proposed metamaterial arranged in the periodic cubic lattice are solved by adopting the plane wave expansion method, and then the results verify the existence of these two NR frequency bands in periodic metamaterials. In this way, the characteristic parameters such as transmission and absorption of light in two NR bands are also analyzed. In the meantime, the finite-deference time-domain method is used to intuitively display the phenomenon of NR and investigate the effects of disorder in particle arrangement. Besides, it is found that the proposed metamaterials have fine robustness to the disorder in particle arrangement, and these two NR bands can be tuned by adjusting volume fraction. In brief, this work provides means for preliminary designing, profound analysis and intuitively exhibition of NR metamaterials based on dielectric particles.

Management of Excess Reactive Nitrogen in the Environment

NASA Astrophysics Data System (ADS)

Galloway, J. N.; Theis, T.; Doering, O.

2011-12-01

Managing the impacts of excessive reactive nitrogen (Nr) in the environment is a complex problem that begins with the recognition of the obligate dietary need for Nr by all living populations. The human solution to this need has been to devise ways to bring Nr into the biosphere (via the Haber-Bosch process) to grow food. Other Nr is created as a by-product of fossil-fuel combustion. The net result is the introduction of more than five times the Nr created by natural processes in the U.S., only a fraction of which is converted back to diatomic nitrogen through denitrification. This presentation summarizes findings and recommendations of the newly-released US EPA Science Advisory Board's Integrated Nitrogen Committee report, "Reactive Nitrogen in the United States: An Analysis of Flows, Consequences, and Management Options", that deal specifically with approaches for solving the excess Nr problem. These can be grouped into four general areas: (1) Recognition of the Problem. Until there is recognition that excess Nr is a serious problem with economic, health, and societal consequences, there will be little willingness to expend resources on this issue. Education, communication and outreach are critically important to engender in regulators, and the public at large, sufficient will to undertake the large scale effort needed to reduce Nr in the environment. (2) Development of Integrated Regulatory Approaches. Given what is known about the way Nr behaves, efforts to deal with excess Nr must be organized in a way that reflects the nature of the problem. Unfortunately, most approaches tend to conceive of Nr issues within a narrowly focused disciplinary model, and our policy and regulatory institutions are often bound by enabling legislation that stresses source-by-source, chemical-by-chemical, and media-by-media. The resulting regulatory structure that has evolved for problems such as Nr that affect human health and the environment is apt to miss the complex nature of the problem. Such silos have to be broken down if the excess Nr problem is to be dealt with holistically. (3) Essential Monitoring and Research. The Committee recommends improved monitoring and research to enhance our understanding of Nr in the environment. In some cases our knowledge has such wide margins of error that we cannot identify or quantify important concentrations or flows sufficiently for necessary decisions. In other cases there is incomplete knowledge about the indirect impacts of Nr, while in still others there is a need for much better understanding of the efficacy of actions that might be taken to control Nr. (4) Setting Goals for Action. In spite of knowledge gaps identified by the Committee, there is sufficient understanding of the Nr problem to enable the responsible regulatory agencies to begin to decrease excess Nr entering the environment. The Committee suggests actions that might be taken by EPA or other management authorities using current technologies and regulatory authority to decrease Nr in the environment by 25% over the near (10-20 year) term, without negatively impacting dietary needs or economic trends.

Turbomachinery Design Using CFD (La Conception des Turbomachines par l’Aerodynamique Numerique).

DTIC Science & Technology

1994-05-01

Method for Flow Calculations in Turbomachines", Vrije Thompkins, W.T.,1981, "A Fortran Program for Calcu- Univ.Brussel, Dienst Stromingsmechanica, VUB- STR ...Model Equation for Simulating Flows in mung um Profile Multistage Turbomachinery MBB-Bericht Nr. UFE 1352, 1977 ASME paper 85-GT-226, Houston, March

Petrogenesis of Near-Ridge Seamounts: AN Investigation of Mantle Source Heterogeneity and Melting Processes

NASA Astrophysics Data System (ADS)

Baxter, N. L.; Perfit, M. R.; Lundstrom, C.; Clague, D. A.

2010-12-01

Near-ridge (NR) seamounts offer an important opportunity to study lavas that have similar sources to ridge basalts but have been less affected by fractionation and homogenization that takes place at adjacent spreading ridge axes. By studying lavas erupted at these off-axis sites, we have the potential to better understand source heterogeneity and melting and transport processes that can be applied to the ridge system as a whole. One purpose of our study is to investigate the role of dunite conduits in the formation of near-ridge seamount chains. We believe that near-ridge seamounts could form due to focusing of melts in dunite channels located slightly off-axis and that such conduits may be important in the formation and transport of melt both on- and off-axis (Lundstrom et al., 2000). New trace element and isotopic analyses of glasses from Rogue, Hacksaw, and T461 seamounts near the Juan de Fuca Ridge (JdFR), the Lamont Seamounts adjacent to the East Pacific Rise (EPR) ~ 10°N, and the Vance Seamounts next to the JdFR ~45°N provide a better understanding of the petrogenesis of NR seamounts. Our data indicate that lavas from these seamounts have diverse incompatible trace element compositions that range from highly depleted to slightly enriched in comparison to associated ridge basalts. Vance A lavas (the oldest in the Vance chain) have the most enriched signatures and lavas from Rogue seamount on the JdFR plate have the most depleted signatures. Sr-Nd-Pb isotopic ratios indicate that NR seamount lava compositions vary within the chains as well as within individual seamounts, and that there is some mixing between heterogeneous, small-scale mantle sources. Using the program PRIMELT2.XLS (Herzberg and Asimow, 2008), we calculated mantle potential temperatures (Tp) for some of the most primitive basalts erupted at these seamounts. Our data indicate that NR seamount lavas have Tp values that are only slightly higher than that of average ambient mantle. Variations in major and trace elements along with geochemical modeling suggest a heterogeneous mantle source that melts to different extents. Shallow level crystal fractionation and mixing cannot explain the geochemical diversity found at NR seamounts. We are using the modeling programs MELTS (Ghiorso et al., 2002) and IRIDIUM (Boudreau, 2003) to model processes hypothesized to form dunite conduits (dissolution of pyroxenes and precipitation of olivine), to evaluate if these dissolution/precipitation processes can produce some of the geochemical diversity observed at these seamounts.

MC1R, KIT, IGF2, and NR6A1 as markers for genetic differentiation in Thai native, wild boars, and Duroc and Chinese Meishan pigs.

PubMed

Klomtong, P; Chaweewan, K; Phasuk, Y; Duangjinda, M

2015-10-19

Mutations in melanocortin 1 receptor (MC1R) gene and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) gene have been shown to affect coat color patterns in pigs. Additional functional marker genes, such as insulin like growth factor-2 (IGF2) and orphan nuclear receptor, germ cell nuclear factor (NR6A1), have been described for variations in factors such as fat deposition, litter size, and vertebra number in pigs. In this study, we investigated 129 pigs representing 4 breeds: Thai indigenous, classified into black (similar to Raad or Ka done pig) and black and white (similar to the Hailum and Kwai pig) coat color types; wild boar; Duroc; and Chinese Meishan. Mutations of MC1R, KIT, IGF2, and NR6A1 were detected using polymerase chain reaction-restriction fragment length polymorphism. The genotypes variation in MC1R and KIT genes could be used to differentiate four groups of coat color: solid black, black and white, red, and wild type. For IGF2, the GG genotype was present in wild boar only; for NR6A1 the TT genotype was found only in Duroc pigs. We identified novel 14-bp deletions in KIT that were associated with black and white coat color in Thai indigenous pigs. Insights into variations in genes presented in this study will be useful in future developmental breeding programs for the Thai native pig.

Exploring the Best Practices of Nursing Research Councils in Magnet® Organizations: Findings From a Qualitative Research Study.

PubMed

Day, Jennifer; Lindauer, Cathleen; Parks, Joyce; Scala, Elizabeth

2017-05-01

The objective of this descriptive qualitative study was to identify best practices of nursing research councils (NRCs) at Magnet®-designated hospitals. Nursing research (NR) is essential, adding to the body of nursing knowledge. Applying NR to the bedside improves care, enhances patient safety, and is an imperative for nursing leaders. We interviewed NR designees at 26 Magnet-recognized hospitals about the structure and function of their NRCs and used structural coding to identify best practices. Most organizations link NR and evidence-based practice. Council membership includes leadership and clinical nurses. Councils conduct scientific reviews for nursing studies, supporting nurse principal investigators. Tracking and reporting of NR vary widely and are challenging. Councils provide education, sponsor research days, and collaborate interprofessionally, including with academic partners. Findings from this study demonstrate the need to create formal processes to track and report NR and to develop outcome-focused NR education.

Mapping loading rates and sources of reactive nitrogen across the United States suggests regional interactions with climate change

EPA Science Inventory

Accurate, up-to-date information describing Nr inputs by source is needed for effective Nr management and for guiding Nr research. Here we present a new synthesis of spatial data describing present Nr inputs to terrestrial and aquatic ecosystems across the conterminous US to hel...

Memory Enhancement by Targeting Cdk5 Regulation of NR2B

PubMed Central

Plattner, Florian; Hernandéz, Adan; Kistler, Tara M.; Pozo, Karine; Zhong, Ping; Yuen, Eunice Y.; Tan, Chunfeng; Hawasli, Ammar H.; Cooke, Sam F.; Nishi, Akinori; Guo, Ailan; Wiederhold, Thorsten; Yan, Zhen; Bibb, James A.

2014-01-01

SUMMARY Many psychiatric and neurological disorders are characterized by learning and memory deficits, for which cognitive enhancement is considered a valid treatment strategy. The N-methyl-D-aspartate receptor (NMDAR) is a prime target for the development of cognitive enhancers due to its fundamental role in learning and memory. In particular, the NMDAR subunit NR2B improves synaptic plasticity and memory when over-expressed in neurons. However, NR2B regulation is not well understood and no therapies potentiating NMDAR function have been developed. Here, we show that serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5). Cdk5-dependent NR2B phosphorylation is regulated by neuronal activity and controls the receptor’s cell surface expression. Disrupting NR2B-Cdk5 interaction using a small interfering peptide (siP) increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation in vivo. Our results reveal a novel regulatory mechanism critical to NR2B function that can be targeted for the development of cognitive enhancers. PMID:24607229

Spontaneous modification of carbon surface with neutral red from its diazonium salts for bioelectrochemical systems.

PubMed

Guo, Kun; Chen, Xin; Freguia, Stefano; Donose, Bogdan C

2013-09-15

This study introduces a novel and simple method to covalently graft neutral red (NR) onto carbon surfaces based on spontaneous reduction of in situ generated NR diazonium salts. Immobilization of neutral red on carbon surface was achieved by immersing carbon electrodes in NR-NaNO2-HCl solution. The functionalized electrodes were characterized by cyclic voltammetry (CV), atomic force microscope (AFM), and X-ray photoelectron spectroscopy (XPS). Results demonstrated that NR attached in this way retains high electrochemical activity and proved that NR was covalently bound to the carbon surface via the pathway of reduction of aryl diazonium salts. The NR-modified electrodes showed a good stability when stored in PBS solution in the dark. The current output of an acetate-oxidising microbial bioanode made of NR-modified graphite felts were 3.63±0.36 times higher than the unmodified electrodes, which indicates that covalently bound NR can act as electron transfer mediator to facilitate electron transfer from bacteria to electrodes. Copyright © 2013 Elsevier B.V. All rights reserved.

Identification of Ser-543 as the major regulatory phosphorylation site in spinach leaf nitrate reductase

NASA Technical Reports Server (NTRS)

Bachmann, M.; Shiraishi, N.; Campbell, W. H.; Yoo, B. C.; Harmon, A. C.; Huber, S. C.; Davies, E. (Principal Investigator)

1996-01-01

Spinach leaf NADH:nitrate reductase (NR) responds to light/dark signals and photosynthetic activity in part as a result of rapid regulation by reversible protein phosphorylation. We have identified the major regulatory phosphorylation site as Ser-543, which is located in the hinge 1 region connecting the cytochrome b domain with the molybdenum-pterin cofactor binding domain of NR, using recombinant NR fragments containing or lacking the phosphorylation site sequence. Studies with NR partial reactions indicated that the block in electron flow caused by phosphorylation also could be localized to the hinge 1 region. A synthetic peptide (NR6) based on the phosphorylation site sequence was phosphorylated readily by NR kinase (NRk) in vitro. NR6 kinase activity tracked the ATP-dependent inactivation of NR during several chromatographic steps and completely inhibited inactivation/phosphorylation of native NR in vitro. Two forms of NRk were resolved by using anion exchange chromatography. Studies with synthetic peptide analogs indicated that both forms of NRk had similar specificity determinants, requiring a basic residue at P-3 (i.e., three amino acids N-terminal to the phosphorylated serine) and a hydrophobic residue at P-5. Both forms are strictly calcium dependent but belong to distinct families of protein kinases because they are distinct immunochemically.

Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration.

PubMed

Vaur, Pauline; Brugg, Bernard; Mericskay, Mathias; Li, Zhenlin; Schmidt, Mark S; Vivien, Denis; Orset, Cyrille; Jacotot, Etienne; Brenner, Charles; Duplus, Eric

2017-12-01

NAD + depletion is a common phenomenon in neurodegenerative pathologies. Excitotoxicity occurs in multiple neurologic disorders and NAD + was shown to prevent neuronal degeneration in this process through mechanisms that remained to be determined. The activity of nicotinamide riboside (NR) in neuroprotective models and the recent description of extracellular conversion of NAD + to NR prompted us to probe the effects of NAD + and NR in protection against excitotoxicity. Here, we show that intracortical administration of NR but not NAD + reduces brain damage induced by NMDA injection. Using cortical neurons, we found that provision of extracellular NR delays NMDA-induced axonal degeneration (AxD) much more strongly than extracellular NAD + Moreover, the stronger effect of NR compared to NAD + depends of axonal stress since in AxD induced by pharmacological inhibition of nicotinamide salvage, both NAD + and NR prevent neuronal death and AxD in a manner that depends on internalization of NR. Taken together, our findings demonstrate that NR is a better neuroprotective agent than NAD + in excitotoxicity-induced AxD and that axonal protection involves defending intracellular NAD + homeostasis.-Vaur, P., Brugg, B., Mericskay, M., Li, Z., Schmidt, M. S., Vivien, D., Orset, C., Jacotot, E., Brenner, C., Duplus, E. Nicotinamide riboside, a form of vitamin B 3 , protects against excitotoxicity-induced axonal degeneration. © FASEB.

A reduced graphene oxide-based fluorescence resonance energy transfer sensor for highly sensitive detection of matrix metalloproteinase 2.

PubMed

Xi, Gaina; Wang, Xiaoping; Chen, Tongsheng

2016-01-01

A novel fluorescence nanoprobe (reduced nano-graphene oxide [nrGO]/fluorescein isothiocyanate-labeled peptide [Pep-FITC]) for ultrasensitive detection of matrix metalloproteinase 2 (MMP2) has been developed by engineering the Pep-FITC comprising the specific MMP2 substrate domain (PLGVR) onto the surface of nrGO particles through non-covalent linkage. The nrGO was obtained by water bathing nano-graphene oxide under 90°C for 4 hours. After mixing the nrGO and Pep-FITC for 30 seconds, the fluorescence from Pep-FITC was almost completely quenched due to the fluorescence resonance energy transfer between fluorescein isothiocyanate (FITC) and nrGO. Upon cleavage of the amide bond between Leu and Gly in the Pep-FITC by protease-MMP2, the FITC bound to nrGO was separated from nrGO surface, disrupting the fluorescence resonance energy transfer process and resulting in fluorescence recovery of FITC. Under optimal conditions, the fluorescence recovery of nrGO/Pep-FITC was found to be directly proportional to the concentration of MMP2 within 0.02-0.1 nM. The detection limit of the nrGO/Pep-FITC was determined to be 3 pM, which is approximately tenfold lower than that of the unreduced carboxylated nano-graphene oxide/Pep-FITC probe.

Broad phenotypes in heterozygous NR5A1 46,XY patients with a disorder of sex development: an oligogenic origin?

PubMed

Camats, Núria; Fernández-Cancio, Mónica; Audí, Laura; Schaller, André; Flück, Christa E

2018-06-11

SF-1/NR5A1 is a transcriptional regulator of adrenal and gonadal development. NR5A1 disease-causing variants cause disorders of sex development (DSD) and adrenal failure, but most affected individuals show a broad DSD/reproductive phenotype only. Most NR5A1 variants show in vitro pathogenic effects, but not when tested in heterozygote state together with wild-type NR5A1 as usually seen in patients. Thus, the genotype-phenotype correlation for NR5A1 variants remains an unsolved question. We analyzed heterozygous 46,XY SF-1/NR5A1 patients by whole exome sequencing and used an algorithm for data analysis based on selected project-specific DSD- and SF-1-related genes. The variants detected were evaluated for their significance in literature, databases and checked in silico using webtools. We identified 19 potentially deleterious variants (one to seven per patient) in 18 genes in four 46,XY DSD subjects carrying heterozygous NR5A1 disease-causing variants. We constructed a scheme of all these hits within the landscape of currently known genes involved in male sex determination and differentiation. Our results suggest that the broad phenotype in these heterozygous NR5A1 46,XY DSD subjects may well be explained by an oligogenic mode of inheritance, in which multiple hits, individually non-deleterious, may contribute to a DSD phenotype unique to each heterozygous SF-1/NR5A1 individual.

Expression Profiling of Nuclear Receptors Identifies Key Roles of NR4A Subfamily in Uterine Fibroids

PubMed Central

Yin, Hanwei; Lo, Jay H.; Kim, Ji-Young; Marsh, Erica E.; Kim, J. Julie; Ghosh, Asish K.; Bulun, Serdar

2013-01-01

Uterine fibroids (UFs), also known as uterine leiomyomas, are benign, fibrotic smooth muscle tumors. Although the GnRH analog leuprolide acetate that suppresses gonadal steroid hormones is used as a treatment, it has significant side effects, thereby limiting its use. Availability of more effective therapy is limited because of a lack of understanding of molecular underpinnings of the disease. Although ovarian steroid hormones estrogen and progesterone and their receptors are clearly involved, the role of other nuclear receptors (NRs) in UFs is not well defined. We used quantitative real-time PCR to systematically profile the expression of 48 NRs and identified several NRs that were aberrantly expressed in UFs. Among others, expression of NR4A subfamily members including NGFIB (NR4A1), NURR1 (NR4A2), and NOR1 (NR4A3) were dramatically suppressed in leiomyoma compared with the matched myometrium. Restoration of expression of each of these NR4A members in the primary leiomyoma smooth muscle cells decreased cell proliferation. Importantly, NR4As regulate expressions of the profibrotic factors including TGFβ3 and SMAD3, and several collagens that are key components of the extracellular matrix. Finally, we identify NR4A members as targets of leuprolide acetate treatment. Together, our results implicate several NRs including the NR4A subfamily in leiomyoma etiology and identify NR4As as potential therapeutic targets for treating fibrotic diseases. PMID:23550059

Perturbing NR2B-PSD-95 interaction relieves neuropathic pain by inactivating CaMKII-CREB signaling.

PubMed

Xu, Fangxia; Zhao, Xin; Liu, Lin; Song, Jia; Zhu, Yingjun; Chu, Shuaishuai; Shao, Xueming; Li, Xiuxiu; Ma, Zhengliang; Gu, Xiaoping

2017-09-06

Neuropathic pain is characterized by central sensitization. The interaction between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein-95 (PSD-95) plays a major role in central sensitization. Here, we aimed to investigate the analgesic effect of disruption of the interaction between NMDAR and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured using western blotting. A mimetic peptide Myr-NR2B9c was injected intrathecally to disrupt the interaction between PSD-95 and NR2B and detected by coimmunoprecipitation. Chronic dorsal root ganglia compression surgery induced thermal hyperalgesia and mechanical allodynia, and upregulated pain-related proteins such as phospho-NR2B, PSD-95, CaMKII, and CREB expressions in the spinal cord. Myr-NR2B9c disrupted the interaction between NR2B-containing NMDARs and PSD-95 in the spinal cord. Intrathecal administration of Myr-NR2B9c attenuated neuropathic pain behaviors and downregulated the expressions of phospho-NR2B, PSD-95, CaMKII, and CREB in the spinal cord. The present study indicates that dissociation of NR2B-containing NMDARs from PSD-95 inactivates CaMKII and CREB signaling and relieves pain.

Bacopa monnieri Extract (CDRI-08) Modulates the NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy Rats

PubMed Central

Mondal, Papia; Trigun, Surendra Kumar

2015-01-01

Hepatic encephalopathy (HE), characterized by impaired cerebellar functions during chronic liver failure (CLF), involves N-methyl-D-aspartate receptor (NMDAR) overactivation in the brain cells. Bacopa monnieri (BM) extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B) and its downstream mediators in cerebellum of rats with chronic liver failure (CLF), induced by administration of 50 mg/kg bw thioacetamide (TAA) i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE. PMID:26413124

Epigenetic silencing of the NR4A3 tumor suppressor, by aberrant JAK/STAT signaling, predicts prognosis in gastric cancer

NASA Astrophysics Data System (ADS)

Yeh, Chung-Min; Chang, Liang-Yu; Lin, Shu-Hui; Chou, Jian-Liang; Hsieh, Hsiao-Yen; Zeng, Li-Han; Chuang, Sheng-Yu; Wang, Hsiao-Wen; Dittner, Claudia; Lin, Cheng-Yu; Lin, Jora M. J.; Huang, Yao-Ting; Ng, Enders K. W.; Cheng, Alfred S. L.; Wu, Shu-Fen; Lin, Jiayuh; Yeh, Kun-Tu; Chan, Michael W. Y.

2016-08-01

While aberrant JAK/STAT signaling is crucial to the development of gastric cancer (GC), its effects on epigenetic alterations of its transcriptional targets remains unclear. In this study, by expression microarrays coupled with bioinformatic analyses, we identified a putative STAT3 target gene, NR4A3 that was downregulated in MKN28 GC daughter cells overexpressing a constitutively activated STAT3 mutant (S16), as compared to an empty vector control (C9). Bisulphite pyrosequencing and demethylation treatment showed that NR4A3 was epigenetically silenced by promoter DNA methylation in S16 and other GC cell lines including AGS cells, showing constitutive activation of STAT3. Subsequent experiments revealed that NR4A3 promoter binding by STAT3 might repress its transcription. Long-term depletion of STAT3 derepressed NR4A3 expression, by promoter demethylation, in AGS GC cells. NR4A3 re-expression in GC cell lines sensitized the cells to cisplatin, and inhibited tumor growth in vitro and in vivo, in an animal model. Clinically, GC patients with high NR4A3 methylation, or lower NR4A3 protein expression, had significantly shorter overall survival. Intriguingly, STAT3 activation significantly associated only with NR4A3 methylation in low-stage patient samples. Taken together, aberrant JAK/STAT3 signaling epigenetically silences a potential tumor suppressor, NR4A3, in gastric cancer, plausibly representing a reliable biomarker for gastric cancer prognosis.

Expression of N-methyl-D-aspartate receptor subunits in the bovine ovum: ova as a potential source of autoantigens causing anti-NMDAR encephalitis.

PubMed

Tachibana, Naoko; Kinoshita, Michiaki; Kametani, Fuyuki; Tanaka, Keiko; Une, Yumi; Komatsu, Yotaro; Kobayashi, Yukihiro; Ikeda, Shu-ichi

2015-03-01

Autoimmune synaptic encephalitis is characterized by the presence of autoantibodies against synaptic constituent receptors and manifests as neurological and psychiatric disorders. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is such an autoimmune disorder that predominantly affects young women. It is associated with antibodies against the extracellular region of the NR1 subunit of postsynaptic NMDAR. Each NMDAR functions as a heterotetrameric complex that is composed of four subunits, including NR1 and NR2A, NR2B, or NR2C. Importantly, ovarian teratoma is a typical complication of anti-NMDAR encephalitis in female patients and may contain antigenic neural tissue; however, antigenic sites remain unknown in female patients without ovarian teratoma. The purpose of this study was to investigate the expression of NMDARs in the ovum. We detected NR1 and NR2B immunoreactivity in protein fractions extracted from the bovine ovary and ova by SDS-polyacrylamide gel electrophoresis and immunoblotting analysis. Immunoprecipitates digested with trypsin were analyzed by reverse phase liquid chromatography coupled to tandem mass spectrometry. We obtained the following five peptides: SPFGRFK and KNLQDR, which are consistent with partial sequences of human NR1, and GVEDALVSLK, QPTVAGAPK, and NEVMSSK, which correspond to those of NR2A, NR2B and NR2C, respectively. Immunocytochemical analysis revealed that the bovine ovum was stained with the immunoglobulin G purified from the serum of a patient with anti-NMDAR encephalitis. Taken together, we propose that the normal ovum expresses NMDARs that have strong affinity for the disease-specific IgG. The presence of NMDARs in ova may help explain why young females without ovarian teratomas are also affected by anti-NMDAR encephalitis.

Highly selective colorimetric and electrochemical sensing of iron (III) using Nile red functionalized graphene film.

PubMed

Sadak, Omer; Sundramoorthy, Ashok K; Gunasekaran, Sundaram

2017-03-15

We report a highly selective method for identification and detection of iron (III) (ferric iron, Fe 3+ ) using Nile red (NR) as a complexing agent. Fe 3+ preferentially binds with NR in dimethylformamide (DMF)/water (1:1) solution over other cations such as Fe 2+ , Cu 2+ , Pb 2+ , Hg 2+ , Mn 2+ , Ni 2+ , Zn 2+ , Co 2+ and Cd 2+ at room temperature. In the presence of Fe 3+ , the color of NR solution changes from purple to dark brown, which is detectable with bare eyes. Using UV-vis spectroscopy, we could measure the amount of Fe 3+ in the sample solution by monitoring changes in absorption from 540 to 580nm; the linear range and the limit of detection are 30-1000µM and 24.9µM, respectively. Taking advantage of the NR selectivity, we treated partially oxidized graphene sheets (po-Gr) with NR to obtain po-Gr-NR dispersion by ultrasonication. The NR-treated po-Gr flakes (po-Gr-NR) were characterized by UV-vis, FT-IR, and Raman spectroscopies and FE-SEM, which indicated attachment of NR on po-Gr sheets. The po-Gr-NR hybrid film deposited glassy carbon electrode (po-Gr-NR/GCE) served as the Fe 3+ sensor. Differential pulse voltammetry was used to investigate the detection of Fe 3+ in 0.05M HCl+0.05M KCl solution. The linear range and the limit of detection of Fe 3+ were from 37.5nM to 21.53µM and 18.7nM, respectively. Furthermore, this sensor was successfully used to measure Fe 3+ content in red wine samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanical properties, morphology, and hydrolytic degradation behavior of polylactic acid / natural rubber blends

NASA Astrophysics Data System (ADS)

Buys, Y. F.; Aznan, A. N. A.; Anuar, H.

2018-01-01

Due to its biodegradability and renewability, polylactic acid (PLA) has been receiving enormous attention as a potential candidate to replace petroleum based polymers. However, PLA has limitation due to its inherent brittleness. In order to overcome this limitation, blending PLA with elastomeric materials such as natural rubber (NR) are commonly reported. In previous, several researches on PLA/NR blend had been reported, with most of them evaluated the mechanical properties. On the other hand, study of degradation behavior is significance of importance, as controlling materials degradation is required in some applications. This research studied the effect of blend composition on mechanical properties, morphology development, and hydrolytic degradation behavior of PLA/NR blends. Various compositions of PLA/NR blends were prepared by melt blending technique. Tensile test and impact test of the blends were performed to evaluate the mechanical properties. Addition of NR improved the elongation at break and impact strength of the blends, but reduced the tensile strength and stiffness of the specimens. Dynamic Mechanical Analysis (DMA) measurements of the blends displayed two peaks at temperature -70˚C which corresponded to T g of NR and 65˚C which corresponded to T g of PLA. Field Emission Scanning Electron Microscopy (FE-SEM) micrograph of 70/30 PLA/NR specimen also showed two distinct phases, which lead to indication that PLA/NR blends are immiscible. Hydrolytic degradation behavior was evaluated by measuring the remaining weight of the samples immersed in sodium hydroxide solution for a predetermined times. It was shown that the degradation behavior of PLA/NR blends is affected by composition of the blends, with 100 PLA and 70/30 PLA/NR blend showed the fastest degradation rate and 100 NR displayed the slowest one.

Altered Levels of Zinc and N-methyl-D-aspartic Acid Receptor Underlying Multiple Organ Dysfunctions After Severe Trauma

PubMed Central

Wang, Guanghuan; Yu, Xiaojun; Wang, Dian; Xu, Xiaohu; Chen, Guang; Jiang, Xuewu

2015-01-01

Background Severe trauma can cause secondary multiple organ dysfunction syndrome (MODS) and death. Oxidative stress and/or excitatory neurotoxicity are considered as the final common pathway in nerve cell injuries. Zinc is the cofactor of the redox enzyme, and the effect of the excitatory neurotoxicity is related to N-methyl-D-aspartic acid receptor (NMDAR). Material/Methods We investigated the levels of zinc and brainstem NMDAR in a rabbit model of severe trauma. Zinc and serum biochemical profiles were determined. Immunohistochemistry was used to detect brainstem N-methyl-D-aspartic acid receptor 1 (NR1), N-methyl-D-aspartic acid receptor 2A (NR2A), and N-methyl-D-aspartic acid receptor 2B (NR2B) expression. Results Brain and brainstem Zn levels increased at 12 h, but serum Zn decreased dramatically after the trauma. NR1 in the brainstem dorsal regions increased at 6 h after injury and then decreased. NR2A in the dorsal regions decreased to a plateau at 12 h after trauma. The levels of NR2B were lowest in the death group in the brainstem. Serum zinc was positively correlated with NR2A and 2B and negatively correlated with zinc in the brain. Correlations were also found between the brainstem NR2A and that of the dorsal brainstem, as well as between brainstem NR2A and changes in NR2B. There was a negative correlation between zinc and NR2A. Conclusions Severe trauma led to an acute reduction of zinc enhancing oxidative stress and the changes of NMDAR causing the neurotoxicity of the nerve cells. This may be a mechanism for the occurrence of MODS or death after trauma. PMID:26335029

Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes.

PubMed

Lee, Hee Jae; Hong, Young-Shick; Jun, Woojin; Yang, Soo Jin

2015-11-01

Low-grade chronic inflammation (metaflammation) is a major contributing factor for the onset and development of metabolic diseases, such as type 2 diabetes, obesity, and cardiovascular disease. Nicotinamide riboside (NR), which is present in milk and beer, is a functional vitamin B3 having advantageous effects on metabolic regulation. However, the anti-inflammatory capacity of NR is unknown. This study evaluated whether NR modulates hepatic nucleotide binding and oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Male, 8-week-old KK/HlJ mice were allocated to the control or NR group. NR (100 mg/kg/day) or vehicle (phosphate-buffered saline) was administrated by an osmotic pump for 7 days. Glucose control, lipid profiles, NLRP3 inflammasome, and inflammation markers were analyzed, and structural and histological analyses were conducted. NR treatment did not affect body weight gain, food intake, and liver function. Glucose control based on the oral glucose tolerance test and levels of serum insulin and adiponectin was improved by NR treatment. Among tested lipid profiles, NR lowered the total cholesterol concentration in the liver. Histological and structural analysis by hematoxylin and eosin staining and transmission electron microscopy, respectively, showed that NR rescued the disrupted cellular integrity of the mitochondria and nucleus in the livers of obese and diabetic KK mice. In addition, NR treatment significantly improved hepatic proinflammatory markers, including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1. These ameliorations were accompanied by significant shifts of NLRP3 inflammasome components (NLRP3, ASC, and caspase1). These results demonstrate that NR attenuates hepatic metaflammation by modulating the NLRP3 inflammasome.

The orphan nuclear receptor NR4A1 attenuates oxidative stress-induced β cells apoptosis via up-regulation of glutathione peroxidase 1.

PubMed

Yang, Yingfeng; Xie, Fangyu; Qin, Dandan; Zong, Chen; Han, Feng; Pu, Zeqing; Liu, Dong; Li, Xia; Zhang, Yuchao; Liu, Yuantao; Wang, Xiangdong

2018-06-15

Our previous study showed that NR4A1 protects against oxidative stress-induced cell apoptosis. However, the targets downstream of NR4A1 are incompletely known. Glutathione peroxidase 1 (GPX1) is the most common antioxidant enzyme in the glutathione peroxidase class. In this study, we aimed to investigate whether GPX1 is a mediator of the protective effects of NR4A1 in pancreatic β cells. A pancreatic β cell line, MIN6, was used to generate NR4A1 over-expression cell line. GPX1 expression and GPX1 promoter trans-activation in these cells was determined. These cells were then treated with H 2 O 2 , and the active caspase3 level was determined. NR4A1 over-expression in MIN6 cells resulted in increased GPX1 expression at both mRNA and protein levels. Dual luciferase assay showed that NR4A1 over-expression was able to enhance the trans-activation of GPX1 promoter, and the critical regulatory elements were narrowed down between 0 to -2000 bp in GPX1 promoter with a putative NR4A1 binding site (-273 to -268). ChIP assays demonstrated that NR4A1 physically associates with the GPX1 promoter. Over-expression of GPX1 reduced the active level of Caspase3 after H 2 O 2 treatment. NR4A1 increases the expression of GPX1 by enhancing the trans-activation of GPX1 promoter through binding to the putative binding site on GPX1 promoter. NR4A1 potentially protects pancreatic β cells against oxidative stress-induced apoptosis by increasing GPX1 expression. Copyright © 2018 Elsevier Inc. All rights reserved.

Mice with subtle reduction of NMDA NR1 receptor subunit expression have a selective decrease in mismatch negativity: Implications for schizophrenia prodromal population.

PubMed

Featherstone, Robert E; Shin, Rick; Kogan, Jeffrey H; Liang, Yuling; Matsumoto, Mitsuyuki; Siegel, Steven J

2015-01-01

Reductions in glutamate function are regarded as an important contributory factor in schizophrenia. However, there is a paucity of animal models characterized by developmental and sustained reductions in glutamate function. Pharmacological models using NMDA antagonists have been widely used but these typically produce only transient changes in behavior and brain function. Likewise, mice with homozygous constitutive reductions in glutamate receptor expression show stable brain and behavioral changes, but many of these phenotypes are more severe than the human disease. The current study examines a variety of schizophrenia-related EEG measures in mice with a heterozygous alteration of the NMDA receptor NR1 subunit gene (NR1) that is known to result in reduced NR1 receptor expression in the homozygous mouse (NR1-/-). (NR1+/-) mice showed a 30% reduction in NR1 receptor expression and were reared after weaning in either group or isolated conditions. Outcome measures include the response to paired white noise stimuli, escalating inter-stimulus intervals (ISIs) and deviance-related mismatch negativity (MMN). In contrast to what has been reported in (NR1-/-) mice and mice treated with NMDA antagonists, (NR1+/-) mice showed no change on obligatory Event Related Potential (ERP) measures including the murine P50 and N100 equivalents (P20 and N40), or measures of baseline or evoked gamma power. Alternatively, (NR1+/-) mice showed a marked reduction in response to a deviant auditory tone during MMN task. Data suggest that EEG response to deviant, rather than static, stimuli may be more sensitive for detecting subtle changes in glutamate function. Deficits in these heterozygous NR1 knockdown mice are consistent with data demonstrating MMN deficits among family members of schizophrenia patients and among prodromal patients. Therefore, the current study suggests that (NR1+/-) mice may be among the most sensitive models for increased vulnerability to schizophrenia. Copyright © 2015. Published by Elsevier Inc.

Genome-wide identification of nuclear receptor (NR) superfamily genes in the copepod Tigriopus japonicus.

PubMed

Hwang, Dae-Sik; Lee, Bo-Young; Kim, Hui-Su; Lee, Min Chul; Kyung, Do-Hyun; Om, Ae-Son; Rhee, Jae-Sung; Lee, Jae-Seong

2014-11-18

Nuclear receptors (NRs) are a large superfamily of proteins defined by a DNA-binding domain (DBD) and a ligand-binding domain (LBD). They function as transcriptional regulators to control expression of genes involved in development, homeostasis, and metabolism. The number of NRs differs from species to species, because of gene duplications and/or lineage-specific gene losses during metazoan evolution. Many NRs in arthropods interact with the ecdysteroid hormone and are involved in ecdysone-mediated signaling in arthropods. The nuclear receptor superfamily complement has been reported in several arthropods, including crustaceans, but not in copepods. We identified the entire NR repertoire of the copepod Tigriopus japonicus, which is an important marine model species for ecotoxicology and environmental genomics. Using whole genome and transcriptome sequences, we identified a total of 31 nuclear receptors in the genome of T. japonicus. Nomenclature of the nuclear receptors was determined based on the sequence similarities of the DNA-binding domain (DBD) and ligand-binding domain (LBD). The 7 subfamilies of NRs separate into five major clades (subfamilies NR1, NR2, NR3, NR4, and NR5/6). Although the repertoire of NR members in, T. japonicus was similar to that reported for other arthropods, there was an expansion of the NR1 subfamily in Tigriopus japonicus. The twelve unique nuclear receptors identified in T. japonicus are members of NR1L. This expansion may be a unique lineage-specific feature of crustaceans. Interestingly, E78 and HR83, which are present in other arthropods, were absent from the genomes of T. japonicus and two congeneric copepod species (T. japonicus and Tigriopus californicus), suggesting copepod lineage-specific gene loss. We identified all NR receptors present in the copepod, T. japonicus. Knowledge of the copepod nuclear receptor repertoire will contribute to a better understanding of copepod- and crustacean-specific NR evolution.

The USA Nr Inventory: Dominant Sources and Primary Transport Pathways

NASA Astrophysics Data System (ADS)

Sabo, R. D.; Clark, C.; Sobota, D. J.; Compton, J.; Cooter, E. J.; Schwede, D. B.; Bash, J. O.; Rea, A.; Dobrowolski, J. P.

2016-12-01

Efforts to mitigate the deleterious effects of excess reactive nitrogen (Nr) on human health and ecosystem goods and service while ensuring food, biofuel, and fiber availability, is one of the most pressing environmental management challenges of this century. Effective management of Nr requires up to date inventories that quantitatively characterize the sources, transport, and transformation of Nr through the environment. The inherent complexity of the nitrogen cycle, however, through multiple exchange points across air, water, and terrestrial media, renders such inventories difficult to compile and manage. Previous Nr Inventories are for 2002 and 2007, and used data sources that have since been improved. Thus, this recent inventory will substantially advance the methodology across many sectors of the inventory (e.g. deposition and biological fixation in crops and natural systems) and create a recent snapshot that is sorely needed for policy planning and trends analysis. Here we use a simple mass balance approach to estimate the input-output budgets for all United States Geologic Survey Hydrologic Unit Code-8 watersheds. We focus on a recent year (i.e. 2012) to update the Nr Inventory, but apply the analytical approach for multiple years where possible to assess trends through time. We also compare various sector estimates using multiple methodologies. Assembling datasets that account for new Nr inputs into watersheds (e.g., atmospheric NOy deposition, food imports, biologic N fixation) and internal fluxes of recycled Nr (e.g., manure, Nr emmissions/volatilization) provide an unprecedented, data driven computation of N flux. Input-output budgets will offer insight into 1) the dominant sources of Nr in a watershed (e.g., food imports, atmospheric N deposition, or fertilizer), 2) the primary loss pathways for Nr (e.g., crop N harvest, volatilization/emissions), and 3) what watersheds are net sources versus sinks of Nr. These insights will provide needed clarity for managers looking to minimize the loss of Nr to atmospheric and aquatic compartments, while also providing a foundational database for researchers assessing the dominant controls of N retention and loss in natural and anthropogenically dominated ecosystems. Disclaimer: Views expressed are the authors' and not views or polices of the U.S.EPA.

Differential regulatory role of nitric oxide in mediating nitrate reductase activity in roots of tomato (Solanum lycocarpum).

PubMed

Jin, Chong Wei; Du, Shao Ting; Zhang, Yong Song; Lin, Xian Yong; Tang, Cai Xian

2009-07-01

Nitric oxide (NO) has been demonstrated to stimulate the activity of nitrate reductase (NR) in plant roots supplied with a low level of nitrate, and to affect proteins differently, depending on the ratio of NO to the level of protein. Nitrate has been suggested to regulate the level of NO in plants. This present study examined interactive effects of NO and nitrate level on NR activity in roots of tomato (Solanum lycocarpum). NR activity, mRNA level of NR gene and concentration of NR protein in roots fed with 0.5 mM or 5 mM nitrate and treated with the NO donors, sodium nitroprusside (SNP) and diethylamine NONOate sodium (NONOate), and the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO), were measured in 25-d-old seedlings. Addition of SNP and NONOate enhanced but cPTIO decreased NR activity in the roots fed with 0.5 mm nitrate. The opposite was true for the roots fed with 5 mM nitrate. However, the mRNA level of the NR gene and the protein concentration of NR enzyme in the roots were not affected by SNP treatment, irrespective of nitrate pre-treatment. Nevertheless, a low rate of NO gas increased while cPTIO decreased the NR activities of the enzyme extracts from the roots at both nitrate levels. Increasing the rate of NO gas further increased NR activity in the enzyme extracts of the roots fed with 0.5 mM nitrate but decreased it when 5 mM nitrate was supplied. Interestingly, the stimulative effect of NO gas on NR activity could be reversed by NO removal through N(2) flushing in the enzyme extracts from the roots fed with 0.5 mM nitrate but not from those with 5 mM nitrate. The effects of NO on NR activity in tomato roots depend on levels of nitrate supply, and probably result from direct interactions between NO and NR protein.

Selective regulation of nuclear orphan receptors 4A by adenosine receptor subtypes in human mast cells

PubMed Central

Zhang, Li; Paine, Catherine

2010-01-01

Nuclear orphan receptors 4A (NR4A) are early responsive genes that belong to the superfamily of hormone receptors and comprise NR4A1, NR4A2 and NR4A3. They have been associated to transcriptional activation of multiple genes involved in inflammation, apoptosis and cell cycle control. Here, we establish a link between NR4As and adenosine, a paradoxical inflammatory molecule that can contribute to persistence of inflammation or mediate inflammatory shutdown. Transcriptomics screening of the human mast cell-line HMC-1 revealed a sharp induction of transcriptionally active NR4A2 and NR4A3 by the adenosine analogue NECA. The concomitant treatment of NECA and the adenosine receptor A2A (A2AAR) selective antagonist SCH-58261 exaggerated this effect, suggesting that upregulation of these factors in mast cells is mediated by other AR subtypes (A2B and A3) and that A2AAR activation counteracts NR4A2 and NR4A3 induction. In agreement with this, A2AAR-silencing amplified NR4A induction by NECA. Interestingly, a similar A2AAR modulatory effect was observed on ERK1/2 phosphorylation because A2AAR blockage exacerbated NECA-mediated phosphorylation of ERK1/2. In addition, PKC or MEK1/2 inhibition prevented ERK1/2 phosphorylation and antagonized AR-mediated induction of NR4A2 and NR4A3, suggesting the involvement of these kinases in AR to NR4A signaling. Finally, we observed that selective A2AAR activation with CGS-21680 blocked PMA-induced ERK1/2 phosphorylation and modulated the overexpression of functional nuclear orphan receptors 4A. Taken together, these results establish a novel PKC/ERK/nuclear orphan receptors 4A axis for adenosinergic signaling in mast cells, which can be modulated by A2AAR activation, not only in the context of adenosine but of other mast cell activating stimuli as well. PMID:21234122

NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity

PubMed Central

Norcini, Monica; Sideris, Alexandra; Adler, Samantha M.; Hernandez, Lourdes A. M.; Zhang, Jin; Blanck, Thomas J. J.; Recio-Pinto, Esperanza

2016-01-01

Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma’s plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23, satellite glia cells (SGCs) displayed an increase in NR2B protein. This study is the first to characterize of cell-specific changes in NR2B expression within the DRG following peripheral nerve injury. We discuss how the observed NR2B changes in DRG can contribute to the different neuropathic pain phenotypes displayed by each SNI variant. PMID:27803647

NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity.

