Tomorrow's School Leaders: What Do We Know about Them?--A Case Study

ERIC Educational Resources Information Center

Ritchie, Jim; Lindstrom, Phyllis H.; Mendoza-Reis, Noni

2004-01-01

Large numbers of projected retirements have created the need for recruiting and preparing capable school leaders for the future. This study explored the characteristics of candidates in an administration preparation program, factors for their career decisions, and the implications of these factors for recruiting candidates and building stronger…

Move Staff Development into the Digital World

ERIC Educational Resources Information Center

Schlechty, Phillip C.

2007-01-01

The way public school educators respond to emerging information technologies will be the defining event for public education over the next decade. This author, however, worries about whether public schools have the capacity to take advantage of the revolution going on around them--a revolution that is affecting not only the way students learn, but…

Memes and their themata.

PubMed

Miranker, Willard L

2010-01-01

When it is instantiated as a neuronal state, a meme is characterized as a phenotype in a novel neuronal sense. A thema is an instantiation of a meme as a conscious experience (a thought-meme). It is a primitive to which no location may be attributed, and it serves as a canonical representative of a class of memes. Memes in such a class may have physical or ideal (Platonic) instantiations. Pairing of this memetic phenotype characterization with the ideal thematic primitive is an example of other pairings in nature that are identified, and in particular it informs a description of the pairing of the unconscious mind and manifestations of consciousness. Interrelationship of these pairings is what illuminates aspects of each of them. These constructs support introduction of a consciousness thesis and then a notion of a dynamic self-referential grammar that generates a growing repertoire of consciousness manifestations. A method showing how a neuronal state generates a specific concept (thema) is introduced, and a sample of a class of examples is given. Pointers to experiments relevant to development of the thesis are given.

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...

Geometrie verstehen: statisch - kinematisch

NASA Astrophysics Data System (ADS)

Kroll, Ekkehard

Dem Allgemeinen steht begrifflich das Besondere gegenüber. In diesem Sinne sind allgemeine Überlegungen zum Verstehen von Mathematik zu ergänzen durch Untersuchungen hinsichtlich des Verstehens der einzelnen mathematischen Disziplinen, insbesondere der Geometrie. Hier haben viele Schülerinnen und Schüler Probleme. Diese rühren hauptsächlich daher, dass eine fertige geometrische Konstruktion in ihrer statischen Präsentation auf Papier nicht mehr die einzelnen Konstruktionsschritte erkennen lässt; zum Nachvollzug müssen sie daher ergänzend in einer Konstruktionsbeschreibung festgehalten werden.

Probleme aus der Physik

NASA Astrophysics Data System (ADS)

Vogel, Helmut

Das beliebte Arbeitsbuch "Probleme aus der Physik" bietet nun auch zur 17. Auflage von Gerthsen Vogel "Physik" (ISBN 3-540-56638-4) mit über 1150 gelösten Aufgaben aus der Physik und ihren Anwendungen in Technik, Astrophysik, Geound Biowissenschaften eine Fülle an Material zum Üben und Weiterlernen, zur Prüfungsvorbereitung und zum Selbststudium. Neu hinzugekommen ist ein Kapitel zur nichtlinearen Dynamik. Aufgaben aller Schwierigkeitsgrade machen "Probleme aus der Physik" unentbehrlich für Studenten der Physik im Haupt- und Nebenfach; Schüler der Leistungskurse Physik finden hier eine hervorragende Ergänzung.

Citizenship Education as an Educational Outcome for Young People in Care: A Phenomenological Account

ERIC Educational Resources Information Center

Spiteri, Damian

2012-01-01

This qualitative study presents a retrospective analysis of how a cohort of young men, who as boys were assigned to residential care in Malta, perceive the citizenship education that they received while "in care" as having empowered them--as boys, adolescents, and eventually as young adults. Rather than focusing on citizenship education…

Thematic Journeys. Words that I Own

ERIC Educational Resources Information Center

Zingher, Gary

2005-01-01

Children may feel a sense of ownership when they learn a new vocabulary word that genuinely excites them--a dynamic word, a poetic word, a word with a delicious sound or interesting meaning. Right away, they like to try out these words, experiment with them, incorporate them into the speaking and writing, and impress others with their mastery.…

Clinical investigation of vestibular damage by antituberculous drugs.

PubMed

Nakayama, M; Natori, Y; Tachi, H; Yoshizawa, M; Takayama, S; Miura, H; Kanayama, M; Kamei, T

1986-01-01

Vestibular function testing was done regularly on the cases given streptomycin, kanamycin, or enviomycin and a method to detect the cases of vestibular dysfunction at an early stage was discussed, as well as the time these drugs should be discontinued. Subjects were 85 cases of tuberculosis treated with streptomycin, kanamycin, or enviomycin who were admitted to our hospital from December 1984 to May 1986. The method of equilibrium examination performed at regular intervals is as follows: standing test (Romberg test), stepping test, and Meyer zum Gottesberge's head-shaking test were done once a week for a month after starting antituberculous injections and they were re-examined once every 2 weeks for at least 3 months after beginning the injections. After the 3 months these tests were done once a month. Eight cases of vestibular damage due to streptomycin or enviomycin could be easily detected at an early stage by performing Meyer zum Gottesberge's head-shaking test, together with the standing test and the stepping test. Vestibular dysfunction is apt to occur after about 1 month or within a month from the start of daily injections especially with streptomycin. Therefore, the method of equilibrium examination, we suggest, is that the Meyer zum Gottesberge's head-shaking test, the standing test (Romberg test), and the stepping test should be performed once a week during the first month after the start of this drug. When the result of the Meyer zum Gottesberge's head-shaking test is less than 50% and swaying and/or rotation occur in the stepping test, the drugs being given should be discontinued.

Gender agreement and multiple referents.

PubMed

Finocchiaro, Chiara; Mahon, Bradford Z; Caramazza, Alfonso

2008-01-01

We report a new pattern of usage in current, spoken Italian that has implications for both psycholinguistic models of language production and linguistic theories of language change. In Italian, gender agreement is mandatory for both singular and plural nouns. However, when two or more nouns of different grammatical gender appear in a conjoined noun phrase (NP), masculine plural agreement is required. In this study, we combined on-line and off-line methodologies in order to assess the mechanisms involved in gender marking in the context of multiple referents. The results of two pronoun production tasks showed that plural feminine agreement was significantly more difficult than plural masculine agreement. In a separate study using offline judgements of acceptability, we found that agreement violations in Italian are tolerated more readily in the case of feminine conjoined noun phrases (e.g., la mela e la banana 'the:fem apple:fem and the: fem banana: fem') than masculine conjoined noun phrases (e.g., il fiore e il libro 'the:mas flower: mas and the:mas book:mas'). Implications of these results are discussed both at the level of functional architecture within the language production system and at the level of changes in language use.

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

Innovative BI-Lösungen als Basis für eine erfolgreiche Transformation zu Utility 4.0

NASA Astrophysics Data System (ADS)

Phillipp, Daniel; Ebert, Sebastian

Für eine erfolgreiche Transformation, vom reinen Energieversorger hin zum Energiedienstleister, werden innovative Business-Intelligence-Lösungen notwendig sein und eine zentrale Rolle einnehmen. Dabei ist es zunächst essenziell, die Herausforderungen zu kennen und ihnen mit geeigneten Analysen zu begegnen. Die Basis hierzu bildet eine abgestimmte und auf die strategischen Unternehmensziele ausgerichtete Architektur und Vorgehensweise. Zwei Beispiele veranschaulichen, wie ein gesamtheitlicher Ansatz, auch bei Datenvielfalt und hoher Komplexität, operative Prozesse optimiert, und fortgeschrittene Analysen zukünftig einen Beitrag zum Unternehmenserfolg liefern können.

Airbag-Systeme

NASA Astrophysics Data System (ADS)

Kramer, Florian

Heutige Pkw sind zum Schutz der Insassen bei Frontalkollisionen zu etwa 90 % fahrerseitig und zu ca. 70 % auf der Beifahrerseite mit Airbags ausgestattet, während die Seiten-Airbags zum Schutz des Kopfes und des Thorax von Insassen bei Seitenkollisionen nur mit ungefähr 40 bis 50% vertreten sind [1]. Weitere Schutzmaßnahmen wie Fuß- und Fond-Airbags befinden sich im Entwicklungsstadium, ihr Einsatz in der Serie ist umstritten und wird sich, wenn überhaupt, nur in Einzelfällen durchsetzen. In Bild C3-1 sind Airbags dargestellt, die heute serienmäßig in Pkw anzutreffen sind.

Meilensteine in der Erforschung der kompakten Objekte

NASA Astrophysics Data System (ADS)

Camenzind, Max

Kompakte Objekte besitzen zum einen eine sehr hohe Dichte, und zum anderen sind sie durch die Tatsache charakterisiert, dass keine nuklearen Reaktionen mehr in ihrem Inneren stattfinden können. Aus diesem Grund können sie im Unterschied zu gewöhnlichen Sternen der Gravitation nicht mehr mit dem Druck des thermischen Gases widerstehen. In den Weißen Zwergen bzw. Neutronensternen wird der Gravitation der Quantendruck eines Elektronengases bzw. einer Neutronenflüssigkeit entgegengesetzt. Ein solches Gas besteht aus Elektronen bzw. Neutronen, die auf ihr niedrigstes Energieniveau zusammengepresst wurden. Durch die daraus resultierende hohe Bewegungsenergie der Fermionen wird der sogenannte Quantendruck erzeugt.

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...

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

Magnetoseed - Vasculäres Tissue Engineering

NASA Astrophysics Data System (ADS)

Perea Saavedra, Héctor; Methe, Heiko; Wintermantel, Erich

Gegenwärtig sind kardiovaskuläre Erkrankungen, allen voran die Arteriosklerose koronarer und zerebraler Gefäße, Ursache für 38% aller Todesfälle in Nordamerika und häufigste Todesursache europäischer Männer < 65 Jahre und zweithäufigste Todesursache bei Frauen [4]. Es wird prognostiziert, dass innerhalb der nächsten 10-15 Jahre kardiovaskuläre Erkrankungen und deren Komplikationen weltweit die häufigste Todesursache stellen werden. Dies ist zum einen Folge der ansteigenden Prävalenz kardiovaskulärer Erkrankungen in Osteuropa und zunehmend auch in den Entwicklungsländern, zum anderen Folge der kontinuierlich ansteigenden Inzidenz von Übergewicht und Diabetes mellitus in den westlichen Ländern.

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.

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

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.

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.

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

S1-Leitlinie Lipödem.

PubMed

Reich-Schupke, Stefanie; Schmeller, Wilfried; Brauer, Wolfgang Justus; Cornely, Manuel E; Faerber, Gabriele; Ludwig, Malte; Lulay, Gerd; Miller, Anya; Rapprich, Stefan; Richter, Dirk Frank; Schacht, Vivien; Schrader, Klaus; Stücker, Markus; Ure, Christian

2017-07-01

Die vorliegende überarbeitete Leitlinie zum Lipödem wurde unter der Federführung der Deutschen Gesellschaft für Phlebologie (DGP) erstellt und finanziert. Die Inhalte beruhen auf einer systematischen Literaturrecherche und dem Konsens von acht medizinischen Fachgesellschaften und Berufsverbänden. Die Leitlinie beinhaltet Empfehlungen zu Diagnostik und Therapie des Lipödems. Die Diagnose ist dabei auf der Basis von Anamnese und klinischem Befund zu stellen. Charakteristisch ist eine umschriebene, symmetrisch lokalisierte Vermehrung des Unterhautfettgewebes an den Extremitäten mit deutlicher Disproportion zum Stamm. Zusätzlich finden sich Ödeme, Hämatomneigung und eine gesteigerte Schmerzhaftigkeit der betroffenen Körperabschnitte. Weitere apparative Untersuchungen sind bisher besonderen Fragestellungen vorbehalten. Die Erkrankung ist chronisch progredient mit individuell unterschiedlichem und nicht vorhersehbarem Verlauf. Die Therapie besteht aus vier Säulen, die individuell kombiniert und an das aktuelle Beschwerdebild angepasst werden sollten: komplexe physikalische Entstauungstherapie (manuelle Lymphdrainage, Kompressionstherapie, Bewegungstherapie, Hautpflege), Liposuktion und plastisch-chirurgische Interventionen, Ernährung und körperliche Aktivität sowie ggf. additive Psychotherapie. Operative Maßnahmen sind insbesondere dann angezeigt, wenn trotz konsequent durchgeführter konservativer Therapie noch Beschwerden bestehen bzw. eine Progredienz des Befundes und/oder der Beschwerden auftritt. Eine begleitend zum Lipödem bestehende morbide Adipositas sollte vor einer Liposuktion therapeutisch angegangen werden. © 2017 The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.

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.

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

Einsatz molekularer Methoden für Starterkulturen

NASA Astrophysics Data System (ADS)

Ehrmann, Matthias A.; Pavlovic, Melanie

Unter Starterkulturen versteht man Mikroorganismen (Bakterien, Hefen, Pilze), die pflanzlichen bzw. tierischen Rohstoffen zur gezielten Veränderung ihrer chemischen Zusammensetzung zugesetzt werden. Sie dienen im Wesentlichen der Aromabildung, der Strukturveränderung und der Konservierung der Lebensmittel und werden aufgrund spezieller, funktioneller Eigenschaften selektiert. Die Zugabe von Starterkulturen erfolgt in der Regel in relativ hohen Keimzahlen in Form von Rein- oder Mischkulturen. Die zum Einsatz kommenden Mikroorganismen sind ebenso zahlreich wie die daraus resultierenden Produkte und reichen von der Fermentation von Milchprodukten, Fleisch und Gemüse durch Milchsäurebakterien über die Essigsäureherstellung bis hin zum Einsatz von Hefen in der Brau- und Weinindustrie. Hieraus ergibt sich auch eine zunehmende Bedeutung schneller und zuverlässiger Methoden zur taxonomischen Identifizierung, aber auch zur Charakterisierung des genetischen Potenzials der jeweiligen Starterkulturen.

S2k-Leitlinie zum Gebrauch von Präparationen zur lokalen Anwendung auf der Haut (Topika).

PubMed

Wohlrab, Johannes; Staubach, Petra; Augustin, Matthias; Eisert, Lisa; Hünerbein, Andreas; Nast, Alexander; Reimann, Holger; Strömer, Klaus; Mahler, Vera

2018-03-01

Diese Leitlinie richtet sich an Assistenz- und Fachärzte der Dermatologie sowie an Kostenträger und politische Entscheidungsgremien. Die Leitlinie wurde im formellen Konsensusverfahren (S2k) von Dermatologen unter Einbindung von Apothekern erstellt. Die Leitlinie stellt allgemeine Aspekte der Pharmakokinetik sowie der regulatorischen Begrifflichkeiten dar. Es werden Empfehlungen zur Indikation von Magistralrezepturen sowie deren Qualitätssicherung gegeben. Die Bedeutung der galenischen Grundlagen und die Problematik bei einer Substitution gegeneinander verschiedener Grundlagen werden dargestellt. Die Leitlinie umfasst Kriterien zur Auswahl einer adäquaten Grundlage sowie spezifische Aspekte zur Therapieplanung. Die Leitlinie gibt Empfehlungen zum Management bei Unverträglichkeiten gegenüber Bestandteilen der Grundlagen oder Hilfsstoffe. © 2018 The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.

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

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.

National SBIR Phase III Commercialization Conference Held in Orlando, Florida on Jun 10 and 11, 1993

DTIC Science & Technology

1993-06-01

design program catted AKCES.BOREVAC, The delivered system will be capable of real gas flows modeling including 3D Navier-Stokes flow, effective...imprrementat’"n of non-thema-l plasma treatment of effluent gases using corona discharge to reduce ermissions of SO2. NGx and other hazardous air...The AWAS is an aircraft mounted sys- tem that provides the flight crew with advance waninq of Low Level Wind Shear (LLWS) and Clear Air Turbulence ( CAT

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

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...

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.

Mikrodaten und statistische Auswertungsmethoden

NASA Astrophysics Data System (ADS)

Hujer, Reinhard

Mit der zunehmenden Verfügbarkeit immer größerer Querschnitts- und Längschnittsdatensätze für Personen, Haushalte und Betriebe sowie deren Verknüpfungen hat sich die mikroökonometrische Forschung in den vergangenen Jahren rasant weiterentwickelt. Dies gilt sowohl aus methodischer als auch aus empirischer, anwendungsorientierter Sicht. Mikrodaten und mikroökonometrische Ansätze dienen dazu, aktuelle, politikrelevante Fragen aufzugreifen, sie zu analysieren und fundierte politische Empfehlungen zu geben, beispielsweise im Rahmen der Arbeitsmarkt- und Sozialpolitik, der Finanzanalyse und der Marketingforschung. Die Deutsche Statistische Gesellschaft (DStatG) und deren Mitglieder haben sich in den Ausschüssen und in Hauptversammlungen kontinuierlich mit den Weiterentwicklungen der mikroökonometrischen Methodik und den empirischen Anwendungen befasst. Zahlreiche Publikationen von Mitgliedern der DStatG haben entscheidend zum kritischen Diskurs und zum wissenschaftlichen Fortschritt in diesem Bereich beigetragen.

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

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.

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.

Reality of Retainers

MedlinePlus

... or bruxism (say: BRUK-sih-zum), which is grinding your teeth while you sleep. Grinding stretches the muscles and joints in your mouth ... closing completely at night, which keeps you from grinding your teeth. Getting Fitted for and Wearing a ...

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

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.

Ocean management plan includes array of recommendations

NASA Astrophysics Data System (ADS)

Showstack, Randy

When U.S. President Bill Clinton and Vice President Al Gore appeared in Monterey, California in June 1998 for a National Oceans Conference, some of the salt water spray from the Pacific Ocean must have clung to them.As a follow-up to the conference, the Clinton Administration on September 2 issued an interagency report to help guide federal efforts in establishing a comprehensive ocean policy.The report, which touches upon a number of global issues including the United Nations Convention on the Law of the Sea, contains nearly 150 recommendations.

Characterizing Deficiencies of Path-Based Routing for Wireless Multi-Hop Networks

DTIC Science & Technology

2017-05-01

called a “ hello ”) to all of its neighbors. If a series of hello messages are exchanged between two users, a link is considered to exist between them...A brief description of ETX is as follows. For a given window of time, the number of hello packets that a user receives from a neighbor is counted. A...cost is then assigned to the link based on how many hello messages were heard; a link that has fewer hellos successfully transmitted across it will be

Construction of In-house Databases in a Corporation

NASA Astrophysics Data System (ADS)

Fujii, Yohzo

The author outlines the inhouse technical information system, OSTI of Osaka Research Institute, Sumitomo Chemical company as an example of inhouse database construction and use at a chemical industry. This system is to compile database for technical information generated inside the Laboratory and to provide online searching as well as title lists of the latest data output from it aiming at effective use of information among the departments, prevention from overlapped research thema, and support of research activities. The system outline, characteristics, materials to be covered, input items and search examples are described.

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…

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

Extrasolare Monde - schöne neue Welten?

NASA Astrophysics Data System (ADS)

Heller, René

2013-10-01

Während mittlerweile rund 950 Planeten außerhalb des Sonnensystems gefunden wurden, steht der Nachweis von extrasolaren Monden noch aus. Aktuelle Studien zeigen, dass dies mit der heutigen Technologie zum ersten Mal möglich ist.

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.

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.

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

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.

Sentinel-Lymphknoten-Biopsie des Melanoms mittels Indocyaningrün und "FOVIS"-System.

PubMed

Göppner, Daniela; Nekwasil, Stephan; Jellestad, Anne; Sachse, Alexander; Schönborn, Karl-Heinz; Gollnick, Harald

2017-02-01

Der Nachweis metastatischer Infiltrate im Sentinel-Lymphkoten (SLN) gilt als wesentlicher prognostischer Faktor des Melanoms. Alternativ zur Farbstoffmethode mit Patentblau zum Goldstandard der SLN-Biopsie (SLNB) mittels Radiokolloid wird die fluoreszenzoptische Darstellung mit Hilfe von Indocyaningrün (ICG) und Nahinfrarot (NIR)-Kamerasystem kommuniziert. Im Vergleich zur konventionellen Methode wurde die Wertigkeit des ICG-/NIR-Verfahrens in Abhängigkeit vom Body-Mass-Index (BMI) des Patienten und der Konzentration von ICG bezüglich der Visualisierung des Lymphabstroms und des SLNs untersucht. An zehn Patienten wurde die SLNB mittels Technetium-99m, Patentblau und ICG durchgeführt. Die Fluoreszenz-Darstellung von Lymphbahnen und SLN erfolgte in Echtzeit mittels der NIR-Kameratechnik "FOVIS". Je nach erzielter Bildqualität wurde ICG in einer Dosis von 0,25 mg bis 2,5 mg intrakutan appliziert. Neun der zehn SLN wurden fluoreszenzoptisch identifiziert (90 %), alle zehn radioaktiv (100 %), nur acht (80 %) mittels ICG-Grünfärbung bzw. Patenblau-Markierung. Transdermal wurde ein SLN dargestellt (10 %). In Korrelation zum BMI waren höhere ICG-Mengen, bis zu 2,5 mg intrakutan absolut, in der Darstellung der Lymphbahnen von Vorteil. Die SLN-Fluoreszenzmarkierung mit dem ICG/NIR-Kamera-System "FOVIS" stellt eine sichere Alternative zur Farbstoffmethode mit Patentblau ergänzend zur Radiokolloidmethode mit Technetium-99m dar. Weitere Studien zur optimalen Dosierung von ICG und transdermalen Bildgebung in Relation zum BMI sind notwendig. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

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 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.

Normung (Standardisierung)

NASA Astrophysics Data System (ADS)

Kostmann, Dirk

Normung ist aus dem täglichen Leben nicht wegzudenken. In allen Bereichen des Lebens begegnet man Normen, die Aktivitäten reichen von Festlegungen für Kindersitze im Auto über Implantate zum Gelenkersatz bis zu Schraubengrößen oder Verfahren zur Optimierung von Unternehmen.

Geschichtlicher Überblick

NASA Astrophysics Data System (ADS)

Bölke, Klaus-Peter

Die Nachweise einer schadlosen Ableitung von Abwässern lassen sich bis weit in die Vergangenheit zurückverfolgen. Sie waren bereits zur damaligen Zeit eine Forderung zur Pflege der öffentlichen Reinlichkeit. Der Kanalisationsbau ist auch immer ein Ausdruck der Kultur eines Volkes gewesen. So kann festgestellt werden, dass im Zusammenhang mit der Hochkultur eines Volkes auch der Kanalbau ein vorherrschendes Thema war. Der Kanalbau steht auch in einem engen Zusammenhang mit dem Wasserleitungsbau. Es ist nur logisch, dass dort wo Wasser teilweise aus großer Entfernung herangeführt worden ist, dieses dann nach Gebrauch auch wieder schadlos beseitigt werden musste.

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.

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.

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.

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

Zum Problem der Hochschulreform in Spanien: Einige ausgewahlte Daten.

ERIC Educational Resources Information Center

Val, Jose Cajide; Philipp, Rita Radl; Castro, Ana Porto

1998-01-01

Investigates the teaching, research, and management entailed in four new degree programs--physics, agricultural engineering, agricultural food-processing technology, and pharmacy courses--at Spain's University of Santiago de Compostela. Reports students' opinions of reforms in these courses, revealing dissatisfaction with facilities for practical…

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.

Theoretische Konzepte der Physik

NASA Astrophysics Data System (ADS)

Longair, Malcolm S.; Simon, B.; Simon, H.

"Dies ist kein Lehrbuch der theoretischen Physik, auch kein Kompendium der Physikgeschichte ... , vielmehr eine recht anspruchsvolle Sammlung historischer Miniaturen zur Vergangenheit der theoretischen Physik - ihrer "Sternstunden", wenn man so will. Frei vom Zwang, etwas Erschöpfendes vorlegen zu müssen, gelingt dem Autor etwas Seltenes: einen "lebendigen" Zugang zum Ideengebäude der modernen Physik freizulegen, ... zu zeigen, wie Physik in praxi entsteht... Als Vehikel seiner Absichten dienen dem Autor geschichtliche Fallstudien, insgesamt sieben an der Zahl. Aus ihnen extrahiert er das seiner Meinung nach Lehrhafte, dabei bestrebt, mathematische Anachronismen womöglich zu vermeiden... Als Student hätte ich mir diese gescheiten Essays zum Werden unserer heutigen physikalischen Weltsicht gewünscht. Sie sind originell, didaktisch klug und genieren sich auch nicht, von der Faszination zu sprechen, die ... von der Physik ausgeht. Unnötig darauf hinzuweisen, das sie ein gründliches "konventionelles" Studium weder ersetzen wollen noch können, sie vermögen aber, dazu zu ermuntern." #Astronomische Nachrichten (zur englischen Ausgabe)#1

Quantensprung Digitalisierung - Energiewirtschaft im 21. Jahrhundert

NASA Astrophysics Data System (ADS)

Thyen, Elmar

Die Energiewende wird ohne eine umfassende Digitalisierung der Energiewirtschaft Stückwerk bleiben. Die historisch gewachsene, aus hunderten fossilen Großkraftwerken getriebene Energieversorgung hat sich durch den Zubau von mehr als einer Millionen dezentraler Erzeugungseinheiten innerhalb der vergangenen 15 Jahren radikal verändert. Zum Ausgleich von Last und Erzeugung, aber auch zum Aufbau neuer Geschäftsfelder ist die digitale Technik unverzichtbar. Ihre Möglichkeiten scheinen nahezu unbegrenzt, ihre Rolle wird in einer zukünftig nahezu vollständig elektrifizierten Gesellschaft zunehmend wichtiger werden. Neue Anbieter drängen auf den Markt und setzen die traditionelle Energiewirtschaft unter Druck. Energieversorger, die sich dem Wandel nicht stellen, drohen den Anschluss zu verpassen. Noch werden Verbundunternehmen und Stadtwerke von weitreichenden regulatorischen Vorgaben geschützt. Beispiele aus anderen Branchen zeigen aber, dass die Digitalisierung im Stande ist, regulatorische Mechanismen außer Kraft zu setzen. Zugleich verhindert die enge Regulierung und ein falsch verstandener Datenschutzbegriff in Deutschland die Entwicklung neuer Geschäftsmodelle, die energie- und volkswirtschaftlich sinnvoll wären.

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

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.

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.

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...

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.

Ein statistisches Modell zum Einfluß der thermischen Bewegung auf NMR-Festkörperspektren

NASA Astrophysics Data System (ADS)

Ploss, W.; Freude, D.; Pfeifer, H.; Schmiedel, H.

Es wird ein statistisches Modell zum Einfluß der thermischen Bewegung auf die NMR-Linienform vorgestellt, das die Verschmälerung von Festkörper-Spektren bei wachsender Temperatur beschreibt. Das Modell geht von der Annahme aus, daß nach einer Ortsveränderung eines Kerns infolge thermischer Bewegung jede beliebige Kernresonanzfrequenz mit der durch das Festkörperspektrum vorgegebenen Wahrscheinlichkeit angenommen werden kann. Am Beispiel der Festkörper-Gaußlinie wird der Unterschied zu dem bekannten Modell von ANDERSON und WEISS verdeutlicht.Translated AbstractA Statistical Model for the Influence of Thermal Motion on N. M. R. Spectra in SolidsA theory is proposed which allows to describe the narrowing of n. m. r.-line width in the presence of thermal motions of the spins. The model is based on the assumption, that the local resonance frequency of a given spin immediately after the jump is distributed according to the n. m. r.-line shape of the rigid lattice. The difference to the well-known ANDERSON-WEISS-model of spectral narrowing is demonstrated for a gaussian line shape.

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.

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.

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.

Oberflächenstrukturierung metallischer Werkstoffe, z. B. für stents

NASA Astrophysics Data System (ADS)

Stöver, Michael; Wintermantel, Erich

Eine topologische Oberflächenmodifikation von metallischen Implantaten kann aus verschiedenen Gründen sinnvoll sein. Im Allgemeinen lassen sich zwei Hauptziele unterscheiden. Zum einen dienen Oberflächen dazu, bestimmte Zellreaktionen zu forcieren. Die Anwendungsbeispiele reichen hier von sehr rauen Oberflächen in Fällen wo eine gute Integration eines Permanentimplantates in das Gewebe erwünscht ist bis hin zu glatt polierten Oberflächen. Letztere werden in erster Linie dort eingesetzt, wo das Implantat in direktem Kontakt mit Blut ist. Ein Beispiel für die Erforderlichkeit einer hohen Rauheit (Rz > 100 μm) sind meist aus Titan gefertigte Schäfte von Gelenksimplantaten [1,2]. Die Autoren machten den Vorschlag, die Aufrauung von Titan- und Edelstahl-Stents analog der Aufrauung bei Hüftprothesenschäften zu versuchen, um eine noch bessere Biokompatibilität zu erreichen. [7, 8 ,9]. Sehr glatte Oberflächen, in der Regel mit Rz Werten von unter 0,1 μm, sind z. B. bei Herzklappenprothesen und der Innenseite von Gefäßstützen gefordert. Mittlere Rauheiten werden oft bei temporären Implantaten eingesetzt, in die in reguliertem Maße Gewebe einwachsen, allerdings keine unlösbare Verbindung bilden sollen. Sehr genau eingestellt werden müssen auch die Oberflächentopographien bei Implantaten in sehr empfindlichen Gebieten wie z. B. der Gehirnregion. Hierbei muss eine gute Verankerung im Gewebe vorhanden sein, um ein Verrutschen des Implantates zu verhindern. Zum anderen darf keine überschüssige Zellproliferation entstehen, um ein Einwachsen in sensible Regionen zu verhindern. Zum anderen werden Oberflächenmikrostrukturen genutzt, um Wirkstoffe in Implantate einzubringen, die lokal über einen bestimmten Zeitraum freigesetzt werden sollen. Als wichtigste Wirkstoffe sind hier Antibiotika und entzündungshemmende Mittel sowie im kardiovaskulären Bereich Proliferationshemmer zu nennen.

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.

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.

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

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.

Zum Ausgleich von generativer und energetischer Sprachbetrachtung (A Comparison of the "Generative" and "Energetic" Views of Language)

ERIC Educational Resources Information Center

Weisgerber, Leo

1972-01-01

Discussion of two basic conceptions: Wilhelm von Humboldt's idea of language as energeia'' existing within and without man, and Noam Chomsky's idea of language generated by the speaker according to an innate apparatus. Revised version of lectures presented at the University of Bonn, West Germany in August 1971. (RS)

MODEL TESTS ON BALL LIGHTNING; Modellversuche zum Kugelblitz

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

nauer, H.

1959-10-31

Ball lightning phenomena and properties gleaned from a collection of observations are examined. The observations of a diffusion combustion of minute gas admixtures in air are thoroughly examined because they display the greatest resemblance to natural ball lightning. A comparison of properties with the qualities of the luminous clouds during diffusion combustion shows very good agreement. (W.D.M.)

Sylvia Plath: a protocol analysis of her last poems.

PubMed

Leenaars, A A; Wenckstern, S

1998-01-01

Personal documents have a significant place in psychological research. Suicide notes, diaries, novels, poems, and so on allow us to better understand the suicidal mind. The works of Sylvia Plath--a poet who killed herself at age 30--are prime examples for such protocol study. This article examines the last 6 months of Plath's poetry, revealing a suicidal malaise. Associating the results to the lives of Cesare Pavese and the case study of Natalie, a Terman-Shneidman subject of the intellectually gifted, the study shows a unit thema that facilitates the process of death. The poems reveal such themes as unbearable pain, loss, and abandonment that likely contributed significantly to death becoming the only solution.

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.

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).

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.

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.

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

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

Irradiation grafting of natural rubber latex with maleic anhydride and its compatibilization of poly(lactic acid)/natural rubber blends

NASA Astrophysics Data System (ADS)

Pongsathit, Siriwan; Pattamaprom, Cattaleeya

2018-03-01

Maleic anhydride (MA) is an interesting monomer to be grafted onto natural rubber(NR) due to its potential as a compatibilizer of hydrophobic rubbers and polymers with higher polarity. So far, radiation grafting of MA onto NR in latex state has not been reported. In this study, the grafting of NR with MA in latex state was investigated by exposing the latex to cobalt-60 gamma irradiation at a fixed MA content of 9% and a varied absorbed doses from 2 to 10 kGy. The FTIR spectrometer, 1H NMR spectrometer and gel content analysis have confirmed successful grafting of MA onto NR after irradiation. The grafted NRs were then used to increase the compatibility and the impact property of PLA/NR blends. It was found that the highest impact strength of the blends was achieved when the grafting was carried out at the absorbed dose of 4 kGy.

Beef and coal are key drivers of Australia’s high nitrogen footprint

NASA Astrophysics Data System (ADS)

Liang, Xia; Leach, Allison M.; Galloway, James N.; Gu, Baojing; Lam, Shu Kee; Chen, Deli

2016-12-01

Anthropogenic release of reactive nitrogen (Nr; all species of N except N2) to the global nitrogen (N) cycle is substantial and it negatively affects human and ecosystem health. A novel metric, the N footprint, provides a consumer-based perspective for Nr use efficiency and connects lifestyle choices with Nr losses. Here we report the first full-scale assessment of the anthropogenic Nr loss by Australians. Despite its ‘clean and green’ image, Australia has the largest N footprint (47 kg N cap-1 yr-1) both in food and energy sectors among all countries that have used the N-Calculator model. About 69% of the Australia’s N footprint is attributed to food consumption and the associated food production, with the rest from energy consumption. Beef consumption and production is the major contributor of the high food N footprint, while the heavy dependence on coal for electricity explains the large energy N footprint. Our study demonstrates opportunities for managing Nr loss and lifestyle choices to reduce the N footprint.

The Nuclear Orphan Receptor NR4A1 is Involved in the Apoptotic Pathway Induced by LPS and Simvastatin in RAW 264.7 Macrophages.

PubMed

Kim, Yong Chan; Song, Seok Bean; Lee, Sang Kyu; Park, Sang Min; Kim, Young Sang

2014-04-01

Macrophage death plays a role in several physiological and inflammatory pathologies such as sepsis and arthritis. In our previous work, we showed that simvastatin triggers cell death in LPS-activated RAW 264.7 mouse macrophage cells through both caspase-dependent and independent apoptotic pathways. Here, we show that the nuclear orphan receptor NR4A1 is involved in a caspase-independent apoptotic process induced by LPS and simvastatin. Simvastatin-induced NR4A1 expression in RAW 264.7 macrophages and ectopic expression of a dominant-negative mutant form of NR4A1 effectively suppressed both DNA fragmentation and the disruption of mitochondrial membrane potential (MMP) during LPS- and simvastatin-induced apoptosis. Furthermore, apoptosis was accompanied by Bcl-2-associated X protein (Bax) translocation to the mitochondria. Our findings suggest that NR4A1 expression and mitochondrial translocation of Bax are related to simvastatin-induced apoptosis in LPS-activated RAW 264.7 macrophages.

The effects of alkanolamide addition on cure characteristics, swelling behaviour and tensile properties of silica-filled natural rubber (NR) / chloroprene rubber (CR) blends

NASA Astrophysics Data System (ADS)

Surya, Indra; Fauzi Siregar, Syahrul; Ismail, Hanafi

2018-03-01

Effects of alkanolamide (ALK) addition on cure characteristics, swelling behaviour and tensile properties of silica-filled natural rubber (NR)/chloroprene rubber (CR) blends were investigated. The ALK was synthesized from Refined Bleached Deodorized Palm Stearin (RBDPS) and diethanolamine, and incorporated into the silica-filled NR/CR blends as a non-toxic rubber additive. The ALK loadings were 0.0, 1.0, 3.0, 5.0 and 7.0 phr. It was found that the ALK exhibited shorter scorch and cure times and higher elongation at break of the silica-filled NR/CR blends. The ALK also exhibited higher torque differences, tensile modulus and tensile strength at a 1.0 phr of ALK loading and then decreased with further increases in the ALK loading. The swelling measurement proved that the 1.0 phr loading of ALK caused the highest degree in crosslink density of the silica-filled NR/CR blends.

Identification of Novel Anti-mycobacterial Compounds by Screening a Pharmaceutical Small-Molecule Library against Nonreplicating Mycobacterium tuberculosis.

PubMed

Warrier, Thulasi; Martinez-Hoyos, Maria; Marin-Amieva, Manuel; Colmenarejo, Gonzalo; Porras-De Francisco, Esther; Alvarez-Pedraglio, Ana Isabel; Fraile-Gabaldon, Maria Teresa; Torres-Gomez, Pedro Alfonso; Lopez-Quezada, Landys; Gold, Ben; Roberts, Julia; Ling, Yan; Somersan-Karakaya, Selin; Little, David; Cammack, Nicholas; Nathan, Carl; Mendoza-Losana, Alfonso

2015-12-11

Identification of compounds that target metabolically diverse subpopulations of Mycobacterium tuberculosis (Mtb) may contribute to shortening the course of treatment for tuberculosis. This study screened 270,000 compounds from GlaxoSmithKline's collection against Mtb in a nonreplicating (NR) state imposed in vitro by a combination of four host-relevant stresses. Evaluation of 166 confirmed hits led to detailed characterization of 19 compounds for potency, specificity, cytotoxicity, and stability. Compounds representing five scaffolds depended on reactive nitrogen species for selective activity against NR Mtb, and two were stable in the assay conditions. Four novel scaffolds with activity against replicating (R) Mtb were also identified. However, none of the 19 compounds was active against Mtb in both NR and R states. There was minimal overlap between compounds found active against NR Mtb and those previously identified as active against R Mtb, supporting the hypothesis that NR Mtb depends on distinct metabolic pathways for survival.

A flexible and transparent graphene/ZnO nanorod hybrid structure fabricated by exfoliating a graphite substrate.

PubMed

Nam, Gwang-Hee; Baek, Seong-Ho; Cho, Chang-Hee; Park, Il-Kyu

2014-10-21

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.

77 FR 74817 - Approval and Promulgation of Air Quality Implementation Plans; Wisconsin; Disapproval of PM2.5

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-18

... hours of business are Monday through Friday, 8:30 a.m. to 4:30 p.m., excluding Federal holidays... to be Confidential Business Information (CBI) or other information whose disclosure is restricted by...) and (4m); (6) amend NR 405.02(25k)(intro.); (7) create NR 405.02(27)(a)5m in Table A; (8) amend NR 405...

Consequences of human modification of the global nitrogen cycle

PubMed Central

Erisman, Jan Willem; Galloway, James N.; Seitzinger, Sybil; Bleeker, Albert; Dise, Nancy B.; Petrescu, A. M. Roxana; Leach, Allison M.; de Vries, Wim

2013-01-01

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. PMID:23713116

PEGylated PAMAM dendrimer-doxorubicin conjugate-hybridized gold nanorod for combined photothermal-chemotherapy.

PubMed

Li, Xiaojie; Takashima, Munenobu; Yuba, Eiji; Harada, Atsushi; Kono, Kenji

2014-08-01

We prepared pH-sensitive drug-dendrimer conjugate-hybridized gold nanorod as a promising platform for combined cancer photothermal-chemotherapy under in vitro and in vivo conditions. Poly(ethylene glycol)-attached PAMAM G4 dendrimers (PEG-PAMAM) were first covalently linked on the surface of mercaptohexadecanoic acid-functionalized gold nanorod (MHA-AuNR), with subsequent conjugation of anti-cancer drug doxorubicin (DOX) to dendrimer layer using an acid-labile-hydrazone linkage to afford PEG-DOX-PAMAM-AuNR particles. The particles with a high PEG-PAMAM dendrimer coverage density (0.28 per nm(2) AuNR) showed uniform sizes and excellent colloidal stability. In vitro drug release studies demonstrated that DOX released from PEG-DOX-PAMAM-AuNR was negligible under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. The efficient intracellular acid-triggered DOX release inside of lysosomes was confirmed using confocal laser scanning microscopy analysis. Furthermore, the combined photothermal-chemo treatment of cancer cells using PEG-DOX-PAMAM-AuNR for synergistic hyperthermia ablation and chemotherapy was demonstrated both in vitro and in vivo to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of PEG-DOX-PAMAM-AuNR particles for cancer therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

nrDNA:mtDNA copy number ratios as a comparative metric for evolutionary and conservation genetics.