PubMed

Norcini, Monica; Sideris, Alexandra; Adler, Samantha M; Hernandez, Lourdes A M; Zhang, Jin; Blanck, Thomas J J; Recio-Pinto, Esperanza

2016-01-01

Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma's plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23, satellite glia cells (SGCs) displayed an increase in NR2B protein. This study is the first to characterize of cell-specific changes in NR2B expression within the DRG following peripheral nerve injury. We discuss how the observed NR2B changes in DRG can contribute to the different neuropathic pain phenotypes displayed by each SNI variant.

"Peer Review: Nonroad (NR) Updates to Population Growth, Compression Ignition (CI) Criteria, Toxic Emission Factors and Speciation Profiles"

EPA Science Inventory

This report focuses on the methodology for estimating growth in NR engine populations as used in the MOVES201X-NONROAD emission inventory model. MOVES NR growth rates start with base year engine populations and estimate growth in the populations of NR engines, while applying cons...

40 CFR 158.2174 - Experimental use permit microbial pesticides nontarget organisms and environmental fate data...

Code of Federal Regulations, 2014 CFR

2014-07-01

..., residential, and industrial). Terrestrial uses include: Food, Feed, Non-Food, Forestry, Residential outdoor, greenhouse (food and food), Indoor (food and nonfood), and Industrial. (c) Key. R=Required; CR=Conditionally... Indoor Food/Nonfood Industrial Test Substance Test Notes 885.4050 Avian oraltoxicity NR R R R R NR NR NR...

40 CFR 158.2174 - Experimental use permit microbial pesticides nontarget organisms and environmental fate data...

Code of Federal Regulations, 2013 CFR

2013-07-01

..., residential, and industrial). Terrestrial uses include: Food, Feed, Non-Food, Forestry, Residential outdoor, greenhouse (food and food), Indoor (food and nonfood), and Industrial. (c) Key. R=Required; CR=Conditionally... Indoor Food/Nonfood Industrial Test Substance Test Notes 885.4050 Avian oraltoxicity NR R R R R NR NR NR...

40 CFR 158.2174 - Experimental use permit microbial pesticides nontarget organisms and environmental fate data...

Code of Federal Regulations, 2012 CFR

2012-07-01

..., residential, and industrial). Terrestrial uses include: Food, Feed, Non-Food, Forestry, Residential outdoor, greenhouse (food and food), Indoor (food and nonfood), and Industrial. (c) Key. R=Required; CR=Conditionally... Indoor Food/Nonfood Industrial Test Substance Test Notes 885.4050 Avian oraltoxicity NR R R R R NR NR NR...

A Meta System for Generating Software Engineering Environments.

DTIC Science & Technology

1985-01-01

CI/NR-85-710 UNCLSSIFIED F/ G 9/2 NL 1.0 2-8! j~j~ 1s 3-15 jjll !2 __ L__ ILlh 1121 ,.., - - NATIONAL BUREAU OF STANDARDS MSCRCOPY RESOLUMIN TEST CHART...34 ". " ....-.... .......-... . . - ...-............’. . -...... -.--..-..-.. : 23 H4eta Dt: t-o (Knowled&e Base) Attributed G raoonr form ___ lepresenta tion of a Kethod...implements a programming environment on a relational database. The IDEOSY system 38’ is a graph-oriented language programming environment. I l t . G = o

The Arthurian Poems of Charles Williams: a critical Annotated Edition

DTIC Science & Technology

1996-01-01

identities imaged in a sapphire sea: beyond Sinai Ararat , beyond Ararat Elburz-- 25 light-sprinkling, flaked-snow-sparkling, chastities of ranged peaks...this time there grew, throughout Logres, a new company, as (earlier) in Tabennisi or (later) on Monte Cassino or in Cappadocia a few found themselves...where Prometheus, the fire-bringer, was chained" (Notes). Ararat : Genesis viii 3-4: ’The water receded steadily from the earth. At the end of the

Ethics: A Selected Bibliography.

DTIC Science & Technology

1985-03-01

Morality and Beyond. New York: Harper & Row, 1963. (BJ1251 T6) 291. TolstoY, Lev N. Tolstoy’s Writings on Civil Disobedience and Non- Violence . 0 New York...Translated by R.H.M. Elwes. New York: Philosophi- cal Library, 1957. (B3973 E5E4) 265. Stack, George J. Kierkegaard’s Existential Ethics. University: Univer...271. Storer, Morris B., ed. Humanist Ethics: Dialogue on Basics. Buffalo: Prometheus Books, 1980. (BJ1360 1185) /4. Stratford, Michael C. Political

Power-Conversion Concept Designed for the Jupiter Icy Moons Orbiter

NASA Technical Reports Server (NTRS)

Mason, Lee S.

2004-01-01

The Jupiter Icy Moons Orbiter (JIMO) is a bold new mission being developed by NASA's Office of Space Science under Project Prometheus. JIMO is examining the potential of nuclear electric propulsion (NEP) technology to efficiently deliver scientific payloads to three of Jupiter's moons: Callisto, Ganymede, and Europa. A critical element of the NEP spacecraft is the space reactor power system (SRPS), consisting of the nuclear reactor, power conversion, heat rejection, and power management and distribution (PMAD).

Wetlands Research Program. Corps of Engineers Wetlands Delineation Manual. Appendix C. Section 1. Region O - California.

DTIC Science & Technology

1987-01-01

baccharis FAG B. sergiZoides A. Gray Squaw waterveed baccharis FAC B. viminea DC. Mule fat FACW 3acopa eiserii (Kell.) Penn. Eisen bacopa OBL B. nobs ia...nr ao Bacopa ORL Barbarea orthoceras Ledeb. Erectpod vintercress B. vutgaris R. Br. Bitter vintercress FACW Bassia hyasopifoZia (Pallas) Kuntze

A reduced graphene oxide-based fluorescence resonance energy transfer sensor for highly sensitive detection of matrix metalloproteinase 2

PubMed Central

Xi, Gaina; Wang, Xiaoping; Chen, Tongsheng

2016-01-01

A novel fluorescence nanoprobe (reduced nano-graphene oxide [nrGO]/fluorescein isothiocyanate-labeled peptide [Pep-FITC]) for ultrasensitive detection of matrix metalloproteinase 2 (MMP2) has been developed by engineering the Pep-FITC comprising the specific MMP2 substrate domain (PLGVR) onto the surface of nrGO particles through non-covalent linkage. The nrGO was obtained by water bathing nano-graphene oxide under 90°C for 4 hours. After mixing the nrGO and Pep-FITC for 30 seconds, the fluorescence from Pep-FITC was almost completely quenched due to the fluorescence resonance energy transfer between fluorescein isothiocyanate (FITC) and nrGO. Upon cleavage of the amide bond between Leu and Gly in the Pep-FITC by protease-MMP2, the FITC bound to nrGO was separated from nrGO surface, disrupting the fluorescence resonance energy transfer process and resulting in fluorescence recovery of FITC. Under optimal conditions, the fluorescence recovery of nrGO/Pep-FITC was found to be directly proportional to the concentration of MMP2 within 0.02–0.1 nM. The detection limit of the nrGO/Pep-FITC was determined to be 3 pM, which is approximately tenfold lower than that of the unreduced carboxylated nano-graphene oxide/Pep-FITC probe. PMID:27143876

NR2B-containing NMDA receptors promote neural progenitor cell proliferation through CaMKIV/CREB pathway

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

Li, Mei, E-mail: limeihit@163.com; Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing; Zhang, Dong-Qing

2011-08-12

Highlights: {yields} The NR2B component of the NMDARs is important for the NSPC proliferation. {yields} pCaMKIV and pCREB exist in NSPCs. {yields} The CaMKIV/CREB pathway mediates NSPC proliferation. -- Abstract: Accumulating evidence indicates the involvement of N-methyl-D-aspartate receptors (NMDARs) in regulating neural stem/progenitor cell (NSPC) proliferation. Functional properties of NMDARs can be markedly influenced by incorporating the regulatory subunit NR2B. Here, we aim to analyze the effect of NR2B-containing NMDARs on the proliferation of hippocampal NSPCs and to explore the mechanism responsible for this effect. NSPCs were shown to express NMDAR subunits NR1 and NR2B. The NR2B selective antagonist, Romore » 25-6981, prevented the NMDA-induced increase in cell proliferation. Moreover, we demonstrated that the phosphorylation levels of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein (CREB) were increased by NMDA treatment, whereas Ro 25-6981 decreased them. The role that NR2B-containing NMDARs plays in NSPC proliferation was abolished when CREB phosphorylation was attenuated by CaMKIV silencing. These results suggest that NR2B-containing NMDARs have a positive role in regulating NSPC proliferation, which may be mediated through CaMKIV phosphorylation and subsequent induction of CREB activation.« less

Genetic component of sensitivity to heat stress for nonreturn rate of Brazilian Holstein cattle.

PubMed

Santana, M L; Bignardi, A B; Stefani, G; El Faro, L

2017-08-01

The objectives of the present study were: 1) to investigate variation in the genetic component of heat stress for nonreturn rate at 56 days after first artificial insemination (NR56); 2) to identify and characterize the genotype by environment interaction (G × E) due to heat stress for NR56 of Brazilian Holstein cattle. A linear random regression model (reaction norm model) was applied to 51,748 NR56 records of 28,595 heifers and multiparous cows. The decline in NR56 due to heat stress was more pronounced in milking cows compared to heifers. The age of females at first artificial insemination and temperature-humidity index (THI) exerted an important influence on the genetic parameters of NR56. Several evidence of G × E on NR56 were found as the high slope/intercept ratio and frequent intersection of reaction norms. Additionally, the genetic correlation between NR56 at opposite extremes of the THI scale reached estimates below zero, indicating that few of the same genes are responsible for NR56 under conditions of thermoneutrality and heat stress. The genetic evaluation and selection for NR56 in Holstein cattle reared under (sub)tropical conditions should therefore take into consideration the genetic variation on age at insemination and G × E due to heat stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis.

PubMed

Conacci-Sorrell, Maralice E; Ben-Yedidia, Tamar; Shtutman, Michael; Feinstein, Elena; Einat, Paz; Ben-Ze'ev, Avri

2002-08-15

beta-catenin and plakoglobin (gamma-catenin) are homologous molecules involved in cell adhesion, linking cadherin receptors to the cytoskeleton. beta-catenin is also a key component of the Wnt pathway by being a coactivator of LEF/TCF transcription factors. To identify novel target genes induced by beta-catenin and/or plakoglobin, DNA microarray analysis was carried out with RNA from cells overexpressing either protein. This analysis revealed that Nr-CAM is the gene most extensively induced by both catenins. Overexpression of either beta-catenin or plakoglobin induced Nr-CAM in a variety of cell types and the LEF/TCF binding sites in the Nr-CAM promoter were required for its activation by catenins. Retroviral transduction of Nr-CAM into NIH3T3 cells stimulated cell growth, enhanced motility, induced transformation, and produced rapidly growing tumors in nude mice. Nr-CAM and LEF-1 expression was elevated in human colon cancer tissue and cell lines and in human malignant melanoma cell lines but not in melanocytes or normal colon tissue. Dominant negative LEF-1 decreased Nr-CAM expression and antibodies to Nr-CAM inhibited the motility of B16 melanoma cells. The results indicate that induction of Nr-CAM transcription by beta-catenin or plakoglobin plays a role in melanoma and colon cancer tumorigenesis, probably by promoting cell growth and motility.

Mutation of the regulatory phosphorylation site of tobacco nitrate reductase results in constitutive activation of the enzyme in vivo and nitrite accumulation.

PubMed

Lillo, Cathrine; Lea, Unni S; Leydecker, Marie-Thérèse; Meyer, Christian

2003-09-01

In wild-type Nicotiana plumbaginifolia and other higher plants, nitrate reductase (NR) is rapidly inactivated/activated in response to dark/light transitions. Inactivation of NR is believed to be caused by phosphorylation at a special conserved regulatory Ser residue, Ser 521, and interactions with divalent cations and inhibitory 14-3-3 proteins. A transgenic N. plumbaginifolia line (S(521)) was constructed where the Ser 521 had been changed by site-directed mutagenesis into Asp. This mutation resulted in complete abolishment of inactivation in response to light/dark transitions or other treatments known to inactivate NR. During prolonged darkness, NR in wild-type plants is in the inactivated form, whereas NR in the S(521) line is always in the active form. Differences in degradation rate between NR from S(521) and lines with non-mutated NR were not found. Kinetic constants like Km values for NADH and NO3(-) were not changed, but a slightly different pH profile was observed for mutated NR as opposed to non-mutated NR. Under optimal growth conditions, the phenotype of the S(521) plants was not different from the wild type (WT). However, when plants were irrigated with high nitrate concentration, 150 mM, the transgenic plants accumulated nitrite in darkness, and young leaves showed chlorosis.

Overexpression of human NR2B receptor subunit in LMAN causes stuttering and song sequence changes in adult zebra finches.

PubMed

Chakraborty, Mukta; Chen, Liang-Fu; Fridel, Emma E; Klein, Marguerita E; Senft, Rebecca A; Sarkar, Abhra; Jarvis, Erich D

2017-04-21

Zebra finches (Taeniopygia guttata) learn to produce songs in a manner reminiscent of spoken language development in humans. One candidate gene implicated in influencing learning is the N-methyl-D-aspartate (NMDA) subtype 2B glutamate receptor (NR2B). Consistent with this idea, NR2B levels are high in the song learning nucleus LMAN (lateral magnocellular nucleus of the anterior nidopallium) during juvenile vocal learning, and decreases to low levels in adults after learning is complete and the song becomes more stereotyped. To test for the role of NR2B in generating song plasticity, we manipulated NR2B expression in LMAN of adult male zebra finches by increasing its protein levels to those found in juvenile birds, using a lentivirus containing the full-length coding sequence of the human NR2B subunit. We found that increased NR2B expression in adult LMAN induced increases in song sequence diversity and slower song tempo more similar to juvenile songs, but also increased syllable repetitions similar to stuttering. We did not observe these effects in control birds with overexpression of NR2B outside of LMAN or with the green fluorescent protein (GFP) in LMAN. Our results suggest that low NR2B subunit expression in adult LMAN is important in conserving features of stereotyped adult courtship song.

Influence of acetone extract from natural rubber on the structure and interface interaction in NR/silica composites

NASA Astrophysics Data System (ADS)

Xu, Tiwen; Jia, Zhixin; Wu, Lianghui; Chen, Yongjun; Luo, Yuanfang; Jia, Demin; Peng, Zheng

2017-11-01

It is well known that the coupling reagents as the additional modifiers were often used to improve the reinforcement effect of silica filled natural rubber. Actually, the commercial raw NR is a mixture consisting of polyisoprene and non-isoprene, where the latter one might have impact on the properties of NR/silica composites as an inartificial modifier inside. Thus, investigating the effect of non-isoprene compounds on the structure and properties of NR/silica composites is a novel approach to disclose the peculiarity of NR, which is meaningful to the assessment of NR quality. In this paper, the influences of acetone extract (AE) from natural rubber on the structure and mechanical properties of NR/silica composites were studied. Then the interfacial interactions between AE and silica were also illustrated through Fourier transform infrared spectroscopy (FTIR), thermogravimetic analysis (TGA), X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). Results demonstrated the existence of hydrogen bond between silica and AE, also the covalent bond induced by esterification reaction between sbnd COOH and Sisbnd OH, which resulted in an increase of constrained regions around silica surface leading to the promotions on mechanical and dynamical properties of NR/silica composites significantly.

[Expression of NR2A in rat auditory cortex after sound insulation and auditory plasticity].

PubMed

Xia, Yin; Long, Haishan; Han, Demin; Gong, Shusheng; Lei, Li; Shi, Jinfeng; Fan, Erzhong; Li, Ying; Zhao, Qing

2009-06-01

To study the changes of N-methyl-D-aspartate (NMDA) receptor subunit 2A (NR2A) expression at local synapses in auditory cortices after early postnatal sound insulation and tone exposure. We prepared highly purified synaptosomes from primary auditory cortex by Optiprep flotation gradient centrifugations, and compared the differences of NR2A expression in sound insulation PND14, PND28, PND42 and Tone exposure after sound insulation for 7 days by Western blotting. The results showed that the NR2A protein expression of PND14 and PND28 decreased significantly (P<0.05). Tone exposure after sound insulation for 7 days, mSIe NR2A protein level increased significantly (P<0.05). It showed bidirectional regulation of NR2A protein. No significant effects of sound insulation and lone exposure were found on the relative expression level of NR2A of PND42 (P>0.05). The results indicate that sound insulation and experience can modify the protein expression level of NR2A during the critical period of rat postnatal development. These findings provide important data for the study on the mechanisms of the developmental plasticity of sensory functions.

Reactive nitrogen requirements to feed the world in 2050 and potential to mitigate nitrogen pollution.

PubMed

Bodirsky, Benjamin Leon; Popp, Alexander; Lotze-Campen, Hermann; Dietrich, Jan Philipp; Rolinski, Susanne; Weindl, Isabelle; Schmitz, Christoph; Müller, Christoph; Bonsch, Markus; Humpenöder, Florian; Biewald, Anne; Stevanovic, Miodrag

2014-05-13

Reactive nitrogen (Nr) is an indispensable nutrient for agricultural production and human alimentation. Simultaneously, agriculture is the largest contributor to Nr pollution, causing severe damages to human health and ecosystem services. The trade-off between food availability and Nr pollution can be attenuated by several key mitigation options, including Nr efficiency improvements in crop and animal production systems, food waste reduction in households and lower consumption of Nr-intensive animal products. However, their quantitative mitigation potential remains unclear, especially under the added pressure of population growth and changes in food consumption. Here we show by model simulations, that under baseline conditions, Nr pollution in 2050 can be expected to rise to 102-156% of the 2010 value. Only under ambitious mitigation, does pollution possibly decrease to 36-76% of the 2010 value. Air, water and atmospheric Nr pollution go far beyond critical environmental thresholds without mitigation actions. Even under ambitious mitigation, the risk remains that thresholds are exceeded.

17 CFR 249.1330 - Form MA-NR, for appointment of agent for service of process by non-resident municipal advisor...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Form MA-NR, for appointment of... Information Regarding Certain Natural Persons § 249.1330 Form MA-NR, for appointment of agent for service of... Register citations affecting Form MA-NR, see the List of CFR Sections Affected, which appears in the...

40 CFR 158.630 - Terrestrial and aquatic nontarget organisms data requirements table.

Code of Federal Regulations, 2012 CFR

2012-07-01

... toxicity R CR R R NR NR TGAI 1 850.3030 Honey bee toxicity of residues on foliage CR CR CR CR NR NR TEP 24... LD50 of bee as determined in the honey bee acute contact study and the use pattern(s) indicate(s) that honey bees may be exposed to the pesticide. 25. Required if any of the following...

40 CFR 158.630 - Terrestrial and aquatic nontarget organisms data requirements table.

Code of Federal Regulations, 2011 CFR

2011-07-01

... toxicity R CR R R NR NR TGAI 1 850.3030 Honey bee toxicity of residues on foliage CR CR CR CR NR NR TEP 24... LD50 of bee as determined in the honey bee acute contact study and the use pattern(s) indicate(s) that honey bees may be exposed to the pesticide. 25. Required if any of the following...

40 CFR 158.630 - Terrestrial and aquatic nontarget organisms data requirements table.

Code of Federal Regulations, 2013 CFR

2013-07-01

... toxicity R CR R R NR NR TGAI 1 850.3030 Honey bee toxicity of residues on foliage CR CR CR CR NR NR TEP 24... LD50 of bee as determined in the honey bee acute contact study and the use pattern(s) indicate(s) that honey bees may be exposed to the pesticide. 25. Required if any of the following...

40 CFR 158.630 - Terrestrial and aquatic nontarget organisms data requirements table.

Code of Federal Regulations, 2014 CFR

2014-07-01

... toxicity R CR R R NR NR TGAI 1 850.3030 Honey bee toxicity of residues on foliage CR CR CR CR NR NR TEP 24... contains one or more active ingredients having an acute LD50 of bee as determined in the honey bee acute contact study and the use pattern(s) indicate(s) that honey bees may be exposed to the...

Wide spectrum of NR5A1‐related phenotypes in 46,XY and 46,XX individuals

PubMed Central

Domenice, Sorahia; Machado, Aline Zamboni; Ferreira, Frederico Moraes; Ferraz‐de‐Souza, Bruno; Lerario, Antonio Marcondes; Lin, Lin; Nishi, Mirian Yumie; Gomes, Nathalia Lisboa; da Silva, Thatiana Evelin; Silva, Rosana Barbosa; Correa, Rafaela Vieira; Montenegro, Luciana Ribeiro; Narciso, Amanda; Costa, Elaine Maria Frade; Achermann, John C

2016-01-01

Steroidogenic factor 1 (NR5A1, SF‐1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1‐related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype‐phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian‐determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1‐related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever‐expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction. Birth Defects Research (Part C) 108:309–320, 2016. © 2016 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc. PMID:28033660

Deep Learning-Based Noise Reduction Approach to Improve Speech Intelligibility for Cochlear Implant Recipients.

PubMed

Lai, Ying-Hui; Tsao, Yu; Lu, Xugang; Chen, Fei; Su, Yu-Ting; Chen, Kuang-Chao; Chen, Yu-Hsuan; Chen, Li-Ching; Po-Hung Li, Lieber; Lee, Chin-Hui

2018-01-20

We investigate the clinical effectiveness of a novel deep learning-based noise reduction (NR) approach under noisy conditions with challenging noise types at low signal to noise ratio (SNR) levels for Mandarin-speaking cochlear implant (CI) recipients. The deep learning-based NR approach used in this study consists of two modules: noise classifier (NC) and deep denoising autoencoder (DDAE), thus termed (NC + DDAE). In a series of comprehensive experiments, we conduct qualitative and quantitative analyses on the NC module and the overall NC + DDAE approach. Moreover, we evaluate the speech recognition performance of the NC + DDAE NR and classical single-microphone NR approaches for Mandarin-speaking CI recipients under different noisy conditions. The testing set contains Mandarin sentences corrupted by two types of maskers, two-talker babble noise, and a construction jackhammer noise, at 0 and 5 dB SNR levels. Two conventional NR techniques and the proposed deep learning-based approach are used to process the noisy utterances. We qualitatively compare the NR approaches by the amplitude envelope and spectrogram plots of the processed utterances. Quantitative objective measures include (1) normalized covariance measure to test the intelligibility of the utterances processed by each of the NR approaches; and (2) speech recognition tests conducted by nine Mandarin-speaking CI recipients. These nine CI recipients use their own clinical speech processors during testing. The experimental results of objective evaluation and listening test indicate that under challenging listening conditions, the proposed NC + DDAE NR approach yields higher intelligibility scores than the two compared classical NR techniques, under both matched and mismatched training-testing conditions. When compared to the two well-known conventional NR techniques under challenging listening condition, the proposed NC + DDAE NR approach has superior noise suppression capabilities and gives less distortion for the key speech envelope information, thus, improving speech recognition more effectively for Mandarin CI recipients. The results suggest that the proposed deep learning-based NR approach can potentially be integrated into existing CI signal processors to overcome the degradation of speech perception caused by noise.

Increased Glutamate Receptor and Transporter Expression in the Cerebral Cortex and Striatum of Gcdh -/- Mice: Possible Implications for the Neuropathology of Glutaric Acidemia Type I

PubMed Central

Lagranha, Valeska Lizzi; Matte, Ursula; de Carvalho, Talita Giacomet; Seminotti, Bianca; Pereira, Carolina Coffi; Koeller, David M.; Woontner, Michael; Goodman, Stephen I.; de Souza, Diogo Onofre Gomes; Wajner, Moacir

2014-01-01

We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits), AMPA (GluR2 subunit) and kainate (GluR6 subunit), as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT) and glutaryl-CoA dehydrogenase deficient (Gchh -/-) mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh -/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh -/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh -/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh -/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh -/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh -/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh -/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I. PMID:24594605

Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of gcdh-/- mice: possible implications for the neuropathology of glutaric acidemia type I.

PubMed

Lagranha, Valeska Lizzi; Matte, Ursula; de Carvalho, Talita Giacomet; Seminotti, Bianca; Pereira, Carolina Coffi; Koeller, David M; Woontner, Michael; Goodman, Stephen I; de Souza, Diogo Onofre Gomes; Wajner, Moacir

2014-01-01

We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits), AMPA (GluR2 subunit) and kainate (GluR6 subunit), as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT) and glutaryl-CoA dehydrogenase deficient (Gchh-/-) mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh-/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh-/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh-/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh-/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh-/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh-/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh-/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I.

Using Bayesian Belief Networks to Explore the Effects of Nitrogen Inputs on Wetland Ecosystem Services

NASA Astrophysics Data System (ADS)

Spence, P. L.; Jordan, S. J.

2011-12-01

Increased reactive nitrogen (Nr) inputs to freshwater wetlands resulting from infrastructure development due to population growth along with intensive agricultural practices associated with food production can threaten regulating (i.e. climate change, water purification, and waste treatment) and supporting (i.e. nutrient cycling) ecosystem services. Wetlands generally respond both by sequestering Nr (i.e. soil accumulation and biomass assimilation) and converting Nr into inert gaseous forms via biogeochemical processes. It is important for wetlands to be efficient in removing excessive Nr inputs from polluted waters to reduce eutrophication in downstream receiving water bodies while producing negligible amounts of nitrous oxide (N2O), a potent greenhouse gas, which results from incomplete denitrification. Wetlands receiving excessive Nr lose their ability to provide a constant balance between regulating water quality and mitigating climate change. The purpose of this study is to explore the effects of Nr inputs on ecosystem services provided by wetlands using a Bayesian Belief Network (BBN). The network was developed from established relationships between a variety of wetland function indicators and biogeochemical process associated with Nr removal. Empirical data for 34 freshwater wetlands were gathered from a comprehensive review of published peer-reviewed and gray literature. The BBN was trained using 30 wetlands (88% of the freshwater wetland case file) and tested using 4 wetlands (12% of the freshwater wetland case file). Sensitivity analysis suggested that Nr removal, water quality, soil Nr accumulation and N2O emissions had the greatest influence on ecosystem service tradeoffs. The magnitude of Nr inputs did not affect ecosystem services. The network implies that Nr removal efficiency has a greater influence on final ecosystem services associated with water quality impairment and atmospheric pollution. A very low error rate, which was based on 4 wetland cases, indicated that a larger dataset is required to provide robust predictions. These findings are considered preliminary and could change as the model is updated.

The N-methyl-D-aspartate receptor subunits NR2A and NR2B bind to the SH2 domains of phospholipase C-gamma.

PubMed

Gurd, J W; Bissoon, N

1997-08-01

The NMDA receptor has recently been found to be phosphorylated on tyrosine. To assess the possible connection between tyrosine phosphorylation of the NMDA receptor and signaling pathways in the postsynaptic cell, we have investigated the relationship between tyrosine phosphorylation and the binding of NMDA receptor subunits to the SH2 domains of phospholipase C-gamma (PLC-gamma). A glutathione S-transferase (GST) fusion protein containing both the N- and the C-proximal SH2 domains of PLC-gamma was bound to glutathione-agarose and reacted with synaptic junctional proteins and glycoproteins. Tyrosine-phosphorylated PSD-GP180, which has been identified as the NR2B subunit of the NMDA receptor, bound to the SH2-agarose beads in a phosphorylation-dependent fashion. Immunoblot analysis with antibodies specific for individual NMDA receptor subunits showed that both NR2A and NR2B subunits bound to the SH2-agarose. No binding occurred to GST-agarose lacking an associated SH2 domain, indicating that binding was specific for the SH2 domains. The binding of receptor subunits increased after the incubation of synaptic junctions with ATP and decreased after treatment of synaptic junctions with exogenous protein tyrosine phosphatase. Immunoprecipitation experiments confirmed that NR2A and NR2B were phosphorylated on tyrosine and further that tyrosine phosphorylation of each of the subunits was increased after incubation with ATP. The results demonstrate that NMDA receptor subunits NR2A and NR2B will bind to the SH2 domains of PLC-gamma and that isolated synaptic junctions contain endogenous protein tyrosine kinase(s) that can phosphorylate both NR2A and NR2B receptor subunits, and suggest that interaction of the tyrosine-phosphorylated NMDA receptor with proteins that contain SH2 domains may serve to link it to signaling pathways in the postsynaptic cell.

The reprogramming factor nuclear receptor subfamily 5, group A, member 2 cannot replace octamer-binding transcription factor 4 function in the self-renewal of embryonic stem cells.

PubMed

Choi, Kyeng-Won; Oh, Hye-Rim; Lee, Jaeyoung; Lim, Bobae; Han, Yong-Mahn; Oh, Junseo; Kim, Jungho

2014-02-01

Although octamer-binding transcription factor 4 (Oct-4) is one of the most intensively studied factors in mammalian development, no cellular genes capable of replacing Oct-4 function in embryonic stem (ES) cells have been found. Recent data show that nuclear receptor subfamily 5, group A, member 2 (Nr5a2) is able to replace Oct-4 function in the reprogramming process; however, it is unclear whether Nr5a2 can replace Oct-4 function in ES cells. In this study, the ability of Nr5a2 to maintain self-renewal and pluripotency in ES cells was investigated. Nr5a2 localized to the nucleus in ES cells, similarly to Oct-4. However, expression of Nr5a2 failed to rescue the stem cell phenotype or to maintain the self-renewal ability of ES cells. Furthermore, as compared with Oct-4-expressing ES cells, Nr5a2-expressing ES cells showed a reduced number of cells in S-phase, did not expand normally, and did not remain in an undifferentiated state. Ectopic expression of Nr5a2 in ES cells was not able to activate transcription of ES cell-specific genes, and gene expression profiling demonstrated differences between Nr5a2-expressing and Oct-4-expressing ES cells. In addition, Nr5a2-expressing ES cells were not able to form teratomas in nude mice. Taken together, these results strongly suggest that the gene regulation properties of Nr5a2 and Oct-4 and their abilities to confer self-renewal and pluripotency of ES cells differ. The present study provides strong evidence that Nr5a2 cannot replace Oct-4 function in ES cells. © 2013 FEBS.

Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway.

PubMed

Wang, Sufan; Wan, Ting; Ye, Mingtong; Qiu, Yun; Pei, Lei; Jiang, Rui; Pang, Nengzhi; Huang, Yuanling; Liang, Baoxia; Ling, Wenhua; Lin, Xiaojun; Zhang, Zhenfeng; Yang, Lili

2018-07-01

Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD + ) precursor which is present in foods such as milk and beer. It was reported that NR can prevent obesity, increase longevity, and promote liver regeneration. However, whether NR can prevent ethanol-induced liver injuries is not known. This study aimed to explore the effect of NR on ethanol induced liver injuries and the underlying mechanisms. We fed C57BL/6 J mice with Lieber-DeCarli ethanol liquid diet with or without 400 mg/kg·bw NR for 16 days. Liver injuries and SirT1-PGC-1α-mitochondrial function were analyzed. In in vitro experiments, HepG2 cells (CYP2E1 over-expressing cells) were incubated with ethanol ± 0.5 mmol/L NR. Lipid accumulation and mitochondrial function were compared. SirT1 knockdown in HepG2 cells were further applied to confirm the role of SirT1 in the protection of NR on lipid accumulation. We found that ethanol significantly decreased the expression and activity of hepatic SirT1 and induced abnormal expression of enzymes of lipid metabolism in mice. Both in vivo and in vitro experiments showed that NR activated SirT1 through increasing NAD + levels, decreased oxidative stress, increased deacetylation of PGC-1α and mitochondrial function. In SirT1 knockdown HepG2 cells, NR lost its ability in enhancing mitochondrial function, and its protection against lipid accumulation induced by ethanol. NR can protect against ethanol induced liver injuries via replenishing NAD + , reducing oxidative stress, and activating SirT1-PGC-1α-mitochondrial biosynthesis. Our data indicate that SirT1 plays an important role in the protection of NR against lipid accumulation and mitochondrial dysfunctions induced by ethanol. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Parathyroid hormone induces the Nrna family of nuclear orphan receptors in vivo

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

Pirih, Flavia Q.; Aghaloo, Tara L.; Bezouglaia, Olga

2005-07-01

Parathyroid hormone (PTH) has both anabolic and catabolic effects on bone metabolism, although the molecular mechanisms mediating these effects are largely unknown. Among the transcription factors induced by Pth in osteoblasts are the nerve growth factor-inducible factor B (NR4A; NGFI-B) family of orphan nuclear receptors: Nurr1, Nur77, and NOR-1. PTH induces NR4A members through the cAMP-protein kinase A (PKA) pathway in vitro. We report here that PTH rapidly and transiently induced expression of all three NR4A genes in PTH-target tissues in vivo. In calvaria, long bones, and kidneys, NR4A induction was maximal 0.5-1 h after a single intraperitoneal (i.p.) injectionmore » of 80 {mu}g/kg PTH. Nur77 demonstrated the highest expression, followed, in order, by Nurr1 and NOR-1. In calvaria and long bone, PTH-induced expression of each NR4A gene was detectable at 10 {mu}g/kg i.p. with maximum induction at 40-80 {mu}g/kg. PTH (3-34) did not induce NR4A mRNA levels in calvaria, long bone, and kidney in vivo, confirming our in vitro results that NR4A genes are induced primarily through the cAMP-PKA pathway. The magnitude of PTH-induced NR4A expression was comparable in vivo and in vitro. However, NR4A mRNA levels peaked and returned to baseline faster in vivo. Both in vivo and in vitro, PTH induced NR4A pre-mRNA levels suggesting that induction of these genes is, at least in part, through activation of mRNA synthesis. The in vivo induction of the NR4A family members by PTH suggests their involvement in, at least some, PTH-induced changes in bone metabolism.« less

DAX1/NR0B1 was expressed during mammalian gonadal development and gametogenesis before it was recruited to the eutherian X chromosome.

PubMed

Stickels, Robert; Clark, Kevin; Heider, Thomas N; Mattiske, Deidre M; Renfree, Marilyn B; Pask, Andrew J

2015-01-01

The nuclear receptor subfamily 0, group B, member 1 (NR0B1) gene is an orphan nuclear receptor that is X-linked in eutherian mammals and plays a critical role in the establishment and function of the hypothalamic-pituitary-adrenal-gonadal axis. Duplication or overexpression of NR0B1 in eutherian males causes male to female sex reversal, and mutation and deletions of NR0B1 cause testicular defects. Thus, gene dosage is critical for the function of NR0B1 in normal gonadogenesis. However, NR0B1 is autosomal in all noneutherian vertebrates, including marsupials and monotreme mammals, and two active copies of the gene are compatible with both male and female gonadal development. In the current study, we examined the evolution and expression of autosomal NR0B1 during gonadal development in a marsupial (the tammar wallaby) as compared to the role of its X-linked orthologues in a eutherian (the mouse). We show that NR0B1 underwent rapid evolutionary change when it relocated from its autosomal position in the nonmammalian vertebrates, monotremes, and marsupials to an X-linked location in eutherian mammals. Despite the acquisition of a novel genomic location and a unique N-terminal domain, NR0B1 protein distribution was remarkably similar between mice and marsupials both throughout gonadal development and during gamete formation. A conserved accumulation of NR0B1 protein was observed in developing oocytes, where its function appears to be critical in the early embryo, prior to zygotic genome activation. Together these findings suggest that NR0B1 had a conserved role in gonadogenesis that existed long before it moved to the X chromosome and despite undergoing significant evolutionary change. © 2015 by the Society for the Study of Reproduction, Inc.

Bis-Indole-Derived NR4A1 Ligands and Metformin Exhibit NR4A1-Dependent Glucose Metabolism and Uptake in C2C12 Cells.

PubMed

Mohankumar, Kumaravel; Lee, Jehoon; Wu, Chia Shan; Sun, Yuxiang; Safe, Stephen

2018-05-01

Treatment of C2C12 muscle cells with metformin or the NR4A1 ligand 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) induced NR4A1 and Glut4 messenger RNA and protein expression. Similar results were observed with buttressed (3- or 3,5-substituted) analogs of DIM-C-pPhOH, including 1,1-bis(3'-indolyl)-1-(3-chloro-4-hydroxy-5-methoxyphenyl)methane (DIM-C-pPhOH-3-Cl-5-OCH3), and the buttressed analogs were more potent than DIM-C-pPhOH NR4A1 agonists. Metformin and the bis-indole substituted analogs also induced expression of several glycolytic genes and Rab4, which has previously been linked to enhancing cell membrane accumulation of Glut4 and overall glucose uptake in C2C12 cells, and these responses were also observed after treatment with metformin and the NR4A1 ligands. The role of NR4A1 in mediating the responses induced by the bis-indoles and metformin was determined by knockdown of NR4A1, and this resulted in attenuating the gene and protein expression and enhanced glucose uptake responses induced by these compounds. Our results demonstrate that the bis-indole-derived NR4A1 ligands represent a class of drugs that enhance glucose uptake in C2C12 muscle cells, and we also show that the effects of metformin in this cell line are NR4A1-dependent.

Fyn kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr1472 is essential for maintenance of neuropathic pain.

PubMed

Abe, Tetsuya; Matsumura, Shinji; Katano, Tayo; Mabuchi, Tamaki; Takagi, Kunio; Xu, Li; Yamamoto, Akitsugu; Hattori, Kotaro; Yagi, Takeshi; Watanabe, Masahiko; Nakazawa, Takanobu; Yamamoto, Tadashi; Mishina, Masayoshi; Nakai, Yoshihide; Ito, Seiji

2005-09-01

Despite abundant evidence implicating the importance of N-methyl-D-aspartate (NMDA) receptors in the spinal cord for pain transmission, the signal transduction coupled to NMDA receptor activation is largely unknown for the neuropathic pain state that lasts over periods of weeks. To address this, we prepared mice with neuropathic pain by transection of spinal nerve L5. Wild-type, NR2A-deficient, and NR2D-deficient mice developed neuropathic pain; in addition, phosphorylation of NR2B subunits of NMDA receptors at Tyr1472 was observed in the superficial dorsal horn of the spinal cord 1 week after nerve injury. Neuropathic pain and NR2B phosphorylation at Tyr1472 were attenuated by the NR2B-selective antagonist CP-101,606 and disappeared in mice lacking Fyn kinase, a Src-family tyrosine kinase. Concomitant with the NR2B phosphorylation, an increase in neuronal nitric oxide synthase activity was visualized in the superficial dorsal horn of neuropathic pain mice by NADPH diaphorase histochemistry. Electron microscopy showed that the phosphorylated NR2B was localized at the postsynaptic density in the spinal cord of mice with neuropathic pain. Indomethacin, an inhibitor of prostaglandin (PG) synthesis, and PGE receptor subtype EP1-selective antagonist reduced the NR2B phosphorylation in these mice. Conversely, EP1-selective agonist stimulated Fyn kinase-dependent nitric oxide formation in the spinal cord. The present study demonstrates that Tyr1472 phosphorylation of NR2B subunits by Fyn kinase may have dual roles in the retention of NMDA receptors in the postsynaptic density and in activation of nitric oxide synthase, and suggests that PGE2 is involved in the maintenance of neuropathic pain via the EP1 subtype.

NR2A- and NR2B-NMDA receptors and drebrin within postsynaptic spines of the hippocampus correlate with hunger-evoked exercise.

PubMed

Chen, Yi-Wen; Actor-Engel, Hannah; Sherpa, Ang Doma; Klingensmith, Lauren; Chowdhury, Tara G; Aoki, Chiye

2017-07-01

Hunger evokes foraging. This innate response can be quantified as voluntary wheel running following food restriction (FR). Paradoxically, imposing severe FR evokes voluntary FR, as some animals choose to run rather than eat, even during limited periods of food availability. This phenomenon, called activity-based anorexia (ABA), has been used to identify brain changes associated with FR and excessive exercise (EX), two core symptoms of anorexia nervosa (AN), and to explore neurobiological bases of AN vulnerability. Previously, we showed a strong positive correlation between suppression of FR-evoked hyperactivity, i.e., ABA resilience, and levels of extra-synaptic GABA receptors in stratum radiatum (SR) of hippocampal CA1. Here, we tested for the converse: whether animals with enhanced expression of NMDA receptors (NMDARs) exhibit greater levels of FR-evoked hyperactivity, i.e., ABA vulnerability. Four groups of animals were assessed for NMDAR levels at CA1 spines: (1) ABA, in which 4 days of FR was combined with wheel access to allow voluntary EX; (2) FR only; (3) EX only; and (4) control (CON) that experienced neither EX nor FR. Electron microscopy revealed that synaptic NR2A-NMDARs and NR2B-NMDARs levels are significantly elevated, relative to CONs'. Individuals' ABA severity, based on weight loss, correlated with synaptic NR2B-NMDAR levels. ABA resilience, quantified as suppression of hyperactivity, correlated strongly with reserve pools of NR2A-NMDARs in spine cytoplasm. NR2A- and NR2B-NMDAR measurements correlated with spinous prevalence of an F-actin binding protein, drebrin, suggesting that drebrin enables insertion of NR2B-NMDAR to and retention of NR2A-NMDARs away from synaptic membranes, together influencing ABA vulnerability.

NR2F2 inhibits Smad7 expression and promotes TGF-β-dependent epithelial-mesenchymal transition of CRC via transactivation of miR-21.

PubMed

Wang, Hao; Nie, Lei; Wu, Lei; Liu, Qiufang; Guo, Xueyan

2017-03-25

Metastasis is one of the most decisive factors influencing CRC patient prognosis and current studies suggest that a molecular mechanism known as EMT broadly regulates cancer metastasis. NR2F2 is a key molecule in the development of CRC, but the roles and underlying mechanisms of NR2F2 in TGF-β induced EMT in CRC remain largely unknown. In the current study, we were interested to examine the role of NR2F2 in the TGF-β-induced EMT in CRC. Here, we found NR2F2 was upregulated in CRC cells and promotes TGF-β-induced EMT in CRC. Using comparative miRNA profiling TGF-β pre-treated CRC cells in which NR2F2 had been knocked down with that of control cells, we identified miR-21 as a commonly downregulated miRNA in HT29 cells treated with TGF-β and NR2F2 siRNA, and its downregulation inhibiting migration and invasion of CRC cells. Moreover, we found NR2F2 could transcriptional activated miR-21 expression by binding to miR-21 promoter in HT29 by ChIP and luciferase assay. In the last, our data demonstrated that Smad7 was the direct target of miR-21 in CRC cells. Thus, NR2F2 could promote TGF-β-induced EMT and inhibit Smad7 expression via transactivation of miR-21, and NR2F2 may be a new common therapeutic target for CRC. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative induction of nitrate reductase by nitrate and nitrite in barley leaves

NASA Technical Reports Server (NTRS)

Aslam, M.; Rosichan, J. L.; Huffaker, R. C.

1987-01-01

The comparative induction of nitrate reductase (NR) by ambient NO3- and NO2- as a function of influx, reduction (as NR was induced) and accumulation in detached leaves of 8-day-old barley (Hordeum vulgare L.) seedlings was determined. The dynamic interaction of NO3- influx, reduction and accumulation on NR induction was shown. The activity of NR, as it was induced, influenced its further induction by affecting the internal concentration of NO3-. As the ambient concentration of NO3- increased, the relative influences imposed by influx and reduction on NO3- accumulation changed with influx becoming a more predominant regulant. Significant levels of NO3- accumulated in NO2(-)-fed leaves. When the leaves were supplied cycloheximide or tungstate along with NO2-, about 60% more NO3- accumulated in the leaves than in the absence of the inhibitors. In NO3(-)-supplied leaves NR induction was observed at an ambient concentration of as low as 0.02 mM. No NR induction occurred in leaves supplied with NO2- until the ambient NO2- concentration was 0.5 mM. In fact, NR induction from NO2- solutions was not seen until NO3- was detected in the leaves. The amount of NO3- accumulating in NO2(-)-fed leaves induced similar levels of NR as did equivalent amounts of NO3- accumulating from NO3(-)-fed leaves. In all cases the internal concentration of NO3-, but not NO2-, was highly correlated with the amount of NR induced. The evidence indicated that NO3- was a more likely inducer of NR than was NO2-.

Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis.