PubMed

Goodall-Copestake, William Paul

2018-05-12

Identifying genetic cues of functional relevance is key to understanding the drivers of evolution and increasingly important for the conservation of biodiversity. This study introduces nuclear ribosomal DNA (nrDNA) to mitochondrial DNA (mtDNA) copy number ratios as a metric with which to screen for this functional genetic variation prior to more extensive omics analyses. To illustrate the metric, quantitative PCR was used to estimate nrDNA (18S) to mtDNA (16S) copy number ratios in muscle tissue from samples of two zooplankton species: Salpa thompsoni caught near Elephant Island (Southern Ocean) and S. fusiformis sampled off Gough Island (South Atlantic). Average 18S:16S ratios in these samples were 9:1 and 3:1, respectively. nrDNA 45S arrays and mitochondrial genomes were then deep sequenced to uncover the sources of intra-individual genetic variation underlying these 18S:16S copy number differences. The deep sequencing profiles obtained were consistent with genetic changes resulting from adaptive processes, including an expansion of nrDNA and damage to mtDNA in S. thompsoni, potentially in response to the polar environment. Beyond this example from zooplankton, nrDNA:mtDNA copy number ratios offer a promising metric to help identify genetic variation of functional relevance in animals more broadly.

Effect of synthesized ZnO nanoparticles on thermal conductivity and mechanical properties of natural rubber

NASA Astrophysics Data System (ADS)

Suntako, R.

2018-01-01

Zinc oxide (ZnO) is widely used in rubber industry as a cure activator for rubber vulcanization. In this work, comparison of cure characteristic, mechanical properties, thermal conductivity and volume swell testing in oil no.1 and oil no.3 between natural rubber (NR) filled synthesized ZnO nanoparticles (sZnO) by precipitation method and NR filled conventional ZnO (cZnO). The particle size of sZnO is 41.50 nm and specific area of 27.92 m2/g, the particle size of cZnO is 312.92 nm and specific surface area of 1.35 m2/g. It has been found that NR filled sZnO not only improves rubber mechanical properties, volume swell testing but also improves thermal conductivity and better than NR filled cZnO. Thermal conductivity of NR filled sZnO increases by 10.34%, 12.90% and 20.00%, respectively when compared with NR filled cZnO in same loading content (various concentrations of ZnO at 5, 8 and 10 parts per hundred parts of rubber). This is due to small particle size and large specific surface area of sZnO which lead to an increase in crosslinking in rubber chain and enhance heat transfer performance.

Effects of volatile solvents on recombinant N-methyl-D-aspartate receptors expressed in Xenopus oocytes

PubMed Central

Cruz, Silvia L; Balster, Robert L; Woodward, John J

2000-01-01

We have previously shown that toluene dose-dependently inhibits recombinant N-methyl-D-aspartate (NMDA) receptors at micromolar concentrations. This inhibition was rapid, almost complete and reversible. The NR1/2B combination was the most sensitive receptor subtype tested with an IC50 value for toluene of 0.17 mM. We now report on the effects of other commonly abused solvents (benzene, m-xylene, ethylbenzene, propylbenzene, 1,1,1-trichlorethane (TCE) and those of a convulsive solvent, 2,2,2-trifluoroethyl ether (flurothyl), on NMDA-induced currents measured in Xenopus oocytes expressing NR1/2A or NR1/2B receptor subtypes. All of the alkylbenzenes and TCE produced a reversible inhibition of NMDA-induced currents that was dose- and subunit-dependent. The NR1/2B receptor subtype was several times more sensitive to these compounds than the NR1/2A subtype. The convulsant solvent flurothyl had no effect on NMDA responses in oocytes but potently inhibited ion flux through recombinant GABA receptors expressed in oocytes. Overall, these results suggest that abused solvents display pharmacological selectivity and that NR1/2B NMDA receptors may be an important target for the actions of these compounds on the brain. PMID:11090101

Nocardia rubra cell-wall skeleton promotes CD4+ T cell activation and drives Th1 immune response.

PubMed

Wang, Guangchuan; Wu, Jie; Miao, Miao; Dou, Heng; Nan, Ning; Shi, Mingsheng; Yu, Guang; Shan, Fengping

2017-08-01

Several lines of evidences have shown that Nocardia rubra cell wall skeleton (Nr-CWS) has immunoregulatory and anti-tumor activities. However, there is no information about the effect of Nr-CWS on CD4 + T cells. The aim of this study was to explore the effect of Nr-CWS on the phenotype and function of CD4 + T cells. Our results of in vitro experiments showed that Nr-CWS could significantly up-regulate the expression of CD69 and CD25 on CD4 + T cells, promote the proliferation of CD4 + T cells, increase the production of IFN-γ, TNF-α and IL-2 in the supernatants, but has no significant effect on the apoptosis and death of CD4 + T cells. Results of in vivo experiments showed that Nr-CWS could promote the proliferation of CD4 + T cells, and increase the production of IL-2, IFN-γ and TNF-α (Th1 type cytokines). These data suggest that Nr-CWS can enhance the activation of CD4 + T cells, promote the proliferation of CD4 + T cells and the differentiation of CD4 + T cells to Th1 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Activity-dependent shedding of the NMDA receptor glycine binding site by matrix metalloproteinase 3: a PUTATIVE mechanism of postsynaptic plasticity.

PubMed

Pauly, Thorsten; Ratliff, Miriam; Pietrowski, Eweline; Neugebauer, Rainer; Schlicksupp, Andrea; Kirsch, Joachim; Kuhse, Jochen

2008-07-16

Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS.

Activity-Dependent Shedding of the NMDA Receptor Glycine Binding Site by Matrix Metalloproteinase 3: A PUTATIVE Mechanism of Postsynaptic Plasticity

PubMed Central

Pietrowski, Eweline; Neugebauer, Rainer; Schlicksupp, Andrea; Kirsch, Joachim; Kuhse, Jochen

2008-01-01

Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS. PMID:18629001

Photopic Negative Response Obtained Using a Handheld Electroretinogram Device: Determining the Optimal Measure and Repeatability

PubMed Central

Wu, Zhichao; Hadoux, Xavier; Hui, Flora; Sarossy, Marc G.; Crowston, Jonathan G.

2016-01-01

Purpose To determine the measure of the photopic negative response (PhNR) of the full-field electroretinogram (ERG) that exhibits the optimal level of test-retest repeatability, and examine its repeatability under different conditions using a handheld, nonmydriatic ERG system and self-adhering skin electrodes. Methods Multiple ERG recordings (using 200 sweeps each) were performed in both eyes of 20 normal participants at two different sessions to compare its coefficient of repeatability (CoR; where 95% of the test-retest difference is expected to lie) between different PhNR measures and under different testing conditions (within and between examiners, and between sessions). Results The ratio between the PhNR trough to b-wave peak and b-wave peak to a-wave trough amplitude (PhNR/B ratio) exhibited the lowest CoR relative to its effective dynamic range (30 ± 4%) when including three recordings. There were no significant changes in the PhNR/B ratio over seven measurements (4 right and 3 left eyes) at either session (P ≥ 0.100), or significant difference in its CoR between different testing conditions (P = 0.314). Conclusion The PhNR/B ratio was the measure that minimized variability, and its measurements using a novel handheld ERG system with self-adhering skin electrodes and the protocols described in this study were comparable under different testing conditions and over multiple recordings. Translational Relevance The PhNR can be measured for clinical and research purposes using a simple-to-implement technique that is consistent within and between visits, and also between examiners. PMID:27540494

Immune-stimulatory and anti-inflammatory activities of Curcuma longa extract and its polysaccharide fraction

PubMed Central

Chandrasekaran, Chinampudur V.; Sundarajan, Kannan; Edwin, Jothie R.; Gururaja, Giligar M.; Mundkinajeddu, Deepak; Agarwal, Amit

2013-01-01

Background: While curcuminoids have been reported to possess diverse biological activities, the anti-inflammatory activity of polar extracts (devoid of curcuminoids) of Curcuma longa (C. longa) has seldom been studied. In this study, we have investigated immune-stimulatory and anti-inflammatory activities of an aqueous based extract of C. longa (NR-INF-02) and its fractions in presence and absence of mitogens. Materials and Methods: Effects of NR-INF-02 (Turmacin™, Natural Remedies Pvt. Ltd., Bangalore, India) on proliferation, nitric oxide (NO), monocyte chemotactic protein-1 (MCP-1), interleukins (ILs) and prostaglandin (PGE2) levels of mouse splenocytes and mouse macrophage (RAW264.7) cells were determined. Results: NR-INF-02 increased splenocytes number in presence and absence of lipopolysaccharide (LPS) or concanavalin A. Treatment of NR-INF-02 showed a significant increase of NO, IL-2, IL-6, IL-10, IL-12, interferon (IFN) gamma, tumor necrosis factor (TNF) alpha and MCP-1 production in unstimulated mouse splenocytes and mouse macrophages. Interestingly, NR-INF-02 showed potent inhibitory effect towards release of PGE2 and IL-12 levels in LPS stimulated mouse splenocytes. Further, NR-INF-02 was fractionated into polysaccharide fraction (F1) and mother liquor (F2) to study their immune-modulatory effects. F1 was found to be more potent than F2 toward inhibiting PGE2 and IL-12 in LPS stimulated splenocytes. Conclusion: Present findings revealed the novel anti-inflammatory property of NR-INF-02 and its polysaccharide fraction by inhibiting the secretion of IL-12 and PGE2 in vitro. PMID:23798880

Facile and green reduction of covalently PEGylated nanographene oxide via a `water-only' route for high-efficiency photothermal therapy

NASA Astrophysics Data System (ADS)

Chen, Jingqin; Wang, Xiaoping; Chen, Tongsheng

2014-02-01

A facile and green strategy is reported for the fabrication of nanosized and reduced covalently PEGylated graphene oxide (nrGO-PEG) with great biocompatibility and high near-infrared (NIR) absorbance. Covalently PEGylated nGO (nGO-PEG) was synthesized by the reaction of nGO-COOH and methoxypolyethylene glycol amine (mPEG-NH2). The neutral and purified nGO-PEG solution was then directly bathed in water at 90°C for 24 h without any additive to obtain nrGO-PEG. Covalent PEGylation not only prevented the aggregation of nGO but also dramatically promoted the reduction extent of nGO during this reduction process. The resulting single-layered nrGO-PEG sheets were approximately 50 nm in average lateral dimension and exhibited great biocompatibility and approximately 7.6-fold increment in NIR absorption. Moreover, this facile reduction process repaired the aromatic structure of GO. CCK-8 and flow cytometry (FCM) assays showed that exposure of A549 cells to 100 μg/mL of nrGO-PEG for 2 h, exhibiting 71.5% of uptake ratio, did not induce significant cytotoxicity. However, after irradiation with 808 nm laser (0.6 W/cm2) for 5 min, the cells incubated with 6 μg/mL of nrGO-PEG solution showed approximately 90% decrease of cell viability, demonstrating the high-efficiency photothermal therapy of nrGO-PEG to tumor cells in vitro. This work established nrGO-PEG as a promising photothermal agent due to its small size, great biocompatibility, high photothermal efficiency, and low cost.

A Conserved Acidic Motif in the N-Terminal Domain of Nitrate Reductase Is Necessary for the Inactivation of the Enzyme in the Dark by Phosphorylation and 14-3-3 Binding1

PubMed Central

Pigaglio, Emmanuelle; Durand, Nathalie; Meyer, Christian

1999-01-01

It has previously been shown that the N-terminal domain of tobacco (Nicotiana tabacum) nitrate reductase (NR) is involved in the inactivation of the enzyme by phosphorylation, which occurs in the dark (L. Nussaume, M. Vincentz, C. Meyer, J.P. Boutin, and M. Caboche [1995] Plant Cell 7: 611–621). The activity of a mutant NR protein lacking this N-terminal domain was no longer regulated by light-dark transitions. In this study smaller deletions were performed in the N-terminal domain of tobacco NR that removed protein motifs conserved among higher plant NRs. The resulting truncated NR-coding sequences were then fused to the cauliflower mosaic virus 35S RNA promoter and introduced in NR-deficient mutants of the closely related species Nicotiana plumbaginifolia. We found that the deletion of a conserved stretch of acidic residues led to an active NR protein that was more thermosensitive than the wild-type enzyme, but it was relatively insensitive to the inactivation by phosphorylation in the dark. Therefore, the removal of this acidic stretch seems to have the same effects on NR activation state as the deletion of the N-terminal domain. A hypothetical explanation for these observations is that a specific factor that impedes inactivation remains bound to the truncated enzyme. A synthetic peptide derived from this acidic protein motif was also found to be a good substrate for casein kinase II. PMID:9880364

Neural stem cells rescue nervous purkinje neurons by restoring molecular homeostasis of tissue plasminogen activator and downstream targets.

PubMed

Li, Jianxue; Imitola, Jaime; Snyder, Evan Y; Sidman, Richard L

2006-07-26

Neural stem cells (NSCs) offer special therapeutic prospects because they can be isolated from the CNS, expanded ex vivo, and re-implanted into diseased CNS where they not only migrate and differentiate according to cues from host tissue but also appear to be capable of affecting host cells. In nervous (nr) mutant mice Purkinje neuron (PN) mitochondria become abnormal by the second postnatal week, and a majority of PNs die in the fourth to fifth weeks. We previously identified in nr cerebellum a 10-fold increase in tissue plasminogen activator (tPA) as a key component of the mechanism causing nr PN death. Here we report that undifferentiated wild-type murine NSCs, when transplanted into the newborn nr cerebellar cortex, do not replace host PNs but contact imperiled PNs and support their mitochondrial function, dendritic growth, and synaptogenesis, subsequently leading to the rescue of host PNs and restoration of motor coordination. This protection of nr PNs also is verified by an in vitro organotypic slice model in which nr cerebellar slices are cocultured with NSCs. Most importantly, the integrated NSCs in young nr cerebellum rectify excessive tPA mRNA and protein to close to normal levels and protect the mitochondrial voltage-dependent anion channel and neurotrophins, downstream targets of the tPA/plasmin proteolytic system. This report demonstrates for the first time that NSCs can rescue imperiled host neurons by rectifying their gene expression, elevating somatic stem cell therapeutic potential beyond solely cell replacement strategy.

Relativistic effects for the reaction Sg + 6 CO → Sg(CO){sub 6}: Prediction of the mean bond energy, atomization energy, and existence of the first organometallic transactinide superheavy hexacarbonyl Sg(CO){sub 6}

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

Malli, Gulzari L., E-mail: malli@sfu.ca

2015-02-14

Our ab initio all-electron fully relativistic Dirac–Fock (DF) and nonrelativistic (NR) Hartree-Fock calculations predict the DF relativistic and NR energies for the reaction: Sg + 6 CO → Sg(CO){sub 6} as −7.39 and −6.96 eV, respectively, i.e., our calculated ground state total DF relativistic and NR energies for the reaction product Sg(CO){sub 6} are lower by 7.39 and 6.96 eV than the total DF and NR ground state energies of the reactants, viz., one Sg atom plus six CO molecules, respectively. Our calculated DF relativistic and NR atomization energies (Ae) are 65.23 and 64.82 eV, respectively, and so the contributionmore » of relativistic effects to the Ae of ∼0.40 eV is marginal. The Sg–C and C–O optimized bond distances for the octahedral geometry as calculated in our DF (NR) calculations are 2.151 (2.318 Å) and 1.119 (1.114 Å), respectively. The BSSE correction calculated using the DIRAC code ∼14 kcal/mol. The relativistic DF and NR mean energies predicted by us are 118.8 and 111.9 kJ/mol, respectively, and the contribution of ∼7 kJ/mol due to relativistic effects to the mean energy of Sg(CO){sub 6} is negligible. Ours are the first calculations of the relativistic effects for the atomization energy, mean bond energy, and energy of the reaction for possible formation of Sg(CO){sub 6}, and both our relativistic DF and the NR treatments clearly predict for the first time the existence of hexacarbonyl of the transactinide superheavy element seaborgium Sg. In conclusion, relativistic effects are not significant for Sg(CO){sub 6}.« less

Plasma long noncoding RNA expression profile identified by microarray in patients with Crohn's disease.

PubMed

Chen, Dong; Liu, Jiang; Zhao, Hui-Ying; Chen, Yi-Peng; Xiang, Zun; Jin, Xi

2016-05-21

To investigate the expression pattern of plasma long noncoding RNAs (lncRNAs) in Chrohn's disease (CD) patients. Microarray screening and qRT-PCR verification of lncRNAs and mRNAs were performed in CD and control subjects, followed by hierarchy clustering, GO and KEGG pathway analyses. Significantly dysregulated lncRNAs were categorized into subgroups of antisense lncRNAs, enhancer lncRNAs and lincRNAs. To predict the regulatory effect of lncRNAs on mRNAs, a CNC network analysis was performed and cross linked with significantly changed lncRNAs. The overlapping lncRNAs were randomly selected and verified by qRT-PCR in a larger cohort. Initially, there were 1211 up-regulated and 777 down-regulated lncRNAs as well as 1020 up-regulated and 953 down-regulated mRNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and AF113016 had the highest fold change of the up- and down-regulated lncRNAs, whereas TBC1D17 and CCL3L3 had the highest fold change of the up- and down-regulated mRNAs. Six (SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 mRNAs and 8 (NR_033913, NR_038218, NR_036512, NR_049759, NR_033951, NR_045408, NR_038377 and NR_039976) of 14 lncRNAs showed the same change trends on the microarray and qRT-PCR results with statistical significance. Based on the qRT-PCR verified mRNAs, 1358 potential lncRNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network. The plasma lncRNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lncRNA-mRNA pathway exploration.

Interactions between reactive nitrogen and the Canadian landscape: A budget approach

NASA Astrophysics Data System (ADS)

Clair, Thomas A.; Pelletier, Nathan; Bittman, Shabtai; Leip, Adrian; Arp, Paul; Moran, Michael D.; Dennis, Ian; Niemi, David; Sterling, Shannon; Drury, Craig F.; Yang, Jingyi

2014-11-01

The movement of excess reactive nitrogen (Nr) from anthropogenic activities to natural ecosystems has been described as one of the most serious environmental threats facing modern society. One of the approaches for tracking this movement is the use of budgets that quantify fluxes. We constructed an Nr budget for Canada using measured and modeled values from the scientific literature, government databases, and data from new agri-environmental indicators, in order to produce information for policy makers and scientists to understand the major flows of nitrogen to allow a better assessment of risks to the Canadian environment. We divided the Canadian territory south of 60°N into areas dominated by natural ecosystems, as well as by agricultural and urban/industrial activities to evaluate Nr flows within, between, and out of these units. We show that Canada is a major exporter of Nr due to the availability of inexpensive commercial fertilizers. The large land area suitable for agriculture makes Canada a significant agricultural Nr exporter of both grain crops and livestock. Finally, Canada exports petroleum N mainly to the United States. Because of its location and prevailing atmospheric transport patterns, Canada is a net receptor of Nr air pollution from the United States, receiving approximately 20% of the Nr leaving the U.S. airshed. We found that overall, terrestrial natural ecosystems as well as the atmosphere are in balance between Nr inputs and outputs when all N reactive and nonreactive fluxes are included. However, when only reactive forms are considered, almost 50% of N entering the Canadian atmosphere cannot be accounted for and is assumed to be lost to the Atlantic and Arctic oceans or to unmeasured dry deposition. However, agricultural and freshwater landscapes are showing large differences between measured inputs and outputs of N as our data suggest that denitrification in soils and aquatic systems is larger than what models predict. Our work also shows that Canada is a major contributor to the global flow of nitrogen through commercial exports.

Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog.

PubMed

Gram, Aykut; Trachsel, Alexandra; Boos, Alois; Kowalewski, Mariusz P

2016-10-01

The endocrine mechanisms that lead to initiation of parturition in dogs are still not fully understood. The prepartum luteolysis is associated with increased prostaglandin (PG) F2α secretion; however, there is no pregnancy- or parturition-related increase in estrogens. Moreover, unlike in other mammalian species, in the dog, increased peripartum levels of cortisol measured sporadically in maternal peripheral blood are not mandatory for normal parturition. Nevertheless, auto/paracrine effects of cortisol at the placental feto-maternal level cannot be excluded. Therefore, the aim of this study was to investigate the expression and localization of glucocorticoid receptor (GR/NR3C1) in canine utero/placental (Ut/Pl) units and uterine interplacental sites at selected time points during pregnancy (pre-implantation, post-implantation and mid-gestation), and at normal and antigestagen-induced parturition. The Ut/Pl expression of GR/NR3C1 did not change significantly from pre-implantation until mid-gestation; however, it was strongly induced during the prepartum luteolysis. Within the interplacental samples, expression of GR/NR3C1-mRNA was greater post-implantation than pre-implantation and did not change afterward, i.e. toward mid-gestation. Compartmentalization studies within the Ut/Pl units, involving placenta, endometrium and myometrium separately, performed at the prepartum luteolysis revealed the highest GR/NR3C1-mRNA levels in placenta compared with endometrium and myometrium. Interestingly, in antigestagen-treated mid-pregnancy dogs, Ut/Pl and interplacental GR/NR3C1-mRNA expression remained unaffected. At the cellular level, placental GR/NR3C1 was clearly detectable in placenta fetalis, i.e. in trophoblast cells. In conclusion, increased expression of GR/NR3C1 during normal parturition, but not following antigestagen-treatment, suggest that it is not required for initiating the signaling cascade of PG synthesis leading to the induction of parturition in the dog. © 2016 Society for Reproduction and Fertility.

Insulin-Like Growth Factor-I Regulates LH Release by Modulation of Kisspeptin and NMDA-Mediated Neurotransmission in Young and Middle-Aged Female Rats

PubMed Central

Yao, Dachun; Shu, Jun; Sun, Yan; Etgen, Anne M.

2014-01-01

This study investigated potential mechanisms by which age and IGF-I receptor (IGF-Ir) signaling in the neuroendocrine hypothalamus affect estradiol-positive feedback effects on GnRH neuronal activation and on kisspeptin and N-methyl-D-aspartate (NMDA)-induced LH release and on the abundance of NMDA receptor subunits Nr1 and Nr2b and Kiss1r transcript and protein in the hypothalamus of young and middle-aged female rats. We infused vehicle, IGF-I, or JB-1, a selective antagonist of IGF-Ir, into the third ventricle of ovariectomized female rats primed with estradiol or vehicle and injected with vehicle, kisspeptin (3 or 30 nmol/kg), or NMDA (15 or 30 mg/kg). Regardless of dose, NMDA and kisspeptin resulted in significantly more LH release, GnRH/c-Fos colabeling, and c-Fos immunoreative cells in young than in middle-aged females. Estradiol priming significantly increased Kiss1r, Nr1, and Nr2b receptor transcript and protein abundance in young but not middle-aged female hypothalamus. JB-1 attenuated kisspeptin and NMDA-induced LH release, numbers of GnRH/c-Fos and c-Fos cells, and Kiss1r, Nr1, and Nr2b transcript and protein abundance in young females to levels observed in middle-aged females. IGF-I significantly enhanced NMDA and kisspeptin-induced LH release in middle-aged females without increasing numbers of GnRH/c-Fos or c-Fos immunoreactive cells. IGF-I infusion in middle-aged females also increased Kiss1r, Nr1, and Nr2b protein and transcript to levels that were equivalent to young estradiol-primed females. These findings indicate that age-related changes in estradiol-regulated responsiveness to excitatory input from glutamate and kisspeptin reflect reduced IGF-Ir signaling. PMID:24617524

Sizing Determination Final Report

DTIC Science & Technology

1988-02-01

A Name: ERIC WHEATLEY Subject No.: 4 S/N: ------------ Sex.: M Race: BLACK Age...z:ni:zum Frcx-tal Arc - Tahc and -Marker Tool 19.= 6- - B-prozy.ncmatic_ ,’entlon Ar- - T"p_ and Marler Tool ......... .. 26.:; i7 Bitragion Mini-o-u- Frc...tape and Marler Tool ............. 24.5 7 . ilt’-aoion inigmu F-ontal Ar-c - -:•c= Oil- ---................... . ?.. S:-.-_,_ . ................. 1

Elektroakustische Wandler

NASA Astrophysics Data System (ADS)

Plaßmann, Wilfried

Um Sprache und Musik über größere Entfernungen zu übertragen, wird der Hörschall mit einem Mikrofon in ein proportionales elektrisches Signal umgewandelt und auf drahtlosem Wege (Beispiel Rundfunkübertragung) oder drahtgebunden (Beispiel Telefon, Kabelrundfunk, oft in Kombination mit dem drahtlosen Weg) zum Empfänger übermittelt. Am Empfangsort setzt z. B. ein Lautsprecher das elektrische Signal wieder in ein akustisches Signal um.

Forschungspolitik USA weisen zunehmend ausländische Physikstudenten ab

NASA Astrophysics Data System (ADS)

Bührke, Thomas

2003-11-01

In keinem anderen Land der Erde ist der Anteil ausländischer Studenten im Fach Physik größer als in den USA. Nach den Terroranschlägen vom 11. September werden jedoch zunehmend ausländische Studenten, insbesondere aus China und dem mittleren Osten, abgewiesen - zum Leidwesen der Studenten und der Universitäten.http://www.aip.org/statistics

Standardization Today and Tomorrow

DTIC Science & Technology

1998-05-01

products and for occupational safety and health protection, into a majority rule, the elaboration and adoption of directives was additionally speeded up...they contain. Safety standards serve to protect life, health and material goods and so, for the field of technology, express the requirements laid...p. 19, 13.02.1996 Press release 05-97: Entscheidung zum Arbeitsschutzmanagement (Decision on industrial safety management ) http://www.din.de

Bioindikation im Grundwasser funktioniert - Erwiderung zum Kommentar von T. Scheytt zum Beitrag "Grundwasserfauna als Indikator für komplexe hydrogeologische Verhältnisse am westlichen Kaiserstuhl" von Gutjahr, S., Bork, J. & Hahn, H.J. in Grundwasser 18 (3), 173-184 (2013)

NASA Astrophysics Data System (ADS)

Hahn, Hans Jürgen; Gutjahr, Simon

2014-09-01

In seinem Kommentar schließt Traugott Scheytt die faunistische Bioindikation über die Nutzung von Grundwassermessstellen aus methodischen Gründen aus. Er postuliert auch, dass die faunistische Indikation hydrogeologischer Zusammenhänge wegen der eingeschränkten Ausbreitungsfähigkeit der Tiere in Porengrundwasserleitern nicht möglich sei und stellt grundsätzlich die Befunde unserer Untersuchungen am Kaiserstuhl in Frage. Dabei überträgt Herr Scheytt seine Erfahrungen aus der unbelebten Hydrogeologie direkt auf den Lebensraum Grundwasser. Seine Argumentation berücksichtigt dabei weder die Prinzipien der Ökologie noch den aktuellen Stand der grundwasserökologischen Forschung. Wir gehen davon aus, dass für die Untersuchungen am Kaiserstuhl sowohl unsere Arbeitshypothese wie auch die angewandten Methoden und die Interpretation der Ergebnisse der Fragestellung angemessen sind und internationalem, wissenschaftlichem Standard entsprechen. Aus den oben benannten Gründen bleiben wir dabei: Biondikation im Grundwasser funktioniert und sie bietet hervorragende Möglichkeiten, gerade auch für die Hydrogeologie.

46 CFR Table 1 to Part 153 - Summary of Minimum Requirements

Code of Federal Regulations, 2011 CFR

2011-10-01

... Acetochlor A P II NR Open Open A .409 NA Acetone cyanohydrin A S/P II B/3 PV Closed A .238(a), .316, .336... Restr A .409, .525, .526, .1020 I-D Acrylamide solution (50% or less) D S II NR Open Closed NSR .409... .526 I-D Alachlor B S/P III NR Open Open A, C .238(a), .409, .440, .488, .908(a), (b) NA Alcohol (C6...

Preparation of Self-Assembled Chitin Nanofiber-Natural Rubber Composite Sheets and Porous Materials

PubMed Central

Kawano, Akito; Yamamoto, Kazuya

2017-01-01

We previously reported the preparation of a self-assembled chitin nanofiber (CNF) film via regeneration from an ion gel with an ionic liquid, followed by sonication and filtration. Based on the finding that CNFs were redispersed in a mixture of the film with ammonia aqueous solution (aq.), in this study, CNF-natural rubber (NR) composite sheets were fabricated by mixing redispersed CNF with NR latex stabilized by ammonia, followed by drying under reduced pressure. Tensile testing of the sheets indicated the reinforcing effect of CNFs. Further, CNF-NR composite porous materials were fabricated by evaporating ammonia from the CNF-NR dispersion, followed by lyophilization. The mechanism for the formation of porous structures was evaluated. PMID:28671578

Robust and biodegradable polymer of cassava starch and modified natural rubber.

PubMed

Riyajan, Sa-Ad

2015-12-10

The application of starch based materials for packaging purposes has attracted significant interest because they are both cheap and renewable resources. The study investigated the preparation and properties of a novel biopolymer sheet produced from a blend of maleated epoxidized natural rubber (MENR) and natural rubber-g-cassava starch (NR-g-CSt). The water resistance, toluene resistance and elongation at break of the polymer blend were enhanced after the addition of the MENR compared to pristine NR-g-CSt. The maximum tensile strength and thermal stability of the NR-g-CSt/MENR blend were found in the 100:50 NR-g-CSt:MENR blend. The novel films demonstrated good biodegradability in soil. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Effects of Ethanol on Phosphorylation Site Mutants of Recombinant NMDA Receptors

PubMed Central

Xu, Minfu; Smothers, Corigan T.; Woodward, John J.

2010-01-01

N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels activated by the neurotransmitter glutamate. These channels are highly expressed by brain neurons and are critically involved in excitatory synaptic transmission. Results from previous studies show that both native and recombinant NMDA receptors are inhibited by ethanol at concentrations associated with signs of behavioral impairment and intoxication. Given the important role that NMDA receptors play in synaptic transmission and brain function, it is important to understand the factors that regulate the ethanol inhibition of these receptors. One dynamic mechanism for regulating ethanol action may be via phosphorylation of NMDA subunits by serine-threonine and tyrosine kinases. Both NR1 and NR2 subunits contain multiple sites of phosphorylation and in the NR1 subunit, most of these are contained within the C1 domain, a carboxy-terminal cassette that is subject to alternative splicing. While results from our previous studies suggest that single phosphorylation sites do not greatly affect ethanol sensitivity of NMDA receptors, it is likely that in vivo, these subunits are phosphorylated at multiple sites by different kinases. In the present study, we constructed a series of NMDA receptor mutants at serine (S) or threonine (T) residues proposed to be sites of phosphorylation by PKA and various isoforms of PKC. Ethanol (100 mM) inhibited currents from wild-type NR1/2A and NR1/2B receptors expressed in HEK293 cells by approximately 25% and 30% respectively. This inhibition was not different in single site mutants expressing alanine (A) or aspartate/glutamate (D/E) at positions T879, S896 or T900. The mutant NR1(S890D) showed greater ethanol inhibition than NR1(890A) containing receptors although this was only observed when it was combined with the NR2A subunit. Ethanol inhibition was not altered by aspartate substitution at four serines (positions 889, 890, 896, 897) or when T879D was added to the four serine-substituted mutant. Ethanol inhibition was increased when T900E was added to the five serine/threonine substituted mutant but again this was selective for NR2A containing receptors. Together with previously published data, these findings suggest that modification of putative phosphorylation sites could contribute to the overall acute ethanol sensitivity of recombinant NMDA receptors. Supported by R37 AA009986. PMID:21163614

Insight into Factors Affecting the Presence, Degree, and Temporal Stability of Fluorescence Intensification on ZnO Nanorod Ends

PubMed Central

Singh, Manpreet; Jiang, Ruibin; Coia, Heidi; Choi, Daniel S.; Alabanza, Anginelle; Chang, Jae Young; Wang, Jianfang; Hahm, Jong-in

2014-01-01

We have carried out a combined experimental and simulation study identifying the key physical and optical parameters affecting the presence and degree of fluorescence intensification measured on zinc oxide nanorod (ZnO NR) ends. Previously, we reported on the highly localized, intensified, and prolonged fluorescence signal measured on the NR ends, termed as fluorescence intensification on NR ends (FINE). As a step towards understanding the mechanism of FINE, the present study aims to provide an insight into the unique optical phenomenon of FINE through experimental and simulation approaches and to elucidate the key factors affecting the occurrence, degree, and temporal stability of FINE. Specifically, we examined the effect of the length, width, and growth orientation of single ZnO NRs on the NR-enhanced biomolecular emission profile after decorating the NR surfaces with different amounts and types of fluorophore-coupled protein molecules. We quantitatively and qualitatively profiled the biomolecular fluorescence signal from individual ZnO NRs as a function of both position along the NR long axis and time. Regardless of the physical dimensions and growth orientations of the NRs, we confirmed the presence of FINE from all ZnO NRs tested by using a range of protein concentrations. We also showed that the manifestation of FINE is not dependent on the spectroscopic signatures of the fluorophores employed. We further observed that the degree of FINE is dependent on the length of the NR with longer NRs showing increased levels of FINE. We also demonstrated that vertically oriented NRs exhibit much stronger fluorescence intensity at the NR ends and a higher level of FINE than the laterally oriented NRs. Additionally, we employed finite-difference time-domain (FDTD) methods to understand the experimental outcomes and to promote our understanding of the mechanism of FINE. Particularly, we utilized the electrodynamic simulations to examine both near-field and far-field emission characteristics when considering various scenarios of fluorophore locations, polarizations, spectroscopic characteristics, and NR dimensions. Our efforts may provide a deeper insight into the unique optical phenomenon of FINE and further be beneficial to highly miniaturized biodetection favoring the use of single ZnO NRs in low-volume and high-throughput protein assays. PMID:25504319

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.

Paleolimnological records of nitrogen deposition in shallow, high-elevation lakes of Grand Teton National Park, Wyoming, USA

USGS Publications Warehouse

Spaulding, Sarah A.; Otu, Megan K.; Wolfe, Alexander P.; Baron, Jill S.

2015-01-01

Reactive nitrogen (Nr) from anthropogenic sources has been altering ecosystem function in lakes of the Rocky Mountains, other regions of western North America, and the Arctic over recent decades. The response of biota in shallow lakes to atmospheric deposition of Nr, however, has not been considered. Benthic algae are dominant in shallow, high-elevation lakes and are less sensitive to nutrient inputs than planktonic algae. Because the benthos is typically more nutrient rich than the water column, shallow lakes are not expected to show evidence of anthropogenic Nr. In this study, we assessed sedimentary evidence for regional Nr deposition, sediment chronology, and the nature of algal community response in five shallow, high-elevation lakes in Grand Teton National Park (GRTE). Over 140 diatom taxa were identified from the sediments, with a relatively high species richness of taxa characteristic of oligotrophic conditions. The diatom assemblages were dominated by benthic taxa, especially motile taxa. The GRTE lakes demonstrate assemblage-wide shifts in diatoms, including 1) synchronous and significant assemblage changes centered on ~1960 AD; 2) pre-1960 assemblages differed significantly from post-1960 assemblages; 3) pre-1960 diatom assemblages fluctuated randomly, whereas post- 1960 assemblages showed directional change; 4) changes in δ15N signatures were correlated with diatom community composition. These results demonstrate recent changes in shallow high18 elevation lakes that are most correlated with anthropogenic Nr. It is also possible, however, that the combined effect of Nr deposition and warming is accelerating species shifts in benthic diatoms. While uncertainties remain about the potential synergy of Nr deposition and warming, this study adds shallow lakes to the growing list of impacted high-elevation localities in western North America.

Transgenic Centipedegrass (Eremochloa ophiuroides [Munro] Hack.) Overexpressing S-Adenosylmethionine Decarboxylase (SAMDC) Gene for Improved Cold Tolerance Through Involvement of H2O2 and NO Signaling.

PubMed

Luo, Jianhao; Liu, Mingxi; Zhang, Chendong; Zhang, Peipei; Chen, Jingjing; Guo, Zhenfei; Lu, Shaoyun

2017-01-01

Centipedegrass ( Eremochloa ophiuroides [Munro] Hack.) is an important warm-season turfgrass species. Transgenic centipedgrass plants overexpressing S-adenosylmethionine decarboxylase from bermudagrass ( CdSAMDC1 ) that was induced in response to cold were generated in this study. Higher levels of CdSAMDC1 transcript and sperimidine (Spd) and spermin (Spm) concentrations and enhanced freezing and chilling tolerance were observed in transgenic plants as compared with the wild type (WT). Transgenic plants had higher levels of polyamine oxidase (PAO) activity and H 2 O 2 than WT, which were blocked by pretreatment with methylglyoxal bis (guanylhydrazone) or MGBG, inhibitor of SAMDC, indicating that the increased PAO and H 2 O 2 were a result of expression of CdSAMDC1 . In addition, transgenic plants had higher levels of nitrate reductase (NR) activity and nitric oxide (NO) concentration. The increased NR activity were blocked by pretreatment with MGBG and ascorbic acid (AsA), scavenger of H 2 O 2 , while the increased NO level was blocked by MGBG, AsA, and inhibitors of NR, indicating that the enhanced NR-derived NO was dependent upon H 2 O 2 , as a result of expression CdSAMDC1 . Elevated superoxide dismutase (SOD) and catalase (CAT) activities were observed in transgenic plants than in WT, which were blocked by pretreatment with MGBG, AsA, inhibitors of NR and scavenger of NO, indicating that the increased activities of SOD and CAT depends on expression of CdSAMDC1 , H 2 O 2 , and NR-derived NO. Our results suggest that the elevated cold tolerance was associated with PAO catalyzed production of H 2 O 2 , which in turn led to NR-derived NO production and induced antioxidant enzyme activities in transgenic plants.

Nucleus reuniens of the thalamus controls fear memory intensity, specificity and long-term maintenance during consolidation.

PubMed

Troyner, Fernanda; Bicca, Maira A; Bertoglio, Leandro J

2018-05-10

The thalamic nucleus reuniens (NR) has been shown to support bidirectional medial prefrontal cortex-hippocampus communication and synchronization relevant for cognitive processing. Using non-selective or prolonged inactivation of the NR, previous studies reported its activity positively modulates aversive memory consolidation. Here we examined the NR's role in consolidating contextual fear memories with varied strength, at both recent and more remote time points, using muscimol-induced temporary inactivation in rats. Results indicate the NR negatively modulates fear memory intensity, specificity and long-term maintenance. The more intense, generalized and enduring fear memory induced by NR inactivation during consolidation was also less prone to behavioral suppression by extinction or reconsolidation disruption induced by clonidine, an alpha-2 adrenergic receptor agonist. Lastly, we used immunohistochemistry for Arc protein, which is involved in synaptic modifications underlying aversive memory consolidation, to investigate whether treatment condition and/or conditioning status could change its levels in the NR, the hippocampus (dorsal and ventral CA1 subregions) and the medial prefrontal cortex (anterior cingulate, prelimbic and infralimbic subregions). Results indicate a significant imbalance in the number of Arc-expressing neurons in the brain areas investigated in muscimol fear conditioned animals when compared with controls. Collectively, present results provide convergent evidence for the NR's role as a hub regulating quantitative and qualitative aspects of a contextual fear memory during its consolidation that seem to influence the subsequent susceptibility to experimental interventions aiming at attenuating its expression. They also indicate the selectivity and duration of a given inactivation approach may influence its outcomes. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Characteristics of a root hair-less line of Arabidopsis thaliana under physiological stresses.