PubMed

Hong, Guangliang; Zheng, Dong; Zhang, Lulu; Ni, Rui; Wang, Grace; Fan, Guo-Chang; Lu, Zhongqiu; Peng, Tianqing

2018-08-01

Sepsis-caused multiple organ failure remains the major cause of morbidity and mortality in intensive care units. Nicotinamide riboside (NR) is a precursor of nicotinamide adenine dinucleotide (NAD + ), which is important in regulating oxidative stress. This study investigated whether administration of NR prevented oxidative stress and organ injury in sepsis. Mouse sepsis models were induced by injection of lipopolysaccharides (LPS) or feces-injection-in-peritoneum. NR was given before sepsis onset. Cultured macrophages and endothelial cells were incubated with various agents. Administration of NR elevated the NAD + levels, and elicited a reduction of oxidative stress, inflammation and caspase-3 activity in lung and heart tissues, which correlated with attenuation of pulmonary microvascular permeability and myocardial dysfunction, leading to less mortality in sepsis models. These protective effects of NR were associated with decreased levels of plasma high mobility group box-1 (HMGB1) in septic mice. Consistently, pre-treatment of macrophages with NR increased NAD + content and reduced HMGB1 release upon LPS stimulation. NR also prevented reactive oxygen species (ROS) production and apoptosis in endothelial cells induced by a conditioned-medium collected from LPS-treated macrophages. Furthermore, inhibition of SIRT1 by EX527 offset the negative effects of NR on HMGB1 release in macrophages, and ROS and apoptosis in endothelial cells. Administration of NR prevents lung and heart injury, and improves the survival in sepsis, likely by inhibiting HMGB1 release and oxidative stress via the NAD + /SIRT1 signaling. Given NR has been used as a health supplement, it may be a useful agent to prevent organ injury in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures.

PubMed

Baker, Jennifer L; Wood, Bernard; Karpinski, Beverly A; LaMantia, Anthony-S; Maynard, Thomas M

2016-01-01

Comparative genomic analysis of the nuclear receptor family suggests that the testicular receptor 2, Nr2c1, undergoes positive selection in the human-chimpanzee clade based upon a significant increase in nonsynonymous compared to synonymous substitutions. Previous in situ analyses of Nr2c1 lacked the temporal range and spatial resolution necessary to characterize cellular expression of this gene from early to mid gestation, when many nuclear receptors are key regulators of tissue specific stem or progenitor cells. Thus, we asked whether Nr2c1 protein is associated with stem cell populations in the mid-gestation mouse embryo. Nr2c1 is robustly expressed in the developing olfactory epithelium. Its expression in the olfactory epithelium shifts from multiple progenitor classes at early stages to primarily transit amplifying cells later in olfactory epithelium development. In the early developing central nervous system, Nr2c1 is limited to the anterior telencephalon/olfactory bulb anlagen, coincident with Nestin-positive neuroepithelial stem cells. Nr2c1 is also seen in additional cranial sensory specializations including cells surrounding the mystacial vibrissae, the retinal pigment epithelium and Scarpa's ganglion. Nr2c1 was also detected in a subset of mesenchymal cells in developing teeth and cranial bones. The timing and distribution of embryonic expression suggests that Nr2c1 is primarily associated with the early genesis of mammalian cranial sensory neurons and craniofacial skeletal structures. Thus, Nr2c1 may be a candidate for mediating parallel adaptive changes in cranial neural sensory specializations such as the olfactory epithelium, retina and mystacial vibrissae and in non-neural craniofacial features including teeth. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Parworth, Caroline; Tilp, Alison; Fast, Jerome

In this study the long-term trends of non-refractory submicrometer aerosol (NR-PM1) composition and mass concentration measured by an Aerosol Chemical Speciation Monitor (ACSM) at the Atmospheric Radiation Measurement (ARM) program's Southern Great Plains (SGP) site are discussed. NR-PM1 data was recorded at ~30 min intervals over a period of 19 months between November 2010 and June 2012. Positive Matrix Factorization (PMF) was performed on the measured organic mass spectral matrix using a rolling window technique to derive factors associated with distinct sources, evolution processes, and physiochemical properties. The rolling window approach also allows us to capture the dynamic variations ofmore » the chemical properties in the organic aerosol (OA) factors over time. Three OA factors were obtained including two oxygenated OA (OOA) factors, differing in degrees of oxidation, and a biomass burning OA (BBOA) factor. Back trajectory analyses were performed to investigate possible sources of major NR-PM1 species at the SGP site. Organics dominated NR-PM1 mass concentration for the majority of the study with the exception of winter, when ammonium nitrate increases due to transport of precursor species from surrounding urban and agricultural areas and also due to cooler temperatures. Sulfate mass concentrations have little seasonal variation with mixed regional and local sources. In the spring BBOA emissions increase and are mainly associated with local fires. Isoprene and carbon monoxide emission rates were obtained by the Model of Emissions of Gases and Aerosols from Nature (MEGAN) and the 2011 U.S. National Emissions Inventory to represent the spatial distribution of biogenic and anthropogenic sources, respectively. The combined spatial distribution of isoprene emissions and air mass trajectories suggest that biogenic emissions from the southeast contribute to SOA formation at the SGP site during the summer.« less

A dual wavelength-activatable gold nanorod complex for synergistic cancer treatment

NASA Astrophysics Data System (ADS)

Pacardo, Dennis B.; Neupane, Bhanu; Rikard, S. Michaela; Lu, Yue; Mo, Ran; Mishra, Sumeet R.; Tracy, Joseph B.; Wang, Gufeng; Ligler, Frances S.; Gu, Zhen

2015-07-01

A multifunctional gold nanorod (AuNR) complex is described with potential utility for theranostic anticancer treatment. The AuNR was functionalized with cyclodextrin for encapsulation of doxorubicin, with folic acid for targeting, and with a photo-responsive dextran-azo compound for intracellular controlled drug release. The interaction of a AuNR complex with HeLa cells was facilitated via a folic acid targeting ligand as displayed in the dark-field images of cells. Enhanced anticancer efficacy was demonstrated through the synergistic combination of promoted drug release upon ultraviolet (UV) light irradiation and photothermal therapy upon infrared (IR) irradiation. This multifunctional AuNR-based system represents a novel theranostic strategy for spatiotemporal delivery of anticancer therapeutics.A multifunctional gold nanorod (AuNR) complex is described with potential utility for theranostic anticancer treatment. The AuNR was functionalized with cyclodextrin for encapsulation of doxorubicin, with folic acid for targeting, and with a photo-responsive dextran-azo compound for intracellular controlled drug release. The interaction of a AuNR complex with HeLa cells was facilitated via a folic acid targeting ligand as displayed in the dark-field images of cells. Enhanced anticancer efficacy was demonstrated through the synergistic combination of promoted drug release upon ultraviolet (UV) light irradiation and photothermal therapy upon infrared (IR) irradiation. This multifunctional AuNR-based system represents a novel theranostic strategy for spatiotemporal delivery of anticancer therapeutics. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01568e

Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet

PubMed Central

Shi, Wenbiao; Hegeman, Maria A.; van Dartel, Dorien A.M.; Tang, Jing; Suarez, Manuel; Swarts, Hans; van der Hee, Bart; Arola, Lluis

2017-01-01

Scope Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined here for a wide range of NR. Design and methods Nine‐week‐old male C57BL/6JRcc mice received a semi‐purified mildly obesogenic (40 en% fat) diet containing 0.14% L‐tryptophan and either 5, 15, 30, 180, or 900 mg NR per kg diet for 15 weeks. Body composition and metabolic parameters were analyzed. Metabolic flexibility was measured using indirect calorimetry. Gene expression in epididymal white adipose tissue (eWAT) was measured using qRT‐PCR . Results The maximum delta respiratory exchange ratio when switching from CHO to FAO (maxΔRERCHO1→FAO) and when switching from FAO to CHO (maxΔRERFAO→CHO2) were largest in 30 mg NR per kg diet (30NR). In eWAT, the gene expression of Pparγ, a master regulator of adipogenesis, and of Sod2 and Prdx3, two antioxidant genes, were significantly upregulated in 30NR compared to 5NR. Conclusion 30NR is most beneficial for metabolic health, in terms of metabolic flexibility and eWAT gene expression, of mice on an obesogenic diet. PMID:28211258

Cellular uptake and intracellular trafficking of PEG-b-PLA polymeric micelles.

PubMed

Zhang, Zhen; Xiong, Xiaoqin; Wan, Jiangling; Xiao, Ling; Gan, Lu; Feng, Youmei; Xu, Huibi; Yang, Xiangliang

2012-10-01

Besides as an inert carrier for hydrophobic anticancer agents, polymeric micelles composed of di-block copolymer poly(ethylene glycol)-poly(lactic acid) (PEG-b-PLA) function as biological response modifiers including reversal of multidrug resistance in cancer. However, the uptake mechanisms and the subsequent intracellular trafficking remain to be elucidated. In this paper, we found that the uptake of PEG-b-PLA polymeric micelles incorporating nile red (M-NR) was significantly inhibited by both dynamin inhibitor dynasore and dynamin-2 dominant negative mutant (dynamin-2 K44A). Exogenously expressed caveolin-1 colocalized with M-NR and upregulated M-NR internalization in HepG2 cells expressing low level of endogenous caveolin-1, while caveolin-1 dominant negative mutant (caveolin-1 Y14F) significantly downregulated M-NR internalization in C6 cells expressing high level of endogenous caveolin-1. Exogenously expressed clathrin light chain A (clathrin LCa) did not mainly colocalize with the internalized M-NR and had no effect on M-NR uptake. These results suggested that dynamin- and caveolin-dependent but clathrin-independent endocytosis was involved in M-NR cellular uptake. We further found that M-NR colocalized with lysosome and microtubulin after internalization. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nuclear receptor-mediated regulation of carboxylesterase expression and activity.

PubMed

Staudinger, Jeff L; Xu, Chenshu; Cui, Yue J; Klaassen, Curtis D

2010-03-01

Emerging evidence demonstrates that several nuclear receptor (NR) family members regulate drug-inducible expression and activity of several important carboxylesterase (CES) enzymes in mammalian liver and intestine. Numerous clinically prescribed anticancer prodrugs, carbamate and pyrethroid insecticides, environmental toxicants and procarcinogens are substrates for CES enzymes. Moreover, a key strategy used in rational drug design frequently utilizes an ester linkage methodology to selectively target a prodrug, or to improve the water solubility of a novel compound. This review summarizes the current state of knowledge regarding NR-mediated regulation of CES enzymes in mammals and highlights their importance in drug metabolism, drug-drug interactions and toxicology. New knowledge regarding the transcriptional regulation of CES enzymes by NR proteins pregnane x receptor (NR1I2) and constitutive androstane receptor (NR1I3) has recently come to light through the use of knockout and transgenic mouse models. Novel insights regarding the species-specific cross-regulation of glucocorticoid receptor (NR3C1) and PPAR-alpha (NR1C1) signaling and CES gene expression are discussed. Elucidation of the role of NR-mediated regulation of CES enzymes in liver and intestine will have a significant impact on rational drug design and the development of novel prodrugs, especially for patients on combination therapy.

How Does the Surface of Al-ITQ-HB 2D-MOF Condition the Intermolecular Interactions of an Adsorbed Organic Molecule?

PubMed

Caballero-Mancebo, Elena; Moreno, José María; Corma, Avelino; Díaz, Urbano; Cohen, Boiko; Douhal, Abderrazzak

2018-05-30

In this work, we unravel how the two-dimensional Al-ITQ-4-heptylbenzoic acid (HB) metal-organic framework (MOF) changes the interactions of Nile red (NR) adsorbed on its surface. Time-resolved emission experiments indicate the occurrence of energy transfer between adsorbed NR molecules, in abnormally long time constant of 2-2.5 ns, which gets shorter (∼0.25 ns) when the concentration of the surface-adsorbed NR increases. We identify the emission from local excited state of aggregates and charge transfer and energy transfer between adsorbed molecules. Femtosecond emission studies reveal an ultrafast process (∼425 fs) in the NR@Al-ITQ-HB composites, assigned to an intramolecular charge transfer in NR molecules. A comparison of the observed photobehavior with that of NR/SiO 2 and NR/Al 2 O 3 composites suggests that the occurrence of energy transfer in the NR@MOF complexes is a result of specific and nonspecific interactions, reflecting the different surface properties of Al-ITQ-HB that are of relevance to the reported high catalytic activity. Our results provide new knowledge for further researches on other composites with the aim to improve understanding of photocatalytic and photonic processes within MOFs.

Market Driven Space Exploration

NASA Astrophysics Data System (ADS)

Gavert, Raymond B.

2004-02-01

Market driven space exploration will have the opportunity to develop to new levels with the coming of space nuclear power and propulsion. NASA's recently established Prometheus program is expected to receive several billion dollars over the next five years for developing nuclear power and propulsion systems for future spacecraft. Not only is nuclear power and propulsion essential for long distance Jupiter type missions, but it also important for providing greater access to planets and bodies nearer to the Earth. NASA has been working with industrial partners since 1987 through its Research Partnerships Centers (RPCs) to utilize the attributes of space in Low Earth Orbit (LEO). Plans are now being made to utilize the RPCs and industrial partners in extending the duration and boundaries of human space flight to create new opportunities for exploration and discovery. Private investors are considering setting up shops in LEO for commercial purposes. The trend is for more industrial involvement in space. Nuclear power and propulsion will hasten the progress. The objective of this paper is to show the progression of space market driven research and its potential for supporting space exploration given nuclear power and propulsion capabilities.

Intelligent on-board system for driving assistance

NASA Astrophysics Data System (ADS)

Rombaut, Michele; Le Fort-Piat, N.

1995-09-01

We present in this paper, an electronic copilot embedded in a real car. The system objective is to help the driver by sending alarms or warnings in order to avoid dangerous situtations. An onboard perception system based on CCD cameras and proprioceptive sensors is used ot provide information concerning the environment and the internal state of the vehicle. From this set of information, the copilot is able to analyze the situation and to generate adequate warnings to the driver according to the circumstances. The definition and the development of such a system deal with multisensor data fusion and supervision strategies. The framework of this work was the European Prometheus Pro-Art program. The electronic copilot has been integrated in a prototype vehicle called Prolab2. This French demonstrator integrates the works of nine research laboratories and two car companies: PSA and RENAULT. After a brief presentation of the global demonstrator, we present the two principal parts developed in our laboratory corresponding to the high level modules of the system: the dynamic data manager and the situation supervision.

A Power Conversion Concept for the Jupiter Icy Moons Orbiter

NASA Technical Reports Server (NTRS)

Mason, Lee S.

2003-01-01

The Jupiter Icy Moons Orbiter (JIMO) mission is currently under study by the Office of Space Science under the Project Prometheus Program. JIMO is examining the use of Nuclear Electric Propulsion (NEP) to carry scientific payloads to three Jovian moons. A potential power system concept includes dual 100 kWe Brayton converters, a deployable pumped loop heat rejection subsystem, and a 400 Vac Power Management and Distribution (PMAD) bus. Many trades were performed in aniving at this candidate power system concept. System-level studies examined design and off-design operating modes, determined startup requirements, evaluated subsystem redundancy options, and quantified the mass and radiator area of reactor power systems from 20 to 200 kWe. In the Brayton converter subsystem, studies were performed to investigate converter packaging options, and assess the induced torque effects on spacecraft dynamics due to rotating machinery. In the heat rejection subsystem, design trades were conducted on heat transport approaches, material and fluid options, and deployed radiator geometries. In the PMAD subsystem, the overall electrical architecture was defined and trade studies examined distribution approaches, voltage levels, and cabling options.

Design and Integration of a Three Degrees-of-Freedom Robotic Vehicle with Control Moment Gyro for the Autonomous Multi-Agent Physically Interacting Spacecraft (AMPHIS) Testbed

DTIC Science & Technology

2006-09-01

required directional control for each thruster due to their high precision and equivalent power and computer interface requirements to those for the...Universal Serial Bus) ports, LPT (Line Printing Terminal) and KVM (Keyboard-Video- Mouse) interfaces. Additionally, power is supplied to the computer through...of the IDE cable to the Prometheus Development Kit ACC-IDEEXT. Connect a small drive power connector from the desktop ATX power supply to the ACC

Scalloped Hibachi and Vacuum-Pressure Foil for Electra: Electron Beam Pumped KrF Laser

DTIC Science & Technology

2007-06-01

confinement fusion energy (IFE) applications [1-8]. The foils are a critical part of this durability and efficiency. The electron beam, generated in a high...and A. W. Maschke, “Design descriptions of the Prometheus- L and -H inertial fusion energy drivers,” Fusion Engineering and Design, vol. 25, pp...inertial fusion energy ,” Fusion Engineering and Design, vol. 44, pp. 371-375, March 1999. [4] I. Okuda, e. Takahashi, and Y. Owadano, “A

Morphological explanation of high tear resistance of EPDM/NR rubber blends.

PubMed

Gögelein, Christoph; Beelen, Henri Jacob Hubert; van Duin, Martin

2017-06-14

The fatigue properties of cross-linked blends of ethylene propylene diene rubber (EPDM) with low natural rubber (NR) content and reinforced with carbon black (CB) are studied. It is found that such EPDM/NR compounds have superior crack growth resistance and fatigue lifetime. For low NR contents, transmission electron microscopy reveals that the NR phase forms small droplets of 20-50 nm. Remarkably, these droplets are even smaller than the primary CB particles. Atomic force microscopy shows that the the NR phase droplets have a higher loss factor and a smaller elastic modulus than the surrounding EPDM matrix. Rheometer measurements are used to study the effect of the phase morphology on the rubber mechanical properties. These rheological data are compared with the prediction of the Eshelby model describing the effect of elastic inclusions on solids. A complex interplay between the rubber phase morphology and the solubility of both the sulfur cross-linking system and CB is observed, which cannot be predicted theoretically. It is proposed that the soft NR droplets effectively inhibit the crack propagation in the EPDM matrix.

Preliminary study of semi-refined carrageenan (SRC) as secondary gelling agent in natural rubber (NR) latex foam

NASA Astrophysics Data System (ADS)

Norhazariah, S.; Azura, A. R.; Azahari, B.; Sivakumar, R.

2017-12-01

Semi-refined carrageenan (SRC) product is considerably cheaper and easier to produce as a natural polysaccharide, which was utilized in food and other product application. However, the application in latex is limited. The aim of this work is to evaluate the SRC produced from low industrial grade seaweed (LIGS) in the latex foam application. The FTIR spectra showed the SRC produced as kappa type carrageenan with lower sulfur content compared to native LIGS. NR latex foam is produced by using the Dunlop method with some modifications. The effect of SRC loading as a secondary gelling agent in NR latex foam is investigated. The density and morphology of the NR latex foam with the addition of the SRC are analyzed. NR latex foam density increased with SRC loading and peaked at 1.8 phr SRC. The addition of SRC has induced the bigger cell size compared to the cell size of the control NR latex foam, as shown in the optical micrograph. It can be concluded that SRC LIGS could be acted as secondary gelling agent in NR latex foam.

Tensile and morphology properties of PLA/LNR blends modified with maleic anhydride grafted-polylactic acid and -natural rubber

NASA Astrophysics Data System (ADS)

Ruf, Mohd Farid Hakim Mohd; Ahmad, Sahrim; Chen, Ruey Shan; Shahdan, Dalila; Zailan, Farrah Diyana

2018-04-01

This research was carried out to investigate the addition of grafted copolymers of maleic anhydride grafted-polylactic acid(PLA-g-MA) and maleic anhydride grafted-natural rubber (NR-g-MA) on the tensile and morphology properties of polylactic acid/ liquid natural rubber (PLA/LNR) blends. Prior to blend preparation, the PLA-g-MA and NR-g-MA was first self-synthesized using maleic anhydride (MA) and dicumyl peroxide (DCP) as initiator together with the PLA and NR respectively. The PLA/LNR, PLA/LNR/PLA-g-MA and PLA/LNR/NR-g-MA blends were prepared via melt-blending method. The loading of PLA-g-MA and NR-g-MA was varied by 5, 10 and 15 wt% respectively. The addition of PLA-g-MA led to increment in tensile strength with 5 and 10 wt% while NR-g-MA gives lower than controlled sample (PLA/LNR blend). Scanning electron microscope (SEM) showed the interaction of the components in the blends. The PLA/LNR compatibilized with PLA-g-MA and NR-g-MA shows greater dispersion and adhesion.

Assimilation of NAD(+) precursors in Candida glabrata.

PubMed

Ma, Biao; Pan, Shih-Jung; Zupancic, Margaret L; Cormack, Brendan P

2007-10-01

The yeast pathogen Candida glabrata is a nicotinamide adenine dinucleotide (NAD(+)) auxotroph and its growth depends on the environmental supply of vitamin precursors of NAD(+). C. glabrata salvage pathways defined in this article allow NAD(+) to be synthesized from three compounds - nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NA is salvaged through a functional Preiss-Handler pathway. NAM is first converted to NA by nicotinamidase and then salvaged by the Preiss-Handler pathway. Salvage of NR in C. glabrata occurs via two routes. The first, in which NR is phosphorylated by the NR kinase Nrk1, is independent of the Preiss-Handler pathway. The second is a novel pathway in which NR is degraded by the nucleosidases Pnp1 and Urh1, with a minor role for Meu1, and ultimately converted to NAD(+) via the nicotinamidase Pnc1 and the Preiss-Handler pathway. Using C. glabrata mutants whose growth depends exclusively on the external NA or NR supply, we also show that C. glabrata utilizes NR and to a lesser extent NA as NAD(+) sources during disseminated infection.

Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis

PubMed Central

Barbaro, Michela; Cook, Jackie; Lagerstedt-Robinson, Kristina; Wedell, Anna

2012-01-01

A 160 kb minimal common region in Xp21 has been determined as the cause of XY gonadal dysgenesis, if duplicated. The region contains the MAGEB genes and the NR0B1 gene; this is the candidate for gonadal dysgenesis if overexpressed. Most patients present gonadal dysgenesis within a more complex phenotype. However, few independent cases have recently been described presenting with isolated XY gonadal dysgenesis caused by relatively small NR0B1 locus duplications. We have identified another NR0B1 duplication in two sisters with isolated XY gonadal dysgenesis with an X-linked inheritance pattern. We performed X-inactivation studies in three fertile female carriers of three different small NR0B1 locus duplications identified by our group. The carrier mothers did not show obvious skewing of X-chromosome inactivation, suggesting that NR0B1 overexpression does not impair ovarian function. We furthermore emphasize the importance to investigate the NR0B1 locus also in patients with isolated XY gonadal dysgenesis. PMID:22518125

Closed-Cycle Engine Program Used to Study Brayton Power Conversion

NASA Technical Reports Server (NTRS)

Johnson, Paul K.

2005-01-01

One form of power conversion under consideration in NASA Glenn Research Center's Thermal Energy Conversion Branch is the closed-Brayton-cycle engine. In the tens-of-kilowatts to multimegawatt class, the Brayton engine lends itself to potential space nuclear power applications such as electric propulsion or surface power. The Thermal Energy Conversion Branch has most recently concentrated its Brayton studies on electric propulsion for Prometheus. One piece of software used for evaluating such designs over a limited tradeoff space has been the Closed Cycle Engine Program (CCEP). The CCEP originated in the mid-1980s from a Fortran aircraft engine code known as the Navy/NASA Engine Program (NNEP). Components such as a solar collector, heat exchangers, ducting, a pumped-loop radiator, a nuclear heat source, and radial turbomachinery were added to NNEP, transforming it into a high-fidelity design and performance tool for closed-Brayton-cycle power conversion and heat rejection. CCEP was used in the 1990s in conjunction with the Solar Dynamic Ground Test Demonstration conducted at Glenn. Over the past year, updates were made to CCEP to adapt it for an electric propulsion application. The pumped-loop radiator coolant can now be n-heptane, water, or sodium-potassium (NaK); liquid-metal pump design tables were added to accommodate the NaK fluid. For the reactor and shield, a user can now elect to calculate a higher fidelity mass estimate. In addition, helium-xenon working-fluid properties were recalculated and updated.

Latex improvement of recycled asphalt pavement

NASA Astrophysics Data System (ADS)

Drennon, C.

1982-08-01

The performance of a single unmodified milled recycled asphalt concrete was compared to milled asphalt concrete modified by addition of three types of rubber latex. Latex was added at 2, 3, 5, and 8 percent latex by weight of asphalt in the asphalt concrete. Lattices used were a styrene butadiene (SBR), a natural rubber (NR), an acrylonitrile butadiene (NBR), and four varieties of out of specification SBR lattices. Marshall tests, while indecisive, showed a modest improvement in properties of SBR and NR added material at 3 and 5 percent latex. Addition of NBR latex caused deterioration in Marshall stability and flow over that of control. Repeated load tests were run using the indirect tensile test, analyzed by the VESYS program, which computes life of pavements. Repeated load tests showed improvement in asphalt concrete life when 3 and 5 percent SBR was added. Improvement was also shown by the out of specification SBR.

NR2A- and NR2B-Containing NMDA Receptors in the Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, and Contextual Fear Conditioning

ERIC Educational Resources Information Center

Gilmartin, Marieke R.; Kwapis, Janine L.; Helmstetter, Fred J.

2013-01-01

Activation of "N"-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially…

Crosslinked bicontinuous biobased PLA/NR blends via dynamic vulcanization using different curing systems.

PubMed

Yuan, Daosheng; Chen, Kunling; Xu, Chuanhui; Chen, Zhonghua; Chen, Yukun

2014-11-26

In this study, blends of entirely biosourced polymers, namely polylactide (PLA) and natural rubber (NR), were prepared through dynamic vulcanization using dicumyl peroxide (DCP), sulphur (S) and phenolic resin (2402) as curing agents, respectively. The crosslinked NR phase was found to be a continuous structure in all the prepared blends. The molecular weight changes of PLA were studied by gel permeation chromatography. Interfacial compatibilization between PLA and NR was investigated using Fourier transform infrared spectroscopy and scanning electron microscopy. The thermal properties of blends were evaluated by differential scanning calorimetry and thermogravimetric analysis instrument. It was found that the molecular weight of PLA and interfacial compatibilizaion between PLA and NR showed a significant influence on the mechanical and thermal properties of blends. The PLA/NR blend (60/40 w/w) by DCP-induced dynamic vulcanization owned the finest mechanical properties and thermal stability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Associations between ADHD symptoms and smoking outcome expectancies in a non-clinical sample of daily cigarette smokers.

PubMed

Goldenson, Nicholas I; Pang, Raina D; Leventhal, Adam M

2016-03-01

Smoking outcome expectancies for positive reinforcement (PR: beliefs that smoking produces desirable outcomes) and negative reinforcement (NR: beliefs that smoking alleviates negative affect) are modifiable cognitive manifestations of affect-mediated smoking motivation. Based on prior data and theory, we hypothesized that NR and PR expectancies are associated with ADHD symptom levels in a non-clinical sample of cigarette smokers. (Am J Addict 2016; XX:XX -XX) METHODS: Daily cigarette smokers (N = 256) completed self-report measures of ADHD symptoms and smoking outcome expectancies. Cross-sectional associations of overall ADHD symptomatology and the ADHD symptom dimensions of inattention (IN: difficulty concentrating and distractibility) and hyperactivity impulsivity (HI: poor inhibitory control and motor activity restlessness) with PR and NR smoking outcome expectancies were examined. Higher levels of overall, IN and HI ADHD symptoms were positively associated with NR smoking expectancies after statistically controlling for anxiety, depression, alcohol/drug use problems, nicotine dependence, and other smoking expectancies. Although neither HI nor IN symptom dimensions exhibited empirically unique relations to NR expectancies over and above one another, the collective variance across IN and HI was associated with NR expectancies. PR expectancies were not associated with ADHD symptoms. Although PR and NR expectancies may be important etiological influences in the overall population of smokers, NR outcome expectancies appear to be disproportionately expressed in smokers with elevated ADHD symptoms. Cognitive manifestations of NR motivation, which may be modifiable via intervention, are prominent in smokers with elevated ADHD symptoms. Beliefs that smoking alleviates negative affect may underlie ADHD-smoking comorbidity. © American Academy of Addiction Psychiatry.

Binding of naringin and naringenin with hen egg white lysozyme: A spectroscopic investigation and molecular docking study

NASA Astrophysics Data System (ADS)

Das, Sourav; Ghosh, Pooja; Koley, Sudipta; Singha Roy, Atanu

2018-03-01

The interactions of naringenin (NG) and naringin (NR) with Hen Egg White Lysozyme (HEWL) in aqueous medium have been investigated using UV-vis spectroscopy, steady-state fluorescence, circular dichroism (CD), Fourier Transform infrared spectroscopy (FT-IR) and molecular docking analyses. Both NG and NR can quench the intrinsic fluorescence of HEWL via static quenching mechanism. At 300 K, the value of binding constant (Kb) of HEWL-NG complex (5.596 ± 0.063 × 104 M- 1) was found to be greater than that of HEWL-NR complex (3.404 ± 0.407 × 104 M- 1). The negative ΔG° values in cases of both the complexes specify the spontaneous binding. The binding distance between the donor (HEWL) and acceptor (NG/NR) was estimated using the Försters theory and the possibility of non-radiative energy transfer from HEWL to NG/NR was observed. The presence of metal ions (Ca2 +, Cu2 + and Fe2 +) decreased the binding affinity of NG/NR towards HEWL. Synchronous fluorescence studies indicate the change in Trp micro-environment due to the incorporation of NG/NR into HEWL. CD and FT-IR studies indicated that the α-helicity of the HEWL was slightly enhanced due to ligand binding. NG and NR inhibited the enzymatic activity of HEWL and exhibited their affinity for the active site of HEWL. Molecular docking studies revealed that both NG and NR bind in the close vicinity of Trp 62 and Trp 63 residues which is vital for the catalytic activity.

Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet.

PubMed

Shi, Wenbiao; Hegeman, Maria A; van Dartel, Dorien A M; Tang, Jing; Suarez, Manuel; Swarts, Hans; van der Hee, Bart; Arola, Lluis; Keijer, Jaap

2017-08-01

Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined here for a wide range of NR. Nine-week-old male C57BL/6JRcc mice received a semi-purified mildly obesogenic (40 en% fat) diet containing 0.14% L-tryptophan and either 5, 15, 30, 180, or 900 mg NR per kg diet for 15 weeks. Body composition and metabolic parameters were analyzed. Metabolic flexibility was measured using indirect calorimetry. Gene expression in epididymal white adipose tissue (eWAT) was measured using qRT-PCR . The maximum delta respiratory exchange ratio when switching from CHO to FAO (maxΔRER CHO1→FAO ) and when switching from FAO to CHO (maxΔRER FAO→CHO2 ) were largest in 30 mg NR per kg diet (30NR). In eWAT, the gene expression of Pparγ, a master regulator of adipogenesis, and of Sod2 and Prdx3, two antioxidant genes, were significantly upregulated in 30NR compared to 5NR. 30NR is most beneficial for metabolic health, in terms of metabolic flexibility and eWAT gene expression, of mice on an obesogenic diet. © 2017 The Authors. Molecular Nutrition & Food Research published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals.

PubMed

Domenice, Sorahia; Machado, Aline Zamboni; Ferreira, Frederico Moraes; Ferraz-de-Souza, Bruno; Lerario, Antonio Marcondes; Lin, Lin; Nishi, Mirian Yumie; Gomes, Nathalia Lisboa; da Silva, Thatiana Evelin; Silva, Rosana Barbosa; Correa, Rafaela Vieira; Montenegro, Luciana Ribeiro; Narciso, Amanda; Costa, Elaine Maria Frade; Achermann, John C; Mendonca, Berenice Bilharinho

2016-12-01

Steroidogenic factor 1 (NR5A1, SF-1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype-phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian-determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1-related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever-expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction. Birth Defects Research (Part C) 108:309-320, 2016. © 2016 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc. © 2016 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc.

The novel fusion transcript NR5A2-KLHL29FT is generated by an insertion at the KLHL29 locus.

PubMed

Sun, Zhenguo; Ke, Xiquan; Salzberg, Steven L; Kim, Daehwan; Antonescu, Valentin; Cheng, Yulan; Huang, Binbin; Song, Jee Hoon; Abraham, John M; Ibrahim, Sariat; Tian, Hui; Meltzer, Stephen J

2017-05-01

Novel fusion transcripts (FTs) caused by chromosomal rearrangement are common factors in the development of cancers. In the current study, the authors used massively parallel RNA sequencing to identify new FTs in colon cancers. RNA sequencing (RNA-Seq) and TopHat-Fusion were used to identify new FTs in colon cancers. The authors then investigated whether the novel FT nuclear receptor subfamily 5, group A, member 2 (NR5A2)-Kelch-like family member 29 FT (KLHL29FT) was transcribed from a genomic chromosomal rearrangement. Next, the expression of NR5A2-KLHL29FT was measured by quantitative real-time polymerase chain reaction in colon cancers and matched corresponding normal epithelia. The authors identified the FT NR5A2-KLHL29FT in normal and cancerous epithelia. While investigating this transcript, it was unexpectedly found that it was due to an uncharacterized polymorphic germline insertion of the NR5A2 sequence from chromosome 1 into the KLHL29 locus at chromosome 2, rather than a chromosomal rearrangement. This germline insertion, which occurred at a population frequency of 0.40, appeared to bear no relationship to cancer development. Moreover, expression of NR5A2-KLHL29FT was validated in RNA specimens from samples with insertions of NR5A2 at the KLHL29 gene locus, but not from samples without this insertion. It is interesting to note that NR5A2-KLH29FT expression levels were significantly lower in colon cancers than in matched normal colonic epithelia (P =.029), suggesting the potential participation of NR5A2-KLHL29FT in the origin or progression of this tumor type. NR5A2-KLHL29FT was generated from a polymorphism insertion of the NR5A2 sequence into the KLHL29 locus. NR5A2-KLHL29FT may influence the origin or progression of colon cancer. Moreover, researchers should be aware that similar FTs may occur due to transchromosomal insertions that are not correctly annotated in genome databases, especially with current assembly algorithms. Cancer 2017;123:1507-1515. © 2017 American Cancer Society. © 2016 American Cancer Society.

[Effect of electroacupuncture on expression of ionotropic glutamate receptor subunits and their genes in lumbar segments of spinal cord in rats with neuropathic pain].

PubMed

Ma, Cheng; Yu, Li; Yan, Li-ping

2010-12-01

To observe the effect of electroacupuncture (EA) on the expression of ionotropic glutamate receptor (iGluR) subunits and their mRNAs in the lumbar segments of spinal cord in rats with neuropathic pain, so as to explore its underlying mechanism in relieving spinal hyperalgesia. Thirty SD rats were randomly divided into control, model, and EA groups, with 10 rats in each. The spared nerve injury (SNI) model was established by ligature of the sural nerve after cutting off the common peroneal nerve and anterior tibial nerve. EA (2 Hz, 1 mA) was applied to "Huantiao" (GB 30) and "Weizhong" (BL 40) for 30 min, once daily for 7 days. Mechanical pain threshold was detected before and after modeling and before and after EA treatment. The expression levels of N-methyl-d-aspartic acid (NMDA) receptor subunits NR1 and NR 2 B,and AMPA receptor subunit GluR 1 of iGluR and their genes were assayed by Western blot and reverse transcription polymerase chain reaction (RT-PCR) separately. In comparison with control group, the mechanical pain thresholds were decreased significantly on day 2, 7 and day 14 following modeling in the model group (P < 0.05, P < 0.01). While compared with the model group, the pain threshold was increased considerably on day 14 in the EA group (P < 0.01). Compared with the control group, the expression levels of lumbar spinal cord NR 2 B and NR 2 B mRNA in the model group were increased significantly (P < 0.05), and those of lumbar spinal cord NR 1 and NR 1 mRNA, GluR 1 and GluR 1 mRNA in the model group increased slightly (P > 0.05). In comparison with the model group, the expression levels of lumbar spinal cord NR 2 B and NR 2 B mRNA in the EA group were downregulated remarkably (P < 0.05), and those of lumbar spinal cord NR 1 and NR 1 mRNA, GluR 1 and GluR 1 mRNA in the EA group down-regulated slightly (P > 0.05). EA can significantly suppress pain reaction in rats with neuropathic pain probably through down-regulating the expression of lumbar spinal cord NR 2 B protein and NR 2 B mRNA.

NR2A contributes to genesis and propagation of cortical spreading depression in rats.

PubMed

Bu, Fan; Du, Ruoxing; Li, Yi; Quinn, John P; Wang, Minyan

2016-03-22

Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 μM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile.

NR2A contributes to genesis and propagation of cortical spreading depression in rats

PubMed Central

Bu, Fan; Du, Ruoxing; Li, Yi; Quinn, John P; Wang, Minyan

2016-01-01

Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 μM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile. PMID:27001011

CDRI-08 Attenuates REST/NRSF-Mediated Expression of NMDAR1 Gene in PBDE-209-Exposed Mice Brain.

PubMed

Verma, Priya; Gupta, Rajaneesh K; Gandhi, Behrose S; Singh, Poonam

2015-01-01

CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the mechanism, present study was designed to examine the role of CDRI-08 on the expression of NMDAR1 (NR1) and the binding of REST/NRSF to NR1 promoter against postnatal exposure of PBDE-209. Male mice pups were orally supplemented with CDRI-08 at the doses of 40, 80, or 120 mg/kg along with PBDE-209 (20 mg/kg) during PND 3-10 and frontal cortex and hippocampus were collected at PND 11 and 60 to study the expression and regulation of NR1 by RT-PCR and electrophoretic mobility shift assay, respectively. The findings showed upregulated expression of NR1 and decreased binding of REST/NRSF to NR1 promoter after postnatal exposure of PBDE-209. Interestingly, supplementation with CDRI-08 significantly restored the expression of NR1 and binding of REST/NRSF to NR1 promoter near to the control value at the dose of 120 mg/kg. In conclusion, the results suggest that CDRI-08 possibly acts on glutamatergic system through expression and regulation of NR1 and may restore memory, impaired by PBDE-209 as reported in our previous study.

Sources and processes contributing to nitrogen deposition: an adjoint model analysis applied to biodiversity hotspots worldwide.

PubMed

Paulot, Fabien; Jacob, Daniel J; Henze, Daven K

2013-04-02

Anthropogenic enrichment of reactive nitrogen (Nr) deposition is an ecological concern. We use the adjoint of a global 3-D chemical transport model (GEOS-Chem) to identify the sources and processes that control Nr deposition to an ensemble of biodiversity hotspots worldwide and two U.S. national parks (Cuyahoga and Rocky Mountain). We find that anthropogenic sources dominate deposition at all continental sites and are mainly regional (less than 1000 km) in origin. In Hawaii, Nr supply is controlled by oceanic emissions of ammonia (50%) and anthropogenic sources (50%), with important contributions from Asia and North America. Nr deposition is also sensitive in complicated ways to emissions of SO2, which affect Nr gas-aerosol partitioning, and of volatile organic compounds (VOCs), which affect oxidant concentrations and produce organic nitrate reservoirs. For example, VOC emissions generally inhibit deposition of locally emitted NOx but significantly increase Nr deposition downwind. However, in polluted boreal regions, anthropogenic VOC emissions can promote Nr deposition in winter. Uncertainties in chemical rate constants for OH + NO2 and NO2 hydrolysis also complicate the determination of source-receptor relationships for polluted sites in winter. Application of our adjoint sensitivities to the representative concentration pathways (RCPs) scenarios for 2010-2050 indicates that future decreases in Nr deposition due to NOx emission controls will be offset by concurrent increases in ammonia emissions from agriculture.

Annotation of the Nuclear Receptors in an Estuarine Fish species, Fundulus heteroclitus

PubMed Central

Baldwin, William S.; Boswell, W. Tyler; Ginjupalli, Gautam; Litoff, Elizabeth J.

2017-01-01

The nuclear receptors (NRs) are ligand-dependent transcription factors that respond to various internal as well as external cues such as nutrients, pheromones, and steroid hormones that play crucial roles in regulation and maintenance of homeostasis and orchestrating the physiological and stress responses of an organism. We annotated the Fundulus heteroclitus (mummichog; Atlantic killifish) nuclear receptors. Mummichog are a non-migratory, estuarine fish with a limited home range often used in environmental research as a field model for studying ecological and evolutionary responses to variable environmental conditions such as salinity, oxygen, temperature, pH, and toxic compounds because of their hardiness. F. heteroclitus have at least 74 NRs spanning all seven gene subfamilies. F. heteroclitus is unique in that no RXRα member was found within the genome. Interestingly, some of the NRs are highly conserved between species, while others show a higher degree of divergence such as PXR, SF1, and ARα. Fundulus like other fish species show expansion of the RAR (NR1B), Rev-erb (NR1D), ROR (NR1F), COUPTF (NR2F), ERR (NR3B), RXR (NR2B), and to a lesser extent the NGF (NR4A), and NR3C steroid receptors (GR/AR). Of particular interest is the co-expansion of opposing NRs, Reverb-ROR, and RAR/RXR-COUPTF. PMID:28804711

A pre-steady state and steady state kinetic analysis of the N-ribosyl hydrolase activity of hCD157.

PubMed

Preugschat, Frank; Carter, Luke H; Boros, Eric E; Porter, David J T; Stewart, Eugene L; Shewchuk, Lisa M

2014-12-15

hCD157 catalyzes the hydrolysis of nicotinamide riboside (NR) and nicotinic acid riboside (NAR). The release of nicotinamide or nicotinic acid from NR or NAR was confirmed by spectrophotometric, HPLC and NMR analyses. hCD157 is inactivated by a mechanism-based inhibitor, 2'-deoxy-2'-fluoro-nicotinamide arabinoside (fNR). Modification of the enzyme during the catalytic cycle by NR, NAR, or fNR increased the intrinsic protein fluorescence by approximately 50%. Pre-steady state and steady state data were used to derive a minimal kinetic scheme for the hydrolysis of NR. After initial complex formation a reversible step (360 and 30s(-1)) is followed by a slow irreversible step (0.1s(-1)) that defined the rate limiting step, or kcat. The calculated KMapp value for NR in the hydrolytic reaction is 6nM. The values of the kinetic constants suggest that one biological function of cell-surface hCD157 is to bind and slowly hydrolyze NR, possibly converting it to a ligand-activated receptor. Differences in substrate preference between hCD157 and hCD38 were rationalized through a comparison of the crystal structures of the two proteins. This comparison identified several residues in hCD157 (F108 and F173) that can potentially hinder the binding of dinucleotide substrates (NAD+). Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic disruption of the nuclear receptor Nur77 (Nr4a1) in rat reduces dopamine cell loss and l-Dopa-induced dyskinesia in experimental Parkinson's disease.

PubMed

Rouillard, Claude; Baillargeon, Joanie; Paquet, Brigitte; St-Hilaire, Michel; Maheux, Jérôme; Lévesque, Catherine; Darlix, Noémie; Majeur, Simon; Lévesque, Daniel

2018-06-01

Parkinson's disease (PD) is an idiopathic progressive neurodegenerative disorder characterized by the loss of midbrain dopamine neurons. Levodopa (l-dopa) is the main pharmacological approach to relieve PD motor symptoms. However, chronic treatment with l-Dopa is inevitably associated with the generation of abnormal involuntary movements (l-Dopa-induced dyskinesia). We have previously shown that Nr4a1 (Nur77), a transcription factor of the nuclear receptor family, is closely associated with dopamine neurotransmission in the mature brain. However, the role of Nr4a1 in the etiology of PD and its treatment remain elusive. We report here that the neurotoxin 6-hydroxydopamine in rat lead to a rapid up-regulation of Nr4a1 in the substantia nigra. Genetic disruption of Nr4a1 in rat reduced neurotoxin-induced dopamine cell loss and l-Dopa-induced dyskinesia, whereas virally-driven striatal overexpression of Nr4a1 enhanced or partially restored involuntary movements induced by chronic l-Dopa in wild type and Nr4a1-deficient rats, respectively. Collectively, these results suggest that Nr4a1 is involved in dopamine cell loss and l-Dopa-induced dyskinesia in experimental PD. Copyright © 2018 Elsevier Inc. All rights reserved.

Using nitrogen concentration and isotopic composition in lichens to spatially assess the relative contribution of atmospheric nitrogen sources in complex landscapes.