PubMed

Tanaka, Natsuki; Kato, Mariko; Tomioka, Rie; Kurata, Rie; Fukao, Yoichiro; Aoyama, Takashi; Maeshima, Masayoshi

2014-04-01

The plasma membrane-associated Ca(2+)-binding protein-2 of Arabidopsis thaliana is involved in the growth of root hair tips. Several transgenic lines that overexpress the 23 residue N-terminal domain of this protein under the control of the root hair-specific EXPANSIN A7 promoter lack root hairs completely. The role of root hairs under normal and stress conditions was examined in one of these root hair-less lines (NR23). Compared with the wild type, NR23 showed a 47% reduction in water absorption, decreased drought tolerance, and a lower ability to adapt to heat. Growth of NR23 was suppressed in media deficient in phosphorus, iron, calcium, zinc, copper, or potassium. Also, the content of an individual mineral in NR23 grown in normal medium, or in medium lacking a specific mineral, was relatively low. In wild-type plants, the primary and lateral roots produce numerous root hairs that become elongated under phosphate-deficient conditions; NR23 did not produce root hairs. Although several isoforms of the plasma membrane phosphate transporters including PHT1;1-PHT1;6 were markedly induced after growth in phosphate-deficient medium, the levels induced in NR23 were less than half those observed in the wild type. In phosphate-deficient medium, the amounts of acid phosphatase, malate, and citrate secreted from NR23 roots were 38, 9, and 16% of the levels secreted from wild-type roots. The present results suggest that root hairs play significant roles in the absorption of water and several minerals, secretion of acid phosphatase(s) and organic acids, and in penetration of the primary roots into gels.

BDE-47 causes developmental retardation with down-regulated expression profiles of ecdysteroid signaling pathway-involved nuclear receptor (NR) genes in the copepod Tigriopus japonicus.

PubMed

Hwang, Dae-Sik; Han, Jeonghoon; Won, Eun-Ji; Kim, Duck-Hyun; Jeong, Chang-Bum; Hwang, Un-Ki; Zhou, Bingsheng; Choe, Joonho; Lee, Jae-Seong

2016-08-01

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is a persistent organic pollutant (POP) in marine environments. Despite its adverse effects (e.g. developmental retardation) in ecdysozoa, the effects of BDE-47 on transcription of ecdysteroid signaling pathway-involved-nuclear receptor (NR) genes and metamorphosis-related genes have not been examined in copepods. To examine the deleterious effect of BDE-47 on copepod molting and metamorphosis, BDE-47 was exposed to the harpacticoid copepod Tigriopus japonicus, followed by monitoring developmental retardation and transcriptional alteration of NR genes. The developmental rate was significantly inhibited (P<0.05) in response to BDE-47 and the agricultural insecticide gamma-hexachlorocyclohexane. Conversely, the ecdysteroid agonist ponasterone A (PoA) led to decreased molting and metamorphosis time (P<0.05) from the nauplius stage to the adult stage. In particular, expression profiles of all NR genes were the highest at naupliar stages 5-6 except for SVP, FTZ-F1, and HR96 genes. Nuclear receptor USP, HR96, and FTZ-F1 genes also showed significant sex differences (P<0.05) in gene expression levels over different developmental stages, indicating that these genes may be involved in vitellogenesis. NR gene expression patterns showed significant decreases (P<0.05) in response to BDE-47 exposure, implying that molting and metamorphosis retardation is likely associated with NR gene expression. In summary, BDE-47 leads to molting and metamorphosis retardation and suppresses transcription of NR genes. This information will be helpful in understanding the molting and metamorphosis delay mechanism in response to BDE-47 exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

GABA neurons are the major cell type of the nucleus reticularis thalami.

PubMed

Houser, C R; Vaughn, J E; Barber, R P; Roberts, E

1980-11-03

Glutamic acid decarboxylase (GAD), the synthesizing enzyme for the neurotransmitter gamma-aminobutyric acid (GABA), has been localized in a large number of neuronal somata within the nucleus reticularis thalami (NR) of rat brain by light microscopic immunocytochemical methods. GAD-positive staining of neuronal somata and proximal dendrites is observed in the NR of normal (untreated) rats, and this staining is substantially enhanced following colchicine injection into the lateral cerebral ventricle. GAD-positive neuronal cell bodies are prominent throughout the dorsoventral and rostrocaudal extents of the NR and, thus, form a band around the entire lateral aspect of the thalamus. In the lateral part of the NR, oval-shaped neurons with elongated GAD-positive dendritic processes are oriented parallel to the narrow axis of the NR and lie perpendicular to the penetrating fascicles of unstained thalamocortical and corticothalamic fibers. Semithin (2 micrometers) sections confirm that GAD-positive reaction product is contain within the cytoplasm of cell bodies and proximal dendrites. In addition, GAD-positive punctate structures, representing axon terminals, are present in the neuropil and, occasionally, are observed in close proximity to positively-stained neuronal somata. This finding suggests that GABA-mediated inhibition of GABA neurons may occur in the NR. The large number of GAD-positive cell bodies within the NR contrasts with a paucity of positively-stained somata in the more internally located thalamic nuclei. Within these nuclei, GAD-positive punctate structures that represent GABAergic synaptic sites are a characteristic feature. Since previous anatomical studies have demonstrated that a large proportion or reticularis neurons project into the thalamus, it is suggested that many of these GAD-positive punctate structures are the axon terminals of reticularis neurons. Through these projections, reticularis neurons may contribute to GABA-mediated inhibition within many of the thalamic nuclei.

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies

PubMed Central

Dalmau, Josep; Gleichman, Amy J; Hughes, Ethan G; Rossi, Jeffrey E; Peng, Xiaoyu; Lai, Meizan; Dessain, Scott K; Rosenfeld, Myrna R; Balice-Gordon, Rita; Lynch, David R

2008-01-01

Summary Background A severe form of encephalitis associated with antibodies against NR1–NR2 heteromers of the NMDA receptor was recently identified. We aimed to analyse the clinical and immunological features of patients with the disorder and examine the effects of antibodies against NMDA receptors in neuronal cultures. Methods We describe the clinical characteristics of 100 patients with encephalitis and NR1–NR2 antibodies. HEK293 cells ectopically expressing single or assembled NR1–NR2 subunits were used to determine the epitope targeted by the antibodies. Antibody titres were measured with ELISA. The effect of antibodies on neuronal cultures was determined by quantitative analysis of NMDA-receptor clusters. Findings Median age of patients was 23 years (range 5–76 years); 91 were women. All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased conciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation. 58 (59%) of 98 patients for whom results of oncological assessments were available had tumours, most commonly ovarian teratoma. Patients who received early tumour treatment (usually with immunotherapy) had better outcome (p=0.004) and fewer neurological relapses (p=0.009) than the rest of the patients. 75 patients recovered or had mild deficits and 25 had severe deficits or died. Improvement was associated with a decrease of serum antibody titres. The main epitope targeted by the antibodies is in the extracellular N-terminal domain of the NR1 subunit. Patients’ antibodies decreased the numbers of cell-surface NMDA receptors and NMDA-receptor clusters in postsynaptic dendrites, an effect that could be reversed by antibody removal. Interpretation A well-defined set of clinical characteristics are associated with anti-NMDA-receptor encephalitis. The pathogenesis of the disorder seems to be mediated by antibodies. PMID:18851928

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies.

PubMed

Dalmau, Josep; Gleichman, Amy J; Hughes, Ethan G; Rossi, Jeffrey E; Peng, Xiaoyu; Lai, Meizan; Dessain, Scott K; Rosenfeld, Myrna R; Balice-Gordon, Rita; Lynch, David R

2008-12-01

A severe form of encephalitis associated with antibodies against NR1-NR2 heteromers of the NMDA receptor was recently identified. We aimed to analyse the clinical and immunological features of patients with the disorder and examine the effects of antibodies against NMDA receptors in neuronal cultures. We describe the clinical characteristics of 100 patients with encephalitis and NR1-NR2 antibodies. HEK293 cells ectopically expressing single or assembled NR1-NR2 subunits were used to determine the epitope targeted by the antibodies. Antibody titres were measured with ELISA. The effect of antibodies on neuronal cultures was determined by quantitative analysis of NMDA-receptor clusters. Median age of patients was 23 years (range 5-76 years); 91 were women. All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased consciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation. 58 (59%) of 98 patients for whom results of oncological assessments were available had tumours, most commonly ovarian teratoma. Patients who received early tumour treatment (usually with immunotherapy) had better outcome (p=0.004) and fewer neurological relapses (p=0.009) than the rest of the patients. 75 patients recovered or had mild deficits and 25 had severe deficits or died. Improvement was associated with a decrease of serum antibody titres. The main epitope targeted by the antibodies is in the extracellular N-terminal domain of the NR1 subunit. Patients' antibodies decreased the numbers of cell-surface NMDA receptors and NMDA-receptor clusters in postsynaptic dendrites, an effect that could be reversed by antibody removal. A well-defined set of clinical characteristics are associated with anti-NMDA-receptor encephalitis. The pathogenesis of the disorder seems to be mediated by antibodies.

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.

Analysis of the combined effects of lanthanum and acid rain, and their mechanisms, on nitrate reductase transcription in plants.

PubMed

Xia, Binxin; Sun, Zhaoguo; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2017-04-01

Rare earth element (REE) pollution and acid rain are major global environmental concerns, and their spatial distributions overlap. Thus, both forms of pollution combine to act on plants. Nitrogen is important for plant growth, and nitrate reductase (NR) is a key plant enzyme that catalyzes nitrogen assimilation. Studying the combined effects of REEs and acid rain on plant nitrogen-based nutrients has important environmental significance. Here, soybean (Glycine max) plants, commonly used for toxicological studies, were exposed to lanthanum (La), a REE, and acid rain to study the NR activities and NR transcriptional levels in the roots. To explain how the pollution affected the NR transcriptional level, we simultaneously observed the contents of intracellular La and nutrient elements, protoplast morphology, membrane lipid peroxidation and intracellular pH. A combined treatment of 0.08mmol/L La and pH 4.5 acid rain increased the NR activity, decreased the NR transcriptional level, increased the intracellular nutrient elements' contents and caused deformations in membrane structures. Other combined treatments significantly decreased the aforementioned parameters and caused serious damage to the membrane structures. The variation in the amplitudes of combined treatments was greater than those of individual treatments. Compared with the control and individual treatments, combined treatments increased membrane permeability, the malondialdehyde content, and intracellular H + and La contents, and with an increasing La concentration or acid strength, the change in amplitude increased. Thus, the combined effects on NR gene transcription in soybean seedling roots were related to the intracellular nutrient elements' contents, protoplast morphology, membranous lipid peroxidation, intracellular pH and La content. Copyright © 2016 Elsevier Inc. All rights reserved.

Gd³⁺ Tethered Gold Nanorods for Combined Magnetic Resonance Imaging and Photo-Thermal Therapy.

PubMed

Pitchaimani, Arunkumar; Duong, Tuyen; Nguyen, Thanh; Maurmann, Leila; Key, Jaehong; Bossmann, Stefan H; Aryal, Santosh

2017-04-01

Near infrared (NIR) mediated photothermal therapy and magnetic resonance imaging (MRI) are promising treatment and imaging modalities in the field of cancer theranostics. Gold nanorods are the first choice of materials for NIR-mediated photothermal therapy due to their strong localized surface plasmon resonance (LSPR) at NIR region. Similarly, gadolinium based MRI contrast agents have an ability to increase the ionic and molecular relaxivity, thereby enhancing the solvent proton relaxation rate resulting in contrast enhancement. Herein, the effort has been made to engineer a dual front theranostic agent with combined photothermal and magnetic resonance imaging capacity using gadolinium tethered gold nanorods (Gd3+-AuNR). NIR-responsive gold nanorods were surface fabricated by means of Au-thiol interaction using a thiolated macrocyclic chelator that chelates Gd3+ ions, and further stabilized by thiolated polyethylene glycol (PEG-SH). The magnetic properties of the Gd3+-AuNR displayed an enhanced r 1 relaxivity of 12.1 mM–1s–1, with higher biological stability, and contrast enhancement in both solution state and in cell pellets. In-vitro (cell-free) and ex-vivo (on pig skin) analysis of the Gd3+-AuNR shows enhanced photothermal properties as equivalent to that of the raw AuNR. Furthermore, Gd3+-AuNR showed competent cellular entry and intracellular distribution as revealed by hyperspectral microscopy. In addition, Gd3+-AuNR also exhibits significant thermal ablation of B16–F10 cells in the presence of NIR. Thus, Gd3+-AuNR features a significant theranostic potential with combined photothermal and imaging modality, suggesting a great potential in anticancer therapy.

Regulation of the trigeminal NR1 subunit expression induced by inflammation of the temporomandibular joint region in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Mao, Jianren

2009-01-01

Expression of the N-methyl-d-aspartate (NMDA) receptor in trigeminal nuclei has been shown to play a role in the mechanisms of trigeminal pain. Here, we examined the hypothesis that the upregulation of the NR1 subunit of the NMDA receptor (NR1) in the trigeminal subnucleus caudalis (Sp5c) following inflammation of the temporomandibular joint (TMJ) region would be regulated by interleukin-6 (IL-6) and the nuclear factor-kappa B (NF-kappaB). Inflammation of a unilateral TMJ region was produced in rats by injecting 50mul of complete Freund's adjuvant (CFA) into a TMJ and adjacent tissues, which resulted in persistent pain behavior as assessed using algometer before (baseline) and on days 1, 3, and 7 after the CFA injection. The CFA injection also induced a significant upregulation of NR1 and NF-kappaB on days 3 and 7, and of IL-6 on days 1, 3, and 7, within the ipsilateral Sp5c, as compared with the sham TMJ injection group. Once daily intracisternal injection of an IL-6 antiserum or NF-kappaB inhibitor (PDTC) for 6 days, beginning on day 1 immediately after the CFA injection, prevented both the upregulation of NR1 in the ipsilateral Sp5C and pain behavior. Moreover, once daily intracisternal IL-6 administration for 6 days in naïve rats induced the NR1 upregulation and pain behavior similar to that after TMJ inflammation. These results indicate that the upregulation of IL-6 and NF-kappaB after inflammation of the unilateral TMJ region is a critical regulatory mechanism for the expression of NR1 in the ipsilateral Sp5c, which contributed to the development of TMJ pain behavior in rats.

The Effects of Memantine on Glutamic Receptor-Associated Nitrosative Stress in a Traumatic Brain Injury Rat Model.

PubMed

Wang, Che-Chuan; Wee, Hsiao-Yue; Hu, Chiao-Ya; Chio, Chung-Ching; Kuo, Jinn-Rung

2018-04-01

The main aim of this study is to elucidate whether the neuroprotective effect of memantine, a noncompetitive N-methyl-d-aspartate receptor 2B (NR2B) antagonist, affects neuronal nitrosative stress, apoptosis, and NR2B expression and improves functional outcomes. Immediately after the onset of fluid percussion traumatic brain injury (TBI), anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + memantine groups. TBI rats were treated with a memantine intraperitoneal injection dose of 20 mg/kg intraperitoneally and then 1 mg/kg every 12 hours intraperitoneally for 6 doses. The motor function, proprioception, infarction volume, and neuronal apoptosis were then measured. Immunofluorescence was used to evaluate astrogliosis, microgliosis, nitrosative stress, and NR2A and NR2B expression in cortical cells. All the parameters were assessed 72 hours after TBI. Compared with the sham-operated controls, the TBI-induced motor and proprioception deficits, and increased infraction volume after TBI were significantly attenuated by memantine therapy. The TBI-induced neuronal apoptosis, astrogliosis, and microgliosis, the numbers of neuronal NO synthase and 3-nitro-l-tyrosine expression in neurons, and inducible NO synthase expression in microglia and astrocyte cells in the ischemic cortex after TBI were significantly improved by memantine therapy. Simultaneously, without affecting the NR2A expression in neuronal cells, the NR2B expression significantly decreased after memantine therapy, as evaluated by an immunofluorescence stain. Intraperitoneal injection of memantine in the acute stage may ameliorate TBI in rats by affecting NR2B expression and decreasing neuronal apoptosis and nitrosative stress in the injured cortex. These effects might represent 1 mechanism by which functional recovery occurred. Copyright © 2018 Elsevier Inc. All rights reserved.

Notoginsenoside R1 attenuates glucose-induced podocyte injury via the inhibition of apoptosis and the activation of autophagy through the PI3K/Akt/mTOR signaling pathway

PubMed Central

Huang, Guodong; Zou, Bingyu; Lv, Jianzhen; Li, Tongyu; Huai, Guoli; Xiang, Shaowei; Lu, Shilong; Luo, Huan; Zhang, Yaping; Jin, Yi; Wang, Yi

2017-01-01

Injury to terminally differentiated podocytes contributes ignificantly to proteinuria and glomerulosclerosis. The aim of this study was to examine the protective effects of notoginsenoside R1 (NR1) on the maintenance of podocyte number and foot process architecture via the inhibition of apoptosis, the induction of autophagy and the maintenance pf podocyte biology in target cells. The effects of NR1 on conditionally immortalized human podocytes under high glucose conditions were evaluated by determining the percentage apoptosis, the percentage autophagy and the expression levels of slit diaphragm proteins. Our results revealed that NR1 protected the podocytes against high glucose-induced injury by decreasing apoptosis, increasing autophagy and by promoting cytoskeletal recovery. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was further investigated in order to elucidate the mechanisms responsible for the protective effects of NR1 on podocytes. Our data indicated that treatment with NR increased the phosphorylation levels of PI3K, Akt and mTOR, leading to the activation of the PI3K/Akt/mTOR signaling pathway in podocytes. To the best of our knowledge, this is the first in vitro study to demonstrate that NR1 protects podocytes by activating the PI3K/Akt/mTOR pathway. PMID:28112381

Nitrate Reductase Knockout Uncouples Nitrate Transport from Nitrate Assimilation and Drives Repartitioning of Carbon Flux in a Model Pennate Diatom[OPEN

PubMed Central

Smith, Sarah R.; McCrow, John P.; Tan, Maxine; Lichtle, Christian; Goodenough, Ursula; Bowler, Chris P.; Dupont, Christopher L.

2017-01-01

The ecological prominence of diatoms in the ocean environment largely results from their superior competitive ability for dissolved nitrate (NO3−). To investigate the cellular and genetic basis of diatom NO3− assimilation, we generated a knockout in the nitrate reductase gene (NR-KO) of the model pennate diatom Phaeodactylum tricornutum. In NR-KO cells, N-assimilation was abolished although NO3− transport remained intact. Unassimilated NO3− accumulated in NR-KO cells, resulting in swelling and associated changes in biochemical composition and physiology. Elevated expression of genes encoding putative vacuolar NO3− chloride channel transporters plus electron micrographs indicating enlarged vacuoles suggested vacuolar storage of NO3−. Triacylglycerol concentrations in the NR-KO cells increased immediately following the addition of NO3−, and these increases coincided with elevated gene expression of key triacylglycerol biosynthesis components. Simultaneously, induction of transcripts encoding proteins involved in thylakoid membrane lipid recycling suggested more abrupt repartitioning of carbon resources in NR-KO cells compared with the wild type. Conversely, ribosomal structure and photosystem genes were immediately deactivated in NR-KO cells following NO3− addition, followed within hours by deactivation of genes encoding enzymes for chlorophyll biosynthesis and carbon fixation and metabolism. N-assimilation pathway genes respond uniquely, apparently induced simultaneously by both NO3− replete and deplete conditions. PMID:28765511

Role of Fyn-mediated NMDA receptor function in prediabetic neuropathy in mice

PubMed Central

Suo, Meng; Wang, Ping

2016-01-01

Diabetic neuropathy is a common complication of diabetes. This study evaluated the role of Fyn kinase and N-methyl-d-aspartate receptors (NMDARs) in the spinal cord in diabetic neuropathy using an animal model of high-fat diet-induced prediabetes. We found that prediabetic wild-type mice exhibited tactile allodynia and thermal hypoalgesia after a 16-wk high-fat diet, relative to normal diet-fed wild-type mice. Furthermore, prediabetic wild-type mice exhibited increased tactile allodynia and thermal hypoalgesia at 24 wk relative to 16 wk. Such phenomena were correlated with increased expression and activation of NR2B subunit of NMDARs, as well as Fyn-NR2B interaction in the spinal cord. Fyn−/− mice developed prediabetes after 16-wk high-fat diet treatment and exhibited thermal hypoalgesia, without showing tactile allodynia or altered expression and activation of NR2B subunit, relative to normal diet-fed Fyn−/− mice. Finally, intrathecal administrations of Ro 25-6981 (selective NR2B subunit-containing NMDAR antagonist) dose-dependently alleviated tactile allodynia, but not thermal hypoalgesia, at 16 and 24 wk in prediabetic wild-type mice. Our results suggested that Fyn-mediated NR2B signaling plays a critical role in regulation of prediabetic neuropathy and that the increased expression/function of NR2B subunit-containing NMDARs may contribute to the progression of neuropathy in type 2 diabetes. PMID:27146985

An insight of in vitro transport of PEGylated non-ionic surfactant vesicles (NSVs) across the intestinal polarized enterocyte monolayers.