PubMed

Pinho, P; Barros, C; Augusto, S; Pereira, M J; Máguas, C; Branquinho, C

2017-11-01

Reactive nitrogen (Nr) is an important driver of global change, causing alterations in ecosystem biodiversity and functionality. Environmental assessments require monitoring the emission and deposition of both the amount and types of Nr. This is especially important in heterogeneous landscapes, as different land-cover types emit particular forms of Nr to the atmosphere, which can impact ecosystems distinctively. Such assessments require high spatial resolution maps that also integrate temporal variations, and can only be feasibly achieved by using ecological indicators. Our aim was to rank land-cover types according to the amount and form of emitted atmospheric Nr in a complex landscape with multiple sources of N. To do so, we measured and mapped nitrogen concentration and isotopic composition in lichen thalli, which we then related to land-cover data. Results suggested that, at the landscape scale, intensive agriculture and urban areas were the most important sources of Nr to the atmosphere. Additionally, the ocean greatly influences Nr in land, by providing air with low Nr concentration and a unique isotopic composition. These results have important consequences for managing air pollution at the regional level, as they provide critical information for modeling Nr emission and deposition across regional as well as continental scales. Copyright © 2017 Elsevier Ltd. All rights reserved.

A flexible and transparent graphene/ZnO nanorod hybrid structure fabricated by exfoliating a graphite substrate

NASA Astrophysics Data System (ADS)

Nam, Gwang-Hee; Baek, Seong-Ho; Cho, Chang-Hee; Park, Il-Kyu

2014-09-01

We demonstrate the fabrication of a graphene/ZnO nanorod (NR) hybrid structure by mechanical exfoliation of ZnO NRs grown on a graphite substrate. We confirmed the existence of graphene sheets on the hybrid structure by analyzing the Raman spectra and current-voltage (I-V) characteristics. The Raman spectra of the exfoliated graphene/ZnO NR hybrid structure show G and 2D band peaks that are shifted to lower wavenumbers, indicating that the exfoliated graphene layer exists under a significant amount of strain. The I-V characteristics of the graphene/ZnO NR hybrid structure show current flow through the graphene layer, while no current flow is observed on the ZnO NR/polydimethylsiloxane (PDMS) composite without graphene, thereby indicating that the few-layer graphene was successfully transferred onto the hybrid structure. A piezoelectric nanogenerator is demonstrated by using the fabricated graphene/ZnO NR hybrid structure. The nanogenerator exhibits stable output voltage up to 3.04 V with alternating current output characteristics.We demonstrate the fabrication of a graphene/ZnO nanorod (NR) hybrid structure by mechanical exfoliation of ZnO NRs grown on a graphite substrate. We confirmed the existence of graphene sheets on the hybrid structure by analyzing the Raman spectra and current-voltage (I-V) characteristics. The Raman spectra of the exfoliated graphene/ZnO NR hybrid structure show G and 2D band peaks that are shifted to lower wavenumbers, indicating that the exfoliated graphene layer exists under a significant amount of strain. The I-V characteristics of the graphene/ZnO NR hybrid structure show current flow through the graphene layer, while no current flow is observed on the ZnO NR/polydimethylsiloxane (PDMS) composite without graphene, thereby indicating that the few-layer graphene was successfully transferred onto the hybrid structure. A piezoelectric nanogenerator is demonstrated by using the fabricated graphene/ZnO NR hybrid structure. The nanogenerator exhibits stable output voltage up to 3.04 V with alternating current output characteristics. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02318h

Constructing a Multiple Covalent Interface and Isolating a Dispersed Structure in Silica/Rubber Nanocomposites with Excellent Dynamic Performance.

PubMed

Zheng, Junchi; Han, Dongli; Zhao, Suhe; Ye, Xin; Wang, Yiqing; Wu, Youping; Dong, Dong; Liu, Jun; Wu, Xiaohui; Zhang, Liqun

2018-06-13

Realizing and manipulating a fine dispersion of silica nanoparticles (NPs) in the polymer matrix is always a great challenge. In this work, we first successfully synthesized N, N'-bis[3-(triethoxysilyl)propyl-isopropanol]-propane-1,3-diamine (TSPD), which was a new interface modifier, aiming to promote the dispersion of silica NPs. Through Fourier transform infrared spectroscopy, nuclear magnetic resonance analysis, and mass spectroscopy, we verified that TSPD contains together six ethoxy groups at its two ends. Then, we used this TSPD to modify the pure silica NPs, and this modified silica was abbreviated as D-MS, which is realized by the thermal gravimetric analysis examination, scanning electron microscopy analysis, and dynamic light scattering results. It was clearly observed that D-MS NPs are connected to one another but are not conglutinated tightly, exhibiting a novel predispersed structure with around 1-2 nm certain extent of interparticle distance. Next, we fabricated the following four elastomer nanocomposites such as pure silica/natural rubber (NR) composite (PS-NR), D-MS/NR composite (DMS-NR), bis-(γ-triethoxysilylpropyl)-tetrasulfide (TESPT)-modified silica/NR composite (TS-NR), and TESPT-modified D-MS/NR composite (T&DMS-NR) and found that the Payne effect is the smallest for T&DMS-NR via the combination use of the D-MS and the traditional coupling agent TESPT, which is attributed to its best dispersion state evidenced by the transmission electron microscopy results. Moreover, by measuring a series of other important mechanical performances such as the stress-strain curve, the dynamic strain dependence of the loss factor, and the heat build-up, we concluded that the T&DMS-NR system greatly exceeds those of the three other rubber composites. In general, this new approach provides a good opportunity to prepare a silica/rubber composite with excellent properties in mechanical strength and dynamic behavior by tailoring the fine dispersion of NPs.

IGF-1-Involved Negative Feedback of NR2B NMDA Subunits Protects Cultured Hippocampal Neurons Against NMDA-Induced Excitotoxicity.

PubMed

Li, Yun; Sun, Wei; Han, Song; Li, Jianing; Ding, Shu; Wang, Wei; Yin, Yanling

2017-01-01

Insulin-like growth factor 1 (IGF-1) is a multifunctional protein involved in neuronal polarity and axonal guidance. In our previous study, it was discovered that IGF-1 alleviated 50-μM NMDA-induced excitotoxicity against neuronal autophagy via depression of NR2B p-Ser1303 activation. However, it was found that NMDA at a higher dose did not cause neuronal autophagy. And, the performance of IGF-1 under severe excitotoxicity still needs to be clarified. In this study, we observed that IGF-1 can salvage the hippocampal neurons in an autophagy-independent manner after 150-μM NMDA exposure using thiazolyl blue tetrazolium bromide (MTT), lactate dehydrogenase (LDH), Western blot assay, and transmission electron microscopy. In addition, over-activation of post-synaptic NMDARs was found with the whole-cell patch clamp recording method. In order to explore whether there is a positive feedback way for post-synaptic NMDARs and the different pathway caused by 150 μM NMDA, the phosphorylation level of Fyn and the phosphorylation site of NR2B were investigated. It was observed that NR2B p-Tyr1472 was increased by the activation of Fyn after 150-μM NMDA exposure. When the neutralizing antibody against NR2B p-Ser1303 was added into the medium, both the activations of Fyn and NR2B p-Tyr1472 were blocked, suggesting NR2B p-Ser1303 may be the initial step of NMDA-induced excitotoxicity. In addition, since IGF-1 can block the initial step of NR2B activation, its effect is concluded to continue with the development of excitotoxicity. Overall, this study strongly indicates that the relationship between different phosphorylation sites of NR2B should be laid more emphasis on, which may be a vital target for the NR2B-involved excitotoxicity.

GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role of Hippocampal NR2B and DISC1

PubMed Central

Zhou, Dongsheng; Lv, Dan; Wang, Zhen; Zhang, Yanhua; Chen, Zhongming; Wang, Chuang

2018-01-01

Background: Evidence supports that the hypofunction of N-methyl-D-aspartate receptor (NMDAR) and downregulation of disrupted-in-schizophrenia 1 (DISC1) contribute to the pathophysiology of schizophrenia. N-Methyl D-aspartate receptor subtype 2B (NR2B)-containing NMDAR are associated with cognitive dysfunction in schizophrenia. GLYX-13 is an NMDAR glycine-site functional partial agonist and cognitive enhancer that does not induce psychotomimetic side effects. However, it remains unclear whether NR2B plays a critical role in the GLYX-13-induced alleviation of schizophrenia-like behaviors in mice. Methods: The effect of GLYX-13 was tested by observing changes in locomotor activity, novel object recognition ability, and prepulse inhibition (PPI) induced by dizocilpine (known as MK-801) in mice. Lentivirus-mediated NR2B knockdown in the hippocampus was assessed to confirm the role of NR2B in GLYX-13 pathophysiology, using Western blots and immunohistochemistry. Results: The systemic administration of GLYX-13 (0.5 and 1 mg/kg, i.p.) ameliorates MK-801 (0.5 mg/kg, i.p.)-induced hyperlocomotion, deficits in memory, and PPI in mice. Additionally, GLYX-13 normalized the MK-801-induced alterations in signaling molecules, including NR2B and DISC1 in the hippocampus. Furthermore, we found that NR2B knockdown produced memory and PPI deficits without any changes in locomotor activity. Notably, DISC1 levels significantly decreased by NR2B knockdown. However, the effective dose of GLYX-13 did not alleviate the memory and PPI dysfunctions or downregulation of DISC1 induced by NR2B knockdown. Conclusion: Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13. PMID:29695955

Combined serial analysis of gene expression and transcription factor binding site prediction identifies novel-candidate-target genes of Nr2e1 in neocortex development.

PubMed

Schmouth, Jean-François; Arenillas, David; Corso-Díaz, Ximena; Xie, Yuan-Yun; Bohacec, Slavita; Banks, Kathleen G; Bonaguro, Russell J; Wong, Siaw H; Jones, Steven J M; Marra, Marco A; Simpson, Elizabeth M; Wasserman, Wyeth W

2015-07-24

Nr2e1 (nuclear receptor subfamily 2, group e, member 1) encodes a transcription factor important in neocortex development. Previous work has shown that nuclear receptors can have hundreds of target genes, and bind more than 300 co-interacting proteins. However, recognition of the critical role of Nr2e1 in neural stem cells and neocortex development is relatively recent, thus the molecular mechanisms involved for this nuclear receptor are only beginning to be understood. Serial analysis of gene expression (SAGE), has given researchers both qualitative and quantitative information pertaining to biological processes. Thus, in this work, six LongSAGE mouse libraries were generated from laser microdissected tissue samples of dorsal VZ/SVZ (ventricular zone and subventricular zone) from the telencephalon of wild-type (Wt) and Nr2e1-null embryos at the critical development ages E13.5, E15.5, and E17.5. We then used a novel approach, implementing multiple computational methods followed by biological validation to further our understanding of Nr2e1 in neocortex development. In this work, we have generated a list of 1279 genes that are differentially expressed in response to altered Nr2e1 expression during in vivo neocortex development. We have refined this list to 64 candidate direct-targets of NR2E1. Our data suggested distinct roles for Nr2e1 during different neocortex developmental stages. Most importantly, our results suggest a possible novel pathway by which Nr2e1 regulates neurogenesis, which includes Lhx2 as one of the candidate direct-target genes, and SOX9 as a co-interactor. In conclusion, we have provided new candidate interacting partners and numerous well-developed testable hypotheses for understanding the pathways by which Nr2e1 functions to regulate neocortex development.

Preparation of a Nile Red-Pd-based fluorescent CO probe and its imaging applications in vitro and in vivo.

PubMed

Liu, Keyin; Kong, Xiuqi; Ma, Yanyan; Lin, Weiying

2018-05-01

Carbon monoxide (CO) is a key gaseous signaling molecule in living cells and organisms. This protocol illustrates the synthesis of a highly sensitive Nile Red (NR)-Pd-based fluorescent probe, NR-PdA, and its applications for detecting endogenous CO in tissue culture cells, ex vivo organs, and zebrafish embryos. In the NR-PdA synthesis process, 3-diethylamine phenol reacts with sodium nitrite in the acidic condition to afford 5-(diethylamino)-2-nitrosophenol hydrochloride (compound 1), which is further treated with 1-naphthalenol at a high temperature to provide the NR dye via a cyclization reaction. Finally, NR is reacted with palladium acetate to obtain the desired Pd-based fluorescent probe NR-PdA. NR-PdA possesses excellent two-photon excitation and near-IR emission properties, high stability, low background fluorescence, and a low detection limit. In addition to the chemical synthesis procedures, we provide step-by-step procedures for imaging endogenous CO in RAW 264.7 cells, mouse organs ex vivo, and live zebrafish embryos. The synthesis process for the probe requires ∼4 d, and the biological imaging experiments take ∼14 d.

NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors

PubMed Central

Hawk, Joshua D.; Bookout, Angie L.; Poplawski, Shane G.; Bridi, Morgan; Rao, Allison J.; Sulewski, Michael E.; Kroener, Brian T.; Manglesdorf, David J.; Abel, Ted

2012-01-01

The formation of a long-lasting memory requires a transcription-dependent consolidation period that converts a short-term memory into a long-term memory. Nuclear receptors compose a class of transcription factors that regulate diverse biological processes, and several nuclear receptors have been implicated in memory formation. Here, we examined the potential contribution of nuclear receptors to memory consolidation by measuring the expression of all 49 murine nuclear receptors after learning. We identified 13 nuclear receptors with increased expression after learning, including all 3 members of the Nr4a subfamily. These CREB-regulated Nr4a genes encode ligand-independent “orphan” nuclear receptors. We found that blocking NR4A activity in memory-supporting brain regions impaired long-term memory but did not impact short-term memory in mice. Further, expression of Nr4a genes increased following the memory-enhancing effects of histone deacetylase (HDAC) inhibitors. Blocking NR4A signaling interfered with the ability of HDAC inhibitors to enhance memory. These results demonstrate that the Nr4a gene family contributes to memory formation and is a promising target for improving cognitive function. PMID:22996661

Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration

PubMed Central

Mukherjee, Sarmistha; Chellappa, Karthikeyani; Moffitt, Andrea; Ndungu, Joan; Dellinger, Ryan W.; Davis, James G.; Agarwal, Beamon; Baur, Joseph A.

2016-01-01

The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing Nicotinamide phosphoribosyltransferase (Nampt), a rate-limiting enzyme for NAD synthesis, specifically in the liver. Nampt overexpressing mice were mildly hyperglycemic at baseline and, similarly to the mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking Nampt in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR. Conclusion NAD availability is limiting during liver regeneration and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury. PMID:27809334

Antinociceptive effects of oxymatrine from Sophora flavescens, through regulation of NR2B-containing NMDA receptor-ERK/CREB signaling in a mice model of neuropathic pain.

PubMed

Wang, Haiyan; Li, Yuxiang; Dun, Linglu; Xu, Yaqiong; Jin, Shaojv; Du, Juan; Ma, Lin; Li, Juan; Zhou, Ru; He, Xiaoliang; Sun, Tao; Yu, Jianqiang

2013-08-15

In this study we investigated antinociceptive effects of oxymatrine through regulation of NR2B-containing NMDA receptor-ERK/CREB signaling in a chronic neuropathic pain model induced by chronic constrictive injury (CCI) of the sciatic nerve. The von Frey and plantar tests were performed to assess the degree of mechanical and thermal changes respectively. Immunohistochemistry assay was used to evaluate the expressions of NR2B. Western blotting assay were used to evaluate the expressions of NR2B, tERK, p-ERK, tCREB and p-CREB. The intraperitoneal administration of OMT (160, 80 mg/kg) could prevent the development of mechanical allodynia, thermal hyperalgesia induced by CCI. Intraperitoneal administration of OMT decreased the mean IOD of NR2B in the dorsal horn and expression of NR2B, p-ERK and p-CREB protein. Regulation of NMDA NR2B receptor-ERK/CREB signaling maybe the targets for the antinociceptive effects of OMT on a chronic neuropathic pain model induced by chronic constrictive injury of the sciatic nerve. Copyright © 2013 Elsevier GmbH. All rights reserved.

The peculiar shapes of Saturn's small inner moons as evidence of mergers of similar-sized moonlets

NASA Astrophysics Data System (ADS)

Leleu, A.; Jutzi, M.; Rubin, M.

2018-05-01

The Cassini spacecraft revealed the spectacular, highly irregular shapes of the small inner moons of Saturn1, ranging from the unique 'ravioli-like' forms of Pan and Atlas2,3 to the highly elongated structure of Prometheus. Closest to Saturn, these bodies provide important clues regarding the formation process of small moons in close orbits around their host planet4, but their range of irregular shapes has not been explained yet. Here, we show that the spectrum of shapes among Saturn's small moons is a natural outcome of merging collisions among similar-sized moonlets possessing physical properties and orbits that are consistent with those of the current moons. A significant fraction of such merging collisions take place either at the first encounter or after 1-2 hit-and-run events, with impact velocities in the range of 1-5 times the mutual escape velocity. Close to head-on mergers result in flattened objects with large equatorial ridges, as observed on Atlas and Pan. With slightly more oblique impact angles, collisions lead to elongated, Prometheus-like shapes. These results suggest that the current forms of the small moons provide direct evidence of the processes at the final stages of their formation, involving pairwise encounters of moonlets of comparable size4-6. Finally, we show that this mechanism may also explain the formation of Iapetus' equatorial ridge7, as well as its oblate shape8.

Determination of the Potential Benefit of Time-Frequency Gain Manipulation

PubMed Central

Anzalone, Michael C.; Calandruccio, Lauren; Doherty, Karen A.; Carney, Laurel H.

2008-01-01

Objective The purpose of this study was to determine the maximum benefit provided by a time-frequency gain-manipulation algorithm for noise-reduction (NR) based on an ideal detector of speech energy. The amount of detected energy necessary to show benefit using this type of NR algorithm was examined, as well as the necessary speed and frequency resolution of the gain manipulation. Design NR was performed using time-frequency gain manipulation, wherein the gains of individual frequency bands depended on the absence or presence of speech energy within each band. Three different experiments were performed: (1) NR using ideal detectors, (2) NR with nonideal detectors, and (3) NR with ideal detectors and different processing speeds and frequency resolutions. All experiments were performed using the Hearing-in-Noise test (HINT). A total of 6 listeners with normal hearing and 14 listeners with hearing loss were tested. Results HINT thresholds improved for all listeners with NR based on the ideal detectors used in Experiment I. The nonideal detectors of Experiment II required detection of at least 90% of the speech energy before an improvement was seen in HINT thresholds. The results of Experiment III demonstrated that relatively high temporal resolution (<100 msec) was required by the NR algorithm to improve HINT thresholds. Conclusions The results indicated that a single-microphone NR system based on time-frequency gain manipulation improved the HINT thresholds of listeners. However, to obtain benefit in speech intelligibility, the detectors used in such a strategy were required to detect an unrealistically high percentage of the speech energy and to perform the gain manipulations on a fast temporal basis. PMID:16957499

Nonuniformity in natural rubber as revealed by small-angle neutron scattering, small-angle X-ray scattering, and atomic force microscopy.

PubMed

Karino, Takeshi; Ikeda, Yuko; Yasuda, Yoritaka; Kohjiya, Shinzo; Shibayama, Mitsuhiro

2007-02-01

The microscopic structures of natural rubber (NR) and deproteinized NR (DPNR) were investigated by means of small-angle neutron scattering (SANS), small-angle X-ray scattering (SAXS), and atomic force microscopy (AFM). They were compared to those of isoprene rubber (IR), which is a synthetic analogue of NR in terms of chemical structure without any non-rubber components like proteins. Comparisons of the structure and mechanical properties of NR, DPNR, and IR lead to the following conclusions. (i) The well-known facts, for example, the outstanding green strength of NR and strain-induced crystallization, are due not much to the presence of proteins but to other components such as the presence of phospholipids and/or the higher stereoregularity of NR. It also became clear the naturally residing proteins accelerate the upturn of stress at low strain. The protein phases work as cross-linking sites and reinforcing fillers in the rubbery matrix. (ii) The microscopic structures of NR were successfully reproduced by SANS intensity functions consisting of squared-Lorentz and Lorentz functions, indicating the presence of inhomogeneities in bulk and thermal concentration fluctuations in swollen state, respectively. On the other hand, IR rubbers were homogeneous in bulk. (iii) The inhomogeneities in NR are assigned to protein aggregates of the order of 200 A or larger. Although these aggregates are larger in size as well as in volume fraction than those of cross-link inhomogeneities introduced by cross-linking, they are removed by deproteinization. (iv) Swelling of both NR and IR networks introduces gel-like concentration fluctuations whose mesh size is of the order of 20 A.

LRH-1 May Rescue SF-1 Deficiency for Steroidogenesis: An in vitro and in vivo Study.

PubMed

Camats, Núria; Audí, Laura; Fernández-Cancio, Mónica; Andaluz, Pilar; Mullis, Primus E; Carrascosa, Antonio; Flück, Christa E

2015-01-01

Steroidogenic factor 1 (NR5A1/SF-1) mutations usually manifest in 46,XY individuals with variable degrees of disordered sex development and in 46,XX women with ovarian insufficiency. So far, there is no genotype-phenotype correlation. The broad spectrum of phenotype with NR5A1 mutations may be due to a second hit in a gene with similar function to NR5A1/SF-1. Liver receptor homologue-1 (LRH-1/NR5A2) might be a good candidate. We performed in vitro studies for the interplay between SF-1, LRH-1 and DAX-1, expression profiles in human steroidogenic tissues, and NR5A2 genetic studies in a cohort (11 patients, 8 relatives, 11 families) harboring heterozygote NR5A1/SF-1 mutations. LRH-1 isoforms transactivate the CYP17A1 and HSD3B2 promoters similarly to SF-1 and compensate for SF-1 deficiency. DAX-1 inhibits SF-1- and LRH-1-mediated transactivation. LRH-1 is found expressed in human adult and fetal adrenals and testes. However, no NR5A2/LRH-1 mutations were detected in 14 individuals with heterozygote NR5A1/SF-1 mutations. These findings demonstrate that in vitro LRH-1 can act like SF-1 and compensate for its deficiency. Expression of LRH-1 in fetal testis suggests a role in male gonadal development. However, as we found no NR5A2/LRH-1 mutations, the 'second genetic hit' in SF-1 patients explaining the broad phenotypic variability remains elusive. © 2015 S. Karger AG, Basel.

Expression of Leaf Nitrate Reductase Genes from Tomato and Tobacco in Relation to Light-Dark Regimes and Nitrate Supply

PubMed Central

Galangau, Fabienne; Daniel-Vedele, Françoise; Moureaux, Thérèse; Dorbe, Marie-France; Leydecker, Marie-Thérèse; Caboche, Michel

1988-01-01

The influence of light-dark cycles and nitrate supply on nitrate reductase (NR) mRNA levels was studied in two plant species, tobacco (Nicotiana tabacum) and tomato (Lycopersicon esculentum) using specific NR DNA probes. In the same series of experiments, changes in the levels of NR protein (NRP) by enzyme-linked immunosorbent assay and changes in the level of NADH-nitrate reductase activity (NRA) were also followed. During a light-dark cycle, it was found that in both tomato and tobacco, NR mRNA accumulation increased rapidly during the dark period and reached a maximum at the beginning of the day, while NRP reached a peak 2 and 4 hours after mRNA peaked, for tomato and tobacco, respectively. At the end of the day, the amount of mRNA was decreased by a factor of at least 100 compared to sunrise in both species. These results demonstrate that light is involved, although probably not directly, in the regulation of the NR gene expression at the mRNA level. The peak of NRA in tobacco coincided with the peak in NR mRNA accumulation (i.e. sunrise), whereas in tomato the peak of NRA was approximately 5 to 6 hours after sunrise. There is no obvious correlation between NRP and NRA levels during the day. In nitrogen starvation experiments, a rapid decrease of NRP and NRA was detected, while NR mRNA levels were not significantly altered. Upon nitrate replenishment, nitrogen-starved plants accumulated NR mRNA rapidly. These results suggest that the availability of nitrogen affects the expression of NR activity at the transcriptional as well as at the post-transcriptional levels. Images Fig. 3 Fig. 5 Fig. 6 PMID:16666313

Utilization of Electrically Reduced Neutral Red by Actinobacillus succinogenes: Physiological Function of Neutral Red in Membrane-Driven Fumarate Reduction and Energy Conservation

PubMed Central

Park, D. H.; Zeikus, J. G.

1999-01-01

Neutral red (NR) functioned as an electronophore or electron channel enabling either cells or membranes purified from Actinobacillus succinogenes to drive electron transfer and proton translocation by coupling fumarate reduction to succinate production. Electrically reduced NR, unlike methyl or benzyl viologen, bound to cell membranes, was not toxic, and chemically reduced NAD. The cell membrane of A. succinogenes contained high levels of benzyl viologen-linked hydrogenase (12.2 U), fumarate reductase (13.1 U), and diaphorase (109.7 U) activities. Fumarate reductase (24.5 U) displayed the highest activity with NR as the electron carrier, whereas hydrogenase (1.1 U) and diaphorase (0.8 U) did not. Proton translocation by whole cells was dependent on either electrically reduced NR or H2 as the electron donor and on the fumarate concentration. During the growth of Actinobacillus on glucose plus electrically reduced NR in an electrochemical bioreactor system versus on glucose alone, electrically reduced NR enhanced glucose consumption, growth, and succinate production by about 20% while it decreased acetate production by about 50%. The rate of fumarate reduction to succinate by purified membranes was twofold higher with electrically reduced NR than with hydrogen as the electron donor. The addition of 2-(n-heptyl)-4-hydroxyquinoline N-oxide to whole cells or purified membranes inhibited succinate production from H2 plus fumarate but not from electrically reduced NR plus fumarate. Thus, NR appears to replace the function of menaquinone in the fumarate reductase complex, and it enables A. succinogenes to utilize electricity as a significant source of metabolic reducing power. PMID:10198002

NMDA Receptors Mediate Olfactory Learning and Memory in Drosophila

PubMed Central

Xia, Shouzhen; Miyashita, Tomoyuki; Fu, Tsai-Feng; Lin, Wei-Yong; Wu, Chia-Lin; Pyzocha, Lori; Lin, Inn-Ray; Saitoe, Minoru; Tully, Tim; Chiang, Ann-Shyn

2011-01-01

Summary Background Molecular and electrophysiological properties of NMDARs suggest that they may be the Hebbian “coincidence detectors” hypothesized to underlie associative learning. Because of the nonspecificity of drugs that modulate NMDAR function or the relatively chronic genetic manipulations of various NMDAR subunits from mammalian studies, conclusive evidence for such an acute role for NMDARs in adult behavioral plasticity, however, is lacking. Moreover, a role for NMDARs in memory consolidation remains controversial. Results The Drosophila genome encodes two NMDAR homologs, dNR1 and dNR2. When coexpressed in Xenopus oocytes or Drosophila S2 cells, dNR1 and dNR2 form functional NMDARs with several of the distinguishing molecular properties observed for vertebrate NMDARs, including voltage/Mg2+-dependent activation by glutamate. Both proteins are weakly expressed throughout the entire brain but show preferential expression in several neurons surrounding the dendritic region of the mushroom bodies. Hypomorphic mutations of the essential dNR1 gene disrupt olfactory learning, and this learning defect is rescued with wild-type transgenes. Importantly, we show that Pavlovian learning is disrupted in adults within 15 hr after transient induction of a dNR1 antisense RNA transgene. Extended training is sufficient to overcome this initial learning defect, but long-term memory (LTM) specifically is abolished under these training conditions. Conclusions Our study uses a combination of molecular-genetic tools to (1) generate genomic mutations of the dNR1 gene, (2) rescue the accompanying learning deficit with a dNR1+ transgene, and (3) rapidly and transiently knockdown dNR1+ expression in adults, thereby demonstrating an evolutionarily conserved role for the acute involvement of NMDARs in associative learning and memory. PMID:15823532

Nitrogen-neutrality: a step towards sustainability

NASA Astrophysics Data System (ADS)

Leip, Adrian; Leach, Allison; Musinguzi, Patrick; Tumwesigye, Trust; Olupot, Giregon; Tenywa, John Stephen; Mudiope, Joseph; Hutton, Olivia; Cordovil, Claudia M. d. S.; Bekunda, Mateete; Galloway, James

2014-11-01

We propose a novel indicator measuring one dimension of the sustainability of an entity in modern societies: Nitrogen-neutrality. N-neutrality strives to offset Nr releases an entity exerts on the environment from the release of reactive nitrogen (Nr) to the environment by reducing it and by offsetting the Nr releases elsewhere. N-neutrality also aims to increase awareness about the consequences of unintentional releases of nitrogen to the environment. N-neutrality is composed of two quantified elements: Nr released by an entity (e.g. on the basis of the N footprint) and Nr reduction from management and offset projects (N offset). It includes management strategies to reduce nitrogen losses before they occur (e.g., through energy conservation). Each of those elements faces specific challenges with regard to data availability and conceptual development. Impacts of Nr releases to the environment are manifold, and the impact profile of one unit of Nr release depends strongly on the compound released and the local susceptibility to Nr. As such, N-neutrality is more difficult to conceptualize and calculate than C-neutrality. We developed a workable conceptual framework for N-neutrality which was adapted for the 6th International Nitrogen Conference (N2013, Kampala, November 2013). Total N footprint of the surveyed meals at N2013 was 66 kg N. A total of US 3050 was collected from the participants and used to offset the conference’s N footprint by supporting the UN Millennium Village cluster Ruhiira in South-Western Uganda. The concept needs further development in particular to better incorporate the spatio-temporal variability of impacts and to standardize the methods to quantify the required N offset to neutralize the Nr releases impact. Criteria for compensation projects need to be sharply defined to allow the development of a market for N offset certificates.

Characterization of a highly conserved human homolog to the chicken neural cell surface protein Bravo/Nr-CAM that maps to chromosome band 7q31

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

Lane, R.P.; Vielmetter, J.; Dreyer, W.J.

1996-08-01

The neuronal cell adhesion molecule Bravo/Nr-CAM is a cell surface protein of the immunoglobulin (Ig) superfamily and is closely related to the L1/NgCAM and neurofascin molecules, all of which contain six immunoglobulin domains, five fibronectin repeats, a transmembrane region, and an intracellular domain. Chicken Bravo/Nr-CAM has been shown to interact with other cell surface molecules of the Ig superfamily and has been implicated in specific pathfinding roles of axonal growth cones in the developing nervous system. We now report the characterization of cDNA clones encoding the human Bravo/Nr-CAM protein, which, like its chicken homolog, is composed of six V-like Igmore » domains and five fibronectin type III repeats. The human Bravo/Nr-CAM homolog also contains a transmembrane and intracellular domain, both of which are 100% conserved at the amino acid level compared to its chicken homolog. Overall, the human Bravo/Nr-CAM homolog is 82% identical to the chicken Bravo/Nr-CAM amino acid sequence. Independent cDNAs encoding four different isoforms were also identified, all of which contain alternatively spliced variants around the fifth fibronectin type III repeat, including one isoform that had been previously identified for chicken Bravo/Nr-CAM. Northern blot analysis reveals one mRNA species of approximately 7.0 kb in adult human brain tissue. Fluorescence in situ hybridization maps the gene for human Bravo/Nr-CAM to human chromosome 7q31.1-q31.2. This chromosomal locus has been previously identified as containing a tumore suppressor candidate gene commonly deleted in certain human cancer tissues. 38 refs., 5 figs.« less

Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

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

Bolado-Carrancio, A.; Riancho, J.A.; Sainz, J.

Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Becausemore » skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity.« less

Optimalization activity of ZnO NR/TiO2 NR-P3HT as an active layer based on hybrid bulk heterojunction on dye sensitized solar cell (DSSC)

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

Saputri, Liya Nikmatul Maula Zulfa; Ramelan, Ari Handono; Hanif, Qonita Awliya

2016-04-19

Dye sensitized solar cell (DSSC) with metal inorganic and conjugated organic polymer mixture, ZnO NR/TiO{sub 2} NR-P3HT as an active layer based on hybrid bulk heterojunction has been studied. The hybrid material was used to optimize DSSC performs for better efficiency than only TiO{sub 2} as an electrode. Synthesis of TiO{sub 2} nanorods (NR) was conducted by ball milling 1000 rpm for 4 hours and strong base reaction by hydrothermal process at 120 °C overnight. And the ZnO NR was synthesized from Zn(NO{sub 3}){sub 2}.4H{sub 2}O precusor by hydrotermal process at 90 °C for 5 hours and calcined on various temperaturemore » s of 400, 600, and 800 °C. ZnO NR was coated into an Tndium Tin Oxide (TTO) glass to collecting electron s effectively, where TiO{sup 2} NR were incorporated with poly(3 -hexylthiophene) (P3HT) on various concentration s of 5, 10, 15 mg/mL to obtain a larger surface area. Material characterization were performed by X -Ray Diffraction (XRD) and Uv-Vis spectrophotometer. For an application of DSSC were measured by T-V Keithley Multimeter and the efficiency of DSSC at various P3HT’s concentrations of 5, 10, 15 mg/mL were 7.44 × 10{sup −3}, 0.0114, 0.0104, respectively. The maximum efficiency of DSSC was showed when TiO{sup 2} NR-P3HT’s concentration was 10 mg/mL.« less

NMDA receptors mediate olfactory learning and memory in Drosophila.

PubMed

Xia, Shouzhen; Miyashita, Tomoyuki; Fu, Tsai-Feng; Lin, Wei-Yong; Wu, Chia-Lin; Pyzocha, Lori; Lin, Inn-Ray; Saitoe, Minoru; Tully, Tim; Chiang, Ann-Shyn

2005-04-12

Molecular and electrophysiological properties of NMDARs suggest that they may be the Hebbian "coincidence detectors" hypothesized to underlie associative learning. Because of the nonspecificity of drugs that modulate NMDAR function or the relatively chronic genetic manipulations of various NMDAR subunits from mammalian studies, conclusive evidence for such an acute role for NMDARs in adult behavioral plasticity, however, is lacking. Moreover, a role for NMDARs in memory consolidation remains controversial. The Drosophila genome encodes two NMDAR homologs, dNR1 and dNR2. When coexpressed in Xenopus oocytes or Drosophila S2 cells, dNR1 and dNR2 form functional NMDARs with several of the distinguishing molecular properties observed for vertebrate NMDARs, including voltage/Mg(2+)-dependent activation by glutamate. Both proteins are weakly expressed throughout the entire brain but show preferential expression in several neurons surrounding the dendritic region of the mushroom bodies. Hypomorphic mutations of the essential dNR1 gene disrupt olfactory learning, and this learning defect is rescued with wild-type transgenes. Importantly, we show that Pavlovian learning is disrupted in adults within 15 hr after transient induction of a dNR1 antisense RNA transgene. Extended training is sufficient to overcome this initial learning defect, but long-term memory (LTM) specifically is abolished under these training conditions. Our study uses a combination of molecular-genetic tools to (1) generate genomic mutations of the dNR1 gene, (2) rescue the accompanying learning deficit with a dNR1+ transgene, and (3) rapidly and transiently knockdown dNR1+ expression in adults, thereby demonstrating an evolutionarily conserved role for the acute involvement of NMDARs in associative learning and memory.

In vitro genotoxicity of neutral red after photo-activation and metabolic activation in the Ames test, the micronucleus test and the comet assay.

PubMed

Guérard, Melanie; Zeller, Andreas; Singer, Thomas; Gocke, Elmar

2012-07-04

Neutral red (Nr) is relatively non-toxic and is widely used as indicator dye in many biological test systems. It absorbs visible light and is known to act as a photosensitizer, involving the generation of reactive oxygen species (type-I reaction) and singlet oxygen (type-II reaction). The mutagenicity of Nr was determined in the Ames test (with Salmonella typhimurium strains TA1535, TA97, TA98, TA98NR, TA100, and TA102) with and without metabolic activation, and with and without photo-activation on agar plates. Similarly to the situation following metabolic activation, photo-mutagenicity of Nr was seen with all Salmonella strains tested, albeit with different effects between these strains. To our knowledge, Nr is the only photo-mutagen showing such a broad action. Since the effects are also observed in strains not known to be responsive to ROS, this indicates that ROS production is not the sole mode of action that leads to photo-genotoxicity. The reactive species produced by irradiation are short-lived as pre-irradiation of an Nr solution did not produce mutagenic effects when added to the bacteria. In addition, mutagenicity in TA98 following irradiation was stronger than in the nitroreductase-deficient strain TA98NR, indicating that nitro derivatives that are transformed by bacterial nitroreductase to hydroxylamines appear to play a role in the photo-mutagenicity of Nr. Photo-genotoxicity of Nr was further investigated in the comet assay and micronucleus test in L5178Y cells. Concentration-dependent increases in primary DNA damage and in the frequency of micronuclei were observed after irradiation. Copyright © 2012 Elsevier B.V. All rights reserved.

Sources of nitrogen deposition in Federal Class I areas in the US

NASA Astrophysics Data System (ADS)

Lee, H.-M.; Paulot, F.; Henze, D. K.; Travis, K.; Jacob, D. J.; Pardo, L. H.; Schichtel, B. A.

2016-01-01

It is desired to control excessive reactive nitrogen (Nr) deposition due to its detrimental impact on ecosystems. Using a three-dimensional atmospheric chemical transport model, GEOS-Chem, Nr deposition in the contiguous US and eight selected Class I areas (Voyageurs (VY), Smoky Mountain (SM), Shenandoah (SD), Big Bend (BB), Rocky Mountain (RM), Grand Teton (GT), Joshua Tree (JT), and Sequoia (SQ)) is investigated. First, modeled Nr deposition is compared with National Trends Network (NTN) and Clean Air Status and Trends Network (CASTNET) deposition values. The seasonality of measured species is generally well represented by the model (R2 > 0.6), except in JT. While modeled Nr is generally within the range of seasonal observations, large overestimates are present in sites such as SM and SD in the spring and summer (up to 0.6 kg N ha month-1), likely owing to model high-biases in surface HNO3. The contribution of non-measured species (mostly dry deposition of NH3) to total modeled Nr deposition ranges from 1 to 55 %. The spatial distribution of the origin of Nr deposited in each Class I area and the contributions of individual emission sectors are estimated using the GEOS-Chem adjoint model. We find the largest role of long-range transport for VY, where 50 % (90 %) of annual Nr deposition originates within 670 (1670) km of the park. In contrast, the Nr emission footprint is most localized for SQ, where 50 % (90 %) of the deposition originates from within 130 (370) km. Emissions from California contribute to the Nr deposition in remote areas in the western US (RM, GT). Mobile NOx and livestock NH3 are found to be the major sources of Nr deposition in all sites except BB, where contributions of NOx from lightning and soils to natural levels of Nr deposition are significant (˜ 40 %). The efficiency in terms of Nr deposition per kg emissions of NH3-N, NOx-N, and SO2-S are also estimated. Unique seasonal features are found in JT (opposing efficiency distributions for winter and summer), RM (large fluctuations in the range of effective regions), and SD (upwind NH3 emissions hindering Nr deposition). We also evaluate the contributions of emissions to the total area of Class I regions in critical load exceedance, and to the total magnitude of exceedance. We find that while it is effective to control emissions in the western US to reduce the area of regions in CL exceedance, it can be more effective to control emissions in the eastern US to reduce the magnitude of Nr deposition above the CL. Finally, uncertainty in the nitrogen deposition caused by uncertainty in the NH3 emission inventory is explored by comparing results based on two different NH3 inventories; noticeable differences in the emission inventories and thus sensitivities of up to a factor of four found in individual locations.

Sources of nitrogen deposition in Federal Class I areas in the US

NASA Astrophysics Data System (ADS)

Lee, H.-M.; Paulot, F.; Henze, D. K.; Travis, K.; Jacob, D. J.; Pardo, L. H.; Schichtel, B. A.

2015-08-01

It is desired to control excessive reactive nitrogen (Nr) deposition due to its detrimental impact on ecosystems. Using a 3-dimensional atmospheric chemical transport model, GEOS-Chem, Nr deposition in the contiguous US and eight selected Class I areas (Voyageurs (VY), Smoky Mountain (SM), Shenandoah (SD), Big Bend (BB), Rocky Mountain (RM), Grand Teton (GT), Joshua Tree (JT), and Sequoia (SQ)) is investigated. First, modeled Nr deposition is compared with National Trends Network (NTN) and Clean Air Status and Trends Network (CASTNET) measurements. The seasonality of measured species is generally well represented by the model (R2 > 0.6), except in JT. While modeled Nr is generally within the range of seasonal observations, large overestimates are present in sites such as SM and SD in the spring and summer (up to 0.6 kg N ha-1 month-1), likely owing to model high-biases in surface HNO3. The contribution of non-measured species (mostly dry deposition of NH3) to total modeled Nr deposition ranges from 1 to 55 %. The spatial distribution of the origin of Nr deposited in each Class I area and the contributions of individual emission sectors are estimated using the GEOS-Chem adjoint model. We find the largest role of long-range transport for VY, where 50 % (90 %) of annual Nr deposition originates within 670 (1670) km of the park. In contrast, the Nr emission footprint is most localized for SQ, where 50 % (90 %) of the deposition originates from within 130 (370) km. Emissions from California contribute to the Nr deposition in remote areas in the western US (RM, GT). Mobile NOx and livestock NH3 are found to be the major sources of Nr deposition in all sites except BB, where contributions of NOx from lightning and soils to natural levels of Nr deposition are significant (~ 40 %). The efficiency in terms of Nr deposition per kg emissions of NH3-N, NOx-N, and SO2-S are also estimated. Unique seasonal features are found in JT (opposing efficiency distributions for winter and summer), RM (large fluctuations in the range of effective regions), and SD (upwind NH3 emissions hindering Nr deposition). We also evaluate the contributions of emissions to the total area of Class I regions in critical load exceedance, and to the total magnitude of exceedance. We find that while it is effective to control emissions in the western US to reduce the area of regions in CL exceedance, it can be more effective to control emissions in the eastern US to reduce the magnitude of Nr deposition above the CL. Finally, uncertainty in the nitrogen deposition caused by uncertainty in the NH3 emission inventory is explored by comparing results based on two different NH3 inventories; noticeable differences in the emission inventories and thus sensitivities of up to factor of four found in individual locations.

Sentence recognition in noise and perceived benefit of noise reduction on the receiver and transmitter sides of a BICROS hearing aid.

PubMed

Oeding, Kristi; Valente, Michael

2013-01-01

In the past, bilateral contralateral routing of signals (BICROS) amplification incorporated omnidirectional microphones on the transmitter and receiver sides and some models utilized noise reduction (NR) on the receiver side. Little research has examined the performance of BICROS amplification in background noise. However, previous studies examining contralateral routing of signals (CROS) amplification have reported that the presence of background noise on the transmitter side negatively affected speech recognition. Recently, NR was introduced as a feature on the receiver and transmitter sides of BICROS amplification, which has the potential to decrease the impact of noise on the wanted speech signal by decreasing unwanted noise directed to the transmitter side. The primary goal of this study was to examine differences in the reception threshold for sentences (RTS in dB) using the Hearing in Noise Test (HINT) in a diffuse listening environment between unaided and three aided BICROS conditions (no NR, mild NR, and maximum NR) in the Tandem 16 BICROS. A secondary goal was to examine real-world subjective impressions of the Tandem 16 BICROS compared to unaided. A randomized block repeated measures single blind design was used to assess differences between no NR, mild NR, and maximum NR listening conditions. Twenty-one adult participants with asymmetric sensorineural hearing loss (ASNHL) and experience with BICROS amplification were recruited from Washington University in St. Louis School of Medicine. Participants were fit with the National Acoustic Laboratories' Nonlinear version 1 prescriptive target (NAL-NL1) with the Tandem 16 BICROS at the initial visit and then verified using real-ear insertion gain (REIG) measures. Participants acclimatized to the Tandem 16 BICROS for 4 wk before returning for final testing. Participants were tested utilizing HINT sentences examining differences in RTS between unaided and three aided listening conditions. Subjective benefit was determined via the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire between the Tandem 16 BICROS and unaided. A repeated measures analysis of variance (ANOVA) was utilized to analyze the results of the HINT and APHAB. Results revealed no significant differences in the RTS between unaided, no NR, mild NR, and maximum NR. Subjective impressions using the APHAB revealed statistically and clinically significant benefit with the Tandem 16 BICROS compared to unaided for the Ease of Communication (EC), Background Noise (BN), and Reverberation (RV) subscales. The RTS was not significantly different between unaided, no NR, mild NR, and maximum NR. None of the three aided listening conditions were significantly different from unaided performance as has been reported for previous studies examining CROS hearing aids. Further, based on comments from participants and previous research studies with conventional hearing aids, manufacturers of BICROS amplification should consider incorporating directional microphones and independent volume controls on the receiver and transmitter sides to potentially provide further improvement in signal-to-noise ratio (SNR) for patients with ASNHL. American Academy of Audiology.

Communications in Task Analysis. Training Manual 4

DTIC Science & Technology

1975-10-01

Training Research Programs Psychological Sciences Division Office of Naval Research Contract No. N00014-74-A-0436-0001 NR 151-370 ADproved for... Testing Testing Understanding 20. ABSTRACT (Continue on reveree elde If neceeemry end Identity by block number) This is the fourth in a series of...recommendations for achieving active listening, testing for understanding, and problems in active listening. The third section is the most detailed

Imido-pyridine Ti(IV) compounds: synthesis of unusual imido-amido heterobimetallic derivatives.

PubMed

Pedrosa, Sergio; Vidal, Fernando; Lee, Lucia Myongwon; Vargas-Baca, Ignacio; Gómez-Sal, Pilar; Mosquera, Marta E G

2015-06-28

The reaction of lithiated picolines and [TiCl3(η(5)-C5Me5)] leads to several bridging or terminal imido compounds, each of which can be selectively formed by controlling the stoichiometry and temperature. Specifically, the dinuclear imido-bridged [TiCl(η(5)-C5Me5)(μ-NR)]2 (1a, NR = 2-imido-3-picoline; 1b, NR = 2-imido-5-picoline) species and the unusual Ti-Li imido-amido heterobimetallic complex [{Li(THF)}{Ti(η(5)-C5Me5)(NR)(NHR)2}] (2a, NR = 2-imido-3-picoline; 2b, NR = 2-imido-5-picoline) were isolated. Compounds 2 are in effect the first structurally characterized examples of titanium(IV) coordinated to terminal imido-pyridines. DFT-D calculations for 2a denote a multiple bond character between titanium and the imido ligand and a strong polarization of the electron density by the alkali cation in spite of the lack of intermetallic bonding.

Photocatalytic dehydrogenation of formic acid on CdS nanorods through Ni and Co redox mediation under mild conditions.

PubMed

Khan, Muhammad Abdullah; Rehman, Zia-Ur-; Nasir, Jamal Abdul; Hafeez, Muhammad; Arshad, Muhammad; Ali, Naveed Zafar; Teixieira, Ivo F; McPherson, Ian

2018-05-30

Selective release of hydrogen from formic acid (FA) is deemed feasible to solve issues associated with the release and storage of hydrogen. Here, we present a new efficient photocatalytic system consisting of CdS nanorods (NR), Ni, and Co to liberate hydrogen from formic acid. The optimised noble metal free catalytic system employs Ni/Co as a redox mediator to relay electrons and holes from CdS-NR to the Ni and Co respectively, which also deters the oxidation of CdS-NR. As a result, a high hydrogen production activity of 32.6 mmolh-1g-1 from the decomposition of FA was noted. Furthermore, the photocatalytic system exhibit sustained H2 production rate for 12 hours with sequential turnover numbers surpassing 4×103, 3×103 and 2×103 for Co-Ni/CdS-NR, Ni-CdS-NR and CoCl2/CdS-NR respectively. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

N2O and N2 production during heterotrophic nitrification by Alcaligenes faecalis strain NR.

PubMed

Zhao, Bin; An, Qiang; He, Yi Liang; Guo, Jin Song

2012-07-01

A heterotrophic nitrifier, strain NR, was isolated from a membrane bioreactor. Strain NR was identified as Alcaligenes faecalis by Auto-Microbic system and 16S rRNA gene sequence analysis. A. faecalis strain NR shows a capability of heterotrophic nitrification and N(2)O and N(2) production as well under the aerobic condition. Further tests demonstrated that neither nitrite nor nitrate could be denitrified aerobically by strain NR. However, when hydroxylamine was used as the sole nitrogen source, nitrogenous gases were detected. With an enzyme assay, a 0.063 U activity of hydroxylamine oxidase was observed, while nitrate reductase and nitrite reductase were undetectable. Thus, nitrogenous gas was speculated to be produced via hydroxylamine. Therefore, two different metabolic pathways might exist in A. faecalis NR. One is heterotrophic nitrification by oxidizing ammonium to nitrite and nitrate. The other is oxidizing ammonium to nitrogenous gas directly via hydroxylamine. Copyright © 2012 Elsevier Ltd. All rights reserved.

TRANC - a novel fast-response converter to measure total reactive atmospheric nitrogen

NASA Astrophysics Data System (ADS)

Marx, O.; Brümmer, C.; Ammann, C.; Wolff, V.; Freibauer, A.

2012-05-01

The input and loss of plant available nitrogen (reactive nitrogen: Nr) from/to the atmosphere can be an important factor for the productivity of ecosystems and thus for its carbon and greenhouse gas exchange. We present a novel converter for reactive nitrogen (TRANC: Total Reactive Atmospheric Nitrogen Converter), which offers the opportunity to quantify the sum of all airborne reactive nitrogen compounds (∑Nr) in high time resolution. The basic concept of the TRANC is the full conversion of all Nr to nitrogen monoxide (NO) within two reaction steps. Initially, reduced Nr compounds are being oxidised, and oxidised Nr compounds are thermally converted to lower oxidation states. Particulate Nr is being sublimated and oxidised or reduced afterwards. In a second step, remaining higher nitrogen oxides or those generated in the first step are catalytically converted to NO with carbon monoxide used as reduction gas. The converter is combined with a fast response chemiluminescence detector (CLD) for NO analysis and its performance was tested for the most relevant gaseous and particulate Nr species under both laboratory and field conditions. Recovery rates during laboratory tests for NH3 and NO2 were found to be 95 and 99%, respectively, and 97% when the two gases were combined. In-field longterm stability over an 11-month period was approved by a value of 91% for NO2. Effective conversion was also found for ammonium and nitrate containing particles. The recovery rate of total ambient Nr was tested against the sum of individual measurements of NH3, HNO3, HONO, NH4+, NO3-, and NOx using a combination of different well-established devices. The results show that the TRANC-CLD system precisely captures fluctuations in ∑Nr concentrations and also matches the sum of all individual Nr compounds measured by the different single techniques. The TRANC features a specific design with very short distance between the sample air inlet and the place where the thermal and catalytic conversions to NO occur. This assures a short residence time of the sample air inside the instrument, and minimises wall sorption problems of water soluble compounds. The fast response time (e-folding times of 0.30 to 0.35 s were found during concentration step changes) and high accuracy in capturing the dominant Nr species enables the converter to be used in an eddy covariance setup. Although a source attribution of specific Nr compounds is not possible, the TRANC is a new reliable tool for permanent measurements of the net ∑Nr flux between ecosystem and atmosphere at a relatively low maintenance and reasonable cost level allowing for diurnal, seasonal and annual investigations.

CDRI-08 Attenuates REST/NRSF-Mediated Expression of NMDAR1 Gene in PBDE-209-Exposed Mice Brain

PubMed Central

Verma, Priya; Gupta, Rajaneesh K.; Gandhi, Behrose S.; Singh, Poonam

2015-01-01

CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the mechanism, present study was designed to examine the role of CDRI-08 on the expression of NMDAR1 (NR1) and the binding of REST/NRSF to NR1 promoter against postnatal exposure of PBDE-209. Male mice pups were orally supplemented with CDRI-08 at the doses of 40, 80, or 120 mg/kg along with PBDE-209 (20 mg/kg) during PND 3–10 and frontal cortex and hippocampus were collected at PND 11 and 60 to study the expression and regulation of NR1 by RT-PCR and electrophoretic mobility shift assay, respectively. The findings showed upregulated expression of NR1 and decreased binding of REST/NRSF to NR1 promoter after postnatal exposure of PBDE-209. Interestingly, supplementation with CDRI-08 significantly restored the expression of NR1 and binding of REST/NRSF to NR1 promoter near to the control value at the dose of 120 mg/kg. In conclusion, the results suggest that CDRI-08 possibly acts on glutamatergic system through expression and regulation of NR1 and may restore memory, impaired by PBDE-209 as reported in our previous study. PMID:26413122

NR3C1 hypermethylation in depressed and bullied adolescents.

PubMed

Efstathopoulos, Paschalis; Andersson, Filip; Melas, Philippe A; Yang, Liu L; Villaescusa, J Carlos; Rȕegg, Joëlle; Ekström, Tomas J; Forsell, Yvonne; Galanti, Maria Rosaria; Lavebratt, Catharina

2018-06-19

The disruption of key epigenetic processes during critical periods of brain development can increase an individual's vulnerability to psychopathology later in life. For instance, DNA methylation in the glucocorticoid receptor gene (NR3C1) in adulthood is known to be associated with early-life adversities and has been suggested to mediate the development of stress-related disorders. However, the association between NR3C1 methylation and the emergence of internalizing symptoms in childhood and adolescence has not been studied extensively. In the present report, we used saliva DNA from a cohort of Swedish adolescents (13-14 years old; N = 1149) to measure NR3C1 methylation in the exon 1F region. Internalizing psychopathological symptoms were assessed using the Center for Epidemiologic Studies Depression Scale for Children (CES-DC). We found that NR3C1 hypermethylation was cross-sectionally associated with high score for internalizing symptoms in the whole group as well as among the female participants. In addition, an analysis of social environmental stressors revealed that reports of bullied or lacking friends were significantly associated with NR3C1 hypermethylation. This cross-sectional association of NR3C1 exon 1F hypermethylation with internalizing psychopathology in adolescents, as well as with bullying and lack of friends are novel results in this field. Longitudinal studies are needed to address whether NR3C1 methylation mediates the link between social stressors and psychopathology in adolescence.

Background field removal technique based on non-regularized variable kernels sophisticated harmonic artifact reduction for phase data for quantitative susceptibility mapping.

PubMed

Kan, Hirohito; Arai, Nobuyuki; Takizawa, Masahiro; Omori, Kazuyoshi; Kasai, Harumasa; Kunitomo, Hiroshi; Hirose, Yasujiro; Shibamoto, Yuta

2018-06-11

We developed a non-regularized, variable kernel, sophisticated harmonic artifact reduction for phase data (NR-VSHARP) method to accurately estimate local tissue fields without regularization for quantitative susceptibility mapping (QSM). We then used a digital brain phantom to evaluate the accuracy of the NR-VSHARP method, and compared it with the VSHARP and iterative spherical mean value (iSMV) methods through in vivo human brain experiments. Our proposed NR-VSHARP method, which uses variable spherical mean value (SMV) kernels, minimizes L2 norms only within the volume of interest to reduce phase errors and save cortical information without regularization. In a numerical phantom study, relative local field and susceptibility map errors were determined using NR-VSHARP, VSHARP, and iSMV. Additionally, various background field elimination methods were used to image the human brain. In a numerical phantom study, the use of NR-VSHARP considerably reduced the relative local field and susceptibility map errors throughout a digital whole brain phantom, compared with VSHARP and iSMV. In the in vivo experiment, the NR-VSHARP-estimated local field could sufficiently achieve minimal boundary losses and phase error suppression throughout the brain. Moreover, the susceptibility map generated using NR-VSHARP minimized the occurrence of streaking artifacts caused by insufficient background field removal. Our proposed NR-VSHARP method yields minimal boundary losses and highly precise phase data. Our results suggest that this technique may facilitate high-quality QSM. Copyright © 2017. Published by Elsevier Inc.

NR4A nuclear receptors are orphans but not lonesome.

PubMed

Kurakula, Kondababu; Koenis, Duco S; van Tiel, Claudia M; de Vries, Carlie J M

2014-11-01

The NR4A subfamily of nuclear receptors consists of three mammalian members: Nur77, Nurr1, and NOR-1. The NR4A receptors are involved in essential physiological processes such as adaptive and innate immune cell differentiation, metabolism and brain function. They act as transcription factors that directly modulate gene expression, but can also form trans-repressive complexes with other transcription factors. In contrast to steroid hormone nuclear receptors such as the estrogen receptor or the glucocorticoid receptor, no ligands have been described for the NR4A receptors. This lack of known ligands might be explained by the structure of the ligand-binding domain of NR4A receptors, which shows an active conformation and a ligand-binding pocket that is filled with bulky amino acid side-chains. Other mechanisms, such as transcriptional control, post-translational modifications and protein-protein interactions therefore seem to be more important in regulating the activity of the NR4A receptors. For Nur77, over 80 interacting proteins (the interactome) have been identified so far, and roughly half of these interactions has been studied in more detail. Although the NR4As show some overlap in interacting proteins, less information is available on the interactome of Nurr1 and NOR-1. Therefore, the present review will describe the current knowledge on the interactomes of all three NR4A nuclear receptors with emphasis on Nur77. Copyright © 2014 Elsevier B.V. All rights reserved.

Tropical Waves and the Quasi-Biennial Oscillation in a 7-km Global Climate Simulation

NASA Technical Reports Server (NTRS)

Holt, Laura A.; Alexander, M. Joan; Coy, Lawrence; Molod, Andrea; Putman, William; Pawson, Steven

2016-01-01

This study investigates tropical waves and their role in driving a quasi-biennial oscillation (QBO)-like signal in stratospheric winds in a global 7-km-horizontal-resolution atmospheric general circulation model. The Nature Run (NR) is a 2-year global mesoscale simulation of the Goddard Earth Observing System Model, version 5 (GEOS-5). In the tropics, there is evidence that the NR supports a broad range of convectively generated waves. The NR precipitation spectrum resembles the observed spectrum in many aspects, including the preference for westward-propagating waves. However, even with very high horizontal resolution and a healthy population of resolved waves, the zonal force provided by the resolved waves is still too low in the QBO region and parameterized gravity wave drag is the main driver of the NR QBO-like oscillation (NRQBO). The authors suggest that causes include coarse vertical resolution and excessive dissipation. Nevertheless, the very-high-resolution NR provides an opportunity to analyze the resolved wave forcing of the NR-QBO. In agreement with previous studies, large-scale Kelvin and small-scale waves contribute to the NRQBO driving in eastward shear zones and small-scale waves dominate the NR-QBO driving in westward shear zones. Waves with zonal wavelength,1000 km account for up to half of the small-scale (,3300 km) resolved wave forcing in eastward shear zones and up to 70% of the small-scale resolved wave forcing in westward shear zones of the NR-QBO.

Attraction of Euwallacea nr. fornicatus to lures containing quercivorol

USDA-ARS?s Scientific Manuscript database

Euwallacea nr. fornicatus is an exotic ambrosia beetle that vectors fungal Fusarium spp. to avocados. Two field trials testing potential attractants to trap Euwallacea spp. were conducted in south Florida. Quercivorol + Ultra High Release Ethanol (URH) was the more powerful attractant for E. nr. for...

HST Astrometry of Saturn's Small Satellites

NASA Astrophysics Data System (ADS)

French, R. G.; McGhee, C. A.

2003-08-01

As part of a long-term program to study Saturn's rings over the full range of inclination and phase angles accessible from Earth, we have accumulated over 300 high resolution images of Saturn and its rings with the Hubble Space Telescope's WFPC2 from 1996-2002. Using these images, we have obtained highly accurate measurements of the positions of Saturn's small moons, primarily with the PC chip of the WFPC2. A major result of these investigations is that Pandora and Prometheus are wandering chaotically from their Voyager-based ephemerides, in roughly equal and opposite directions. They seem clearly to be exchanging orbital angular momentum and energy. These results were published in French et al. 2003 Icarus 162, 143-170. In that paper, we compared the astrometric measurements to orbital predictions by R. Jacobson (personal communication), and showed that the typical astrometric accuracy of our measurements is about 0.02 arcsec. There was not room in that paper for the full set of measurements for all satellites, which we present here, and which will be submitted to the NASA Planetary Data System Rings Node. These will be useful for construction of accurate orbital models for all of the observed satellites, and for planning for the upcoming Cassini mission to Saturn. This work was supported in part by the NASA Geology and Geophysics Program, Massachusetts Space Grant, the Keck Northeast Astronomy Consortium, and the Space Telescope Science Institute.

Host range expansion and increased damage potential of Euwallacea nr. fornicatus (Coleoptera: Curculionidae) in Florida

USDA-ARS?s Scientific Manuscript database

Ambrosia beetles in the Euwallacea nr. fornicatus complex (Coleoptera: Curculionidae) vector Fusarium spp. fungi pathogenic to susceptible hosts, including avocado. The Florida avocado production area in Miami-Dade County was surveyed for E. nr. fornicatus upon observations of initial damage in 2016...

Interactions Between Monetary and Fiscal Policies in the Euro Area

DTIC Science & Technology

2006-03-01

185-210. "* Haucap, Justus, Uwe Pauly & Christian Wey, Collective Wage Setting When Wages Are Generally Binding: An Antitrust Perspective, Nr. 106 (2000...Generations Model, Nr. 8/1999. "* Henning, Andreas & Wolfgang Greiner, Organknappheit im Transplantationswesen - L6sungs- ansditze aus 6konomischer Sicht, Nr. 7

Ligand binding was acquired during evolution of nuclear receptors

PubMed Central

Escriva, Hector; Safi, Rachid; Hänni, Catherine; Langlois, Marie-Claire; Saumitou-Laprade, Pierre; Stehelin, Dominique; Capron, André; Pierce, Raymond; Laudet, Vincent

1997-01-01

The nuclear receptor (NR) superfamily comprises, in addition to ligand-activated transcription factors, members for which no ligand has been identified to date. We demonstrate that orphan receptors are randomly distributed in the evolutionary tree and that there is no relationship between the position of a given liganded receptor in the tree and the chemical nature of its ligand. NRs are specific to metazoans, as revealed by a screen of NR-related sequences in early- and non-metazoan organisms. The analysis of the NR gene duplication pattern during the evolution of metazoans shows that the present NR diversity arose from two waves of gene duplications. Strikingly, our results suggest that the ancestral NR was an orphan receptor that acquired ligand-binding ability during subsequent evolution. PMID:9192646

Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors.

PubMed

Omdal, R; Brokstad, K; Waterloo, K; Koldingsnes, W; Jonsson, R; Mellgren, S I

2005-05-01

To determine whether neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE) are influenced by antibodies against the human N-methyl-D-aspartate (NMDA) receptor types NR2a or NR2b. A decapeptide was synthesized containing a sequence motif present in the extracellular ligand-binding domain of NMDA receptors NR2a and NR2b, bound by the monoclonal murine anti-DNA antibody R4A. In an ELISA with the murine monoclonal R4v as positive control, plasma samples of 57 patients with SLE were examined for the anti-peptide (anti-NR2) antibody after the patients had been subjected to comprehensive psychological and cognitive testing. Poor performance on the Visual Paired Associates test (immediate), the Grooved Pegboard test, as well as high scores on the Beck Depression Inventory, and scales D-2 (depression), Pd-4 (psychopathic deviate), Sc-8 (schizophrenia), and Ma-9 (hypomania) of the MMPI-2 were significantly associated with elevated levels of anti-NR2 antibodies. The findings in several domains indicate an association between anti-NR2 antibodies and depressed mood in addition to decreased short-time memory and learning. Antibodies to NMDA receptors thus may represent one of several mechanisms for cerebral dysfunction in patients with SLE.

[Identification of NMDA receptor in normal bovine ovary and ovum].

PubMed

Tachibana, Naoko; Ikeda, Shu-ichi

2014-01-01

To clarify the pathogenesis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients without ovarian teratoma, we investigate normal human ovary, normal bovine ovary and bovine ova. On the basis of immunohistochemical studies, normal human ovary expressed NR2B epitope in primordial oocytes. The results of SDS-PAGE and immunoblotting using bovine ovarian tissues and ova, we identified two bands of NR1 and NR2B. Moreover, reverse phase liquid chromatography coupled to tandem mass spectrometry showed peptides fractions of NR1, NR2A, NR2B and NR2C. Immunocytochemical study disclosed that normal bovine oocyte has a strong affinity for a patient's disease-specific IgG. Anti-NMDAR encephalitis involves mainly young women who are in their reproductive age. Ovarian teratoma is important as simultaneous tumor, the percentage of patients with ovarian teratoma is less than 40%. It is obvious that the origin of ovarian teratoma is oocyte. So the existence of NMDAR in normal oocytes is very important to assert that ovary itself is the antigen presenting tissue. And also it is helpful to explain why young women are mainly affected from this disease. It seems to conclude that anti-NMDAR encephalitis is one form of autoimmune synaptic encephalitis and that the antigen presenting tissue is ovary itself.

Krüppel-like factors are effectors of nuclear receptor signaling

PubMed Central

Knoedler, Joseph R.; Denver, Robert J.

2015-01-01

Binding of steroid and thyroid hormones to their cognate nuclear receptors (NRs) impacts virtually every aspect of postembryonic development, physiology and behavior, and inappropriate signaling by NRs may contribute to disease. While NRs regulate genes by direct binding to hormone response elements in the genome, their actions may depend on the activity of other transcription factors (TFs) that may or may not bind DNA. The Krüppel-like family of transcription factors (KLF) is an evolutionarily conserved class of DNA-binding proteins that influence many aspects of development and physiology. Several members of this family have been shown to play diverse roles in NR signaling. For example, KLFs 1) act as accessory transcription factors for NR actions, 2) regulate expression of NR genes, and 3) as gene products of primary NR response genes function as key players in NR-dependent transcriptional networks. In mouse models, deletion of different KLFs leads to aberrant transcriptional and physiological responses to hormones, underscoring the importance of these proteins in the regulation of hormonal signaling. Understanding the functional relationships between NRs and KLFs will yield important insights into mechanisms of NR signaling. In this review we present a conceptual framework for understanding how KLFs participate in NR signaling, and we provide examples of how these proteins function to effect hormone action. PMID:24642391

Super-Resolution Fluorescence Imaging of Spatial Organization of Proteins and Lipids in Natural Rubber.

PubMed

Wu, Jinrong; Qu, Wei; Huang, Guangsu; Wang, Siyuan; Huang, Cheng; Liu, Han

2017-06-12

Natural rubber (NR) with proteins and lipids has superior mechanical properties to its synthetic counterpart, polyisoprene rubber. However, it is a challenge to unravel the morphology of proteins and lipids. Here we used two-color stochastic optical reconstruction microscopy (STORM) to directly visualize the spatial organization of proteins and lipids in NR. We found that the proteins and lipids form an interdispersed stabilizing layer on the surface of NR latex particles. After drying, the proteins and lipids form aggregates of up to 300 nm in diameter. The aggregates physically interact with the terminal groups of polyisoprene chains, leading to the formation of a network, which contributes to the high elasticity and mechanical property of NR. If we remove proteins in NR, the large phospholipid aggregates disintegrate into small ones. However, it does not decompose the network but rather reduces the effective cross-linking density, thus the deproteinized NR is still elastic-like with decreased mechanical property. Removing both proteins and lipids wholly decomposes the network, thus, results in a liquid-like behavior of the rubber. The STORM measurements in this paper enable more insight into the structure-property relationship of NR, which also shows a great potential of STORM in studying the fine structure of polymeric materials and nanocomposites.

Fluorescent reversible regulation based on the interactions of topotecan hydrochloride, neutral red and quantum dots

NASA Astrophysics Data System (ADS)

Wang, Linlin; Shen, Yizhong; Liu, Shaopu; Yang, Jidong; Liang, Wanjun; Li, Dan; He, Youqiu

2015-02-01

The interactions of topotecan hydrochloride (THC), neutral red (NR) and thioglycolic acid (TGA) capped CdTe/CdS quantum dots (QDs) built a solid base for the controlling of the fluorescent reversible regulation of the system. This study was developed by means of ultraviolet-visible (UV-vis) absorption, fluorescence (FL), resonance Rayleigh scattering (RRS) spectroscopy and transmission electron microscopy (TEM). Corresponding experimental results revealed that the fluorescence of TGA-CdTe/CdS QDs could be effectively quenched by NR, while the RRS of the QDs enhanced gradually with the each increment of NR concentration. After the addition of THC, the strong covalent conjugation between NR and THC which was in carboxylate state enabled NR to be dissociated from the surface of TGA-CdTe/CdS QDs to form more stable complex with THC, thereby enhancing the fluorescence of the TGA-CdTe/CdS QDs-NR system. What is more, through analyzing the optical properties and experimental data of the reaction between TGA-CdTe/CdS QDs and NR, the possible reaction mechanism of the whole system was discussed. This combination of multiple spectroscopic techniques could contribute to the investigation for the fluorescent reversible regulation of QDs and a method could also be established to research the interactions between camptothecin drugs and dyes.

Polar extract of Curcuma longa protects cartilage homeostasis: possible mechanism of action.

PubMed

Velusami, Chandrasekaran Chinampudur; Richard, Edwin Jothie; Bethapudi, Bharathi

2018-01-08

Curcuma longa has been well documented for managing joint inflammation and pain. The present study investigated the effect of polar extract of C. longa (NR-INF-02) on cartilage homeostasis in human articular chondrocytes knee (NHAC-kn) cells to understand its plausible mechanism of action. Dysregulation of cartilage homeostasis was induced by IL-1β and H 2 O 2 . Modulating effects of NR-INF-02 on degradation markers viz., chondrocyte apoptosis, senescence, cytokine, eicosanoids, and cartilage synthesis markers viz., glycosaminoglycans and type II collagen degradation was evaluated in human articular chondrocytes knee (NHAC-kn) cells. Further, the effect of NR-INF-02 on lipopolysaccharide (LPS)-induced expression of NF-kB in RAW264.7 macrophages was investigated. NR-INF-02 significantly attenuated IL-1β-induced chondrocyte cytotoxicity, apoptosis and release of chondrocyte degradation markers such as IL-6, IL-8, COX-2, PGE 2 , TNF-α, ICAM-1 in NHAC-kn cells. Also, NR-INF-02 protected IL-1β-induced damage to synthesis markers such as glycosaminoglycans, type II collagen and further attenuated H 2 O 2 -induced chondrocyte senescence. In addition NR-INF-02 suppressed LPS-induced NF-kB expression in RAW264.7 cells. NR-INF-02 protects cartilage homeostasis by maintaining the balance between synthesis and degradation of cartilage matrix.

Synergistic effect of nano calcium carbonate (NCC)/carbon black (CB) on the cure characteristics and physico-mechanical properties of NR/SBR blends

NASA Astrophysics Data System (ADS)

Mamauod, Siti Nur Liyana; Romli, Ahmad Zafir; Rizuan, Mohd Ismail Rifdi

2017-09-01

This research was carried out as to develop hybrid filler reinforced into the blend of natural rubber (NR) and styrene butadiene rubber (SBR). The NR/SBR blend was reinforced using carbon black (CB) and nano calcium carbonate (NCC). The NCC content varied from 2-10 phr which was incorporated into the NR/SBR blend filled with fixed 50 phr of CB. The main aim of this project was to study the synergistic effect of NCC and CB reinforced NR/SBR blends towards the curing characteristics using cure rheometer, the viscosity of uncured NR/SBR compounds, physical and mechanical property blends. From the results obtained, the optimum ratio of blending was identified at 4 phr of NCC loading. Tensile strength, elongation at break, modulus and hardness increased progressively with increasing the NCC loading from 0 phr up to a maximum value at 4 phr. This increment occurs due to consolidation of the network structure of the polymer chains with the increasing NCC content. Up to the optimum amount of NCC, the tendency for NCC particles to form aggregate was very high and hence reduces the properties of rubber blends. It proved that NCC acts as a co-reinforcing agent for CB to improve the performance in the NR/SBR blends.

The NR1-4 C-terminus interferes with N-methyl-D-aspartate receptor-mediated excitotoxicity: evidence against a typical T/SXV-PDZ interaction.

PubMed

Mattar, P A; Holmes, K D; Dekaban, G A

2005-01-01

The N-methyl-D-aspartate receptor (NMDAR) plays a key role in the neural plasticity that underlies learning and memory in vivo. The plasticity exhibited by NMDARs may also contribute to disease pathogenesis, as a number of disorders are caused or exacerbated by exaggerated NMDAR activity. The NMDAR is composed of two obligatory types of subunits, NR1 and NR2. These transmembrane proteins include large intracellular C-termini that have yet to be fully characterized. We have developed a three-color fluorescence system in order to visualize NMDAR expression in living cells. Using excitotoxicity as a proxy for exaggerated NMDAR activity, we analyzed the effect of over-expressing NR1-4 and NR2A C-terminal domains on exaggerated NMDAR function. We demonstrate that a determinant within the C-terminal domain of NR1-4 (C02') is important for NMDAR excitotoxicity, whereas no novel determinants were identified in the NR2A C-terminus. Through the use of heterologous cells, and by examining the interaction between the prototypical NMDAR-binding partner postsynaptic density-95 (PSD-95), we show that this effect is unlikely to be mediated through a classical interaction with PSD-95.

Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration.

PubMed

Mukherjee, Sarmistha; Chellappa, Karthikeyani; Moffitt, Andrea; Ndungu, Joan; Dellinger, Ryan W; Davis, James G; Agarwal, Beamon; Baur, Joseph A

2017-02-01

The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing nicotinamide phosphoribosyltransferase, a rate-limiting enzyme for NAD synthesis, specifically in the liver. Nicotinamide phosphoribosyltransferase overexpressing mice were mildly hyperglycemic at baseline and, similar to mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking nicotinamide phosphoribosyltransferase in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR. NAD availability is limiting during liver regeneration, and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury. (Hepatology 2017;65:616-630). © 2016 by the American Association for the Study of Liver Diseases.

Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice

PubMed Central

Trammell, Samuel A.J.; Weidemann, Benjamin J.; Chadda, Ankita; Yorek, Matthew S.; Holmes, Amey; Coppey, Lawrence J.; Obrosov, Alexander; Kardon, Randy H.; Yorek, Mark A.; Brenner, Charles

2016-01-01

Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD+ metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP+ and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies. PMID:27230286

Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice.

PubMed

Trammell, Samuel A J; Weidemann, Benjamin J; Chadda, Ankita; Yorek, Matthew S; Holmes, Amey; Coppey, Lawrence J; Obrosov, Alexander; Kardon, Randy H; Yorek, Mark A; Brenner, Charles

2016-05-27

Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP(+) and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies.

Cure characteristics, crosslink density and degree of filler dispersion of kaolin-filled natural rubber compounds in the presence of alkanolamide

NASA Astrophysics Data System (ADS)

Surya, I.; Hayeemasae, N.; Ginting, M.

2018-03-01

The effects of alkanolamide (ALK) addition on cure characteristics, crosslink density and degree of filler dispersion of kaolin-filled natural rubber (NR) compounds were investigated. The kaolin filler was incorporated into NR compounds with a fixed loading, 30.0 phr. The ALK was prepared from Refined Bleached Deodorized Palm Stearin (RBDPS), a waste product of cooking oil production, and diethanolamine. The ALK is an oily material and added into the filled NR compounds as a rubber additive at different loadings, 0.0, 3.0, 5.0 and 7.0. The kaolin-filled NR compounds with and without ALK were vulcanized using a semi-efficient vulcanization system. It was found that ALK decreased the scorch and cure times and improved filler dispersion of the kaolin-filled NR compounds. The higher the ALK loading, the shorter were the scorch and cure times. It was also found that ALK increased the crosslink density of kaolin-filled NR compound up to 5.0 phr of loading. Due to its oily properties, The ALK acted as an internal plasticizer which decreased the minimum torque and improved the degree of kaolin dispersion in NR phases. The higher the ALK loading; the lower the minimum torque and better the filler dispersion.

Spinal SIRPα1-SHP2 interaction regulates spinal nerve ligation-induced neuropathic pain via PSD-95-dependent NR2B activation in rats.

PubMed

Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuang; Hsieh, Ming-Chun; Lin, Tzer-Bin

2012-05-01

The fact that neuropathic pain mechanisms are not well understood is a major impediment in the development of effective clinical treatments. We examined whether the interaction between signal regulatory protein alpha 1 (SIRPα1) and Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2), and the downstream spinal SHP2/postsynaptic density 95 (PSD-95)/N-methyl-d-aspartate receptor NR2B subunit signaling cascade play a role in neuropathic pain. Following spinal nerve ligation (L5), we assessed tactile allodynia using the von Frey filament test and analyzed dorsal horn samples (L4-5) by Western blotting, reverse transcription polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. Nerve ligation induced allodynia, SIRPα1, SHP2, phosphorylated SHP2 (pSHP2), and phosphorylated NR2B (pNR2B) expression, and SHP2-PSD-95, pSHP2-PSD-95, PSD-95-NR2B, and PSD-95-pNR2B coimmunoprecipitation in the ipsilateral dorsal horn. In allodynic rats, injury-induced SHP2 immunoreactivity was localized in the ipsilateral dorsal horn neurons and coincident with PSD-95 and NR2B immunoreactivity. SIRPα1 silencing using small interfering RNA (siRNA; 1, 3, or 5μg/rat for 7days) prevented injury-induced allodynia and the associated changes in protein expression, phosphorylation, and coimmunoprecipitation. Intrathecal administration of NSC-87877 (an SHP2 antagonist; 1, 10, or 100μM/rat) and SIRPα1-neutralizing antibodies (1, 10, or 30μg/rat) suppressed spinal nerve ligation-induced allodynia, spinal SHP2 and NR2B phosphorylation, and SHP2/phosphorylated SHP2-PSD-95 and PSD-95-NR2B/phosphorylated NR2B coprecipitation. SHP2 siRNA led to similar effects as the NSC-87877 and SIRPα1 antibody treatments, except it prevented the allodynia-associated spinal SHP2 expression. In conclusion, our results suggest that a spinal SIRPα1-SHP2 interaction exists that subsequently triggers SHP2/PSD-95/NR2B signaling, thereby playing a role in neuropathic pain development. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Generation and Use of Thermal Energy in the Industrial Sector and Opportunities to Reduce its Carbon Emissions

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

McMillan, Colin; Boardman, Richard; McKellar, Michael

Changes are occurring throughout the U.S. economy, especially in regard to how energy is generated and used in the electricity, buildings, industrial, and transportation sectors. These changes are being driven by environmental and energy security concerns and by economics. The electric-sector market share of natural gas and variable renewable generation, such as wind and solar photovoltaics (PV), continues to grow. The buildings sector is evolving to meet efficiency standards, the transportation sector is evolving to meet efficiency and renewable fuels standards, and the industrial sector is evolving to reduce emissions. Those changes are driving investment and utilization strategies for generationmore » and other assets. Nuclear and renewable energy sources are important to consider in the energy sector’s evolution because both are considered to be clean and non-carbon-emitting energy sources. The Idaho National Laboratory (INL) and the National Renewable Energy Laboratory (NREL) are jointly investigating potential synergies between technologies exploiting nuclear and renewable energy sources. The two laboratories have held several joint workshops since 2011. Those workshops brought together experts in both areas to identify synergies and potential opportunities to work together. Workshop participants identified nuclear-renewable hybrid energy systems (N-R HESs) as one of the opportunities and recommended investigating whether N-R HESs could both generate dispatchable electricity without carbon emissions and provide clean energy to industrial processes. They also recommended analyzing the potential for N-R HESs to provide dispatchable capacity to a grid with high penetrations of non-dispatchable resources and to investigate whether real inertia provided by thermal power cycles within N-R HESs provides value to the grid. This report is one of a series of reports INL and NREL are producing to investigate the technical and economic aspects of N-R HESs. Previous reports focused on tightly coupled N-R HESs. Previously, INL analyzed the dynamic performance of two hypothetical N-R HESs and NREL analyzed the optimal economic configurations and operation of the same two N-R HESs. The first of those two is a Texas-synthetic gasoline scenario that includes four subsystems: a nuclear reactor, thermal power cycle, wind power plant, and synthetic gasoline production technology. The second hypothetical N-R HES is an Arizona-desalination scenario with four subsystems: a nuclear reactor, thermal power cycle, PV, and a desalination plant. INL analyzed the technical performance of the same two N-R HESs in another report. In another report NREL used the Texas-synthetic gasoline scenario provides the basis; however, the industrial process was removed. Instead, that N-R HES sells heat directly to an industrial customer. Subsystems that convert electricity to heat were also included. Future analyses are planned for other N-R HES options including one where hydrogen is produced within an N-R HES. This report quantifies greenhouse gas (GHG) emissions from the industrial sector and identifies opportunities for non-GHG-emitting thermal energy sources, such as N-R HESs, to replace the most significant GHG-emitting U.S. industries based on targeted, process-level analysis of industrial heat requirements.« less

The global nitrogen cycle in the twenty-first century

PubMed Central

Fowler, David; Coyle, Mhairi; Skiba, Ute; Sutton, Mark A.; Cape, J. Neil; Reis, Stefan; Sheppard, Lucy J.; Jenkins, Alan; Grizzetti, Bruna; Galloway, James N.; Vitousek, Peter; Leach, Allison; Bouwman, Alexander F.; Butterbach-Bahl, Klaus; Dentener, Frank; Stevenson, David; Amann, Marcus; Voss, Maren

2013-01-01

Global nitrogen fixation contributes 413 Tg of reactive nitrogen (Nr) to terrestrial and marine ecosystems annually of which anthropogenic activities are responsible for half, 210 Tg N. The majority of the transformations of anthropogenic Nr are on land (240 Tg N yr−1) within soils and vegetation where reduced Nr contributes most of the input through the use of fertilizer nitrogen in agriculture. Leakages from the use of fertilizer Nr contribute to nitrate (NO3−) in drainage waters from agricultural land and emissions of trace Nr compounds to the atmosphere. Emissions, mainly of ammonia (NH3) from land together with combustion related emissions of nitrogen oxides (NOx), contribute 100 Tg N yr−1 to the atmosphere, which are transported between countries and processed within the atmosphere, generating secondary pollutants, including ozone and other photochemical oxidants and aerosols, especially ammonium nitrate (NH4NO3) and ammonium sulfate (NH4)2SO4. Leaching and riverine transport of NO3 contribute 40–70 Tg N yr−1 to coastal waters and the open ocean, which together with the 30 Tg input to oceans from atmospheric deposition combine with marine biological nitrogen fixation (140 Tg N yr−1) to double the ocean processing of Nr. Some of the marine Nr is buried in sediments, the remainder being denitrified back to the atmosphere as N2 or N2O. The marine processing is of a similar magnitude to that in terrestrial soils and vegetation, but has a larger fraction of natural origin. The lifetime of Nr in the atmosphere, with the exception of N2O, is only a few weeks, while in terrestrial ecosystems, with the exception of peatlands (where it can be 102–103 years), the lifetime is a few decades. In the ocean, the lifetime of Nr is less well known but seems to be longer than in terrestrial ecosystems and may represent an important long-term source of N2O that will respond very slowly to control measures on the sources of Nr from which it is produced. PMID:23713126

Upregulation of growth signaling and nutrient transporters in cotyledons of early to mid-gestational nutrient restricted ewes

PubMed Central

Ma, Yan; Zhu, Mei J.; Uthlaut, Adam B.; Nijland, Mark J.; Nathanielsz, Peter W.; Hess, Bret W.; Ford, Stephen P.

2011-01-01

Multiparous ewes received 100% (control, C, n=13) or 50% (nutrient restricted, NR, n=14) of NRC dietary requirements from d28-d78 of gestation. On d78, 5 C and 6 NR ewes were necropsied. The remaining 8 C and 8 NR ewes were fed to 100% of NRC from d78-d135 and necropsied. Maternal blood was collected at both necropsies and at weekly intervals for assay of glucose, insulin and leptin. Fetal blood was collected at d78 and d135 necropsies for assay of glucose and lipids. Cotyledonary (COT) tissue was evaluated for protein and mRNA expression [fatty acid transporter (FATP)1, FATP4, CD36, glucose transporter (GLUT)1 and GLUT3], mRNA expression only [placenta fatty acid binding protein (FABPpm) and lipoprotein lipase (LPL)], or expression of phosphorylated and total protein forms [AMP kinase (AMPK)α, acetyl-CoA carboxylase (ACC), extracellular signal-regulated kinase (Erk)1/2, mammalian target of rapamycin (mTOR) and protein kinase B (Akt)]. On d78, but not d135, placental and fetal weights were reduced (P < 0.05) in NR vs. C ewes. Maternal circulating glucose, insulin and leptin levels were decreased in NR vs. C ewes on d78 (P < 0.05) but similar at d135. Fetal blood glucose and triglyceride levels were lower in NR vs. C ewes (P < 0.05) on d78, but similar on d135. On d78, GLUT1, FATP4, CD36 mRNA and protein expression levels, FABPpm mRNA level, and leptin protein level were all increased (P < 0.05) in COT of NR vs. C ewes. AMPK, ACC, and Erk1/2 activities were also increased (P < 0.05) in NR vs. C COT on d78. In contrast, only FATP4 was increased (P < 0.05) at both the mRNA and protein levels in COT of NR realimented vs. C ewes on d135. These data demonstrate placental adaptation to maternal NR through increasing nutrient transporter production and growth signaling activity. PMID:21292322

Quantitative computed tomography applied to interstitial lung diseases.

PubMed

Obert, Martin; Kampschulte, Marian; Limburg, Rebekka; Barańczuk, Stefan; Krombach, Gabriele A

2018-03-01

To evaluate a new image marker that retrieves information from computed tomography (CT) density histograms, with respect to classification properties between different lung parenchyma groups. Furthermore, to conduct a comparison of the new image marker with conventional markers. Density histograms from 220 different subjects (normal = 71; emphysema = 73; fibrotic = 76) were used to compare the conventionally applied emphysema index (EI), 15 th percentile value (PV), mean value (MV), variance (V), skewness (S), kurtosis (K), with a new histogram's functional shape (HFS) method. Multinomial logistic regression (MLR) analyses was performed to calculate predictions of different lung parenchyma group membership using the individual methods, as well as combinations thereof, as covariates. Overall correct assigned subjects (OCA), sensitivity (sens), specificity (spec), and Nagelkerke's pseudo R 2 (NR 2 ) effect size were estimated. NR 2 was used to set up a ranking list of the different methods. MLR indicates the highest classification power (OCA of 92%; sens 0.95; spec 0.89; NR 2 0.95) when all histogram analyses methods were applied together in the MLR. Highest classification power among individually applied methods was found using the HFS concept (OCA 86%; sens 0.93; spec 0.79; NR 2 0.80). Conventional methods achieved lower classification potential on their own: EI (OCA 69%; sens 0.95; spec 0.26; NR 2 0.52); PV (OCA 69%; sens 0.90; spec 0.37; NR 2 0.57); MV (OCA 65%; sens 0.71; spec 0.58; NR 2 0.61); V (OCA 66%; sens 0.72; spec 0.53; NR 2 0.66); S (OCA 65%; sens 0.88; spec 0.26; NR 2 0.55); and K (OCA 63%; sens 0.90; spec 0.16; NR 2 0.48). The HFS method, which was so far applied to a CT bone density curve analysis, is also a remarkable information extraction tool for lung density histograms. Presumably, being a principle mathematical approach, the HFS method can extract valuable health related information also from histograms from complete different areas. Copyright © 2018 Elsevier B.V. All rights reserved.

NMDA receptor expression and C terminus structure in the rotifer Brachionus plicatilis and long-term potentiation across the Metazoa.

PubMed

Kenny, Nathan J; Dearden, Peter K

2013-12-01

The C termini of N-methyl-D-aspartate (NMDA) receptor NR2 subunits are thought to play a major role in the molecular establishment of memory across the Bilateria, via the phenomenon known as long-term potentiation (LTP). Despite their long history of use as models in the study of memory, the expression and structure of the NR2 subunit in the Lophotrochozoa has remained uncategorized. Here, we report the phylogenic relationships of NR subunits across the Bilateria, and the cloning and in situ analysis of expression of NMDA NR1 and NR2 subunits in the monogont rotifer Brachionus plicatilis. RNA in situ hybridization suggests expression of NMDA receptor subunits in B. plicatilis is neural, consistent with expression observed in other species, and ours is the first report confirming NR2 expression in the lophotrochozoan clade. However, the single NR2 subunit identified in B. plicatilis was found to lack the long C terminal domain found in vertebrates, which is believed to modulate LTP. Further investigation revealed that mollusc and annelid NR2 subunits possess long intracellular C terminal domains. As data from molluscs (and particularly Aplysia californica) are the basis for much of our understanding of LTP, understanding how these diverse lophotrochozoan C termini function in vivo will have many implications for how we consider the evolution of the molecular control of learning and memory across the Metazoa as a whole and interpret the results of experiments into this vital component of cognition.