PubMed

Primavera, Rosita; Palumbo, Paola; Celia, Christian; Cinque, Benedetta; Carata, Elisabetta; Carafa, Maria; Paolino, Donatella; Cifone, Maria Grazia; Di Marzio, Luisa

2018-06-01

PEGylated non-ionic surfactant-based vesicles (NSVs) are promising drug delivery systems for the local, oral and systemic administrations of therapeutics. The aim of this study was to test the cellular biocompatibility and transport of Nile Red-loaded NSVs (NR-NSVs) across the Caco-2-cell monolayers, which represent an in vitro model of human intestinal epithelium. The NR-NSVs assumed a spherical shape with a mean size of 140 nm, and a narrow size distribution. The NR-NSVs did not modify Caco-2 cell viability, which remained unaltered in vitro up to a concentration of 1 mM. The transport studies demonstrated that the NR-NSVs moved across the Caco-2 monolayers without affecting the transepithelial electrical resistance. These results were supported by flow cytometry analysis, which demonstrated that NR-NSVs were internalized inside the Caco-2 cells. Nanoparticle tracking and Transmission Electron Microscopy (TEM) analysis showed the presence of NR-NSVs in the basolateral side of the Caco-2 monolayers. TEM images also showed that NSVs were transported intact across the Caco-2 monolayers, thus demonstrating a predominant transcytosis mechanism of transport through endocytosis. The NSVs did not affect the integrity of the membrane barrier in vitro, and can potentially be used in clinics to increase the oral bioavailability and delivery of therapeutics. Copyright © 2018 Elsevier B.V. All rights reserved.

Fast biodegradation of toxic bisphenol a by Pseudomonas aeruginosa NR.22 (Ps.NR.22) isolated from Malaysian local lake

NASA Astrophysics Data System (ADS)

Him, Nik Raikhan Nik; Zainuddin, Mohammad Fiqri; Basha, Anuar Zain Anuar

2017-12-01

The paper focused on microbial degradation of Bisphenol A (BPA) as a safe and fast method to reduce BPA contamination in water. BPA is found in waste water, sea water and home water pipeline and it is nondegradable pollutant. Biodegradation is suggested to be practical solution for large volume of BPA. Biodegradation plays an important role and the effect of low concentration significantly decreased the degradation rate. Pseudomonas aeruginosa NR.22 (Ps.NR.22) which has been isolated from a lake at Seksyen 2, Shah Alam, was used. In Malaysia, Ps.NR.22 isolation agar is used for the BPA degradation process. It was stained with Gram negative-rod shaped bacteria that confirmed to carry a 16S rRNA gene. BPA as a sole carbon has been tested at various concentrations. The research showed that BPA was degraded at 10, 20, 30, 40 and 50 ppm and the bacteria growth rate was excellent in 20 ppm BPA. Degradation of BPA was carried out for 9 hours to 18 hours and the maximum degradation was recorded at 9 hours. The value of the highest peak of growth at 540 nm was 2.0617 using 20 ppm BPA. This novel Pseudomonas aeruginosa NR.22 has great potential to be used in waste water treatment.

Nitrate Reductase Knockout Uncouples Nitrate Transport from Nitrate Assimilation and Drives Repartitioning of Carbon Flux in a Model Pennate Diatom

DOE PAGES

McCarthy, James K.; Smith, Sarah R.; McCrow, John P.; ...

2017-09-07

The ecological prominence of diatoms in the ocean environment largely results from their superior competitive ability for dissolved nitrate (NO 3 -). To investigate the cellular and genetic basis of diatom NO 3 - assimilation, in this paper we generated a knockout in the nitrate reductase gene (NR-KO) of the model pennate diatom Phaeodactylum tricornutum. In NR-KO cells, N-assimilation was abolished although NO 3 - transport remained intact. Unassimilated NO 3 - accumulated in NR-KO cells, resulting in swelling and associated changes in biochemical composition and physiology. Elevated expression of genes encoding putative vacuolar NO 3 - chloride channel transportersmore » plus electron micrographs indicating enlarged vacuoles suggested vacuolar storage of NO 3 -. Triacylglycerol concentrations in the NR-KO cells increased immediately following the addition of NO 3 -, and these increases coincided with elevated gene expression of key triacylglycerol biosynthesis components. Simultaneously, induction of transcripts encoding proteins involved in thylakoid membrane lipid recycling suggested more abrupt repartitioning of carbon resources in NR-KO cells compared with the wild type. Conversely, ribosomal structure and photosystem genes were immediately deactivated in NR-KO cells following NO 3 - addition, followed within hours by deactivation of genes encoding enzymes for chlorophyll biosynthesis and carbon fixation and metabolism. Finally, N-assimilation pathway genes respond uniquely, apparently induced simultaneously by both NO 3 - replete and deplete conditions.« less

Solution Synthesis, Structure, and CO2 Reduction Reactivity of a Scandium(II) Complex, {Sc[N(SiMe3 )2 ]3 }.

PubMed

Woen, David H; Chen, Guo P; Ziller, Joseph W; Boyle, Timothy J; Furche, Filipp; Evans, William J

2017-02-13

The first crystallographically characterizable complex of Sc 2+ , [Sc(NR 2 ) 3 ] - (R=SiMe 3 ), has been obtained by LnA 3 /M reactions (Ln=rare earth metal; A=anionic ligand; M=alkali metal) involving reduction of Sc(NR 2 ) 3 with K in the presence of 2.2.2-cryptand (crypt) and 18-crown-6 (18-c-6) and with Cs in the presence of crypt. Dark maroon [K(crypt)] + , [K(18-c-6)] + , and [Cs(crypt)] + salts of the [Sc(NR 2 ) 3 ] - anion are formed, respectively. The formation of this oxidation state of Sc is also indicated by the eight-line EPR spectra arising from the I=7/2 45 Sc nucleus. The Sc(NR 2 ) 3 reduction differs from Ln(NR 2 ) 3 reactions (Ln=Y and lanthanides) in that it occurs under N 2 without formation of isolable reduced dinitrogen species. [K(18-c-6)][Sc(NR 2 ) 3 ] reacts with CO 2 to produce an oxalate complex, {K 2 (18-c-6) 3 }{[(R 2 N) 3 Sc] 2 (μ-C 2 O 4 -κ 1 O:κ 1 O'')}, and a CO 2 - radical anion complex, [(R 2 N) 3 Sc(μ-OCO-κ 1 O:κ 1 O')K(18-c-6)] n . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nitrate Reductase Knockout Uncouples Nitrate Transport from Nitrate Assimilation and Drives Repartitioning of Carbon Flux in a Model Pennate Diatom

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

McCarthy, James K.; Smith, Sarah R.; McCrow, John P.

The ecological prominence of diatoms in the ocean environment largely results from their superior competitive ability for dissolved nitrate (NO 3 -). To investigate the cellular and genetic basis of diatom NO 3 - assimilation, in this paper we generated a knockout in the nitrate reductase gene (NR-KO) of the model pennate diatom Phaeodactylum tricornutum. In NR-KO cells, N-assimilation was abolished although NO 3 - transport remained intact. Unassimilated NO 3 - accumulated in NR-KO cells, resulting in swelling and associated changes in biochemical composition and physiology. Elevated expression of genes encoding putative vacuolar NO 3 - chloride channel transportersmore » plus electron micrographs indicating enlarged vacuoles suggested vacuolar storage of NO 3 -. Triacylglycerol concentrations in the NR-KO cells increased immediately following the addition of NO 3 -, and these increases coincided with elevated gene expression of key triacylglycerol biosynthesis components. Simultaneously, induction of transcripts encoding proteins involved in thylakoid membrane lipid recycling suggested more abrupt repartitioning of carbon resources in NR-KO cells compared with the wild type. Conversely, ribosomal structure and photosystem genes were immediately deactivated in NR-KO cells following NO 3 - addition, followed within hours by deactivation of genes encoding enzymes for chlorophyll biosynthesis and carbon fixation and metabolism. Finally, N-assimilation pathway genes respond uniquely, apparently induced simultaneously by both NO 3 - replete and deplete conditions.« less

Atypical antibody responses in dengue vaccine recipients.

PubMed

Kanesa-Thasan, N; Sun, W; Ludwig, G V; Rossi, C; Putnak, J R; Mangiafico, J A; Innis, B L; Edelman, R

2003-12-01

Eight of 69 (12%) healthy adult volunteers vaccinated with monovalent live-attenuated dengue virus (DENV) vaccine candidates had atypical antibody responses, with depressed IgM:IgG antibody ratios and induction of high-titer hemagglutination-inhibiting and neutralizing (NT) antibodies to all four DENV serotypes. These features suggested flavivirus exposure prior to DENV vaccination, yet no volunteer had a history of previous flavivirus infection, flavivirus vaccination, or antibody to flaviviruses evident before DENV vaccination. Moreover, production of antibody to DENV by atypical responders (AR) was not accelerated compared with antibody responses in the 61 flavivirus-naive responders (NR). Further evaluation revealed no differences in sex, age, race, DENV vaccine candidate received, or clinical signs and symptoms following vaccination between AR and NR. However, viremia was delayed at the onset in AR compared with NR. A comparative panel of all AR and five randomly selected NR found flavivirus cross-reactive antibody after vaccination only in AR. Unexpectedly, six of eight AR had NT antibodies to yellow fever virus (YFV) > 1:10 before vaccination while NR had none (P = 0.04). The AR also universally demonstrated YFV NT antibody titers > or = 1:160 after DENV vaccination, whereas four of five NR failed to seroconvert (P = 0.02). Yellow fever virus priming broadens the antibody response to monovalent DENV vaccination. The effect of flavivirus priming on the clinical and immunologic response to tetravalent DENV vaccine remains to be determined.

The relationship between NMDA receptors and microwave-induced learning and memory impairment: a long-term observation on Wistar rats.

PubMed

Wang, Hui; Peng, Ruiyun; Zhao, Li; Wang, Shuiming; Gao, Yabing; Wang, Lifeng; Zuo, Hongyan; Dong, Ji; Xu, Xinping; Zhou, Hongmei; Su, Zhentao

2015-03-01

Abstract Purpose: To investigate whether high power microwave could cause continuous disorders to learning and memory in Wistar rats and to explore the underlying mechanisms. Eighty Wistar rats were exposed to a 2.856 GHz pulsed microwave source at a power density of 0 mW/cm(2) and 50 mW/cm(2) microwave for 6 min. The spatial memory ability, the structure of the hippocampus, contents of amino acids neurotransmitters in hippocampus and the expression of N-methyl-D-aspartic acid receptors (NMDAR) subunit 1, 2A and 2B (NR1, NR2A and NR2B) were detected at 1, 3, 6, 9, 12 and 18 months after microwave exposure. Our results showed that the microwave-exposed rats showed consistent deficiencies in spatial learning and memory. The level of amino acid neurotransmitters also decreased after microwave radiation. The ratio of glutamate (Glu) and gammaaminobutyric acid (GABA) significantly decreased at 6 months. Besides, the hippocampus showed varying degrees of degeneration of neurons, increased postsynaptic density and blurred synaptic clefts in the exposure group. The NR1 and NR2B expression showed a significant decrease, especially the NR2B expression. This study indicated that the content of amino acids neurotransmitters, the expression of NMDAR subunits and the variation of hippocampal structure might contribute to the long-term cognitive impairment after microwave exposure.

Pharmacogenetics of CYP1A2 activity and inducibility in smokers and exsmokers.

PubMed

Dobrinas, Maria; Cornuz, Jacques; Eap, Chin B

2013-05-01

There is a high interindividual variability in cytochrome P4501A2 (CYP1A2) activity and in its inducibility by smoking, only poorly explained by known CYP1A2 polymorphisms. We aimed to study the contribution of other regulatory pathways, including transcription factors and nuclear receptors, toward this variability. CYP1A2 activity was determined by the paraxanthine/caffeine ratio in 184 smokers and in 113 of them who were abstinent for 4 weeks. Participants were genotyped for 22 polymorphisms in 12 genes. A significant influence on CYP1A2 inducibility was observed for the NR1I3 rs2502815 (P=0.0026), rs4073054 (P=0.029), NR2B1 rs3818740 (P=0.0045), rs3132297 (P=0.036), AhR rs2282885 (P=0.040), rs2066853 (P=0.019), NR1I1 rs2228570 (P=0.037), and NR1I2 rs1523130 (P=0.044) polymorphisms. Among these, the NR1I3 rs2502815 (P=0.0045), rs4073054 (P=0.048), and NR2B1 rs3818740 (P=0.031) also influenced CYP1A2 basal activity. This is the first in-vivo demonstration of the influence of genes involved in CYP1A2 regulatory pathways on its basal activity and inducibility by smoking. These results need to be confirmed by other studies.

Affective Motives for Smoking Among Early Stage Smokers

PubMed Central

Wahlquist, Amy E.; Garrett-Mayer, Elizabeth; Gray, Kevin M.; Saladin, Michael E.; Carpenter, Matthew J.

2014-01-01

Background: As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence. Methods: Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16–20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerström Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS). Results: Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR − NR), such that higher dependence was associated with more prominent NR motives for smoking. Conclusions: Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers. PMID:24924155

Negative Allosteric Modulators Selective for The NR2B Subtype of The NMDA Receptor Impair Cognition in Multiple Domains

PubMed Central

Weed, Michael R; Bookbinder, Mark; Polino, Joseph; Keavy, Deborah; Cardinal, Rudolf N; Simmermacher-Mayer, Jean; Cometa, Fu-ni L; King, Dalton; Thangathirupathy, Srinivasan; Macor, John E; Bristow, Linda J

2016-01-01

Antidepressant activity of N-methyl-D-aspartate (NMDA) receptor antagonists and negative allosteric modulators (NAMs) has led to increased investigation of their behavioral pharmacology. NMDA antagonists, such as ketamine, impair cognition in multiple species and in multiple cognitive domains. However, studies with NR2B subtype-selective NAMs have reported mixed results in rodents including increased impulsivity, no effect on cognition, impairment or even improvement of some cognitive tasks. To date, the effects of NR2B-selective NAMs on cognitive tests have not been reported in nonhuman primates. The current study evaluated two selective NR2B NAMs, CP101,606 and BMT-108908, along with the nonselective NMDA antagonists, ketamine and AZD6765, in the nonhuman primate Cambridge Neuropsychological Test Automated Battery (CANTAB) list-based delayed match to sample (list-DMS) task. Ketamine and the two NMDA NR2B NAMs produced selective impairments in memory in the list-DMS task. AZD6765 impaired performance in a non-specific manner. In a separate cohort, CP101,606 impaired performance of the nonhuman primate CANTAB visuo-spatial Paired Associates Learning (vsPAL) task with a selective impairment at more difficult conditions. The results of these studies clearly show that systemic administration of a selective NR2B NAM can cause transient cognitive impairment in multiple cognitive domains. PMID:26105137

Carcass and meat quality of Assaf milk fed lambs: Effect of rearing system and sex.

PubMed

Rodríguez, A B; Landa, R; Bodas, R; Prieto, N; Mantecón, A R; Giráldez, F J

2008-10-01

The effect of sex and rearing system on growth and carcass and meat characteristics of milk fed Assaf lambs was studied. Thirty-six lambs, 18 males and 18 females were used. Twelve lambs remained with their mothers throughout the experiment (NR). Within 24-36h of birth, the rest were housed individually and fed twice a day ad libitum (AAR) or at 70% of ad libitum consumption (RAR) with reconstituted cow's milk. Sex did not affect animal performance, yet females showed higher carcass and non-carcass fat deposits. NR lambs showed greater BWG than AAR fed lambs, and AAR, higher than the RAR. Differences between naturally and artificially reared lambs in CCW and killing out percentage were not significant. Empty digestive tract and mesenteric fat weights were greater for RAR than NR lambs, with the AAR lambs demonstrating intermediate values; conversely, omental fat was greater in NR lambs. Carcass ether extract content was greater for NR lambs, possibly due to the greater growth. Use of ad libitum cow's milk substitute in suckling lambs twice a day resulted in less body weight gain but similar killing out percentages compared to naturally raised lambs. A 70% restricted supply increased the days in suckling and reduced carcass fatness and compactness. Except for water loss, which was less in NR than artificially fed lambs, no differences were found in meat characteristics.

[Difficulties medical care of persons placed under hand of justice].

PubMed

Brahmy, Betty

2013-01-01

The "contrôleur général des lieux de privation de liberté", french, national mechanism of prevention is an independant authorithy in charge of making sure since 2008 that rights of deprivation of freedom people--particularly access to health--are respected, in any place they are in captivity. The reports of the controllers present that the care of these persons is still a subject of concern as well for them--as the number of letters received by the Contrôleur général shows--as for professionals working in these places. The exercising of these health professionals in these institutions is a care mission to be done in a real partnership with the other actors.

Comparing post-Newtonian and numerical relativity precession dynamics

NASA Astrophysics Data System (ADS)

Ossokine, Serguei; Boyle, Michael; Kidder, Lawrence E.; Pfeiffer, Harald P.; Scheel, Mark A.; Szilágyi, Béla

2015-11-01

Binary black-hole systems are expected to be important sources of gravitational waves for upcoming gravitational-wave detectors. If the spins are not colinear with each other or with the orbital angular momentum, these systems exhibit complicated precession dynamics that are imprinted on the gravitational waveform. We develop a new procedure to match the precession dynamics computed by post-Newtonian (PN) theory to those of numerical binary black-hole simulations in full general relativity. For numerical relativity (NR) simulations lasting approximately two precession cycles, we find that the PN and NR predictions for the directions of the orbital angular momentum and the spins agree to better than ˜1 ° with NR during the inspiral, increasing to 5° near merger. Nutation of the orbital plane on the orbital time scale agrees well between NR and PN, whereas nutation of the spin direction shows qualitatively different behavior in PN and NR. We also examine how the PN equations for precession and orbital-phase evolution converge with PN order, and we quantify the impact of various choices for handling partially known PN terms.

Comparing Post-Newtonian and Numerical-Relativity Precession Dynamics

NASA Astrophysics Data System (ADS)

Kidder, Lawrence; Ossokine, Sergei; Boyle, Michael; Pfeiffer, Harald; Scheel, Mark; Szilagyi, Bela

2015-04-01

Binary black-hole systems are expected to be important sources of gravitational waves for upcoming gravitational-wave detectors. If the spins are not colinear with each other or with the orbital angular momentum, these systems exhibit complicated precession dynamics that are imprinted on the gravitational waveform. We develop a new procedure to match the precession dynamics computed by post-Newtonian (PN) theory to those of numerical binary black-hole simulations in full general relativity. For numerical relativity (NR) simulations lasting approximately two precession cycles, we find that the PN and NR predictions for the directions of the orbital angular momentum and the spins agree to better than ~1° with NR during the inspiral, increasing to 5° near merger. Nutation of the orbital plane on the orbital time-scale agrees well between NR and PN, whereas nutation of the spin direction shows qualitatively different behavior in PN and NR. We also examine how the PN equations for precession and orbital-phase evolution converge with PN order, and we quantify the impact of various choices for handling partially known PN terms.