Chimeric Peptide Tat-HA-NR2B9c Improves Regenerative Repair after Transient Global Ischemia.

PubMed

Zhou, Hai-Hui; Zhang, Li; Zhang, Hai-Xia; Zhang, Jin-Ping; Ge, Wei-Hong

2017-01-01

Transient global ischemia (TGI) is a major public health problem, and it heightens the need of effective treatments. The present study was undertaken to investigate whether recombinant polypeptide Tat-HA-NR2B9c improves spatial learning and memory deficits in rats after TGI. Rats were subjected to 20-min ischemia induced by four-vessel occlusion (4-VO) method and daily injected with Tat-HA-NR2B9c (1.12 mg/kg) for 1 week. Tat-HA-NR2B9c increased CREB activity, upregulated B-cell lymphoma-2 (Bcl-2) expression after treated for 24 h. There was a significant increase in dendrite spine density in hippocampal CA1 region and BrdU-positive cells and BrdU/NeuN-positive cells in the dentate gyrus after Tat-HA-NR2B9c treatment, compared with ischemia group at postischemic day 28. Inhibition of the CREB activation by recombinant lentivirus, LV-CREB133-GFP, abolished the upregulation effects of Tat-HA-NR2B9c on Bcl-2 expression. Moreover, Tat-HA-NR2B9c improved the impaired spatial learning and memory ability in Morris water maze. These results suggest that Tat-HA-NR2B9c substantially ameliorated the TGI-induced loss of dendrite spine in hippocampal CA1, increased neurogenesis in dentate gyrus, and significantly improved cognitive abilities by the CREB pathway in rats after transient global cerebral ischemia. It may be served as a treatment for TGI.

Steroids and the scientist.

PubMed

Gustafsson, Jan-Ake

2005-06-01

Our interest in nuclear receptors (NRs) originated from early studies on hepatic steroid metabolism. We discovered a new hypothalamo-pituitary-liver axis, imprinted neonatally by androgens and operating through sexually differentiated GH secretory patterns. Male and female patterns have opposite effects on sexually differentiated hepatic genes, explaining sexually dimorphic liver patterns. To further understand steroid action, we purified the glucocorticoid receptor (GR) leading to our discovery of the NR three-domain structure, with separable DNA binding domain and ligand binding domains and a third domain now known to have transcriptional regulatory properties. Knowledge of this domain structure has been immensely important for deciphering NR actions. Using this first purified NR, we collaborated with Keith Yamamoto and first demonstrated specific NR binding to DNA. This also was the first demonstration of a mammalian transcription factor, a breakthrough that led to discovery of NR response elements. In further collaboration with Yamamoto, we cloned the first NR cDNA sequences, leading to cloning of the superfamily of NR genes. With Yamamoto and Kaptein, we determined the first three-dimensional NR structure, that of DNA binding domain. Later work on orphan receptors resulted in the first discovery of: 1) endogenous ligands for an orphan receptor (fatty acids as activators of peroxisomal proliferator-activated receptor alpha); 2) liver X receptor beta (OR-1) and its role in central nervous system cholesterol homeostasis; and 3) estrogen receptor beta, leading to a paradigm shift in understanding of estrogen signaling, of importance in endocrinology, immunology, and oncology and to development of estrogen receptor beta agonists for treatment of autoimmune diseases, prostate disease, depression, and ovulatory dysfunction.

Effect of organo clay on curing, mechanical and dielectric properties of NR/SBR blends

NASA Astrophysics Data System (ADS)

Ravikumar, K.; Joseph, Reji; Ravichandran, K.

2018-04-01

Natural rubber (NR) and styrene butadiene rubber (SBR) based elastomeric blends reinforced with organically modified Sodium bentonite clay were prepared by two roll mills. Vulcanization parameters such as minimum and maximum torque values scorch and cure times are measured by Oscillating Disc Rheometer. Mechanical properties such as Tensile strength, modulus at 100%, 200% and 300% elongation and elongation at break and Hardness were measured by Universal testing machine and Durometer Shore A hardness meter respectively. Dielectric properties such as dielectric constant (ε’), dissipation factor (tanδ) and volume resistivity (ρv) were measured at room temperature. The curing studies show that torque values are increasing in NR/SBR blends by increase NR content. The scorch and optimum cure time in NR/SBR blends reinforced organo modified clay was found through increase in the SBR content. This may be due to better processing safety of the NR/SBR blends reinforced with organo modified clay. Mechanical properties show that addition of SBR in blends, tensile strength, elongation modulus increases, but 100% modulus slightly increases and no change was observed in Hardness. Dielectric studies show that dielectric constant of NR and SBR rubbers are almost same, it may due to their non-polar nature. But addition of SBR in NR/SBR blend, dielectric constant gradually increases and maximum value observed at 50/50 ratio. But no considerable change was observed in dissipation factor. Frequency dependant resistivity shows that volume resistivity was not changed with respect to frequency up to 3.5 kHz and beyond that the frequency dependence resistivity was found.

Understanding the Broad Substrate Repertoire of Nitroreductase Based on Its Kinetic Mechanism*

PubMed Central

Pitsawong, Warintra; Hoben, John P.; Miller, Anne-Frances

2014-01-01

The oxygen-insensitive nitroreductase from Enterobacter cloacae (NR) catalyzes two-electron reduction of nitroaromatics to the corresponding nitroso compounds and, subsequently, to hydroxylamine products. NR has an unusually broad substrate repertoire, which may be related to protein dynamics (flexibility) and/or a simple non-selective kinetic mechanism. To investigate the possible role of mechanism in the broad substrate repertoire of NR, the kinetics of oxidation of NR by para-nitrobenzoic acid (p-NBA) were investigated using stopped-flow techniques at 4 °C. The results revealed a hyperbolic dependence on the p-NBA concentration with a limiting rate of 1.90 ± 0.09 s−1, indicating one-step binding before the flavin oxidation step. There is no evidence for a distinct binding step in which specificity might be enforced. The reduction of p-NBA is rate-limiting in steady-state turnover (1.7 ± 0.3 s−1). The pre-steady-state reduction kinetics of NR by NADH indicate that NADH reduces the enzyme with a rate constant of 700 ± 20 s−1 and a dissociation constant of 0.51 ± 0.04 mm. Thus, we demonstrate simple transient kinetics in both the reductive and oxidative half-reactions that help to explain the broad substrate repertoire of NR. Finally, we tested the ability of NR to reduce para-hydroxylaminobenzoic acid, demonstrating that the corresponding amine does not accumulate to significant levels even under anaerobic conditions. Thus E. cloacae NR is not a good candidate for enzymatic production of aromatic amines. PMID:24706760

Cloning and characterization of nitrate reductase gene in Ulva prolifera (Ulvophyceae, Chlorophyta).

PubMed

Guo, Yang; Wang, Hao Zhe; Wu, Chun Hui; Fu, Hui Hui; Jiang, Peng

2017-10-01

Ulva spp. dominates green tides around the world, which are occurring at an accelerated rate. The competitive nitrogen assimilation efficiency in Ulva is suggested to result in ecological success against other seaweeds. However, molecular characterization of genes involved in nitrogen assimilation has not been conducted. Here, we describe the identification of the nitrate reductase (NR) gene from a green seaweed Ulva prolifera, an alga which is responsible for the world's largest green tide in the Yellow Sea. Using rapid amplification of cDNA ends and genome walking, the NR gene from U. prolifera (UpNR) was cloned, which consisted of six introns and seven exons encoding 863 amino acids. According to sequence alignment, the NR in U. prolifera was shown to possess all five essential domains and 21 key invariant residues in plant NRs. The GC content of third codon position of UpNR (82.75%) was as high as those of green microalgae, and the intron number supported a potential loss issue from green microalga to land plant. Real-time quantitative PCR results showed that UpNR transcript level was induced by nitrate and repressed by ammonium, which could not be removed by addition of extra nitrate, indicating that U. prolifera preferred ammonium to nitrate. Urea would not repress NR transcription by itself, while it weakened the induction effect of nitrate, implying it possibly inhibited nitrate uptake rather than nitrate reduction. These results suggest the use of UpNR as a gene-sensor to probe the N assimilation process in green tides caused by Ulva. © 2017 Phycological Society of America.

40 CFR 158.260 - Experimental use permit data requirements for environmental fate.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Experimental use permit data requirements for environmental fate. 158.260 Section 158.260 Protection of Environment ENVIRONMENTAL PROTECTION... R R TGAI or PAIRA 1 Metabolism Studies - Laboratory 835.4100 Aerobic soil R CR NR NR R NR TGAI or...

Nicotinamide ribosyl uptake mutants in Haemophilus influenzae.

PubMed

Herbert, Mark; Sauer, Elizabeta; Smethurst, Graeme; Kraiss, Anita; Hilpert, Anna-Karina; Reidl, Joachim

2003-09-01

The gene for the nicotinamide riboside (NR) transporter (pnuC) was identified in Haemophilus influenzae. A pnuC mutant had only residual NR uptake and could survive in vitro with high concentrations of NR, but could not survive in vivo. PnuC may represent a target for the development of inhibitors for preventing H. influenzae disease.

Degradation of blending vulcanized natural rubber and nitril rubber (NR/NBR) by dimethyl ether through variation of elastomer ratio

NASA Astrophysics Data System (ADS)

Saputra, A. H.; Juneva, S.; Sari, T. I.; Cifriadi, A.

2018-04-01

Dimethyl ether can cause degradation of the rubber material seal in some applications. In order to use of natural rubber in industry, research about a blending of natural rubber (NR) and nitrile rubber (NBR) to produce rubber to meet the standard seal material application were conducted. This study will observe the degradation mechanisms that occur in the blending natural rubber and nitrile rubber (NR/NBR) by dimethyl ether. Nitrile rubber types used in this study is medium quality nitrile rubber with 33% of acrylonitrile content (NBR33). The observed parameters are percent change in mass, mechanical properties and surface morphology. This study is limited to see the effect of variation vulcanized blending ratio (NR/NBR33) against to swelling. The increase of nitrile rubber (NBR33) ratio of blending rubber vulcanized can reduce the tensile strength and elongation. The best elastomer variation was obtained after comparing with the standard feasibility material of seal is rubber vulcanized blending (NR/NBR33) with ratio 40:60 NR: NBR.

Optimal design of minimum mean-square error noise reduction algorithms using the simulated annealing technique.

PubMed

Bai, Mingsian R; Hsieh, Ping-Ju; Hur, Kur-Nan

2009-02-01

The performance of the minimum mean-square error noise reduction (MMSE-NR) algorithm in conjunction with time-recursive averaging (TRA) for noise estimation is found to be very sensitive to the choice of two recursion parameters. To address this problem in a more systematic manner, this paper proposes an optimization method to efficiently search the optimal parameters of the MMSE-TRA-NR algorithms. The objective function is based on a regression model, whereas the optimization process is carried out with the simulated annealing algorithm that is well suited for problems with many local optima. Another NR algorithm proposed in the paper employs linear prediction coding as a preprocessor for extracting the correlated portion of human speech. Objective and subjective tests were undertaken to compare the optimized MMSE-TRA-NR algorithm with several conventional NR algorithms. The results of subjective tests were processed by using analysis of variance to justify the statistic significance. A post hoc test, Tukey's Honestly Significant Difference, was conducted to further assess the pairwise difference between the NR algorithms.

Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with Testicular Tissues.

PubMed

Igarashi, Maki; Takasawa, Kei; Hakoda, Akiko; Kanno, Junko; Takada, Shuji; Miyado, Mami; Baba, Takashi; Morohashi, Ken-Ichirou; Tajima, Toshihiro; Hata, Kenichiro; Nakabayashi, Kazuhiko; Matsubara, Yoichi; Sekido, Ryohei; Ogata, Tsutomu; Kashimada, Kenichi; Fukami, Maki

2017-01-01

The role of monogenic mutations in the development of 46,XX testicular/ovotesticular disorders of sex development (DSD) remains speculative. Although mutations in NR5A1 are known to cause 46,XY gonadal dysgenesis and 46,XX ovarian insufficiency, such mutations have not been implicated in testicular development of 46,XX gonads. Here, we identified identical NR5A1 mutations in two unrelated Japanese patients with 46,XX testicular/ovotesticular DSD. The p.Arg92Trp mutation was absent from the clinically normal mothers and from 200 unaffected Japanese individuals. In silico analyses scored p.Arg92Trp as probably pathogenic. In vitro assays demonstrated that compared with wild-type NR5A1, the mutant protein was less sensitive to NR0B1-induced suppression on the SOX9 enhancer element. Other sequence variants found in the patients were unlikely to be associated with the phenotype. The results raise the possibility that specific mutations in NR5A1 underlie testicular development in genetic females. © 2016 WILEY PERIODICALS, INC.

Reactive nitrogen losses from China's food system for the shared socioeconomic pathways (SSPs).

PubMed

Wang, Mengru; Kroeze, Carolien; Strokal, Maryna; Ma, Lin

2017-12-15

Food production in China has been changing fast as a result of socio-economic development. This resulted in an increased use of nitrogen (N) in food production, and also to increased reactive nitrogen (Nr) losses to the environment, causing nitrogen pollution. Our study is the first to quantify future Nr losses from China's food system for the Shared Socio-economic Pathways (SSPs). We show that Nr losses differ largely among SSPs. We first qualitatively described the five SSP storylines for China with a focus on food production and consumption. Next, we interpreted these SSP scenarios quantitatively for 2030 and 2050, using the NUFER (NUtrient Flows in Food chains, Environment and Resources use) model to project the Nr losses from China's food system. The results indicate that Nr losses from future food system in China are relatively low for SSP1 and SSP2, and relatively high for SSP3 and SSP4. In SSP5 Nr losses from China's food system are projected to be slightly lower than the level of today. Copyright © 2017 Elsevier B.V. All rights reserved.

Monosialotetrahexosylganglioside Inhibits the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus.

PubMed

Song, Rui-Biao; Lou, Wei-Hua

2015-01-01

This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element-binding protein (CREB) in the auditory cortex of rats with tinnitus. Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p-CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats. Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration. These data suggest that chronic salicylate administration induces tinnitus via upregulation of p-CREB and NR2B expression, and that GM1 can potentially be used to treat tinnitus.

Survey of Sea Strait Data Around Japan.

DTIC Science & Technology

1981-07-01

study was financially supported by the Office of Naval Research, Coastal Sciences Program, under contract N00014-809-C-0039, Project No. NR 388-159/9...Objective The principal objective of this study is to review and consolidate existing oceanographic information relating to three major sea straits...these sea straits are shown in Figure 1-1. More specifically, the study called for ccmpiling the following products: 1. Data Inventory System o Search

Synthesis, Electrochemistry, and Reactivity of the Actinide Trisulfides [K(18-crown-6)][An(η(3)-S3)(NR2)3] (An = U, Th; R = SiMe3).

PubMed

Smiles, Danil E; Wu, Guang; Hayton, Trevor W

2016-09-19

The reaction of [Th(I)(NR2)3] (R = SiMe3) with [K(18-crown-6)]2[S4] results in the formation of [K(18-crown-6)][Th(η(3)-S3)(NR2)3] (2). Oxidation of 2, or its uranium analogue, [K(18-crown-6)][U(η(3)-S3)(NR2)3] (1), with AgOTf, in an attempt to generate an [S3](•-) complex, results in the formation of [K(18-crown-6)][An(OTf)2(NR2)3] (3, An = U; 4, An = Th) as the only isolable products. These results suggest that the putative [S3](•-) ligand is only weakly coordinating and can be easily displaced by nucleophiles.

Network pharmacology analysis of the anti-cancer pharmacological mechanisms of Ganoderma lucidum extract with experimental support using Hepa1-6-bearing C57 BL/6 mice.

PubMed

Zhao, Ruo-Lin; He, Yu-Min

2018-01-10

Ganoderma lucidum (GL) is an oriental medical fungus, which was used to prevent and treat many diseases. Previously, the effective compounds of Ganoderma lucidum extract (GLE) were extracted from two kinds of GL, [Ganoderma lucidum (Leyss. Ex Fr.) Karst.] and [Ganoderma sinense Zhao, Xu et Zhang], which have been used for adjuvant anti-cancer clinical therapy for more than 20 years. However, its concrete active compounds and its regulation mechanisms on tumor are unclear. In this study, we aimed to identify the main active compounds from GLE and to investigate its anti-cancer mechanisms via drug-target biological network construction and prediction. The main active compounds of GLE were identified by HPLC, EI-MS and NMR, and the compounds related targets were predicted using docking program. To investigate the functions of GL holistically, the active compounds of GL and related targets were predicted based on four public databases. Subsequently, the Identified-Compound-Target network and Predicted-Compound-Target network were constructed respectively, and they were overlapped to detect the hub potential targets in both networks. Furthermore, the qRT-PCR and western-blot assays were used to validate the expression levels of target genes in GLE treated Hepa1-6-bearing C57 BL/6 mice. In our work, 12 active compounds of GLE were identified, including Ganoderic acid A, Ganoderenic acid A, Ganoderic acid B, Ganoderic acid H, Ganoderic acid C2, Ganoderenic acid D, Ganoderic acid D, Ganoderenic acid G, Ganoderic acid Y, Kaemferol, Genistein and Ergosterol. Using the docking program, 20 targets were mapped to 12 compounds of GLE. Furthermore, 122 effective active compounds of GL and 116 targets were holistically predicted using public databases. Compare with the Identified-Compound-Target network and Predicted-Compound-Target network, 6 hub targets were screened, including AR, CHRM2, ESR1, NR3C1, NR3C2 and PGR, which was considered as potential markers and might play important roles in the process of GLE treatment. GLE effectively inhibited tumor growth in Hepa1-6-bearing C57 BL/6 mice. Finally, consistent with the results of qRT-PCR data, the results of western-blot assay demonstrated the expression levels of PGR and ESR1 were up-regulated, as well as the expression levels of NR3C2 and AR were down-regulated, while the change of NR3C1 and CHRM2 had no statistical significance. The results indicated that these 4 hub target genes, including NR3C2, AR, ESR1 and PGR, might act as potential markers to evaluate the curative effect of GLE treatment in tumor. And, the combined data provide preliminary study of the pharmacological mechanisms of GLE, which may be a promising potential therapeutic and chemopreventative candidate for anti-cancer. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Shell structure of natural rubber particles: evidence of chemical stratification by electrokinetics and cryo-TEM.

PubMed

Rochette, Christophe N; Crassous, Jérôme J; Drechsler, Markus; Gaboriaud, Fabien; Eloy, Marie; de Gaudemaris, Benoît; Duval, Jérôme F L

2013-11-26

The interfacial structure of natural rubber (NR) colloids is investigated by means of cryogenic transmission electron microscopy (cryo-TEM) and electrokinetics over a broad range of KNO3 electrolyte concentrations (4-300 mM) and pH values (1-8). The asymptotic plateau value reached by NR electrophoretic mobility (μ) in the thin double layer limit supports the presence of a soft (ion- and water-permeable) polyelectrolytic type of layer located at the periphery of the NR particles. This property is confirmed by the analysis of the electron density profile obtained from cryo-TEM that evidences a ∼2-4 nm thick corona surrounding the NR polyisoprene core. The dependence of μ on pH and salt concentration is further marked by a dramatic decrease of the point of zero electrophoretic mobility (PZM) from 3.6 to 0.8 with increasing electrolyte concentration in the range 4-300 mM. Using a recent theory for electrohydrodynamics of soft multilayered particles, this "anomalous" dependence of the PZM on electrolyte concentration is shown to be consistent with a radial organization of anionic and cationic groups across the peripheral NR structure. The NR electrokinetic response in the pH range 1-8 is indeed found to be equivalent to that of particles surrounded by a positively charged ∼3.5 nm thick layer (mean dissociation pK ∼ 4.2) supporting a thin and negatively charged outermost layer (0.6 nm in thickness, pK ∼ 0.7). Altogether, the strong dependence of the PZM on electrolyte concentration suggests that the electrostatic properties of the outer peripheral region of the NR shell are mediated by lipidic residues protruding from a shell containing a significant amount of protein-like charges. This proposed NR shell interfacial structure questions previously reported NR representations according to which the shell consists of either a fully mixed lipid-protein layer, or a layer of phospholipids residing exclusively beneath an outer proteic film.

Prenatal exposure to neurotoxic metals is associated with increased placental glucocorticoid receptor DNA methylation

PubMed Central

Appleton, Allison A.; Jackson, Brian P.; Marsit, Carmen J.

2017-01-01

ABSTRACT Epigenetic alterations related to prenatal neurotoxic metals exposure may be key in understanding the origins of cognitive and neurobehavioral problems in children. Placental glucocorticoid receptor (NR3C1) methylation has been linked to neurobehavioral risk in early life, but has not been examined in response to neurotoxic metals exposure despite parallel lines of research showing metals exposure and NR3C1 methylation each contribute to a similar set of neurobehavioral phenotypes. Thus, we conducted a study of prenatal neurotoxic metals exposure and placental NR3C1 methylation in a cohort of healthy term singleton pregnancies from Rhode Island, USA (n = 222). Concentrations of arsenic (As; median 0.02 ug/g), cadmium (Cd; median 0.03 μg/g), lead (Pb; median 0.40 μg/g), manganese (Mn; median 0.56 μg/g), mercury (Hg; median 0.02 μg/g), and zinc (Zn; 145.18 μg/g) measured in infant toenails were categorized as tertiles. Multivariable linear regression models tested the independent associations for each metal with NR3C1 methylation, as well as the cumulative risk of exposure to multiple metals simultaneously. Compared to the lowest exposure tertiles, higher levels of As, Cd, Pb, Mn, and Hg were each associated with increased placental NR3C1 methylation (all P<0.02). Coefficients for these associations corresponded with a 0.71–1.41 percent increase in NR3C1 methylation per tertile increase in metals concentrations. For Zn, the lowest exposure tertile compared with the highest tertile was associated with 1.26 percent increase in NR3C1 methylation (P=0.01). Higher cumulative metal risk scores were marginally associated with greater NR3C1 methylation. Taken together, these results indicate that prenatal exposure to neurotoxic metals may affect the offspring's NR3C1 activity, which may help explain cognitive and neurodevelopmental risk later in life. PMID:28548590

Prenatal exposure to neurotoxic metals is associated with increased placental glucocorticoid receptor DNA methylation.

PubMed

Appleton, Allison A; Jackson, Brian P; Karagas, Margaret; Marsit, Carmen J

2017-08-01

Epigenetic alterations related to prenatal neurotoxic metals exposure may be key in understanding the origins of cognitive and neurobehavioral problems in children. Placental glucocorticoid receptor (NR3C1) methylation has been linked to neurobehavioral risk in early life, but has not been examined in response to neurotoxic metals exposure despite parallel lines of research showing metals exposure and NR3C1 methylation each contribute to a similar set of neurobehavioral phenotypes. Thus, we conducted a study of prenatal neurotoxic metals exposure and placental NR3C1 methylation in a cohort of healthy term singleton pregnancies from Rhode Island, USA (n = 222). Concentrations of arsenic (As; median 0.02 ug/g), cadmium (Cd; median 0.03 μg/g), lead (Pb; median 0.40 μg/g), manganese (Mn; median 0.56 μg/g), mercury (Hg; median 0.02 μg/g), and zinc (Zn; 145.18 μg/g) measured in infant toenails were categorized as tertiles. Multivariable linear regression models tested the independent associations for each metal with NR3C1 methylation, as well as the cumulative risk of exposure to multiple metals simultaneously. Compared to the lowest exposure tertiles, higher levels of As, Cd, Pb, Mn, and Hg were each associated with increased placental NR3C1 methylation (all P<0.02). Coefficients for these associations corresponded with a 0.71-1.41 percent increase in NR3C1 methylation per tertile increase in metals concentrations. For Zn, the lowest exposure tertile compared with the highest tertile was associated with 1.26 percent increase in NR3C1 methylation (P=0.01). Higher cumulative metal risk scores were marginally associated with greater NR3C1 methylation. Taken together, these results indicate that prenatal exposure to neurotoxic metals may affect the offspring's NR3C1 activity, which may help explain cognitive and neurodevelopmental risk later in life.

Structural insight into the role of Streptococcus parasanguinis Fap1 within oral biofilm formation

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

Garnett, James A.; Simpson, Peter J.; Taylor, Jonathan

2012-01-06

Highlights: Black-Right-Pointing-Pointer Crystal structure of Streptococcus parasanguinis Fap1-NR{sub {alpha}} at pH 5.0. Black-Right-Pointing-Pointer pH-dependent conformational changes mediated through electrostatic potential of Fap1-NR{sub {alpha}}. Black-Right-Pointing-Pointer Fap1 facilitates pH-dependent biofilms. Black-Right-Pointing-Pointer We model inter-Fap1 biofilm interactions. -- Abstract: The fimbriae-associated protein 1 (Fap1) is a major adhesin of Streptococcus parasanguinis, a primary colonizer of the oral cavity that plays an important role in the formation of dental plaque. Fap1 is an extracellular adhesive surface fibre belonging to the serine-rich repeat protein (SRRP) family, which plays a central role in the pathogenesis of streptococci and staphylococci. The N-terminal adhesive region of Fap1 (Fap1-NR)more » is composed of two domains (Fap1-NR{sub {alpha}} and Fap1-NR{sub {beta}}) and is projected away from the bacterial surface via the extensive serine-rich repeat region, for adhesion to the salivary pellicle. The adhesive properties of Fap1 are modulated through a pH switch in which a reduction in pH results in a rearrangement between the Fap1-NR{sub {alpha}} and Fap1-NR{sub {beta}} domains, which assists in the survival of S. parasanguinis in acidic environments. We have solved the structure of Fap1-NR{sub {alpha}} at pH 5.0 at 3.0 A resolution and reveal how subtle rearrangements of the 3-helix bundle combined with a change in electrostatic potential mediates 'opening' and activation of the adhesive region. Further, we show that pH-dependent changes are critical for biofilm formation and present an atomic model for the inter-Fap1-NR interactions which have been assigned an important role in the biofilm formation.« less

Impact of nitrogen deposition on forest and lake food webs in nitrogen-limited environments.

PubMed

Meunier, Cédric L; Gundale, Michael J; Sánchez, Irene S; Liess, Antonia

2016-01-01

Increased reactive nitrogen (Nr ) deposition has raised the amount of N available to organisms and has greatly altered the transfer of energy through food webs, with major consequences for trophic dynamics. The aim of this review was to: (i) clarify the direct and indirect effects of Nr deposition on forest and lake food webs in N-limited biomes, (ii) compare and contrast how aquatic and terrestrial systems respond to increased Nr deposition, and (iii) identify how the nutrient pathways within and between ecosystems change in response to Nr deposition. We present that Nr deposition releases primary producers from N limitation in both forest and lake ecosystems and raises plants' N content which in turn benefits herbivores with high N requirements. Such trophic effects are coupled with a general decrease in biodiversity caused by different N-use efficiencies; slow-growing species with low rates of N turnover are replaced by fast-growing species with high rates of N turnover. In contrast, Nr deposition diminishes below-ground production in forests, due to a range of mechanisms that reduce microbial biomass, and decreases lake benthic productivity by switching herbivore growth from N to phosphorus (P) limitation, and by intensifying P limitation of benthic fish. The flow of nutrients between ecosystems is expected to change with increasing Nr deposition. Due to higher litter production and more intense precipitation, more terrestrial matter will enter lakes. This will benefit bacteria and will in turn boost the microbial food web. Additionally, Nr deposition promotes emergent insects, which subsidize the terrestrial food web as prey for insectivores or by dying and decomposing on land. So far, most studies have examined Nr -deposition effects on the food web base, whereas our review highlights that changes at the base of food webs substantially impact higher trophic levels and therefore food web structure and functioning. © 2015 John Wiley & Sons Ltd.

The nuclear hormone receptor family member NR5A2 controls aspects of multipotent progenitor cell formation and acinar differentiation during pancreatic organogenesis.

PubMed

Hale, Michael A; Swift, Galvin H; Hoang, Chinh Q; Deering, Tye G; Masui, Toshi; Lee, Youn-Kyoung; Xue, Jumin; MacDonald, Raymond J

2014-08-01

The orphan nuclear receptor NR5A2 is necessary for the stem-like properties of the epiblast of the pre-gastrulation embryo and for cellular and physiological homeostasis of endoderm-derived organs postnatally. Using conditional gene inactivation, we show that Nr5a2 also plays crucial regulatory roles during organogenesis. During the formation of the pancreas, Nr5a2 is necessary for the expansion of the nascent pancreatic epithelium, for the subsequent formation of the multipotent progenitor cell (MPC) population that gives rise to pre-acinar cells and bipotent cells with ductal and islet endocrine potential, and for the formation and differentiation of acinar cells. At birth, the NR5A2-deficient pancreas has defects in all three epithelial tissues: a partial loss of endocrine cells, a disrupted ductal tree and a >90% deficit of acini. The acinar defects are due to a combination of fewer MPCs, deficient allocation of those MPCs to pre-acinar fate, disruption of acinar morphogenesis and incomplete acinar cell differentiation. NR5A2 controls these developmental processes directly as well as through regulatory interactions with other pancreatic transcriptional regulators, including PTF1A, MYC, GATA4, FOXA2, RBPJL and MIST1 (BHLHA15). In particular, Nr5a2 and Ptf1a establish mutually reinforcing regulatory interactions and collaborate to control developmentally regulated pancreatic genes by binding to shared transcriptional regulatory regions. At the final stage of acinar cell development, the absence of NR5A2 affects the expression of Ptf1a and its acinar specific partner Rbpjl, so that the few acinar cells that form do not complete differentiation. Nr5a2 controls several temporally distinct stages of pancreatic development that involve regulatory mechanisms relevant to pancreatic oncogenesis and the maintenance of the exocrine phenotype. © 2014. Published by The Company of Biologists Ltd.

SETDB1 HISTONE METHYLTRANSFERASE REGULATES MOOD-RELATED BEHAVIORS AND EXPRESSION OF THE NMDA RECEPTOR SUBUNIT NR2B

PubMed Central

Jiang, Yan; Jakovcevski, Mira; Bharadwaj, Rahul; Connor, Caroline; Schroeder, Frederick A.; Lin, Cong L.; Straubhaar, Juerg; Martin, Gilles; Akbarian, Schahram

2010-01-01

Histone methyltransferases specific for the histone H3-lysine 9 (H3K9) residue, including Setdb1 (Set domain, bifurcated 1)/Eset/Kmt1e are associated with repressive chromatin remodeling and expressed in adult brain, but potential effects on neuronal function and behavior remain unexplored. Here, we report that transgenic mice with increased Setdb1 expression in adult forebrain neurons show antidepressant-like phenotypes in behavioral paradigms for anhedonia, despair and learned helplessness. Chromatin immunoprecipitation in conjunction with DNA tiling arrays (ChIP-chip) revealed that genomic occupancies of neuronal Setdb1 are limited to less than 1% of annotated genes, which include the NMDA receptor subunit NR2B/Grin2B and other ionotropic glutamate receptor genes. Chromatin conformation capture (“3C”) and Setdb1-ChIP revealed a loop formation tethering the NR2B/Grin2b promoter to the Setdb1 target site positioned 30Kb downstream of the transcription start site. In hippocampus and ventral striatum, two key structures in the neuronal circuitry regulating mood-related behaviors, Setdb1-mediated repressive histone methylation at NR2B/Grin2b was associated with decreased NR2B expression and EPSP insensitivity to pharmacological blockade of NR2B, and accelerated NMDA receptor desensitization consistent with a shift in NR2A/B subunit ratios. In wildtype mice, systemic treatment with the NR2B antagonist, Ro-256981, and hippocampal siRNA-mediated NR2B/Grin2b knockdown, resulted in behavioral changes similar to those elicited by the Setdb1 transgene. Together, these findings point to a role for neuronal Setdb1 in the regulation of affective and motivational behaviors through repressive chromatin remodeling at a select set of target genes, resulting in altered NMDA receptor subunit composition and other molecular adaptations. PMID:20505083

The qEEG Signature of Selective NMDA NR2B Negative Allosteric Modulators; A Potential Translational Biomarker for Drug Development

PubMed Central

Keavy, Deborah; Bristow, Linda J.; Sivarao, Digavalli V.; Batchelder, Margaret; King, Dalton; Thangathirupathy, Srinivasan; Macor, John E.; Weed, Michael R.

2016-01-01

The antidepressant activity of the N-methyl-D-aspartate (NMDA) receptor channel blocker, ketamine, has led to the investigation of negative allosteric modulators (NAMs) selective for the NR2B receptor subtype. The clinical development of NR2B NAMs would benefit from a translational pharmacodynamic biomarker that demonstrates brain penetration and functional inhibition of NR2B receptors in preclinical species and humans. Quantitative electroencephalography (qEEG) is a translational measure that can be used to demonstrate pharmacodynamic effects across species. NMDA receptor channel blockers, such as ketamine and phencyclidine, increase the EEG gamma power band, which has been used as a pharmacodynamic biomarker in the development of NMDA receptor antagonists. However, detailed qEEG studies with ketamine or NR2B NAMs are lacking in nonhuman primates. The aim of the present study was to determine the effects on the qEEG power spectra of the NR2B NAMs traxoprodil (CP-101,606) and BMT-108908 in nonhuman primates, and to compare them to the NMDA receptor channel blockers, ketamine and lanicemine. Cynomolgus monkeys were surgically implanted with EEG radio-telemetry transmitters, and qEEG was measured after vehicle or drug administration. The relative power for a number of frequency bands was determined. Ketamine and lanicemine increased relative gamma power, whereas the NR2B NAMs traxoprodil and BMT-108908 had no effect. Robust decreases in beta power were elicited by ketamine, traxoprodil and BMT-108908; and these agents also produced decreases in alpha power and increases in delta power at the doses tested. These results suggest that measurement of power spectra in the beta and delta bands may represent a translational pharmacodynamic biomarker to demonstrate functional effects of NR2B NAMs. The results of these studies may help guide the selection of qEEG measures that can be incorporated into early clinical evaluation of NR2B NAMs in healthy humans. PMID:27035340

IL-1ra alleviates inflammatory hyperalgesia through preventing phosphorylation of NMDA receptor NR-1 subunit in rats.

PubMed

Zhang, Rui-Xin; Li, Aihui; Liu, Bing; Wang, Linbo; Ren, Ke; Zhang, Haiqing; Berman, Brian M; Lao, Lixing

2008-04-01

Although it has been shown that pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) facilitate perception of noxious inputs at the spinal level, the mechanisms have not been understood. This study determined the cell type that produces IL-1beta, the co-localization of IL-1 receptor type I (IL-1RI) and Fos and NR1 in the spinal cord, and the effects of IL-1 receptor antagonist (IL-1ra) on NR1 phosphorylation and hyperalgesia in a rat model of inflammatory pain. Phosphorylation of NR1, an essential subunit of the NMDA receptor (NMDAR), is known to modulate NMDAR activity and facilitate pain. Hyperalgesia was induced by injecting complete Freund's adjuvant (CFA, 0.08ml, 40microg Mycobacterium tuberculosis) into one hind paw of each rat. Paw withdrawal latency (PWL) was tested before CFA (-48h) for baseline and 2 and 24h after CFA to assess hyperalgesia. IL-1ra was given (i.t.) 24h before CFA to block the action of basal IL-1beta and 2h prior to each of two PWL tests to block CFA-induced IL-1beta. Spinal cords were removed for double immunostaining of IL-1beta/neuronal marker and IL-1beta/glial cell markers, IL-1RI/Fos and IL-1RI/NR1, and for Western blot to measure NR1 phosphorylation. The data showed that: (1) astrocytes produce IL-1beta, (2) IL-1RI is localized in Fos- and NR1-immunoreactive neurons within the spinal dorsal horn, and (3) IL-1ra at 0.01mg/rat significantly increased PWL (P<0.05) and inhibited NR1 phosphorylation compared to saline control. The results suggest that spinal IL-1beta is produced by astrocytes and enhances NR1 phosphorylation to facilitate inflammatory pain.

The Test–Retest Reliability of the Photopic Negative Response (PhNR)

PubMed Central

Tang, Jessica; Edwards, Thomas; Crowston, Jonathan G.; Sarossy, Marc

2014-01-01

Purpose The photopic negative response (PhNR) may be useful as a tool to monitor longitudinal change in retinal ganglion cell (RGC) function. The goal was to assess PhNR test–retest reliability, and to estimate the amount of change between tests that is likely to be statistically significant for an individual test subject. Methods Photopic electroretinograms (ERGs) were recorded from 49 visually normal subjects (mean age, 38.9 years; range, 21–72 years). Signals were acquired using Dawson-Trick-Litzkow (DTL) electrodes in response to red stimulus at four flash energies (0.5, 1, 2.25, 3 cd·s/m2) on a blue background (10 cd/m2). The PhNR amplitude was recorded from prestimulus baseline to trough (BT), prestimulus baseline to fixed time point (BF), and b-wave peak to trough (PT). The ratio of baseline PhNR to b-wave amplitude (BT/b-wave) was calculated. Reliability was assessed using the intraclass correlation coefficient (ICC2,1) and coefficient of repeatability (CoR). Results Flash energy of 1.00 cd·s/m2 produced reliable, well-defined traces. At this stimulus, the a- and b-wave amplitudes were reproduced with moderate reliability (ICC, 0.62; CoR%, 90.0%; and ICC, 0.74; CoR%, 54.3%; respectively). For PhNR, the order from most to least reliable measurement was: PT (ICC, 0.64; CoR%, 59.1%), BT (ICC, 0.40; CoR%, 148.3%), and BF (ICC, 0.22; CoR%, 166.1%). The BT/b-wave did not improve reliability (ICC, 0.37; CoR%, 181.5). Conclusion The b-wave peak-to-PhNR trough amplitude produced the most reliable measurement. Translational Relevance A relatively large magnitude of change in PhNR amplitude is required to make clinical inferences about changes in RGC function. Refinement to the technique of acquisition and/or processing of the PhNR is recommended to improve reliability. PMID:25374770

Functional Uncoupling NMDAR NR2A Subunit from PSD-95 in the Prefrontal Cortex: Effects on Behavioral Dysfunction and Parvalbumin Loss after Early-Life Stress

PubMed Central

Ganguly, Prabarna; Holland, Freedom H; Brenhouse, Heather C

2015-01-01

Exposure to early-life stress increases vulnerability to psychiatric disorders, including depression, schizophrenia, and anxiety. Growing evidence implicates aberrant development of the prefrontal cortex (PFC) in the effects of early-life stress, which often emerge in adolescence or young adulthood. Specifically, early-life stress in the form of maternal separation (MS) in rodents has been shown to decrease parvalbumin (PVB)-positive interneurons in the adolescent PFC; however, the mechanism underpinning behavioral dysfunction and PVB loss is not yet known. We recently reported that MS causes overexpression of the NMDA subunit NR2A in the PFC of adolescent rats. Elevated PFC NR2A is also found in developmental models of schizophrenia and is correlated with behavioral deficits, acting largely through its association with the postsynaptic protein PSD-95. In addition, adolescent maturation of PVB-positive interneurons relies on NR2A-driven NMDA activity. Therefore, it is possible that the NR2A/PSD-95 signaling complex has a role in adolescent MS effects. Here, we aimed to determine whether a discrete manipulation of PFC NR2A could prevent MS effects on PFC-controlled behaviors, including cognition, anxiety, and novelty-induced hyperlocomotion, as well as PVB loss in adolescence. We intracranially infused the NR2A-specific blocking peptide TAT2A in order to uncouple NR2A from PSD-95 in the early-adolescent PFC, without antagonizing the NMDA receptor. We demonstrated that MS rats treated with TAT2A during early adolescence were protected from MS-induced PVB loss and exhibited less anxious behavior than those infused with control peptide. These data implicate NR2A-related N-methyl-D-aspartate receptor development in adolescent behavioral and neural consequences of early-life stress. PMID:25953359

Studies on the nitrate reductase activities of the fruit and the source leaf in pepper

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

Achhireddy, N.R.; Beevers, L.; Fletcher, J.S.

Nitrate reductase (NR) activity (NO/sub 2//sup -/ produced in the dark and under anaerobic conditions) of 30-day-old fruit of Capsicum annuum L. was 2.2% that in tissues of a single leaf adjacent to each fruit (33 vs. 1500 nmoles/hr-g fresh weight). The optimal NR activity in one source leaf could only account for about 17% of the fruit's total nitrogen accumulation, while the fruit's own NR activity was almost negligible. Covered and uncovered fruits did not differ significantly in NR activities. 19 references, 1 figure, 1 table.

Seeking a valid gold standard for an innovative, dialect-neutral language test.

PubMed

Pearson, Barbara Zurer; Jackson, Janice E; Wu, Haotian

2014-04-01

PURPOSE In this study, the authors explored alternative gold standards to validate an innovative, dialect-neutral language assessment. METHOD Participants were 78 African American children, ages 5;0 (years;months) to 6;11. Twenty participants had previously been identified as having language impairment. The Diagnostic Evaluation of Language Variation-Norm Referenced (DELV-NR; Seymour, Roeper, & J. de Villiers, 2005) was administered, and concurrent language samples (LSs) were collected. Using LS profiles as the gold standard, sensitivity, specificity, and other measures of diagnostic accuracy were compared for diagnoses made from the DELV-NR and participants' clinical status prior to recruitment. In a second analysis, the authors used results from the first analysis to make evidence-based adjustments in the estimates of DELV-NR diagnostic accuracy. RESULTS Accuracy of the DELV-NR relative to LS profiles was greater than that of prior diagnoses, indicating that the DELV-NR was an improvement over preexisting diagnoses for this group. Specificity met conventional standards, but sensitivity was somewhat low. Reanalysis using the positive and negative predictive power of the preexisting diagnosis in a discrepant-resolution procedure revealed that estimates for sensitivity and specificity for the DELV-NR were .85 and .93, respectively. CONCLUSION The authors found that, even after making allowances for the imperfection of available gold standards, clinical decisions made with the DELV-NR achieved high values on conventional measures of diagnostic accuracy.

Loss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer.

PubMed

Khanal, Tilak; Choi, Kwangmin; Leung, Yuet-Kin; Wang, Jiang; Kim, Dasom; Janakiram, Vinothini; Cho, Sung-Gook; Puga, Alvaro; Ho, Shuk-Mei; Kim, Kyounghyun

2017-09-06

The aryl hydrocarbon receptor (AHR) plays crucial roles in inflammation, metabolic disorder, and cancer. However, the molecular mechanisms regulating AHR expression remain unknown. Here, we found that an orphan nuclear NR2E3 maintains AHR expression, and forms an active transcriptional complex with transcription factor Sp1 and coactivator GRIP1 in MCF-7 human breast and HepG2 liver cancer cell lines. NR2E3 loss promotes the recruitment of LSD1, a histone demethylase of histone 3 lysine 4 di-methylation (H3K4me2), to the AHR gene promoter region, resulting in repression of AHR expression. AHR expression and responsiveness along with H3K4me2 were significantly reduced in the livers of Nr2e3 rd7 (Rd7) mice that express low NR2E3 relative to the livers of wild-type mice. SP2509, an LSD1 inhibitor, fully restored AHR expression and H3K4me2 levels in Rd7 mice. Lastly, we demonstrated that both AHR and NR2E3 are significantly associated with good clinical outcomes in liver cancer. Together, our results reveal a novel link between NR2E3, AHR, and liver cancer via LSD1-mediated H3K4me2 histone modification in liver cancer development.

Peripheral inflammation increased the synaptic expression of NMDA receptors in spinal dorsal horn.

PubMed

Yang, Xian; Yang, Hong-Bin; Xie, Qin-Jian; Liu, Xiao-Hua; Hu, Xiao-Dong

2009-07-01

Considerable evidence has indicated that the aberrant, sustained enhancement of spinal NMDA receptors (NMDARs) function is closely associated with behavioral sensitization during inflammatory pain. However, the molecular mechanisms underlying inflammation-induced NMDARs hyperfunction remain poorly understood. The present study performed immunoblotting analysis to evaluate the possible changes in the protein expression of spinal NMDARs after injection of complete Freund's adjuvant (CFA) in mice. We found that CFA did not affect the total protein level of NMDARs subunit NR1 in spinal dorsal horn. However, NR1 immunoreactivity at synapses significantly increased after CFA injection, which was correlated in the time course with the development of mechanical allodynia. Inhibition of spinal NMDARs with D-APV completely eliminated the CFA-induced increase in NR1 immunoreactive density at synapses, and direct application of NMDA onto the spinal cord of naïve mice mimicked the effects of CFA, suggesting the importance of NMDARs activity in regulating the synaptic content of NR1 during inflammatory pain. Moreover, cAMP-dependent protein kinase (PKA) downstream to NMDARs was also required for NR1 synaptic expression because inhibition of PKA activity abolished the enhancement of synaptic NR1 immunoreactivity evoked by either CFA or NMDA. Thus, our data suggested that NMDARs- and PKA-dependent increase in NR1 synaptic expression represented an important mechanism for the hyperfunction of spinal NMDARs following peripheral inflammation.

Steroidogenic Factor-1 (SF-1, Ad4BP, NR5A1) and Disorders of Testis Development

PubMed Central

Lin, L.; Achermann, J.C.

2009-01-01

Steroidogenic factor-1 (SF-1) (Ad4BP, NR5A1) is a nuclear receptor that regulates many aspects of adrenal and reproductive development and function. Consequently, deletion of the gene (Nr5a1) encoding Sf-1 in XY mice results in impaired adrenal development, complete testicular dysgenesis with Müllerian structures, and female external genitalia. Initial efforts to identify NR5A1 changes in humans focused on 46,XY individuals with combined adrenogonadal failure and Müllerian structures. Although this combination of clinical features is rare, 2 such patients harboring NR5A1 mutations have been described within the past decade. More recently, however, it has emerged that heterozygous loss of function mutations in NR5A1 can be found relatively frequently in children and adults with 46,XY disorders of sex development (DSD) but with apparently normal adrenal function. The phenotypic spectrum associated with these changes ranges from complete testicular dysgenesis with Müllerian structures, through individuals with mild clitoromegaly or genital ambiguity, to severe penoscrotal hypospadias or even anorchia. Furthermore, a non-synonymous polymorphism in NR5A1 may be associated with micropenis or undescended testes within the population. Taken together, these reports suggest that variable loss of SF-1 function can be associated with a wide range of reproductive phenotypes in humans. PMID:18987494

Enantioselectivity and Thermostability of a Novel Hyperhermotolerant Lipase from Geobacillus Thermodenitrificans nr68 (Lip.nr-68) on Secondary Racemic Alcohols Acetylation

NASA Astrophysics Data System (ADS)

Nik Him, N. R.; Ibrahim, D.

2018-05-01

In our previous work, a new lipase enzyme has been purified from a species identified as a Gram negative Geobacillus thermodenitrificans nr68, isolated from a hot spring in Malaysia with growth temperature of 48°C. This new lipase, called Lip.nr-68 has been characterized as a hyperthermotolerant protein with high stability at 65°C and has been showing excellent characteristics that are very much comparable yet better than some of those of well-known industrially-used lipases. It shows high activity against long-chain triglycerides with molecular weight of the purified enzyme estimated to be 33.5 kDa using SDS-PAGE analysis. This paper is focusing on hyperthermotolerant Lip.nr-68 performance in promoting for enantioselectivity activities towards three secondary racemic alcohols namely 1-phenylethanol, 1-cyclohexilethanol and 1-(naft-2-il) ethanol by acetylation with vinyl acetate. Lip.nr-68 has been confirmed to show high and usual enantioselectivitiy according to the Kazlauskas Rule towards all secondary racemic alcohols and has significantly approved as an enantiomer selective biocatalyst towards 1-phenylethanol and 1-cyclohexylethanol at 65°C. Lip.nr-68 has showed a reduction of (R) and (S) enantiomers as well as the production of 68-98% ee and almost 94% yield of 3-4 mg/ml for 1-cyclohexilethanol.

Noise reduction improves memory for target language speech in competing native but not foreign language speech.

PubMed

Ng, Elaine Hoi Ning; Rudner, Mary; Lunner, Thomas; Rönnberg, Jerker

2015-01-01

A hearing aid noise reduction (NR) algorithm reduces the adverse effect of competing speech on memory for target speech for individuals with hearing impairment with high working memory capacity. In the present study, we investigated whether the positive effect of NR could be extended to individuals with low working memory capacity, as well as how NR influences recall performance for target native speech when the masker language is non-native. A sentence-final word identification and recall (SWIR) test was administered to 26 experienced hearing aid users. In this test, target spoken native language (Swedish) sentence lists were presented in competing native (Swedish) or foreign (Cantonese) speech with or without binary masking NR algorithm. After each sentence list, free recall of sentence final words was prompted. Working memory capacity was measured using a reading span (RS) test. Recall performance was associated with RS. However, the benefit obtained from NR was not associated with RS. Recall performance was more disrupted by native than foreign speech babble and NR improved recall performance in native but not foreign competing speech. Noise reduction improved memory for speech heard in competing speech for hearing aid users. Memory for native speech was more disrupted by native babble than foreign babble, but the disruptive effect of native speech babble was reduced to that of foreign babble when there was NR.

Reinforcement of natural rubber latex using lignocellulosic nanofibers isolated from spinifex grass.

PubMed

Hosseinmardi, Alireza; Annamalai, Pratheep K; Wang, Lianzhou; Martin, Darren; Amiralian, Nasim

2017-07-13

Reinforcement of natural rubber (NR) using nanofillers often results in an enhancement of the tensile strength, but at the expense of elongation at break and toughness. In this study, with the objective of strengthening NR without compromising its compliance, we investigate the reinforcement efficiency of a series of cellulose nanofibers (CNF) with variations in residual hemicellulose, lignin and therefore surface chemistry. Different types of high aspect ratio CNF isolated from Triodia pungens (T. pungens), an Australian arid grass commonly known as spinifex, were added at 0.1-2 wt% loadings into a pre-vulcanized NR latex. CNF/NR nanocomposites then were benchmarked against NR nanocomposites incorporating a well-known wood-derived CNF. It was found that the presence of residual lignin and hemicellulose, and the pretreatment with a deep eutectic solvent, a mixture of choline chloride and urea (CCU), could increase the compatibility of CNF with the NR matrix, while still enabling stability and handling of the colloidal latex mixture. Incorporation of 0.5 and 0.1 wt% of the sodium hydroxide treated CNF and choline chloride/urea treated CNF into the NR latex showed respectively 11 and 17% enhancement in tensile stress, and importantly without compromising viscoelastic properties; while addition of 0.1 wt% wood-derived CNF resulted in 18% decrease in both tensile stress and strain coupled with more pronounced latex stiffening.

Genome-wide identification of nuclear receptor (NR) genes and the evolutionary significance of the NR1O subfamily in the monogonont rotifer Brachionus spp.

PubMed

Kim, Duck-Hyun; Kim, Hui-Su; Hwang, Dae-Sik; Kim, Hee-Jin; Hagiwara, Atsushi; Lee, Jae-Seong; Jeong, Chang-Bum

2017-10-01

Nuclear receptors (NRs) are a large family of transcription factors that are involved in many fundamental biological processes. NRs are considered to have originated from a common ancestor, and are highly conserved throughout the whole animal taxa. Therefore, the genome-wide identification of NR genes in an animal taxon can provide insight into the evolutionary tendencies of NRs. Here, we identified all the NR genes in the monogonont rotifer Brachionus spp., which are considered an ecologically key species due to their abundance and world-wide distribution. The NR family was composed of 40, 32, 29, and 32 genes in the genomes of the rotifers B. calyciflorus, B. koreanus, B. plicatilis, and B. rotundiformis, respectively, which were classified into seven distinct subfamilies. The composition of each subfamily was highly conserved between species, except for NR1O genes, suggesting that they have undergone sporadic evolutionary processes for adaptation to their different environmental pressures. In addition, despite the dynamics of NR evolution, the significance of the conserved endocrine system, particularly for estrogen receptor (ER)-signaling, in rotifers was discussed on the basis of phylogenetic analyses. The results of this study may help provide a better understanding the evolution of NRs, and expand our knowledge of rotifer endocrine systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting

NASA Astrophysics Data System (ADS)

Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

2016-07-01

Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency.

Long-term measurements of submicrometer aerosol chemistry at the Southern Great Plains (SGP) using an Aerosol Chemical Speciation Monitor (ACSM)

DOE PAGES

Parworth, Caroline; Tilp, Alison; Fast, Jerome; ...

2015-04-01

In this study the long-term trends of non-refractory submicrometer aerosol (NR-PM1) composition and mass concentration measured by an Aerosol Chemical Speciation Monitor (ACSM) at the Atmospheric Radiation Measurement (ARM) program's Southern Great Plains (SGP) site are discussed. NR-PM1 data was recorded at ~30 min intervals over a period of 19 months between November 2010 and June 2012. Positive Matrix Factorization (PMF) was performed on the measured organic mass spectral matrix using a rolling window technique to derive factors associated with distinct sources, evolution processes, and physiochemical properties. The rolling window approach also allows us to capture the dynamic variations ofmore » the chemical properties in the organic aerosol (OA) factors over time. Three OA factors were obtained including two oxygenated OA (OOA) factors, differing in degrees of oxidation, and a biomass burning OA (BBOA) factor. Back trajectory analyses were performed to investigate possible sources of major NR-PM1 species at the SGP site. Organics dominated NR-PM1 mass concentration for the majority of the study with the exception of winter, when ammonium nitrate increases due to transport of precursor species from surrounding urban and agricultural areas and also due to cooler temperatures. Sulfate mass concentrations have little seasonal variation with mixed regional and local sources. In the spring BBOA emissions increase and are mainly associated with local fires. Isoprene and carbon monoxide emission rates were obtained by the Model of Emissions of Gases and Aerosols from Nature (MEGAN) and the 2011 U.S. National Emissions Inventory to represent the spatial distribution of biogenic and anthropogenic sources, respectively. The combined spatial distribution of isoprene emissions and air mass trajectories suggest that biogenic emissions from the southeast contribute to SOA formation at the SGP site during the summer.« less

40 CFR 158.1300 - Environmental fate data requirements table.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Greenhouse Indoor Forestry Residential Outdoor Test substance Test Note No. Degradation Studies - Laboratory... Photodegradation in air CR NR CR NR CR CR TGAI or PAIRA 4 Metabolism Studies - Laboratory 835.4100 Aerobic soil R... -- Mobility Studies 835.1230835.1240 Leaching and adsorption/desorption R R R NR R R TGAI or PAIRA 6 835.1410...

40 CFR 158.1300 - Environmental fate data requirements table.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Greenhouse Indoor Forestry Residential Outdoor Test substance Test Note No. Degradation Studies - Laboratory... Photodegradation in air CR NR CR NR CR CR TGAI or PAIRA 4 Metabolism Studies - Laboratory 835.4100 Aerobic soil R... -- Mobility Studies 835.1230835.1240 Leaching and adsorption/desorption R R R NR R R TGAI or PAIRA 6 835.1410...

40 CFR 158.1300 - Environmental fate data requirements table.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Greenhouse Indoor Forestry Residential Outdoor Test substance Test Note No. Degradation Studies - Laboratory... Photodegradation in air CR NR CR NR CR CR TGAI or PAIRA 4 Metabolism Studies - Laboratory 835.4100 Aerobic soil R... -- Mobility Studies 835.1230835.1240 Leaching and adsorption/desorption R R R NR R R TGAI or PAIRA 6 835.1410...

40 CFR 158.1300 - Environmental fate data requirements table.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Greenhouse Indoor Forestry Residential Outdoor Test substance Test Note No. Degradation Studies - Laboratory... Photodegradation in air CR NR CR NR CR CR TGAI or PAIRA 4 Metabolism Studies - Laboratory 835.4100 Aerobic soil R... -- Mobility Studies 835.1230835.1240 Leaching and adsorption/desorption R R R NR R R TGAI or PAIRA 6 835.1410...

40 CFR 158.1300 - Environmental fate data requirements table.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Greenhouse Indoor Forestry Residential Outdoor Test substance Test Note No. Degradation Studies - Laboratory... Photodegradation in air CR NR CR NR CR CR TGAI or PAIRA 4 Metabolism Studies - Laboratory 835.4100 Aerobic soil R... -- Mobility Studies 835.1230835.1240 Leaching and adsorption/desorption R R R NR R R TGAI or PAIRA 6 835.1410...

Nicotinamide Ribosyl Uptake Mutants in Haemophilus influenzae

PubMed Central

Herbert, Mark; Sauer, Elizabeta; Smethurst, Graeme; Kraiβ, Anita; Hilpert, Anna-Karina; Reidl, Joachim

2003-01-01

The gene for the nicotinamide riboside (NR) transporter (pnuC) was identified in Haemophilus influenzae. A pnuC mutant had only residual NR uptake and could survive in vitro with high concentrations of NR, but could not survive in vivo. PnuC may represent a target for the development of inhibitors for preventing H. influenzae disease. PMID:12933892

Bmal1 is a direct transcriptional target of the orphan nuclear receptor, NR2F1

USDA-ARS?s Scientific Manuscript database

Orphan nuclear receptor NR2F1 (also known as COUP-TFI, Chicken Ovalbumin Upstream Promoter Transcription Factor I) is a highly conserved member of the nuclear receptor superfamily. NR2F1 plays a critical role during embryonic development, particularly in the central and peripheral nervous systems a...

Impaired Discrimination Learning in Mice Lacking the NMDA Receptor NR2A Subunit

ERIC Educational Resources Information Center

Brigman, Jonathan L.; Feyder, Michael; Saksida, Lisa M.; Bussey, Timothy J.; Mishina, Masayoshi; Holmes, Andrew

2008-01-01

N-Methyl-D-aspartate receptors (NMDARs) mediate certain forms of synaptic plasticity and learning. We used a touchscreen system to assess NR2A subunit knockout mice (KO) for (1) pairwise visual discrimination and reversal learning and (2) acquisition and extinction of an instrumental response requiring no pairwise discrimination. NR2A KO mice…

Evaluating DLAB as a Predictor of Foreign Language Learning

DTIC Science & Technology

2012-05-01

JT - Italian KP - Korean ML - Malay NE - Nepalese NR - Norwegian PF - Persian-Iranian PG - Persian-Afghan PJ - Punjabi PL - Polish...Lithuanian NR - Norwegian PF - Persian-Iranian PG - Persian-Afghan PJ - Punjabi PL - Polish PQ - Portuguese-Brazilian PT - Portuguese...Lithuanian NR - Norwegian PF - Persian-Iranian PG - Persian-Afghan PJ - Punjabi PL - Polish PQ - Portuguese-Brazilian PT - Portuguese-European

Phenotype analysis of Russian dandelion root tissues from the national plant germplasm system collection

USDA-ARS?s Scientific Manuscript database

Russian dandelion (Taraxacum kok-saghyz) (TKS) produces high quality natural rubber (NR), cis-1,4 polyisoprene, by biosynthesis, and has been used historically as a source of NR during times of short supply or high prices for Hevea NR. The rubber is primarily located in root tissues along with appre...

40 CFR 80.572 - What labeling requirements apply to retailers and wholesale purchaser-consumers of NR and NRLM...

Code of Federal Regulations, 2010 CFR

2010-07-01

... retailers and wholesale purchaser-consumers of NR and NRLM diesel fuel and heating oil beginning June 1... apply to retailers and wholesale purchaser-consumers of NR and NRLM diesel fuel and heating oil beginning June 1, 2010? Any retailer or wholesale purchaser-consumer who sells, dispenses, or offers for...

Distribution, Pest Status and Fungal Associates of Euwallacea nr. fornicatus in Florida Avocado Groves

PubMed Central

Carrillo, Daniel; Cruz, Luisa F.; Kendra, Paul E.; Narvaez, Teresa I.; Montgomery, Wayne S.; Monterroso, Armando; De Grave, Charlotte; Cooperband, Miriam F.

2016-01-01

Members of a complex of cryptic species, that correspond morphologically to the ambrosia beetle Euwallacea fornicatus (Eichhoff) (Coleoptera: Curculionidae: Scolytinae), were recently found attacking avocado (Persea americana Mill.) in Israel and California. In early 2016, an outbreak of another member of this species complex was detected infesting approximately 1500 avocado trees in an avocado orchard at Homestead, Florida. An area-wide survey was conducted in commercial avocado groves of Miami-Dade County, Florida to determine the distribution and abundance of E. nr. fornicatus, to identify different populations of E. nr. fornicatus and their fungal associates, and to assess the extent of damage to avocado trees. Ewallacea nr. fornicatus were captured in 31 of the 33 sampled sites. A sample of 35 beetles from six different locations was identified as E. nr. fornicatus sp. #2, which is genetically distinct from the species causing damage in California and Israel. Eleven fungal associates were identified: an unknown Fusarium sp., AF-8, AF-6, Graphium euwallaceae, Acremonium sp. Acremonium morum, Acremonium masseei, Elaphocordyceps sp. and three yeast species. The unknown Fusarium isolates were the most abundant and frequently found fungus species associated with adult beetles and lesions surrounding the beetle galleries. In addition to fungal associates, three bacteria species were found associated with adult E. nr. fornicatus. Visual inspections detected significant damage in only two orchards. A large number of beetles were captured in locations with no apparent damage on the avocado trees suggesting that E. nr. fornicatus are associated with other host(s) outside the groves or with dead trees or branches inside the groves. More research is needed to determine the potential threat E. nr. fornicatus and its fungal associates pose to the avocado industry and agricultural and natural ecosystems in Florida. PMID:27754408

The nuclear receptor Tlx regulates motor, cognitive and anxiety-related behaviours during adolescence and adulthood.

PubMed

O'Leary, James D; Kozareva, Danka A; Hueston, Cara M; O'Leary, Olivia F; Cryan, John F; Nolan, Yvonne M

2016-06-01

The nuclear receptor Tlx is a key regulator of embryonic and adult hippocampal neurogenesis and has been genetically linked to bipolar disorder. Mice lacking Tlx (Nr2e1(-/-)) display deficits in adult hippocampal neurogenesis and behavioural abnormalities. However, whether Tlx regulates behaviour during adolescence or in a sex-dependent manner remains unexplored. Therefore, we investigated the role of Tlx in a series of behavioural tasks in adolescent male and female mice with a spontaneous deletion of Tlx (Nr2e1(-/-) mice). Testing commenced at adolescence (postnatal day 28) and continued until adulthood (postnatal day 67). Adolescent male and female Nr2e1(-/-) mice were hyperactive in an open field, an effect that persisted in adulthood. Male but not female Nr2e1(-/-) mice exhibited reduced thigmotaxis during adolescence and adulthood. Impairments in rotarod motor performance developed in male and female Nr2e1(-/-) mice at the onset of adulthood. Spontaneous alternation in the Y-maze, a hippocampus-dependent task, was impaired in adolescent but not adult male and female Nr2e1(-/-) mice. Contextual fear conditioning was impaired in adolescent male Nr2e1(-/-) mice only, but both male and female adolescent Nr2e1(-/-) mice showed impaired cued fear conditioning, a hippocampal-amygdala dependent cognitive process. These deficits persisted into adulthood in males but not females. In conclusion, deletion of Tlx impairs motor, cognitive and anxiety-related behaviours during adolescence and adulthood in male and female mice with most effects occurring during adolescence rather than adulthood, independent of housing conditions. This suggests that Tlx has functions beyond regulation of adult hippocampal neurogenesis, and may be an important target in understanding neurobiological disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Antagonism at the NR2B subunit of NMDA receptors induces increased connectivity of the prefrontal and subcortical regions regulating reward behavior.

PubMed

Gass, Natalia; Becker, Robert; Sack, Markus; Schwarz, Adam J; Reinwald, Jonathan; Cosa-Linan, Alejandro; Zheng, Lei; von Hohenberg, Christian Clemm; Inta, Dragos; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang; Gass, Peter; Sartorius, Alexander

2018-04-01

Evidence indicates that ketamine's rapid antidepressant efficacy likely results from its antagonism of NR2B-subunit-containing NMDA receptors (NMDAR). Since ketamine equally blocks NR2A- and NR2B-containing NMDAR, and has affinity to other receptors, NR2B-selective drugs might have improved therapeutic efficiency and side effect profile. We aimed to compare the effects of (S)-ketamine and two different types of NR2B-selective antagonists on functional brain networks in rats, in order to find common circuits, where their effects intersect, and that might explain their antidepressant action. The experimental design comprised four parallel groups of rats (N = 37), each receiving (S)-Ketamine, CP-101,606, Ro 25-6981 or saline. After compound injection, we acquired resting-state functional magnetic resonance imaging time series. We used graph theoretical approach to calculate brain network properties. Ketamine and CP-101,606 diminished the global clustering coefficient and small-worldness index. At the nodal level, all compounds induced increased connectivity of the regions mediating reward and cognitive aspects of emotional processing, such as ventromedial prefrontal cortex, septal nuclei, and nucleus accumbens. The dorsal hippocampus and regions involved in sensory processing and aversion, such as superior and inferior colliculi, exhibited an opposite effect. The effects common to ketamine and NR2B-selective compounds were localized to the same brain regions as those reported in depression, but in the opposite direction. The upregulation of the reward circuitry might partially underlie the antidepressant and anti-anhedonic effects of the antagonists and could potentially serve as a translational imaging phenotype for testing putative antidepressants, especially those targeting the NR2B receptor subtype.

Probing N-methyl-D-aspartate receptor desensitization with the substituted-cysteine accessibility method.

PubMed

Thomas, Christopher G; Krupp, Johannes J; Bagley, Elena E; Bauzon, Reginald; Heinemann, Stephen F; Vissel, Bryce; Westbrook, Gary L

2006-04-01

Several forms of macroscopic N-methyl-D-aspartate (NMDA) receptor desensitization affect the amplitude and duration of postsynaptic responses. In addition to its functional significance, desensitization provides one means to examine the conformational coupling of ligand binding to channel gating. Segments flanking the ligand binding domain in the extracellular N terminus of the NMDA receptor NR2 subunit influence the glycine-independent form of desensitization. The NR2A pre-M1 region, the linker between the glutamate binding domain and the channel pore, plays a critical role in desensitization. Thus, we used the substituted-cysteine accessibility method to scan the accessibility of residues in the pre-M1 region and the first transmembrane domain (M1) of NR2A. Cysteine mutants were expressed with NR1 in human embryonic kidney 293 cells and were assayed by whole-cell recording. With activation of the receptor by glutamate and glycine, only a single mutant, V557C, which is located at the beginning of M1, led to irreversible inhibition by the methanethiosulfonate derivative methanethiosulfonate ethyltrimethylammonium (MTSET). The NR2 ligand glutamate was insufficient on its own to induce modification of V557C by MTSET, suggesting that the change in accessibility required channel gating. The rate of MTSET modification of the homologous residue on NR1 (NR1-1a(L562C)/NR2A) was much slower than V557C. We also substituted cysteine in the V557 site of mutant subunits that exhibit either enhanced or reduced desensitization. Modification by MTSET correlated with the degree of desensitization for these subunits, suggesting that V557C is a sensitive detector of desensitization gating.

Postsynaptic density levels of the NMDA receptor NR1 subunit and PSD-95 protein in prefrontal cortex from people with schizophrenia

PubMed Central

Catts, Vibeke Sørensen; Derminio, Dominique Suzanne; Hahn, Chang-Gyu; Weickert, Cynthia Shannon

2015-01-01

Background: There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor hypofunction in the pathophysiology of schizophrenia. Our group recently identified a decrease in total NR1 mRNA and protein expression in the dorsolateral prefrontal cortex in a case-control study of individuals with schizophrenia (n=37/group). The NR1 subunit is critical to NMDA receptor function at the postsynaptic density, a cellular structure rich in the scaffolding protein, PSD-95. The extent to which the NMDA receptor NR1 subunit is altered at the site of action, in the postsynaptic density, is not clear. Aims: To extend our previous results by measuring levels of NR1 and PSD-95 protein in postsynaptic density-enriched fractions of prefrontal cortex from the same individuals in the case-control study noted above. Methods: Postsynaptic density-enriched fractions were isolated from fresh-frozen prefrontal cortex (BA10) and subjected to western blot analysis for NR1 and PSD-95. Results: We found a 20% decrease in NR1 protein (t(66)=−2.874, P=0.006) and a 30% decrease in PSD-95 protein (t(63)=−2.668, P=0.010) in postsynaptic density-enriched fractions from individuals with schizophrenia relative to unaffected controls. Conclusions: Individuals with schizophrenia have less NR1 protein, and therefore potentially fewer functional NMDA receptors, at the postsynaptic density. The associated decrease in PSD-95 protein at the postsynaptic density suggests that not only are glutamate receptors compromised in individuals with schizophrenia, but the overall spine architecture and downstream signaling supported by PSD-95 may also be deficient. PMID:27336043

Postsynaptic density levels of the NMDA receptor NR1 subunit and PSD-95 protein in prefrontal cortex from people with schizophrenia.

PubMed

Catts, Vibeke Sørensen; Derminio, Dominique Suzanne; Hahn, Chang-Gyu; Weickert, Cynthia Shannon

2015-01-01

There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor hypofunction in the pathophysiology of schizophrenia. Our group recently identified a decrease in total NR1 mRNA and protein expression in the dorsolateral prefrontal cortex in a case-control study of individuals with schizophrenia (n=37/group). The NR1 subunit is critical to NMDA receptor function at the postsynaptic density, a cellular structure rich in the scaffolding protein, PSD-95. The extent to which the NMDA receptor NR1 subunit is altered at the site of action, in the postsynaptic density, is not clear. To extend our previous results by measuring levels of NR1 and PSD-95 protein in postsynaptic density-enriched fractions of prefrontal cortex from the same individuals in the case-control study noted above. Postsynaptic density-enriched fractions were isolated from fresh-frozen prefrontal cortex (BA10) and subjected to western blot analysis for NR1 and PSD-95. We found a 20% decrease in NR1 protein (t(66)=-2.874, P=0.006) and a 30% decrease in PSD-95 protein (t(63)=-2.668, P=0.010) in postsynaptic density-enriched fractions from individuals with schizophrenia relative to unaffected controls. Individuals with schizophrenia have less NR1 protein, and therefore potentially fewer functional NMDA receptors, at the postsynaptic density. The associated decrease in PSD-95 protein at the postsynaptic density suggests that not only are glutamate receptors compromised in individuals with schizophrenia, but the overall spine architecture and downstream signaling supported by PSD-95 may also be deficient.

Mechanical & morphological properties of attapulgite/NR composites: Effect of mixing time variation

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

Nor, Nor Aina Mohd, E-mail: ayena90@yahoo.com; Othman, Nadras, E-mail: srnadras@usm.my; Ismail, Hanafi, E-mail: ihanafi@usm.my

2015-07-22

The development of composite material based on attapulgite clay (ATP) as a filler and natural rubber (NR) matrices were prepared by combination of melt mixing and latex compounding methods. Sonication technique was chosen in this work to disperse the attapulgite suspension. 6 phr of attapulgite loading was fabricated using different time of mixing ranging from 30 minutes until 2 hours and sonication time was kept constant at 15 minutes. Then, co-coagulating HA latex with attapulgite clay suspension through latex compounding method produced the masterbatch. The masterbatch was compounded with natural rubber by melt mixing method. The mechanical and morphological characteristicsmore » were investigated in this work. From mechanical testing, M1 showed the highest value of tensile and tear strength. By comparing with M30 and M2, M1 shows high 300% tensile modulus and lower crosslink density. However, when the time of mixing was prolonged to 2 hours, the results for tensile strength, elongation at break and tear strength were decreased. This is due to flocculation of attapulgite particles. Sonication techniques also proved that the tensile strength and elongation at break of these three samples were higher compared to gum NR (NR) and attapulgite compounded with NR using a conventional method (in-situ 6). From field emission scanning electron microscope (FESEM) results, it revealed that M1 had good dispersion in the NR system. It is proved that the higher tensile strength was due to good dispersion of attapulgite clay in the NR matrix. It was also supported from crosslink density, which is lower than NR and in-situ 6 results. It showed that the penetration of toluene solvent into rubber compound was restricted. The optimum time, M1 give the best results, which can be compared to control the sample.« less

Notoginsenoside R1 attenuates renal ischemia-reperfusion injury in rats.

PubMed

Liu, Wen-Jun; Tang, Hong-Tai; Jia, Yi-Tao; Ma, Bing; Fu, Jin-Feng; Wang, Yu; Lv, Kai-Yang; Xia, Zhao-Fan

2010-09-01

Ischemia-reperfusion (I/R) injury of the kidney is a complex pathophysiological process and a major cause of acute renal failure. It has been shown that I/R injury is related to inflammatory responses and activation of apoptotic pathways. Inhibition of certain elements of inflammatory responses and apoptotic pathway seemed to ameliorate renal I/R injury. As an effective element of Panax notoginseng, NR1 has antioxidant, anti-inflammatory, antiapoptotic, and immune-stimulatory activities. Therefore, we speculate that NR1 can attenuate renal I/R injury. Ischemia-reperfusion injury was induced by renal pedicle ligation followed by reperfusion along with a contralateral nephrectomy. Male Sprague-Dawley rats were randomized to four groups: sham group, I/R control group, NR1-1 group (rats treated with NR1, 20 mg.kg.d) and NR1-2 group (rats treated with NR1, 40 mg.kg.d). All animals were killed 72 h after I/R induction. Blood and renal tissues were collected. Renal dysfunction was observed by the level of serum creatinine and histological evaluation. Apoptosis and inflammatory response in the tissue of kidney were detected mainly with molecular biological methods. NR1 attenuated I/R-induced renal dysfunction as indicated by the level of serum creatinine and histological evaluation. It prevented the I/R-induced increases in the levels of proinflammatory cytokine TNF-alpha, myeloperoxidase activity, phosphorylation of p38, and activation of nuclear factor kappaB with cell apoptosis in the kidney and enhanced expression of antiapoptosis cytokine bcl-2. Treatment with NR1 improves renal function after I/R associated with a significant reduction in cell apoptosis and inflammatory responses, which may be related to p38 and nuclear factor kappaB inhibition.

Effect of NR-ANX-C (a polyherbal formulation) on haloperidol induced catalepsy in albino mice.

PubMed

Nair, Vinod; Arjuman, Albina; Dorababu, P; Gopalakrishna, H N; Chakradhar Rao, U; Mohan, Lalit

2007-11-01

Use of typical antipsychotics like haloperidol in treatment of schizophrenia is associated with a high incidence of extrapyramidal side effects. In rodents, administration of haloperidol leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we evaluated the anticataleptic efficacy of NR-ANX-C, a polyherbal formulation containing bioactives of Withania somnifera, Ocimum sanctum, Camellia sinensis, triphala and shilajit in haloperidol induced catalepsy in mice. Five groups (n = 6) of male albino mice were used in the study. Catalepsy was induced by ip administration of haloperidol (1mg/kg). The degree of catalepsy (cataleptic score) was measured as the time the animal maintained an imposed posture. We compared the anticataleptic efficacy of NR-ANX-C (10, 25 and 50 mg/kg) with scopolamine (1 mg/kg). The superoxide dismutase (SOD) level in brain tissue was also estimated to correlate the levels of oxidative stress and degree of catalepsy in the animal. Significant (P<0.01) reduction in the cataleptic scores was observed in all NR-ANX-C treated groups and maximum reduction was observed in the NR-ANX-C (25 mg/kg) treated group. Significant (P<0.05) reduction in SOD activity was observed in NR-ANX-C (25 and 50 mg/kg) treated groups and maximum reduction was observed in NR-ANX-C (25mg/kg) treated group. In our study, maximum reduction in cataleptic score was observed in NR-ANX-C (25 mg/kg) treated group. The maximum reduction in SOD activity was also observed in the same group. These findings suggest a possible involvement of the antioxidant potential of NRANX- C in alleviating haloperidol induced catalepsy.

Association of neointimal morphology by optical coherence tomography with rupture of neoatherosclerotic plaque very late after coronary stent implantation.

NASA Astrophysics Data System (ADS)

Karanasos, Antonios; Ligthart, Jurgen; Witberg, Karen; Toutouzas, Konstantinos; Daemen, Joost; van Soest, Gijs; Gnanadesigan, Muthukaruppan; van Geuns, Robert-Jan; de Jaegere, Peter; Regar, Evelyn

2013-03-01

Purpose: Neoatherosclerosis within a stent has been recently described as a culprit of late stent failure. We investigated by optical coherence tomography (OCT) the association of neoatherosclerotic plaque morphology with neointimal rupture (NR) and clinical presentation in patients late after coronary stent implantation. Methods: From 1/1/2007 to 31/1/2012, 74 patients from two institutions underwent OCT assessment of a coronary stent implanted at least 18 months prior to OCT study. Native atherosclerosis criteria were used for neointimal characterization. Results: Neoatherosclerosis was observed in 59.5% of the stents (n=44). Stents with neoatherosclerosis were more often associated with symptoms compared to stents without neoatherosclerosis (59.1% acute coronary syndrome (ACS), 25% stable angina (SA), and 15.9% asymptomatic versus 43.3% ACS, 6.7% SA, 50% asymptomatic, p<0.01). Among neoatherosclerotic lesions (n=44), NR was detected in 19 (43.2%) and had higher incidence in ACS (61.5%) than in SA (18.2%) and asymptomatic (14.3%) (p<0.05). Thrombus was detected in all NR cases. Fibrous cap thickness was lower in NR lesions compared to lesions without NR (48+/-21 μm versus 104+/-58μm, p<0.01). Lipid content tended to be higher in lesions with NR (260+/-103° versus 203+/-85°, p=0.051). Lesions with NR had more often dense macrophage infiltration (84.2% versus 44.0%, p<0.05). There were no differences in neovascularization or calcifications between lesions with or without NR. Conclusions: Neoatherosclerosis is frequent and more common among symptomatic patients. Importantly, neointimal rupture is associated with ACS late after stent implantation. Specific morphological characteristics, such as cap thickness and macrophage infiltration are associated with rupture of neoatherosclerotic plaques.

Data for effects of lanthanum complex on the thermo-oxidative aging of natural rubber.

PubMed

Zheng, Wei; Liu, Li; Zhao, Xiuying; He, Jingwei; Wang, Ao; Chan, Tung W; Wu, Sizhu

2015-12-01

Novel mixed antioxidants composed of antioxidant IPPD and lanthanum (La) complex were added as a filler to form natural rubber (NR) composites. By mechanical testing, Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) and thermogravimetric analysis (TGA), a string of data, including the mechanical properties, the variation of internal groups and the thermal and thermo-oxidative decompositions of NR, was presented in this data article. The data accompanying its research article [1] studied the thermo-oxidative aging properties of NR in detail. The density function theoretical (DFT) calculations were also used as an assistant to study the thermo-oxidative aging mechanism of NR. The data revealed that this new rare-earth antioxidant could indeed enhance the thermo-oxidative aging resistance of NR, which is associated with its different function mechanism from that of the pure antioxidant IPPD.

Data for effects of lanthanum complex on the thermo-oxidative aging of natural rubber

PubMed Central

Zheng, Wei; Liu, Li; Zhao, Xiuying; He, Jingwei; Wang, Ao; Chan, Tung W.; Wu, Sizhu

2015-01-01

Novel mixed antioxidants composed of antioxidant IPPD and lanthanum (La) complex were added as a filler to form natural rubber (NR) composites. By mechanical testing, Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) and thermogravimetric analysis (TGA), a string of data, including the mechanical properties, the variation of internal groups and the thermal and thermo-oxidative decompositions of NR, was presented in this data article. The data accompanying its research article [1] studied the thermo-oxidative aging properties of NR in detail. The density function theoretical (DFT) calculations were also used as an assistant to study the thermo-oxidative aging mechanism of NR. The data revealed that this new rare-earth antioxidant could indeed enhance the thermo-oxidative aging resistance of NR, which is associated with its different function mechanism from that of the pure antioxidant IPPD. PMID:26693513

High-Power Krypton Hall Thruster Technology Being Developed for Nuclear-Powered Applications

NASA Technical Reports Server (NTRS)

Jacobson, David T.; Manzella, David H.

2004-01-01

The NASA Glenn Research Center has been performing research and development of moderate specific impulse, xenon-fueled, high-power Hall thrusters for potential solar electric propulsion applications. These applications include Mars missions, reusable tugs for low-Earth-orbit to geosynchronous-Earth-orbit transportation, and missions that require transportation to libration points. This research and development effort resulted in the design and fabrication of the NASA-457M Hall thruster that has been tested at input powers up to 95 kW. During project year 2003, NASA established Project Prometheus to develop technology in the areas of nuclear power and propulsion, which are enabling for deep-space science missions. One of the Project-Prometheus-sponsored Nuclear Propulsion Research tasks is to investigate alternate propellants for high-power Hall thruster electric propulsion. The motivation for alternate propellants includes the disadvantageous cost and availability of xenon propellant for extremely large scale, xenon-fueled propulsion systems and the potential system performance benefits of using alternate propellants. The alternate propellant krypton was investigated because of its low cost relative to xenon. Krypton propellant also has potential performance benefits for deep-space missions because the theoretical specific impulse for a given voltage is 20 percent higher than for xenon because of krypton's lower molecular weight. During project year 2003, the performance of the high-power NASA-457M Hall thruster was measured using krypton as the propellant at power levels ranging from 6.4 to 72.5 kW. The thrust produced ranged from 0.3 to 2.5 N at a discharge specific impulse up to 4500 sec.

A graphical approach to radio frequency quadrupole design

NASA Astrophysics Data System (ADS)

Turemen, G.; Unel, G.; Yasatekin, B.

2015-07-01

The design of a radio frequency quadrupole, an important section of all ion accelerators, and the calculation of its beam dynamics properties can be achieved using the existing computational tools. These programs, originally designed in 1980s, show effects of aging in their user interfaces and in their output. The authors believe there is room for improvement in both design techniques using a graphical approach and in the amount of analytical calculations before going into CPU burning finite element analysis techniques. Additionally an emphasis on the graphical method of controlling the evolution of the relevant parameters using the drag-to-change paradigm is bound to be beneficial to the designer. A computer code, named DEMIRCI, has been written in C++ to demonstrate these ideas. This tool has been used in the design of Turkish Atomic Energy Authority (TAEK)'s 1.5 MeV proton beamline at Saraykoy Nuclear Research and Training Center (SANAEM). DEMIRCI starts with a simple analytical model, calculates the RFQ behavior and produces 3D design files that can be fed to a milling machine. The paper discusses the experience gained during design process of SANAEM Project Prometheus (SPP) RFQ and underlines some of DEMIRCI's capabilities.

Consequences of human modification of the global nitrogen cycle.

PubMed

Erisman, Jan Willem; Galloway, James N; Seitzinger, Sybil; Bleeker, Albert; Dise, Nancy B; Petrescu, A M Roxana; Leach, Allison M; de Vries, Wim

2013-07-05

The demand for more food is increasing fertilizer and land use, and the demand for more energy is increasing fossil fuel combustion, leading to enhanced losses of reactive nitrogen (Nr) to the environment. Many thresholds for human and ecosystem health have been exceeded owing to Nr pollution, including those for drinking water (nitrates), air quality (smog, particulate matter, ground-level ozone), freshwater eutrophication, biodiversity loss, stratospheric ozone depletion, climate change and coastal ecosystems (dead zones). Each of these environmental effects can be magnified by the 'nitrogen cascade': a single atom of Nr can trigger a cascade of negative environmental impacts in sequence. Here, we provide an overview of the impact of Nr on the environment and human health, including an assessment of the magnitude of different environmental problems, and the relative importance of Nr as a contributor to each problem. In some cases, Nr loss to the environment is the key driver of effects (e.g. terrestrial and coastal eutrophication, nitrous oxide emissions), whereas in some other situations nitrogen represents a key contributor exacerbating a wider problem (e.g. freshwater pollution, biodiversity loss). In this way, the central role of nitrogen can remain hidden, even though it actually underpins many trans-boundary pollution problems.

RGO/AuNR/HA-5FU nanocomposite with multi-stage release behavior and efficient antitumor activity for synergistic therapy.

PubMed

Yang, Ying; Wang, Yunlong; Zhu, Manzhou; Chen, Yan; Xiao, Yazhong; Shen, Yuhua; Xie, Anjian

2017-05-02

A reduced graphene oxide (RGO)/gold nanorod (AuNR)/hydroxyapatite (HA) nanocomposite was designed and successfully synthesized for the first time. An anticancer drug, 5-fluorouracil (5FU), was chosen as a model drug to be loaded in RGO/AuNR/HA. The fabricated RGO/AuNR/HA-5FU showed robust, selective targeting and penetrating efficiency against HeLa cells due to the good compatibility and nontoxicity of HA, and showed excellent synergetic antitumor effects through combined chemotherapy (CT) by 5FU and photothermal therapy (PTT) by both RGO and AuNRs under near-infrared (NIR) laser irradiation. More importantly, this synergistic dual therapy based on RGO/AuNR/HA can also minimize side effects in normal cells and exhibits greater antitumor activity because of a multi-stage drug release ability triggered by the pH sensitivity of HA in the first stage and the combined photothermal conversion capabilities of RGO and AuNRs by means of the NIR laser irradiation in the second stage. This study suggests that the novel RGO/AuNR/HA multi-stage drug delivery system may represent a promising potential application of multifunctional composite materials in the biomedical field.

Coupling of NAD+ Biosynthesis and Nicotinamide Ribosyl Transport: Characterization of NadR Ribonucleotide Kinase Mutants of Haemophilus influenzae

PubMed Central

Merdanovic, Melisa; Sauer, Elizabeta; Reidl, Joachim

2005-01-01

Previously, we characterized a pathway necessary for the processing of NAD+ and for uptake of nicotinamide riboside (NR) in Haemophilus influenzae. Here we report on the role of NadR, which is essential for NAD+ utilization in this organism. Different NadR variants with a deleted ribonucleotide kinase domain or with a single amino acid change were characterized in vitro and in vivo with respect to cell viability, ribonucleotide kinase activity, and NR transport. The ribonucleotide kinase mutants were viable only in a nadV+ (nicotinamide phosphoribosyltransferase) background, indicating that the ribonucleotide kinase domain is essential for cell viability in H. influenzae. Mutations located in the Walker A and B motifs and the LID region resulted in deficiencies in both NR phosphorylation and NR uptake. The ribonucleotide kinase function of NadR was found to be feedback controlled by NAD+ under in vitro conditions and by NAD+ utilization in vivo. Taken together, our data demonstrate that the NR phosphorylation step is essential for both NR uptake across the inner membrane and NAD+ synthesis and is also involved in controlling the NAD+ biosynthesis rate. PMID:15968050

Safety assessment of nicotinamide riboside, a form of vitamin B3.

PubMed

Conze, D B; Crespo-Barreto, J; Kruger, C L

2016-01-20

Nicotinamide riboside (NR) is a naturally occurring form of vitamin B 3 present in trace amounts in some foods. Like niacin, it has been shown to be a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). The safety of Niagen™, a synthetic form of NR, was determined using a bacterial reverse mutagenesis assay (Ames), an in vitro chromosome aberration assay, an in vivo micronucleus assay, and acute, 14-day and 90-day rat toxicology studies. NR was not genotoxic. There was no mortality at an oral dose of 5000 mg/kg. Based on the results of a 14-day study, a 90-day study was performed comparing NR at 300, 1000, and 3000 mg/kg/day to an equimolar dose of nicotinamide at 1260 mg/kg/day as a positive control. Results from the study show that NR had a similar toxicity profile to nicotinamide at the highest dose tested. Target organs of toxicity were liver, kidney, ovaries, and testes. The lowest observed adverse effect level for NR was 1000 mg/kg/day, and the no observed adverse effect level was 300 mg/kg/day. © The Author(s) 2016.

Coupling of NAD+ biosynthesis and nicotinamide ribosyl transport: characterization of NadR ribonucleotide kinase mutants of Haemophilus influenzae.