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

Enyedi, A.J.; Pell, E.J.

Ozone (O{sub 3}) induced a reduction in quantity of rubisco in potato foliage. In vitro, O{sub 3} predisposed purified rubisco to elevated proteolysis; reagents which protected sulfhydryl (SH) groups suppressed this effect. We hypothesized that rubisco SH content correlated directly with foliar O{sub 3} sensitivity. Rubisco was purified from Solanum tuberosum L. O{sub 3}-tolerant cv. Superior (SP) and Norgold Russet (NR), and O{sub 3}-susceptible cv. Norland (NL) and Cherokee (CK). When native rubisco was titrated with DTNB, protein of NL contained 1.33 and 1.26 times more SH groups than SP and NR, respectively. Rubisco from CK also contained more SHmore » groups than SP and NR, but the difference was not significant. Rubisco of SP, NR and CK denatured by SDS exhibited identical number of SH groups, however, NL exhibited 1.15 times more SH groups. The greater number of SH groups in rubisco from NL versus SP and NR may explain its relative sensitivity to ozone. The role of SH groups in ozone-sensitivity of CK will require further study.« less

Effect of type and content of tackifier on adhesion of natural rubber and reclaimed natural rubber based sealant

NASA Astrophysics Data System (ADS)

Raethong, P.; Boonkerd, K.

2017-07-01

Adhesion property of natural rubber (NR) and reclaimed natural rubber (RNR) based sealant with concrete was studied here. The effect of tackifier type and loading on the tensile properties of the rubber based sealant sandwished between two flat cements was evaluated. There are three different tackifiers including Coumarone-indene resin (CI), petro resin (PE) and gum rosin (GR). The result initially showed that at the 20 phr of tackifier both NR and RNR sealant mixed with CI consumed the highest force to separate the rubber based sealant from the concrete. This might be due to the highest compatiblility between CI and rubber. Regardless of the tackifier type, all NR based sealants showed the cohesive failure while all RNR based sealants only showed the adhesive failure. Moreover, the NR based sealant seemed to be stronger than the RNR based one. When considering the effect of CI loading on the adhesion, it was shown that for both NR and RNR based sealents, the highest stress was observed when the rubber based sealant loaded with the 20 phr of CI.

The Economic Potential of Two Nuclear-Renewable Hybrid Energy Systems

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

Ruth, Mark; Cutler, Dylan; Flores-Espino, Francisco

Tightly coupled nuclear-renewable hybrid energy systems (N-R HESs) are an option that can generate zero-carbon, dispatchable electricity and provide zero-carbon energy for industrial processes at a lower cost than alternatives. N-R HESs are defined as systems that are managed by a single entity and link a nuclear reactor that generates heat, a thermal power cycle for heat to electricity conversion, at least one renewable energy source, and an industrial process that uses thermal and/or electrical energy. This report provides results of an analysis of two N-R HES scenarios. The first is a Texas-synthetic gasoline scenario that includes four subsystems: amore » nuclear reactor, thermal power cycle, wind power plant, and synthetic gasoline production technology. The second is an Arizona-desalination scenario with its four subsystems a nuclear reactor, thermal power cycle, solar photovoltaics, and a desalination plant. The analysis focuses on the economics of the N-R HESs and how they compare to other options, including configurations without all the subsystems in each N-R HES and alternatives where the energy is provided by natural gas.« less

Direct electrochemistry of nitrate reductase from the fungus Neurospora crassa.

PubMed

Kalimuthu, Palraj; Ringel, Phillip; Kruse, Tobias; Bernhardt, Paul V

2016-09-01

We report the first direct (unmediated) catalytic electrochemistry of a eukaryotic nitrate reductase (NR). NR from the filamentous fungus Neurospora crassa, is a member of the mononuclear molybdenum enzyme family and contains a Mo, heme and FAD cofactor which are involved in electron transfer from NAD(P)H to the (Mo) active site where reduction of nitrate to nitrite takes place. NR was adsorbed on an edge plane pyrolytic graphite (EPG) working electrode. Non-turnover redox responses were observed in the absence of nitrate from holo NR and three variants lacking the FAD, heme or Mo cofactor. The FAD response is due to dissociated cofactor in all cases. In the presence of nitrate, NR shows a pronounced cathodic catalytic wave with an apparent Michaelis constant (KM) of 39μM (pH7). The catalytic cathodic current increases with temperature from 5 to 35°C and an activation enthalpy of 26kJmol(-1) was determined. In spite of dissociation of the FAD cofactor, catalytically activity is maintained. Copyright © 2016. Published by Elsevier B.V.

Beef and coal are key drivers of Australia’s high nitrogen footprint

PubMed Central

Liang, Xia; Leach, Allison M.; Galloway, James N.; Gu, Baojing; Lam, Shu Kee; Chen, Deli

2016-01-01

Anthropogenic release of reactive nitrogen (Nr; all species of N except N2) to the global nitrogen (N) cycle is substantial and it negatively affects human and ecosystem health. A novel metric, the N footprint, provides a consumer-based perspective for Nr use efficiency and connects lifestyle choices with Nr losses. Here we report the first full-scale assessment of the anthropogenic Nr loss by Australians. Despite its ‘clean and green’ image, Australia has the largest N footprint (47 kg N cap−1 yr−1) both in food and energy sectors among all countries that have used the N-Calculator model. About 69% of the Australia’s N footprint is attributed to food consumption and the associated food production, with the rest from energy consumption. Beef consumption and production is the major contributor of the high food N footprint, while the heavy dependence on coal for electricity explains the large energy N footprint. Our study demonstrates opportunities for managing Nr loss and lifestyle choices to reduce the N footprint. PMID:28008979

Origin of phase shift in atomic force microscopic investigation of the surface morphology of NR/NBR blend film.

PubMed

Thanawan, S; Radabutra, S; Thamasirianunt, P; Amornsakchai, T; Suchiva, K

2009-01-01

Atomic force microscopy (AFM) was used to study the morphology and surface properties of NR/NBR blend. Blends at 1/3, 1/1 and 3/1 weight ratios were prepared in benzene and formed film by casting. AFM phase images of these blends in tapping mode displayed islands in the sea morphology or matrix-dispersed structures. For blend 1/3, NR formed dispersed phase while in blends 1/1 and 3/1 phase inversion was observed. NR showed higher phase shift angle in AFM phase imaging for all blends. This circumstance was governed by adhesion energy hysteresis between the device tip and the rubber surface rather than surface stiffness of the materials, as proved by force distance measurements in the AFM contact mode.

Zum Problem des Tests, insbesondere des Einstufungstests, im Deutschunterricht fuer Auslaender (On the Problem of Tests, Particularly Placement Tests, in Teaching German to Foreigners)

ERIC Educational Resources Information Center

Breitung, H. A.; And Others

1974-01-01

New placement procedure at Humboldt University includes interviews and placement tests. Interviews reveal response ability, tempo, pronunciation, comprehension, etc. The 60-minute test that follows is described and results discussed, as well as difficulty level and grading. Results: better grouping of students, less shifting, better work. (Text is…

Die Indirekte Rede als Diskursstrategie: Innovative Lehrmethoden zum Konjunktiv I (Indirect Speech as a Discourse Strategy: Innovative Teaching Methods for the Subjunctive).

ERIC Educational Resources Information Center

Gramberg, Anne-Kathrin; Heinze, Karin U.

1993-01-01

This article talks about the subjunctive of indirect speech, in which its important functions and meanings are depicted. An analysis of the instructional materials used in the first and second years of language study, followed by practical curriculum recommendations, demonstrates how this grammatical phenomenon can be established in an advanced…

Ergebnisse einer Lehrerbefragung zum Hintergrund des Englischunterrichts in der Hauptschuloberstufe (Results of a Teacher Questionnaire on the Background of Instruction in English in the Upper Grades of the Hauptschule [9-grade "terminal" school]).

ERIC Educational Resources Information Center

Hellwig, Karlheinz

1980-01-01

The questionnaire dealt with: earmarks of weaker students, parents' attitude, the teachers' training and working conditions, problems of individual instruction, time-frame, existence of professional associations, evaluation of professional conferences, and the use of media. Some evaluations are appended. (IFS/WGA)

Differences Between Tg2576 and Wild Type Mice in the NMDA Receptor-Nitric Oxide Pathway After Prolonged Application of a Diet High in Advanced Glycation End Products.

PubMed

Kristofikova, Zdena; Ricny, Jan; Sirova, Jana; Ripova, Daniela; Lubitz, Irit; Schnaider-Beeri, Michal

2015-08-01

It has been suggested that advanced glycation end (AGE) products, via cognate receptor activation, are implicated in several diseases, including Alzheimer's disease. The NMDA receptor-nitric oxide pathway appears to be influenced by AGE products and involved in the pathogenesis of this type of dementia. In this study, C57BL/6J (WT) and transgenic (Tg2576) mice expressing human mutant amyloid precursor protein were kept on prolonged (8 months) diets containing regular or high amounts of AGE products. After the decapitation of 11-months old mice, brain tissue analyses were performed [expressions of the NR1, NR2A and NR2B subunits of NMDA receptors, activities of neuronal, endothelial and inducible nitric oxide synthase (nNOS, eNOS and iNOS)]. Moreover, levels of malondialdehyde and of human amyloid β 1-42 were estimated. We found increased activity of nNOS in WT mice maintained on a high compared to regular AGE diet; however, no similar differences were found in Tg2576 mice. In addition, we observed an increase in NR1 expression in Tg2576 compared to WT mice, both kept on a diet high in AGE products. Correlation analyses performed on mice kept on the regular AGE diet supported close links between particular subunits (NR2A-NR2B, in WT as well as in Tg2576 mice), between subunits and synthase (NR2A/NR2B-nNOS, only in WT mice) or between particular synthases (nNOS-iNOS, only in WT). Correlation analysis also revealed differences between WT mice kept on both diets (changed correlations between NR2A/NR2B-nNOS, between nNOS-eNOS and between eNOS-iNOS). Malondialdehyde levels were increased in both Tg2576 groups when compared to the corresponding WT mice, but no effects of the diets were observed. Analogously, no significant effects of diets were found in the levels of soluble or insoluble amyloid β 1-42 in Tg2576 mice. Our results demonstrate that prolonged ingestion of AGE products can influence the NMDA receptor-nitric oxide pathway in the brain and that only WT mice, not Tg2576 mice, are able to maintain homeostasis among subunits and synthases or among particular synthases. The prolonged application of AGE products enhanced differences between 11-months old Tg2576 and WT mice regarding this pathway. Observed differences in the pathway between WT mice kept on regular or high AGE diets suggest that the prolonged application of a diet low in AGE products could have beneficial effects in older or diabetic people and perhaps also in people with Alzheimer's disease.

Limited radiographic progression and sustained reductions in MRI inflammation in patients with axial spondyloarthritis: 4-year imaging outcomes from the RAPID-axSpA phase III randomised trial.

PubMed

van der Heijde, Désirée; Baraliakos, Xenofon; Hermann, Kay-Geert A; Landewé, Robert B M; Machado, Pedro M; Maksymowych, Walter P; Davies, Owen R; de Peyrecave, Natasha; Hoepken, Bengt; Bauer, Lars; Nurminen, Tommi; Braun, Juergen

2018-05-01

To report 4-year imaging outcomes in the RAPID-axSpA (NCT01087762) study of patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA), treated with certolizumab pegol (CZP). This phase III, randomised trial was placebo-controlled and double-blind to week 24, dose-blind to week 48 and open-label to week 204. Patients fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axSpA criteria with active disease were stratified (AS/nr-axSpA) according to the modified New York (mNY) criteria at randomisation. Spinal radiographs were assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). MRI inflammation used the Spondyloarthritis Research Consortium of Canada (SPARCC) score for sacroiliac joints (SIJ) and the Berlin spinal score (remission defined as SPARCC <2 and Berlin ≤2, respectively). MRI improvements from baseline (BL) to week 12 were maintained to week 204 (SPARCC BL: AS=8.5, nr-axSpA=7.5; SPARCC week 204: AS=1.3, nr-axSpA=2.4; Berlin BL: AS=7.4, nr-axSpA=4.4; Berlin week 204: AS=2.6, nr-axSpA=1.9). 66.7% of patients with AS and 69.6% of patients with nr-axSpA with BL SPARCC scores ≥2, and 65.4% of patients with AS and 57.3% of patients with nr-axSpA with BL Berlin score >2, achieved remission at week 204. Mean mSASSS change in AS from BL to week 204 was 0.98 (95% CI 0.34, 1.63); 0.67 (95% CI 0.21,1.13) from BL to week 96; and 0.31 (95% CI 0.02,0.60) from week 96 to week 204. Corresponding nr-axSpA changes were 0.06 (95% CI -0.17,0.28), -0.01 (95% CI -0.19,0.17) and 0.07 (95% CI -0.07,0.20). 4.5% of patients with nr-axSpA fulfilled the mNY criteria at week 204, while 4.3% of patients with AS no longer did so. In patients with CZP-treated axSpA, rapid decreases in spinal and SIJ MRI inflammation were maintained to week 204. Overall, 4-year spinal progression was low, with less progression during years 2-4 than 0-2. Radiographic SIJ grading changes demonstrated limited progression. NCT01087762; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

75 FR 2929 - Proposed Collection; Comment Request for Form 13614-NR

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... comments concerning Form 13614-NR, Nonresident Alien Intake and Interview Sheet. DATES: Written [email protected] . SUPPLEMENTARY INFORMATION: Title: Nonresident Alien Intake and Interview Sheet. OMB...

High spatial resolution free-breathing 3D late gadolinium enhancement cardiac magnetic resonance imaging in ischaemic and non-ischaemic cardiomyopathy: quantitative assessment of scar mass and image quality.

PubMed

Bizino, Maurice B; Tao, Qian; Amersfoort, Jacob; Siebelink, Hans-Marc J; van den Bogaard, Pieter J; van der Geest, Rob J; Lamb, Hildo J

2018-04-06

To compare breath-hold (BH) with navigated free-breathing (FB) 3D late gadolinium enhancement cardiac MRI (LGE-CMR) MATERIALS AND METHODS: Fifty-one patients were retrospectively included (34 ischaemic cardiomyopathy, 14 non-ischaemic cardiomyopathy, three discarded). BH and FB 3D phase sensitive inversion recovery sequences were performed at 3T. FB datasets were reformatted into normal resolution (FB-NR, 1.46x1.46x10mm) and high resolution (FB-HR, isotropic 0.91-mm voxels). Scar mass, scar edge sharpness (SES), SNR and CNR were compared using paired-samples t-test, Pearson correlation and Bland-Altman analysis. Scar mass was similar in BH and FB-NR (mean ± SD: 15.5±18.0 g vs. 15.5±16.9 g, p=0.997), with good correlation (r=0.953), and no bias (mean difference ± SD: 0.00±5.47 g). FB-NR significantly overestimated scar mass compared with FB-HR (15.5±16.9 g vs 14.4±15.6 g; p=0.007). FB-NR and FB-HR correlated well (r=0.988), but Bland-Altman demonstrated systematic bias (1.15±2.84 g). SES was similar in BH and FB-NR (p=0.947), but significantly higher in FB-HR than FB-NR (p<0.01). SNR and CNR were lower in BH than FB-NR (p<0.01), and lower in FB-HR than FB-NR (p<0.01). Navigated free-breathing 3D LGE-CMR allows reliable scar mass quantification comparable to breath-hold. During free-breathing, spatial resolution can be increased resulting in improved sharpness and reduced scar mass. • Navigated free-breathing 3D late gadolinium enhancement is reliable for myocardial scar quantification. • High-resolution 3D late gadolinium enhancement increases scar sharpness • Ischaemic and non-ischaemic cardiomyopathy patients can be imaged using free-breathing LGE CMR.

Nitrogen-source preference in blueberry (Vaccinium sp.): Enhanced shoot nitrogen assimilation in response to direct supply of nitrate.

PubMed

Alt, Douglas S; Doyle, John W; Malladi, Anish

2017-09-01

Blueberry (Vaccinium sp.) is thought to display a preference for the ammonium (NH 4 + ) form over the nitrate (NO 3 - ) form of inorganic nitrogen (N). This N-source preference has been associated with a generally low capacity to assimilate the NO 3 - form of N, especially within the shoot tissues. Nitrate assimilation is mediated by nitrate reductase (NR), a rate limiting enzyme that converts NO 3 - to nitrite (NO 2 - ). We investigated potential limitations of NO 3 - assimilation in two blueberry species, rabbiteye (Vaccinium ashei) and southern highbush (Vaccinium corymbosum) by supplying NO 3 - to the roots, leaf surface, or through the cut stem. Both species displayed relatively low but similar root uptake rates for both forms of inorganic N. Nitrate uptake through the roots transiently increased NR activity by up to 3.3-fold and root NR gene expression by up to 4-fold. However, supplying NO 3 - to the roots did not increase its transport in the xylem, nor did it increase NR activity in the leaves, indicating that the acquired N was largely assimilated or stored within the roots. Foliar application of NO 3 - increased leaf NR activity by up to 3.5-fold, but did not alter NO 3 - metabolism-related gene expression, suggesting that blueberries are capable of post translational regulation of NR activity in the shoots. Additionally, supplying NO 3 - to the cut ends of stems resulted in around a 5-fold increase in NR activity, a 10-fold increase in NR transcript accumulation, and up to a 195-fold increase in transcript accumulation of NITRITE REDUCTASE (NiR1) which codes for the enzyme catalyzing the conversion of NO 2 - to NH 4 + . These data indicate that blueberry shoots are capable of assimilating NO 3 - when it is directly supplied to these tissues. Together, these data suggest that limitations in the uptake and translocation of NO 3 - to the shoots may limit overall NO 3 - assimilation capacity in blueberry. Copyright © 2017 Elsevier GmbH. All rights reserved.

Pseudo-constitutivity of nitrate-responsive genes in nitrate reductase mutants

PubMed Central

Schinko, Thorsten; Gallmetzer, Andreas; Amillis, Sotiris; Strauss, Joseph

2013-01-01

In fungi, transcriptional activation of genes involved in NO3- assimilation requires the presence of an inducer (nitrate or nitrite) and low intracellular concentrations of the pathway products ammonium or glutamine. In Aspergillus nidulans, the two transcription factors NirA and AreA act synergistically to mediate nitrate/nitrite induction and nitrogen metabolite derepression, respectively. In all studied fungi and in plants, mutants lacking nitrate reductase (NR) activity express nitrate-metabolizing enzymes constitutively without the addition of inducer molecules. Based on their work in A. nidulans, Cove and Pateman proposed an “autoregulation control” model for the synthesis of nitrate metabolizing enzymes in which the functional nitrate reductase molecule would act as co-repressor in the absence and as co-inducer in the presence of nitrate. However, NR mutants could simply show “pseudo-constitutivity” due to induction by nitrate which accumulates over time in NR-deficient strains. Here we examined this possibility using strains which lack flavohemoglobins (fhbs), and are thus unable to generate nitrate internally, in combination with nitrate transporter mutations (nrtA, nrtB) and a GFP-labeled NirA protein. Using different combinations of genotypes we demonstrate that nitrate transporters are functional also in NR null mutants and show that the constitutive phenotype of NR mutants is not due to nitrate accumulation from intracellular sources but depends on the activity of nitrate transporters. However, these transporters are not required for nitrate signaling because addition of external nitrate (10 mM) leads to standard induction of nitrate assimilatory genes in the nitrate transporter double mutants. We finally show that NR does not regulate NirA localization and activity, and thus the autoregulation model, in which NR would act as a co-repressor of NirA in the absence of nitrate, is unlikely to be correct. Results from this study instead suggest that transporter-mediated NO3- accumulation in NR deficient mutants, originating from traces of nitrate in the media, is responsible for the constitutive expression of NirA-regulated genes, and the associated phenotype is thus termed “pseudo-constitutive”. PMID:23454548

Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models

PubMed Central

Gong, Bing; Pan, Yong; Vempati, Prashant; Zhao, Wei; Knable, Lindsay; Ho, Lap; Wang, Jun; Sastre, Magdalena; Ono, Kenjiro; Sauve, Anthony A.; Pasinetti, Giulio M.