PubMed

Merdanovic, Melisa; Sauer, Elizabeta; Reidl, Joachim

2005-07-01

Previously, we characterized a pathway necessary for the processing of NAD+ and for uptake of nicotinamide riboside (NR) in Haemophilus influenzae. Here we report on the role of NadR, which is essential for NAD+ utilization in this organism. Different NadR variants with a deleted ribonucleotide kinase domain or with a single amino acid change were characterized in vitro and in vivo with respect to cell viability, ribonucleotide kinase activity, and NR transport. The ribonucleotide kinase mutants were viable only in a nadV+ (nicotinamide phosphoribosyltransferase) background, indicating that the ribonucleotide kinase domain is essential for cell viability in H. influenzae. Mutations located in the Walker A and B motifs and the LID region resulted in deficiencies in both NR phosphorylation and NR uptake. The ribonucleotide kinase function of NadR was found to be feedback controlled by NAD+ under in vitro conditions and by NAD+ utilization in vivo. Taken together, our data demonstrate that the NR phosphorylation step is essential for both NR uptake across the inner membrane and NAD+ synthesis and is also involved in controlling the NAD+ biosynthesis rate.

In situ synthesized SnO2 nanorod/reduced graphene oxide low-dimensional structure for enhanced lithium storage

NASA Astrophysics Data System (ADS)

Zhang, Wei; Xiao, Xuezhang; Zhang, Yiwen; Li, Junpeng; Zhong, Jiayi; Li, Meng; Fan, Xiulin; Wang, Chuntao; Chen, Lixin

2018-03-01

A unique SnO2 nanorod (NR)/reduced graphene oxide (RGO) composite morphology has been synthesized using the in situ hydrothermal method, for use as an anode material in lithium-ion batteries. The SnO2 NR adhering to the RGO exhibits a length of 250-400 nm and a diameter of 60-80 nm without any obvious aggregation. The initial discharge/charge capacities of the SnO2 NR/RGO composite are 1761.3 mAh g-1 and 1233.1 mAh g-1, with a coulombic efficiency (CE) of 70% under a current density of 200 mA g-1, and a final capacity of 1101 mAh g-1 after 50 cycles. The rate capability of the SnO2 NR/RGO is also improved compared to that of bare SnO2 NR. The superior electrochemical performance is ascribed to the special morphology of the SnO2 NRs—which plays a role in shorting the transmission path—and the sheet-like 2D graphene, which prevents the agglomeration of SnO2 and enhances conductivity during the electrochemical reaction of SnO2 NR/RGO.

The Realistic Job Preview as a Persuasive Communication.

DTIC Science & Technology

1982-02-01

10. PROGRAM ELEMENT, PROJECT. TAK AREA 6 WORK UNIT NUMBERS Michigan State Uiversity NR 170-894 Ii. CONTROLLING OFFICE NAME AND ADDRESS IS. REPORT...RJP research seems to show a stronger preview effect using more intelligent subjects. That is, studies of life insurance agents (Weitz, 1956; Youngberg...University Department of Psychological Sciences west Lafayette, INl 47907 1 Dr. Philip G. Zi±bardo*2 ~ Staniford Uiversity Department of Psychology Stanford, CA 94305 <El

Effect of combination ultrasonic and ball milling techniques of commercial fillers dispersion on mechanical properties of natural rubber (NR) latex films

NASA Astrophysics Data System (ADS)

Hamran, Noramirah; Rashid, Azura A.

2017-07-01

Commercial fillers such as silica and carbon black generally impart the reinforcing effects in dry rubber compound, but have an adverse effect on Natural rubber (NR) latex compounds. The addition of commercial fillers in NR latex has reduced the mechanical properties of NR latex films due to the destabilization effect in the NR latex compounds which govern by the dispersion quality, particle size and also the pH of the dispersion itself. The ball milling process is the conventional meth od of preparation of dispersions and ultrasonic has successfully used in preparation of nano fillers such as carbon nanotube (CNT). In this study the combination between the conventional methods; ball milling together the ultrasonic method were used to prepare the silica and carbon black dispersions. The different duration of ball milling (24, 48 and 72 hours) was compared with the ultrasonic method (30, 60, 90 and 120 minutes). The combination of ball milling and ultrasonic from the optimum individual technique was used to investigate the reduction of particle size of the fillers. The particle size analyzer, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) test were carried out to investigate the obtained particle size and the tensile and tear test were carried out to investigate the mechanical properties of the NR latex films. The reduction of filler particle size is expected to impart the properties of NR latex films.

Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

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

Shi, Wen-Zhu; Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853; Miao, Yu-Liang

Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation ofmore » hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.« less

Photothermal Therapy Employing Gold Nanoparticle- Loaded Macrophages as Delivery Vehicles: Comparing the Efficiency of Nanoshells Versus Nanorods.

PubMed

Christie, Catherine; Madsen, Steen J; Peng, Qian; Hirschberg, Henry

2017-01-01

Macrophages (Ma) loaded with gold based nanoparticles, which convert near infrared light to heat, have been studied as targeted transport vectors for photothermal therapy (PTT) of tumors. The purpose of the experiments reported here was to compare the efficacy of gold-silica nanoshells (AuNS) and gold nanorods (AuNR) in macrophage mediated PTT. PTT efficacy was evaluated in hybrid glioma spheroids consisting of human glioma cells and either AuNS or AuNR loaded Ma, designated MaNS and MaNR respectivly. Spheroids were irradiated for 10 min. with light from an 810 nm diode laser at irradiances ranging from 0 to 28 W/cm2. PTT efficacy was determined from spheroid growth over a 14-day period. The uptake by Ma of pegylated AuNR (3.9 ± 0.9 %) was twice that of pegylated AuNS, (7.9 ± 0.7 %). Hybrid spheroids consisting of a 5:1 ratio of glioma cells to loaded Ma exhibited significant growth inhibition with MaNS when subjected to irradiances of 7 W/cm2 or greater. In contrast, no significant growth inhibition was observed for the MaNR hybrid spheroids at this 5:1 ratio, even at the highest irradiance investigated (28 W/cm2). Although AuNR were taken up by Ma in larger numbers then AuNS, MaNS were shown to have greater PTT efficacy compared to MaNR for equivalent numbers of loaded Ma.

NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP).

PubMed

Schorderet, Daniel F; Escher, Pascal

2009-11-01

NR2E3, also called photoreceptor-specific nuclear receptor (PNR), is a transcription factor of the nuclear hormone receptor superfamily whose expression is uniquely restricted to photoreceptors. There, its physiological activity is essential for proper rod and cone photoreceptor development and maintenance. Thirty-two different mutations in NR2E3 have been identified in either homozygous or compound heterozygous state in the recessively inherited enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), and clumped pigmentary retinal degeneration (CPRD). The clinical phenotype common to all these patients is night blindness, rudimental or absent rod function, and hyperfunction of the "blue" S-cones. A single p.G56R mutation is inherited in a dominant manner and causes retinitis pigmentosa (RP). We have established a new locus-specific database for NR2E3 (www.LOVD.nl/eye), containing all reported mutations, polymorphisms, and unclassified sequence variants, including novel ones. A high proportion of mutations are located in the evolutionarily-conserved DNA-binding domains (DBDs) and ligand-binding domains (LBDs) of NR2E3. Based on homology modeling of these NR2E3 domains, we propose a structural localization of mutated residues. The high variability of clinical phenotypes observed in patients affected by NR2E3-linked retinal degenerations may be caused by different disease mechanisms, including absence of DNA-binding, altered interactions with transcriptional coregulators, and differential activity of modifier genes.

Inflammatory pain-induced signaling events following a conditional deletion of the N-methyl-D-aspartate receptor in spinal cord dorsal horn.

PubMed

Cheng, H T; Suzuki, M; Hegarty, D M; Xu, Q; Weyerbacher, A R; South, S M; Ohata, M; Inturrisi, C E

2008-08-26

The N-methyl-d-aspartate (NMDA) receptor in the spinal cord dorsal horn (SCDH) is one of the mechanisms involved in central sensitization during chronic pain. Previously, this laboratory created a spatio-temporal knockout (KO) of the N-methyl-d-aspartate receptor I (NR1) subunit in the mouse SCDH. The NR1 KO completely blocks NR1 gene and subsequent NMDA receptor expression and function in SCDH neurons. In the NR1 KO mice, the mechanical and cold allodynia induced at 24 h after complete Freund's adjuvant (CFA) was reduced. However, the protective effects of KO were transient and were not seen at 48 h after CFA. These observations suggest the presence of NMDA-independent pathways that contribute to CFA-induced pain. CFA induces the activation of several signaling cascades in the SCDH, including protein kinase C (PKC)gamma and extracellular signal-regulated kinases (ERK1/2). The phosphorylation of PKCgamma and ERK1/2 was inhibited in the SCDH of NR1 KO mice up to 48 h after CFA treatment, suggesting that these pathways are NMDA receptor-dependent. Interestingly, neuronal cyclooxygenase (COX) -2 expression and microglial p38 phosphorylation were induced in the SCDH of the NR1 KO at 48 h after CFA. Our findings provide evidence that inflammatory reactions are responsible for the recurrence of pain after NR1 KO in the SCDH.

Binder-free ZnO@ZnSnO3 quantum dots core-shell nanorod array anodes for lithium-ion batteries

NASA Astrophysics Data System (ADS)

Tan, Hsiang; Cho, Hsun-Wei; Wu, Jih-Jen

2018-06-01

In this work, ZnSnO3 quantum dots (QDs), instead of commonly used conductive carbon, are grown on the ZnO nanorod (NR) array to construct the binder-free ZnO@ZnSnO3 QDs core-shell NR array electrode on carbon cloth for lithium-ion battery. The ZnO@ZnSnO3 QDs core-shell NR array electrode exhibits excellent lithium storage performance with an improved cycling performance and superior rate capability compared to the ZnO NR array electrode. At a current density of 200 mAg-1, 15.8% capacity loss is acquired in the ZnO@ZnSnO3 QDs core-shell NR array electrode after 110 cycles with capacity retention of 1073 mAhg-1. Significant increases in reversible capacities from 340 to 545 mAhg-1 and from 95 to 390 mAhg-1 at current densities of 1000 and 2000 mAg-1, respectively, are achieved as the ZnO NR arrays are coated with the ZnSnO3 QD shells. The remarkably improved electrochemical performances result from that the configuration of binder-free ZnO@ZnSnO3 QDs core-shell NR array electrode not only facilitates the charge transfer through the solid electrolyte interface and the electronic/ionic conduction boundary as well as lithium ion diffusion but also effectively accommodates the volume change during repeated charge/discharge processes.

A co-immobilized mediator and microorganism mediated method combined pretreatment by TiO2 nanotubes used for BOD measurement.

PubMed

Liu, Ling; Zhang, Shengsen; Xing, Li; Zhao, Huijun; Dong, Shaojun

2012-05-15

In this paper, we proposed a method by using co-immobilized Escherichia coli (E. coli) as a biocatalyst and neutral red (NR) as an artificial electronic acceptor to modify glassy carbon electrode (GCE) for biochemical oxygen demand (BOD) measurement. Two different modification approaches of GCE were utilized and compared. In one approach, NR was electropolymerized on the surface of GCE, and E. coli cells were mixed with grafting copolymer PVA-g-PVP (briefly gPVP) and covered on NR polymer film to obtain a (gPVP/E. coli)/PNR/GCE. In the second approach, both NR and E. coli cells were mixed with the copolymer gPVP and modified GCE, after drying, which was electrochemically treated similar as above for obtaining a (gPVP/E. coli/NR)p/GCE. Based on the electrochemical evaluation, the performance of the latter was better, which may be caused by that the NR deposited on the surface of E. coli resulting in a good electron transport and permeability of cells membrane. To develop the results obtained at (gPVP/E. coli/NR)p/GCE further, the pretreatment by TiO(2) nanotubes arrays (TNTs) was employed, and different effects on samples of GGA, OECD, urea and real wastewater were evaluated. These results suggest that the present method holds a potential application for rapid BOD biosensor. Copyright © 2012 Elsevier B.V. All rights reserved.

Fluxes of total reactive atmospheric nitrogen using eddy covariance above arable land

NASA Astrophysics Data System (ADS)

Brummer, C.; Marx, O.; Kutsch, W. L.; Ammann, C.; Wolff, V.; Freibauer, A.

2011-12-01

A novel measurement technique (TRANC: Total Reactive Atmospheric Nitrogen Converter) was used to determine the biosphere-atmosphere exchange of the sum of all airborne reactive nitrogen (Nr) compounds. While concentration and flux measurements of Nr species from agriculture are still challenging from a metrological point of view and well-established measurement techniques (e.g., chemiluminescence detector (CLD), molybdenum converter, denuder/impinger with ion chromatography analysis) are usually limited to single compounds or provide concentration values and flux rates in poor time resolution and require labour and cost-intensive lab analyses, we present results from a campaign where the TRANC in combination with a fast-response analyzer (CLD) was used in an eddy-covariance (EC) setup to quantify total Nr. The basic measurement concept of the TRANC is the full conversion of all Nr compounds in the sample air to nitrogen monoxide (NO) within two reaction steps. Initially, reduced N compounds are being oxidized, whereas oxidized N compounds are thermally converted to compounds of lower oxidation states. Particulate N is being sublimated and oxidized or reduced afterwards. In a second reaction step, remaining higher N oxides in the sample air or those originated in the first reaction step are catalytically converted to NO. Carbon monoxide is used as reduction gas. The 10-months field campaign was conducted at an agricultural site planted with winter wheat in Thuringia, Germany. Total Nr concentrations were usually in the range of 5 to 30 ppb showing distinctive diurnal patterns with relatively low values from midday to late afternoon and highest values at night. Amplitudes were observed to be higher during the period of growth when no fertilizer was added. After fertilization events, total Nr concentrations were as high as 200 ppb for a short period of time. Different diurnal flux patterns depending on season and time passed since the last fertilization could be identified. In periods following fertilization, mean diurnal fluxes with peak emission rates of 5 ng m-2 s-1 in the afternoon were observed. On average up to 2 ng m-2 s-1 were taken up in the early morning hours during the vegetation period before the first fertilizer was applied. A strong linear correlation (R2=0.78) was found between the total Nr flux and stomatal conductance multiplied by total Nr concentration. The cumulative curve of the total Nr fluxes after 10 months of measurements showed that the three fertilization events almost compensated the usually observed slight total Nr deposition. The net total Nr uptake at the end of our campaign was ~2 kg N ha-1. The results of our campaign show that the usage of the TRANC within an EC setup was successfully established and allows for the permanent determination of the net total Nr exchange between ecosystem and atmosphere.

Space Reflector Materials for Prometheus Application

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

J. Nash; V. Munne; LL Stimely

2006-01-31

The two materials studied in depth which appear to have the most promise in a Prometheus reflector application are beryllium (Be) and beryllium oxide (BeO). Three additional materials, magnesium oxide (MgO), alumina (Al{sub 2}O{sub 3}), and magnesium aluminate spinel (MgAl{sub 2}O{sub 4}) were also recently identified to be of potential interest, and may have promise in a Prometheus application as well, but are expected to be somewhat higher mass than either a Be or BeO based reflector. Literature review and analysis indicates that material properties for Be are largely known, but there are gaps in the properties of Be0 relativemore » to the operating conditions for a Prometheus application. A detailed preconceptual design information document was issued providing material properties for both materials (Reference (a)). Beryllium oxide specimens were planned to be irradiated in the JOY0 Japanese test reactor to partially fill the material property gaps, but more testing in the High Flux Isotope Reactor (HFIR) test reactor at Oak Ridge National Laboratory (ORNL) was expected to be needed. A key issue identified for BeO was obtaining material for irradiation testing with an average grain size of {approx}5 micrometers, reminiscent of material for which prior irradiation test results were promising. Current commercially available material has an average grain size of {approx}10 micrometers. The literature indicated that improved irradiation performance could be expected (e.g., reduced irradiation-induced swelling) with the finer grain size material. Confirmation of these results would allow the use of historic irradiated materials test results from the literature, reducing the extent of required testing and therefore the cost of using this material. Environmental, safety and health (ES&H) concerns associated with manufacturing are significant but manageable for Be and BeO. Although particulate-generating operations (e.g., machining, grinding, etc.) involving Be-bearing materials require significant controls, handling of clean, finished products requires only modest controls. Neither material was initially considered to be viable as a structural material, however, based on improved understanding of its unirradiated properties, Be should be evaluated due to having potentially acceptable structural properties in the unirradiated condition, i. e., during launch, when loads might be most limiting. All three of the alternative materials are non-hazardous, and thus do not engender the ES&H concerns associated with use of Be or BeO. Aluminum oxide is a widely available ceramic material with well characterized physical properties and well developed processing practices. Although the densest (3.97 g/cm{sup 3} versus Be: 1.85, BeO: 3.01, MgO: 3.58, and MgAl{sub 2}O{sub 4}: 3.60, all theoretical density), and therefore the heaviest, of all the materials considered for this application, its ease of fabrication, mechanical properties, availability and neutronic characteristics warrant its evaluation. Similarly, MgO is widely used in the refractory materials industry and has a large established manufacturing base while being lighter than Al{sub 2}O{sub 3}. Most of the commercially available MgO products incorporate additives or a second phase to avoid the formation of Mg(OH){sub 2} due to spontaneous reaction with ambient humidity. The hygroscopicity of MgO makes it a more difficult material to work with than Al{sub 2}O{sub 3} or MgAl{sub 2}O{sub 4}. Magnesium aluminate spinel, although not as widely available as either Al{sub 2}O{sub 3} or MgO, has the advantage of a density almost as low as MgO without being hygroscopic, and shares comparable neutronic performance characteristics in the reflector application.« less

Effect of expanded organoclay by stearic acid to curing, mechanical and swelling properties of natural rubber nanocomposites

NASA Astrophysics Data System (ADS)

Ramadhan, A.; Fathurrohman, M. Irfan; Falaah, A. F.; Setyawan, N.; Soegijono, B.

2017-07-01

The interlayer basal spacing of organoclay (OC) could be increased with stearic acid (SA) added, thus OC changed into expanded organoclay by SA (OCSA). The effect of various loadings of OCSA on the curing, mechanical and swelling properties of natural rubber (NR) nanocomposites were studied. The natural rubber/expanded organoclay (NR/OCSA) nanocomposites were prepared by melt intercalation using a laboratory open mill. The curing characteristics of NR compounds were determined using a Moving Die Rheometer (MDR). The X-ray Diffraction (XRD), Attenuated Total Reflectance Infrared (ATR-IR) Spectroscopy and Field Emission Scanning Electron Microscopy (FESEM) were used to study the dispersion of OCSA in the NR matrix. The mechanical properties of NR/OCSA nanocomposites such as tensile strength, elongation at break and hardness were determined using ISO standard and swelling of NR/OCSA nanocomposites in toluene were determined using ISO 1817. The results showed that the SA intercalated into the gallery of OC and reacted with the hydroxyl groups in OC. It was indicated with the shifting of the negative peak 1,700 to 1,723 cm-1 in the ATR-IR spectrum and increase the d-spacing of OC. The adding of various loadings of OCSA into NR could increase the torque and accelerate the curing of nanocomposites and it also could increase the mechanical and swelling properties of nanocomposites. The change in modulus at 100% elongation significantly increased with increasing the OCSA load until maximum loading at 10 phr. This trend was same with the hardness and modulus at 300% elongation. Meanwhile, the improvement of tensile strength and elongation at break was higher at 4 phr OCSA compared with the other loading. The increase of mechanical and swelling properties of NR/OCSA nanocomposites was due to intercalation/exfoliation of OCSA in NR matrix. It was revealed by appearing of the out-of-plane Si-O-(Al) stretch with peak value 1080 cm-1 in the ATR-IR spectrum and the peaks of OCSA in the XRD pattern was disappeared until the loading of OCSA 8 phr and the thickness of morphology of OCSA below 100 nm.

Bisphenol-A rapidly promotes dynamic changes in hippocampal dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDA receptor subunit NR2B

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

Xu Xiaohong, E-mail: xuxh63@zjnu.cn; Ye Yinping; Li Tao

Bisphenol-A (BPA) is known to be a potent endocrine disrupter. Evidence is emerging that estrogen exerts a rapid influence on hippocampal synaptic plasticity and the dendritic spine density, which requires activation of NMDA receptors. In the present study, we investigated the effects of BPA (ranging from 1 to 1000 nM), focusing on the rapid dynamic changes in dendritic filopodia and the expressions of estrogen receptor (ER) {beta} and NMDA receptor, as well as the phosphorylation of NMDA receptor subunit NR2B in the cultured hippocampal neurons. A specific ER antagonist ICI 182,780 was used to examine the potential involvement of ERs.more » The results demonstrated that exposure to BPA (ranging from 10 to 1000 nM) for 30 min rapidly enhanced the motility and the density of dendritic filopodia in the cultured hippocampal neurons, as well as the phosphorylation of NR2B (pNR2B), though the expressions of NMDA receptor subunits NR1, NR2B, and ER{beta} were not changed. The antagonist of ERs completely inhibited the BPA-induced increases in the filopodial motility and the number of filopodia extending from dendrites. The increased pNR2B induced by BPA (100 nM) was also completely eliminated. Furthermore, BPA attenuated the effects of 17{beta}-estradiol (17{beta}-E{sub 2}) on the dendritic filopodia outgrowth and the expression of pNR2B when BPA was co-treated with 17{beta}-E{sub 2}. The present results suggest that BPA, like 17{beta}-E{sub 2}, rapidly results in the enhanced motility and density of dendritic filopodia in the cultured hippocampal neurons with the concomitant activation of NMDA receptor subunit NR2B via an ER-mediated signaling pathway. Meanwhile, BPA suppressed the enhancement effects of 17{beta}-E{sub 2} when it coexists with 17{beta}-E{sub 2}. These results provided important evidence suggesting the neurotoxicity of the low levels of BPA during the early postnatal development of the brain.« less

Simultaneous tracking of drug molecules and carriers using aptamer-functionalized fluorescent superstable gold nanorod-carbon nanocapsules during thermo-chemotherapy

NASA Astrophysics Data System (ADS)

Wang, Xue-Wei; Gao, Wei; Fan, Huanhuan; Ding, Ding; Lai, Xiao-Fang; Zou, Yu-Xiu; Chen, Long; Chen, Zhuo; Tan, Weihong

2016-04-01

Controlling and monitoring the drug delivery process is critical to its intended therapeutic function. Many nanocarrier systems for drug delivery have been successfully developed. However, biocompatibility, stability, and simultaneously tracing drugs and nanocarriers present significant limitations. Herein, we have fabricated a multifunctional nanocomposite by coating the gold nanorod (AuNR) with a biocompatible, superstable and fluorescent carbon layer, obtaining the AuNR@carbon core-shell nanocapsule. In this system, the carbon shell, originally obtained in aqueous glucose solutions and, therefore, biocompatible in physiological environments, could be simply loaded with cell-specific aptamers and therapeutic molecules through π-π interactions, a useful tool for cancer-targeted cellular imaging and therapy. Moreover, such a stable and intrinsic fluorescence effect of the AuNR@carbon enabled simultaneous tracking of released therapeutic molecules and nanocarriers under thermo-chemotherapy. The AuNR@carbons had high surface areas and stable shells, as well as unique optical and photothermal properties, making them promising nanostructures for biomedical applications.Controlling and monitoring the drug delivery process is critical to its intended therapeutic function. Many nanocarrier systems for drug delivery have been successfully developed. However, biocompatibility, stability, and simultaneously tracing drugs and nanocarriers present significant limitations. Herein, we have fabricated a multifunctional nanocomposite by coating the gold nanorod (AuNR) with a biocompatible, superstable and fluorescent carbon layer, obtaining the AuNR@carbon core-shell nanocapsule. In this system, the carbon shell, originally obtained in aqueous glucose solutions and, therefore, biocompatible in physiological environments, could be simply loaded with cell-specific aptamers and therapeutic molecules through π-π interactions, a useful tool for cancer-targeted cellular imaging and therapy. Moreover, such a stable and intrinsic fluorescence effect of the AuNR@carbon enabled simultaneous tracking of released therapeutic molecules and nanocarriers under thermo-chemotherapy. The AuNR@carbons had high surface areas and stable shells, as well as unique optical and photothermal properties, making them promising nanostructures for biomedical applications. Electronic supplementary information (ESI) available: Experimental details and characterization data for all new compounds. See DOI: 10.1039/c6nr00369a

Greenhouse gas emissions and reactive nitrogen releases during the life-cycles of staple food production in China and their mitigation potential.

PubMed

Xia, Longlong; Ti, Chaopu; Li, Bolun; Xia, Yongqiu; Yan, Xiaoyuan

2016-06-15

Life-cycle analysis of staple food (rice, flour and corn-based fodder) production and assessments of the associated greenhouse gas (GHG) and reactive nitrogen (Nr) releases, from environmental and economic perspectives, help to develop effective mitigation options. However, such evaluations have rarely been executed in China. We evaluated the GHG and Nr releases per kilogram of staple food production (carbon and Nr footprints) and per unit of net economic benefit (CO2-NEB and Nr-NEB), and explored their mitigation potential. Carbon footprints of food production in China were obviously higher than those in some developed countries. There was a high spatial variation in the footprints, primarily attributable to differences in synthetic N use (or CH4 emissions) per unit of food production. Provincial carbon footprints had a significant linear relationship with Nr footprints, attributed to large contribution of N fertilizer use to both GHG and Nr releases. Synthetic N fertilizer applications and CH4 emissions dominated the carbon footprints, while NH3 volatilization and N leaching were the main contributors to the Nr footprints. About 564 (95% uncertainty range: 404-701) TgCO2eqGHG and 10 (7.4-12.4) Tg Nr-N were released every year during 2001-2010 from staple food production. This caused the total damage costs of 325 (70-555) billion ¥, equivalent to nearly 1.44% of the Gross Domestic Product of China. Moreover, the combined damage costs and economic input costs, accounted for 66%-80% of the gross economic benefit generated from food production. A reduction of 92.7TgCO2eqyr(-1) and 2.2TgNr-Nyr(-1) could be achieved by reducing synthetic N inputs by 20%, increasing grain yields by 5% and implementing off-season application of straw and mid-season drainage practices for rice cultivation. In order to realize these scenarios, an ecological compensation scheme should be established to incentivize farmers to gradually adopt knowledge-based managements. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of a catalyst-based conversion technique to measure total particulate nitrogen and organic carbon and comparison to a particle mass measurement instrument

NASA Astrophysics Data System (ADS)

Stockwell, Chelsea E.; Kupc, Agnieszka; Witkowski, Bartłomiej; Talukdar, Ranajit K.; Liu, Yong; Selimovic, Vanessa; Zarzana, Kyle J.; Sekimoto, Kanako; Warneke, Carsten; Washenfelder, Rebecca A.; Yokelson, Robert J.; Middlebrook, Ann M.; Roberts, James M.

2018-05-01

The chemical composition of aerosol particles is a key aspect in determining their impact on the environment. For example, nitrogen-containing particles impact atmospheric chemistry, air quality, and ecological N deposition. Instruments that measure total reactive nitrogen (Nr = all nitrogen compounds except for N2 and N2O) focus on gas-phase nitrogen and very few studies directly discuss the instrument capacity to measure the mass of Nr-containing particles. Here, we investigate the mass quantification of particle-bound nitrogen using a custom Nr system that involves total conversion to nitric oxide (NO) across platinum and molybdenum catalysts followed by NO-O3 chemiluminescence detection. We evaluate the particle conversion of the Nr instrument by comparing to mass-derived concentrations of size-selected and counted ammonium sulfate ((NH4)2SO4), ammonium nitrate (NH4NO3), ammonium chloride (NH4Cl), sodium nitrate (NaNO3), and ammonium oxalate ((NH4)2C2O4) particles determined using instruments that measure particle number and size. These measurements demonstrate Nr-particle conversion across the Nr catalysts that is independent of particle size with 98 ± 10 % efficiency for 100-600 nm particle diameters. We also show efficient conversion of particle-phase organic carbon species to CO2 across the instrument's platinum catalyst followed by a nondispersive infrared (NDIR) CO2 detector. However, the application of this method to the atmosphere presents a challenge due to the small signal above background at high ambient levels of common gas-phase carbon compounds (e.g., CO2). We show the Nr system is an accurate particle mass measurement method and demonstrate its ability to calibrate particle mass measurement instrumentation using single-component, laboratory-generated, Nr-containing particles below 2.5 µm in size. In addition we show agreement with mass measurements of an independently calibrated online particle-into-liquid sampler directly coupled to the electrospray ionization source of a quadrupole mass spectrometer (PILS-ESI/MS) sampling in the negative-ion mode. We obtain excellent correlations (R2 = 0.99) of particle mass measured as Nr with PILS-ESI/MS measurements converted to the corresponding particle anion mass (e.g., nitrate, sulfate, and chloride). The Nr and PILS-ESI/MS are shown to agree to within ˜ 6 % for particle mass loadings of up to 120 µg m-3. Consideration of all the sources of error in the PILS-ESI/MS technique yields an overall uncertainty of ±20 % for these single-component particle streams. These results demonstrate the Nr system is a reliable direct particle mass measurement technique that differs from other particle instrument calibration techniques that rely on knowledge of particle size, shape, density, and refractive index.

Ankylosing Spondylitis versus Nonradiographic Axial Spondyloarthritis: Comparison of Tumor Necrosis Factor Inhibitor Effectiveness and Effect of HLA-B27 Status. An Observational Cohort Study from the Nationwide DANBIO Registry.

PubMed

Glintborg, Bente; Sørensen, Inge J; Østergaard, Mikkel; Dreyer, Lene; Mohamoud, Abdiweli A; Krogh, Niels S; Hendricks, Oliver; Andersen, Lis S; Raun, Johnny L; Kowalski, Marcin R; Danielsen, Laura; Pelck, Randi; Nordin, Henrik; Pedersen, Jens K; Kraus, Dorte G A; Christensen, Susan R; Hansen, Inger M J; Esbesen, Jakob; Schlemmer, Annette; Loft, Anne G; Al Chaer, Nabil; Salomonsen, Lone; Hetland, Merete L

2017-01-01

To compare baseline disease activity and treatment effectiveness in biologic-naive patients with nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) who initiate tumor necrosis factor inhibitor (TNFi) treatment and to study the role of potential confounders (e.g., HLA-B27 status). Observational cohort study based on prospectively registered data in the nationwide DANBIO registry. We used Kaplan-Meier plots, Cox, and logistic regression analyses to study the effect of diagnosis (nr-axSpA vs AS) and potential confounders (sex/age/start yr/HLA-B27/disease duration/TNFi-type/smoking/baseline disease activity) on TNFi adherence and response [e.g., Bath Ankylosing Spondylitis Activity Index (BASDAI) 50%/20 mm]. The study included 1250 TNFi-naive patients with axSpA (29% nr-axSpA, 50% AS, 21% lacked radiographs of sacroiliac joints). Patients with nr-axSpA were more frequently women (50%/27%) and HLA-B27-negative (85/338 = 25%), compared to AS (81/476 = 17%; p < 0.01). At TNFi start patients with nr-axSpA had higher visual analog scale scores [median (quartiles)] for pain: 72 mm (55-84)/65 mm (48-77); global: 76 mm (62-88)/68 mm (50-80); fatigue: 74 mm (55-85)/67 mm (50-80); and BASDAI: 64 (54-77)/59 (46-71); all p < 0.01. However, patients with nr-axSpA had lower C-reactive protein: 7 mg/l (3-17)/11 mg/l (5-22); and BAS Metrology Index: 20 (10-40)/40 (20-50); all p < 0.01. Median (95% CI) treatment adherence was poorer in nr-axSpA than in AS: 1.59 years (1.15-2.02) versus 3.67 years (2.86-4.49), p < 0.0001; but only in univariate and not confounder-adjusted analyses (p > 0.05). Response rates were similar in AS and nr-axSpA (p > 0.05). HLA-B27 negativity was associated with poorer treatment adherence [HLA-B27 negative/positive, nr-axSpA: HR 1.74 (1.29-2.36), AS: HR 2.04 (1.53-2.71), both p < 0.0001]; and lower response rates (nr-axSpA: 18/61 = 30% vs 93/168 = 55%; AS: 17/59 = 29% vs 157/291 = 54%, both p < 0.05). In this nationwide cohort, patients with nr-axSpA had higher subjective disease activity at start of first TNFi treatment, but similar outcomes to patients with AS after confounder adjustment. HLA-B27 positivity was associated with better outcomes irrespective of axSpA subdiagnosis.

Study of rheological, viscoelastic and vulcanization behavior of sponge EPDM/NR blended nano- composites

NASA Astrophysics Data System (ADS)

Arshad Bashir, M.; Shahid, M.; Ahmed, Riaz; Yahya, A. G.

2014-06-01

In this research paper the effect of blending ratio of natural rubber (NR) with Ethylene Propylene Diene Monomer (EPDM) were investigated. Different samples of EPDM/NR ratio were prepared to study the variation of NR in EPDM on rheology, curing characteristics, tangent δ, and viscosity variation during vulcanization of sponge nano composites.The main aim of present research is to develop elastomeric based sponge composites with the blending ratio of base elastomers along with the carbon nano particles for high energy absorbing and damping applications. The curing characteristics, rheology and viscoelastic nature of the composite is remarkably influenced with the progressive blending ratio of the base elastomeric matrix.

Nuclear Receptor Variants in Liver Disease

PubMed Central

Müllenbach, Roman; Weber, Susanne N.; Lammert, Frank

2012-01-01

This review aims to provide a snapshot of the actual state of knowledge on genetic variants of nuclear receptors (NR) involved in regulating important aspects of liver metabolism. It recapitulates recent evidence for the application of NR in genetic diagnosis of monogenic (“Mendelian”) liver disease and their use in clinical diagnosis. Genetic analysis of multifactorial liver diseases such as viral hepatitis or fatty liver disease identifies key players in disease predisposition and progression. Evidence from these analyses points towards a role of NR polymorphisms in common diseases, linking regulatory networks to complex and variable phenotypes. The new insights into NR variants also offer perspectives and cautionary advice for their use as handles towards diagnosis and treatment. PMID:22523693

Electric Propulsion Technology Development for the Jupiter Icy Moons Orbiter Project

NASA Technical Reports Server (NTRS)

2004-01-01

During 2004, the Jupiter Icy Moons Orbiter project, a part of NASA's Project Prometheus, continued efforts to develop electric propulsion technologies. These technologies addressed the challenges of propelling a spacecraft to several moons of Jupiter. Specific challenges include high power, high specific impulse, long lived ion thrusters, high power/high voltage power processors, accurate feed systems, and large propellant storage systems. Critical component work included high voltage insulators and isolators as well as ensuring that the thruster materials and components could operate in the substantial Jupiter radiation environment. A review of these developments along with future plans is discussed.

Active Magnetic Regenerative Liquefier

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

Barclay, John A.; Oseen-Send, Kathryn; Ferguson, Luke

2016-01-12

This final report for the DOE Project entitled Active Magnetic Regenerative Liquefier (AMRL) funded under Grant DE-FG36-08GO18064 to Heracles Energy Corporation d.b.a. Prometheus Energy (Heracles/Prometheus) describes an active magnetic regenerative refrigerator (AMRR) prototype designed and built during the period from July 2008 through May 2011. The primary goal of this project was to make significant technical advances toward highly efficient liquefaction of hydrogen. Conventional hydrogen liquefiers at any scale have a maximum FOM of ~0.35 due primarily to the intrinsic difficulty of rapid, efficient compression of either hydrogen or helium working gases. Numerical simulation modeling of high performance AMRL designsmore » indicates certain designs have promise to increase thermodynamic efficiency from a FOM of ~0.35 toward ~0.5 to ~0.6. The technical approach was the use of solid magnetic working refrigerants cycled in and out of high magnetic fields to build an efficient active regenerative magnetic refrigeration module providing cooling power for AMRL. A single-stage reciprocating AMRR with a design temperature span from ~290 K to ~120 K was built and tested with dual magnetic regenerators moving in and out of the conductively-cooled superconducting magnet subsystem. The heat transfer fluid (helium) was coupled to the process stream (refrigeration/liquefaction load) via high performance heat exchangers. In order to maximize AMRR efficiency a helium bypass loop with adjustable flow was incorporated in the design because the thermal mass of magnetic refrigerants is higher in low magnetic field than in high magnetic field. Heracles/Prometheus designed experiments to measure AMRR performance under a variety of different operational parameters such as cycle frequency, magnetic field strength, heat transfer fluid flow rate, amount of bypass flow of the heat transfer fluid while measuring work input, temperature span, cooling capability as a function of cold temperature as a function of the amount of bypass flow of the heat transfer fluid. The operational AMRR prototype can be used to answer key questions such as the best recipe for multiple layers of different magnetic refrigerants in one or more integrated regenerators with varying amounts of bypass flow of the heat transfer fluid. Layered regenerators are necessary to span the AMRR range from 290 K to 120K. Our AMRR performance simulation model predicts that ~10-15 % of bypass flow should significantly improve the thermodynamic performance. Initial results obtained with regenerators made of gadolinium spheres were very encouraging; a temperature span of ~ 50 K (between 295K and 245 K) across both regenerators was achieved with zero bypass flow of the heat transfer fluid and with the magnetic field strength of ~4 T.« less

Co-delivery of doxorubicin and siRNA using octreotide-conjugated gold nanorods for targeted neuroendocrine cancer therapy

NASA Astrophysics Data System (ADS)

Xiao, Yuling; Jaskula-Sztul, Renata; Javadi, Alireza; Xu, Wenjin; Eide, Jacob; Dammalapati, Ajitha; Kunnimalaiyaan, Muthusamy; Chen, Herbert; Gong, Shaoqin

2012-10-01

A multifunctional gold (Au) nanorod (NR)-based nanocarrier capable of co-delivering small interfering RNA (siRNA) against achaete-scute complex-like 1 (ASCL1) and an anticancer drug (doxorubicin (DOX)) specifically to neuroendocrine (NE) cancer cells was developed and characterized for combined chemotherapy and siRNA-mediated gene silencing. The Au NR was conjugated with (1) DOX, an anticancer drug, via a pH-labile hydrazone linkage to enable pH-controlled drug release, (2) polyarginine, a cationic polymer for complexing siRNA, and (3) octreotide (OCT), a tumor-targeting ligand, to specifically target NE cancer cells with overexpressed somatostatin receptors. The Au NR-based nanocarriers exhibited a uniform size distribution as well as pH-sensitive drug release. The OCT-conjugated Au NR-based nanocarriers (Au-DOX-OCT, targeted) exhibited a much higher cellular uptake in a human carcinoid cell line (BON cells) than non-targeted Au NR-based nanocarriers (Au-DOX) as measured by both flow cytometry and confocal laser scanning microscopy (CLSM). Moreover, Au-DOX-OCT-ASCL1 siRNA (Au-DOX-OCT complexed with ASCL1 siRNA) resulted in significantly higher gene silencing in NE cancer cells than Au-DOX-ASCL1 siRNA (non-targeted Au-DOX complexed with ASCL1 siRNA) as measured by an immunoblot analysis. Additionally, Au-DOX-OCT-ASCL1 siRNA was the most efficient nanocarrier at altering the NE phenotype of NE cancer cells and showed the strongest anti-proliferative effect. Thus, combined chemotherapy and RNA silencing using NE tumor-targeting Au NR-based nanocarriers could potentially enhance the therapeutic outcomes in treating NE cancers.A multifunctional gold (Au) nanorod (NR)-based nanocarrier capable of co-delivering small interfering RNA (siRNA) against achaete-scute complex-like 1 (ASCL1) and an anticancer drug (doxorubicin (DOX)) specifically to neuroendocrine (NE) cancer cells was developed and characterized for combined chemotherapy and siRNA-mediated gene silencing. The Au NR was conjugated with (1) DOX, an anticancer drug, via a pH-labile hydrazone linkage to enable pH-controlled drug release, (2) polyarginine, a cationic polymer for complexing siRNA, and (3) octreotide (OCT), a tumor-targeting ligand, to specifically target NE cancer cells with overexpressed somatostatin receptors. The Au NR-based nanocarriers exhibited a uniform size distribution as well as pH-sensitive drug release. The OCT-conjugated Au NR-based nanocarriers (Au-DOX-OCT, targeted) exhibited a much higher cellular uptake in a human carcinoid cell line (BON cells) than non-targeted Au NR-based nanocarriers (Au-DOX) as measured by both flow cytometry and confocal laser scanning microscopy (CLSM). Moreover, Au-DOX-OCT-ASCL1 siRNA (Au-DOX-OCT complexed with ASCL1 siRNA) resulted in significantly higher gene silencing in NE cancer cells than Au-DOX-ASCL1 siRNA (non-targeted Au-DOX complexed with ASCL1 siRNA) as measured by an immunoblot analysis. Additionally, Au-DOX-OCT-ASCL1 siRNA was the most efficient nanocarrier at altering the NE phenotype of NE cancer cells and showed the strongest anti-proliferative effect. Thus, combined chemotherapy and RNA silencing using NE tumor-targeting Au NR-based nanocarriers could potentially enhance the therapeutic outcomes in treating NE cancers. Electronic supplementary information (ESI) available: Additional flow cytometry histogram profiles of DOX fluorescence and ASCL1 knockdown results. See DOI: 10.1039/c2nr31853a

Novel de novo pathogenic variant in the NR2F2 gene in a boy with congenital heart defect and dysmorphic features.

PubMed

Upadia, Jariya; Gonzales, Patrick R; Robin, Nathaniel H

2018-04-16

The NR2F2 gene plays an important role in angiogenesis and heart development. Moreover, this gene is involved in organogenesis in many other organs in mouse models. Variants in this gene have been reported in a number of patients with nonsyndromic atrioventricular septal defect, and in one patient with congenital heart defect and dysmorphic features. Here we report an 11-month-old Caucasian male with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect. He was later found to have a pathogenic mutation in the NR2F2 gene by whole exome sequencing. This is the second instance in which an NR2F2 mutation has been identified in a child with a congenital heart defect and other anomalies. This case suggests that some variants in NR2F2 may cause syndromic forms of congenital heart defect. © 2018 Wiley Periodicals, Inc.

Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer

PubMed Central

Park, Yun-Yong; Kim, Kyounghyun; Kim, Sang-Bae; Hennessy, Bryan T; Kim, Soo Mi; Park, Eun Sung; Lim, Jae Yun; Li, Jane; Lu, Yiling; Gonzalez-Angulo, Ana Maria; Jeong, Woojin; Mills, Gordon B; Safe, Stephen; Lee, Ju-Seog

2012-01-01

ESR1 is one of the most important transcription factors and therapeutic targets in breast cancer. By applying systems-level re-analysis of publicly available gene expression data, we uncovered a potential regulator of ESR1. We demonstrated that orphan nuclear receptor NR2E3 regulates ESR1 via direct binding to the ESR1 promoter with concomitant recruitment of PIAS3 to the promoter in breast cancer cells, and is essential for physiological cellular activity of ESR1 in estrogen receptor (ER)-positive breast cancer cells. Moreover, expression of NR2E3 was significantly associated with recurrence-free survival and a favourable response to tamoxifen treatment in women with ER-positive breast cancer. Our results provide mechanistic insights on the regulation of ESR1 by NR2E3 and the clinical relevance of NR2E3 in breast cancer. PMID:22174013

The role of industrial nitrogen in the global nitrogen biogeochemical cycle

PubMed Central

Gu, Baojing; Chang, Jie; Min, Yong; Ge, Ying; Zhu, Qiuan; Galloway, James N.; Peng, Changhui

2013-01-01

Haber-Bosch nitrogen (N) has been increasingly used in industrial products, e.g., nylon, besides fertilizer. Massive numbers of species of industrial reactive N (Nr) have emerged and produced definite consequences but receive little notice. Based on a comprehensive inventory, we show that (1) the industrial N flux has increased globally from 2.5 to 25.4 Tg N yr−1 from 1960 through 2008, comparable to the NOx emissions from fossil fuel combustion; (2) more than 25% of industrial products (primarily structural forms, e.g., nylon) tend to accumulate in human settlements due to their long service lives; (3) emerging Nr species define new N-assimilation and decomposition pathways and change the way that Nr is released to the environment; and (4) the loss of these Nr species to the environment has significant negative human and ecosystem impacts. Incorporating industrial Nr into urban environmental and biogeochemical models could help to advance urban ecology and environmental sciences. PMID:23999540