2013-01-01

Nicotinamide adenine dinucleotide (NAD)+, a coenzyme involved in redox activities in the mitochondrial electron transport chain, has been identified as a key regulator of the lifespan-extending effects, and the activation of NAD+ expression has been linked with a decrease in beta-amyloid (Aβ) toxicity in Alzheimer’s disease (AD). Nicotinamide riboside (NR) is a NAD+ precursor, it promotes peroxisome proliferator-activated receptor-γ coactivator 1 (PGC)-1α expression in the brain. Evidence has shown that PGC-1α is a crucial regulator of Aβ generation because it affects β-secretase (BACE1) degradation. In this study we tested the hypothesis that NR treatment in an AD mouse model could attenuate Aβ toxicity through the activation of PGC-1α-mediated BACE1 degradation. Using the Tg2576 AD mouse model, using in vivo behavioral analyses, biochemistry assays, small hairpin RNA (shRNA) gene silencing and electrophysiological recording, we found (1) dietary treatment of Tg2576 mice with 250 mg/kg/day of NR for 3 months significantly attenuates cognitive deterioration in Tg2576 mice and coincides with an increase in the steady-state levels of NAD+ in the cerebral cortex; (2) application of NR to hippocampal slices (10 µM) for 4 hours abolishes the deficits in long-term potentiation recorded in the CA1 region of Tg2576 mice; (3) NR treatment promotes PGC-1α expression in the brain coinciding with enhanced degradation of BACE1 and the reduction of Aβ production in Tg2576 mice. Further in vitro studies confirmed that BACE1 protein content is decreased by NR treatment in primary neuronal cultures derived from Tg2576 embryos, in which BACE1 degradation was prevented by PGC-1α-shRNA gene silencing; and (4) NR treatment and PGC-1α overexpression enhance BACE1 ubiquitination and proteasomal degradation. Our studies suggest that dietary treatment with NR might benefit AD cognitive function and synaptic plasticity, inpart by promoting PGC-1α-mediated BACE1 ubiquitination and degradation, thus preventing Aβ production in the brain. PMID:23312803

The prevalence and clinical characteristics of nonradiographic axial spondyloarthritis among patients with inflammatory back pain in rheumatology practices: a multinational, multicenter study.

PubMed

Burgos-Varga, Ruben; Wei, James Cheng-Chung; Rahman, Mahboob U; Akkoc, Nurullah; Haq, Syed Atiqul; Hammoudeh, Mohammed; Mahgoub, Ehab; Singh, Ena; Llamado, Lyndon John; Shirazy, Khalid; Kotak, Sameer; Hammond, Constance; Pedersen, Ron; Shen, Qi; Vlahos, Bonnie

2016-06-07

Patients with ankylosing spondylitis (AS), who by definition have radiographic sacroiliitis, typically experience symptoms for a decade or more before being diagnosed. Yet, even patients without radiographic sacroiliitis (i.e., nonradiographic axial spondyloarthritis [nr-axSpA]) report a significant disease burden. The primary objective of this study was to estimate the prevalence and clinical characteristics of nr-axSpA among patients with inflammatory back pain (IBP) in rheumatology clinics in a number of countries across the world. A secondary objective was to estimate the prevalence of IBP among patients with chronic low back pain (CLBP). Data were collected from 51 rheumatology outpatient clinics in 19 countries in Latin America, Africa, Europe, and Asia. As consecutive patients with CLBP (N = 2517) were seen by physicians at the sites, their clinical histories were evaluated to determine whether they met the new Assessment of SpondyloArthritis international Society criteria for IBP. For those who did, their available clinical history (e.g., family history, C-reactive protein [CRP] levels) was documented in a case report form to establish whether they met criteria for nr-axSpA, AS, or other IBP. Patients diagnosed with nr-axSpA or AS completed patient-reported outcome measures to assess disease activity and functional limitations. A total of 2517 patients with CLBP were identified across all sites. Of these, 974 (38.70 %) fulfilled the criteria for IBP. Among IBP patients, 29.10 % met criteria for nr-axSpA, and 53.72 % met criteria for AS. The prevalence of nr-axSpA varied significantly by region (p < 0.05), with the highest prevalence reported in Asia (36.46 %) and the lowest reported in Africa (16.02 %). Patients with nr-axSpA reported mean ± SD Ankylosing Spondylitis Disease Activity Scores based on erythrocyte sedimentation rate and CRP of 2.62 ± 1.17 and 2.52 ± 1.21, respectively, indicating high levels of disease activity (patients with AS reported corresponding scores of 2.97 ± 1.13 and 2.93 ± 1.18). Similarly, the overall Bath Ankylosing Spondylitis Disease Activity Index score of 4.03 ± 2.23 for patients with nr-axSpA (4.56 ± 2.17 for patients with AS) suggested suboptimal disease control. These results suggest that, in the centers that participated in the study, 29 % of patients with IBP met the criteria for nr-axSpA and 39 % of patients with CLBP had IBP. The disease burden in nr-axSpA is substantial and similar to that of AS, with both groups of patients experiencing inadequate disease control. These findings suggest the need for early detection of nr-axSpA and initiation of available treatment options to slow disease progression and improve patient well-being.

Microwave-assisted synthesis of palladium nanoparticles intercalated nitrogen doped reduced graphene oxide and their electrocatalytic activity for direct-ethanol fuel cells.

PubMed

Kumar, Rajesh; da Silva, Everson T S G; Singh, Rajesh K; Savu, Raluca; Alaferdov, Andrei V; Fonseca, Leandro C; Carossi, Lory C; Singh, Arvind; Khandka, Sarita; Kar, Kamal K; Alves, Oswaldo L; Kubota, Lauro T; Moshkalev, Stanislav A

2018-04-01

Palladium nanoparticles decorated reduced graphene oxide (Pd-rGO) and palladium nanoparticles intercalated inside nitrogen doped reduced graphene oxide (Pd-NrGO) hybrids have been synthesized by applying a very simple, fast and economic route using microwave-assisted in-situ reduction and exfoliation method. The Pd-NrGO hybrids materials show good activity as catalyst for ethanol electro oxidation for direct ethanol fuel cells (DEFCs) as compared to Pd-rGO hybrids. The enhanced direct ethanol fuel cell can serve as alternative to fossil fuels because it is renewable and environmentally-friendly with a high energy conversion efficiency and low pollutant emission. As proof of concept, the electrocatalytic activity of Pd-NrGO hybrid material was accessed by cyclic voltammetry in presence of ethanol to evaluate its applicability in direct-ethanol fuel cells (DEFCs). The Pd-NrGO catalyst presented higher electro active surface area (∼6.3 m 2  g -1 ) for ethanol electro-oxidation when compared to Pd-rGO hybrids (∼3.7 m 2  g -1 ). Despite the smaller catalytic activity of Pd-NrGO, which was attributed to the lower exfoliation rate of this material in relation to the Pd-rGO, Pd-NrGO showed to be very promising and its catalytic activity can be further improved by tuning the synthesis parameters to increase the exfoliation rate. Copyright © 2018 Elsevier Inc. All rights reserved.

The regulatory effect of electro-acupuncture on the expression of NMDA receptors in a SCI rat model.

PubMed

Tu, Wen-Zhan; Chen, Wen-Ci; Xia, Wan; He, Rong; Hu, Jie; Jiang, Ming-Chen; Jiang, Song-He

2017-05-15

In early spinal cord injury (SCI), glutamate receptors, including N-methyl-d-aspartate (NMDA) receptors (NMDARs), are over-stimulated by excessively released glutamate. The enhanced activity of NMDARs may cause cell death by overloading calcium (Ca 2+ ) into cells based on their high permeability to Ca 2+ . Studies in SCI animals have shown that treatment with electro-acupuncture (EA) is able to reduce cell death and to improve functional recovery. One possible mechanism of this neuroprotective effect is that EA has regulatory effect on NMDARs. To test whether EA could protect the spinal cord after SCI by decreasing the expression levels of NR1 and NR2A. We conducted EA treatment on a rat SCI model produced with a New York University (NYU) Impactor and measured hindlimb locomotor function by Basso, Beattie and Bresnahan Locomotor Rating Scale (BBB Scale). The expression of NR1 and NR2, the subunits of NMDARs, in the injured spinal cord was measured by Immunofluorescence stainings, western blot and real-time quantitative PCR (RT-qPCR). Our results showed that two days after the SCI the expression of NR1 and NR2 were dramatically enhanced at both protein and mNRA levels, which were significantly reduced by EA treatment at two specific acupoints, Dazhui (DU14) and Mingmen (DU4). EA is a potential therapeutic method for treating early SCI in human. Copyright © 2017 Elsevier Inc. All rights reserved.

NR4A orphan nuclear receptors influence retinoic acid and docosahexaenoic acid signaling via up-regulation of fatty acid binding protein 5

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

Volakakis, Nikolaos; Joodmardi, Eliza; Perlmann, Thomas, E-mail: thomas.perlmann@licr.ki.se

2009-12-25

The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult nervous system and is also induced as an immediate early gene in a variety of cell types. In silico analysis of human promoters identified fatty acid binding protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated PPAR{beta}/{delta} signaling, as a potential Nurr1 target gene. Nurr1 has previously been implicated in retinoid signaling via its heterodimerization partner RXR. Since NRs are commonly involved in cross-regulatory control we decided to further investigate the regulatory relationship between Nurr1 and FABP5. FABP5 expression was up-regulated by Nurr1 and other NR4Amore » NRs in HEK293 cells, and Nurr1 was shown to activate and bind to the FABP5 promoter, supporting that FABP5 is a direct downstream target of NR4A NRs. We also show that the RXR ligand docosahexaenoic acid (DHA) can induce nuclear translocation of FABP5. Moreover, via up-regulation of FABP5 Nurr1 can enhance retinoic acid-induced signaling of PPAR{beta}/{delta} and DHA-induced activation of RXR. We also found that other members of the NR4A orphan NRs can up-regulate FABP5. Thus, our findings suggest that NR4A orphan NRs can influence signaling events of other NRs via control of FABP5 expression levels.« less

The most powerful astrophysical events: Gravitational-wave peak luminosity of binary black holes as predicted by numerical relativity

NASA Astrophysics Data System (ADS)

Keitel, David; Forteza, Xisco Jiménez; Husa, Sascha; London, Lionel; Bernuzzi, Sebastiano; Harms, Enno; Nagar, Alessandro; Hannam, Mark; Khan, Sebastian; Pürrer, Michael; Pratten, Geraint; Chaurasia, Vivek

2017-07-01

For a brief moment, a binary black hole (BBH) merger can be the most powerful astrophysical event in the visible Universe. Here we present a model fit for this gravitational-wave peak luminosity of nonprecessing quasicircular BBH systems as a function of the masses and spins of the component black holes, based on numerical relativity (NR) simulations and the hierarchical fitting approach introduced by X. Jiménez-Forteza et al. [Phys. Rev. D 95, 064024 (2017)., 10.1103/PhysRevD.95.064024]. This fit improves over previous results in accuracy and parameter-space coverage and can be used to infer posterior distributions for the peak luminosity of future astrophysical signals like GW150914 and GW151226. The model is calibrated to the ℓ≤6 modes of 378 nonprecessing NR simulations up to mass ratios of 18 and dimensionless spin magnitudes up to 0.995, and includes unequal-spin effects. We also constrain the fit to perturbative numerical results for large mass ratios. Studies of key contributions to the uncertainty in NR peak luminosities, such as (i) mode selection, (ii) finite resolution, (iii) finite extraction radius, and (iv) different methods for converting NR waveforms to luminosity, allow us to use NR simulations from four different codes as a homogeneous calibration set. This study of systematic fits to combined NR and large-mass-ratio data, including higher modes, also paves the way for improved inspiral-merger-ringdown waveform models.

Affective motives for smoking among early stage smokers.

PubMed

Mathew, Amanda R; Wahlquist, Amy E; Garrett-Mayer, Elizabeth; Gray, Kevin M; Saladin, Michael E; Carpenter, Matthew J

2014-10-01

As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence. Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16-20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerström Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS). Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR - NR), such that higher dependence was associated with more prominent NR motives for smoking. Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells.

PubMed

Fletcher, Rachel S; Ratajczak, Joanna; Doig, Craig L; Oakey, Lucy A; Callingham, Rebecca; Da Silva Xavier, Gabriella; Garten, Antje; Elhassan, Yasir S; Redpath, Philip; Migaud, Marie E; Philp, Andrew; Brenner, Charles; Canto, Carles; Lavery, Gareth G

2017-08-01

Augmenting nicotinamide adenine dinucleotide (NAD + ) availability may protect skeletal muscle from age-related metabolic decline. Dietary supplementation of NAD + precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) appear efficacious in elevating muscle NAD + . Here we sought to identify the pathways skeletal muscle cells utilize to synthesize NAD + from NMN and NR and provide insight into mechanisms of muscle metabolic homeostasis. We exploited expression profiling of muscle NAD + biosynthetic pathways, single and double nicotinamide riboside kinase 1/2 (NRK1/2) loss-of-function mice, and pharmacological inhibition of muscle NAD + recycling to evaluate NMN and NR utilization. Skeletal muscle cells primarily rely on nicotinamide phosphoribosyltransferase (NAMPT), NRK1, and NRK2 for salvage biosynthesis of NAD + . NAMPT inhibition depletes muscle NAD + availability and can be rescued by NR and NMN as the preferred precursors for elevating muscle cell NAD + in a pathway that depends on NRK1 and NRK2. Nrk2 knockout mice develop normally and show subtle alterations to their NAD+ metabolome and expression of related genes. NRK1, NRK2, and double KO myotubes revealed redundancy in the NRK dependent metabolism of NR to NAD + . Significantly, these models revealed that NMN supplementation is also dependent upon NRK activity to enhance NAD + availability. These results identify skeletal muscle cells as requiring NAMPT to maintain NAD + availability and reveal that NRK1 and 2 display overlapping function in salvage of exogenous NR and NMN to augment intracellular NAD + availability.

The impact of photon flight path on S1 pulse shape analysis in liquid xenon two-phase detectors

NASA Astrophysics Data System (ADS)

Moongweluwan, M.

2016-02-01

The LUX dark matter search experiment is a 350 kg dual-phase xenon time projection chamber located at the 4850 ft level of the Sanford Underground Research Facility in Lead, SD. The success of two-phase xenon detectors for dark matter searches relies on their ability to distinguish electron recoil (ER) background events from nuclear recoil (NR) signal events. Typically, the NR-ER discrimination is obtained from the ratio of the electroluminescence light (S2) to the prompt scintillation light (S1). Analysis of the S1 pulse shape is an additional discrimination technique that can be used to distinguish NR from ER. Pulse-shape NR-ER discrimination can be achieved based on the ratio of the de-excitation processes from singlet and triplet states that generate the S1. The NR S1 is dominated by the de-excitation process from singlet states with a time constant of about 3 ns while the ER S1 is dominated by the de-excitation process from triplet states with a time constant of about 24 ns. As the size of the detectors increases, the variation in the S1 photon flight path can become comparable to these decay constants, reducing the utility of pulse-shape analysis to separate NR from ER. The effect of path length variations in the LUX detector has been studied using the results of simulations and the impact on the S1 pulse shape analysis is discussed.

Atypical Antischizophrenic Drugs Prevent Changes in Cortical N-Methyl-D-Aspartate Receptors and Behavior Following Sub-chronic Phencyclidine Administration in Developing Rat Pups

PubMed Central

Anastasio, Noelle C.; Johnson, Kenneth M.

2008-01-01

We sought to determine the relationship between phencyclidine (PCP)-induced alterations in behavior and NMDAR expression in the cortex by examining the effect of antischizophrenic drug treatment on both. Sprague-Dawley rat pups were pretreated with risperidone or olanzapine prior to treatment with PCP on postnatal day 7 (PN7) or sub-chronically on PN7, 9, and 11. Pre-pulse inhibition (PPI) of acoustic startle was measured on PN24–26 and following a challenge dose of 4 mg/kg PCP, locomotor activity was measured on PN28–35. PCP treatment on PN7 did not cause a deficit in PPI, but did cause locomotor sensitization. This was prevented by both antipsychotics. PCP treatment on PN7 caused an up-regulation of NR1 and NR2B, which was not affected by either antischizophrenic drug. PCP treatment on PN7, 9, and 11 caused a deficit in PPI and a sensitized locomotor response to PCP challenge as well as an up-regulation of NR1 and NR2A, all of which were prevented by both atypical antischizophrenic drugs. These data support the hypothesis that subchronic, but not single injection PCP treatment in developing rats results in behavioral alterations that are sensitive to antipsychotic drugs and these behavioral changes observed could be related to up-regulation of cortical NR1/NR2A receptors. PMID:18544461

[Applylication of new type combined fragments: nrDNA ITS+ nad 1-intron 2 for identification of Dendrobium species of Fengdous].

PubMed

Geng, Li-xia; Zheng, Rui; Ren, Jie; Niu, Zhi-tao; Sun, Yu-long; Xue, Qing-yun; Liu, Wei; Ding, Xiao-yu

2015-08-01

In this study, 17 kinds of Dendrobium species of Fengdous including 39 individuals were collected from 4 provinces. Mitochondrial gene sequences co I, nad 5, nad 1-intron 2 and chloroplast gene sequences rbcL, matK amd psbA-trnH were amplified from these materials, as well as nrDNA ITS. Furthermore, suitable sequences for identification of Dendrobium species of Fengdous were screened by K-2-P and P-distance. The results showed that during the mentioned 7 sequences, nrDNA ITS, nad 1-intron 2 and psbA-trnH which had a high degree of variability could be used to identify Dendrobium species of Fengdous. However, single fragment could not be used to distinguish D. moniliforme and D. huoshanense. Moreover, compared to other combined fragments, new type combined fragments nrDNA ITS+nad 1-intron 2 was more effective in identifying the original plants of Dendrobium species and could be used to identify D. huoshanense and D. moniliforme. Besides, according to the UPGMA tree constructed with nrDNA ITS+nad 1-intron 2, 3 inspected Dendrobium plants were identified as D. huoshanense, D. moniliforme and D. officinale, respectively. This study identified Dendrobium species of Fengdous by combined fragments nrDNA ITS+nad 1-intron 2 for the first time, which provided a more effective basis for identification of Dendrobium species. And this study will be helpful for regulating the market of Fengdous.

Anthropogenic nitrogen emissions during the Holocene and their possible effects on remote ecosystems

NASA Astrophysics Data System (ADS)

KopáčEk, Jiří; Posch, Maximilian

2011-06-01

Reactive nitrogen (Nr = NH3-N + NOx-N) is an important atmospheric pollutant, contributing to acidification, eutrophication and biodiversity changes in ecosystems. This study estimates Nr emissions from anthropogenic sources on a global scale since the advent of agriculture ˜8000 B.C., using a simple model based on the development of human population and per capita factors of Nr emissions originating from livestock production, biomass burning (biofuel use and forest and savannah burning), and other anthropogenic sources (humans and pets, N-fertilizer use, and fossil fuel combustion). The estimated global cumulative anthropogenic emissions of Nr to the atmosphere are ˜17.4 Pg N (8.6 Pg NH3-N and 8.8 Pg NOx-N) for 8000 B.C. through the year 2000 A.D., with 28% of this amount emitted during 1850-2000 A.D., 42% during 1-1850 A.D., and 30% during the previous 8000 years. Forest and savannah burning represent the major cumulative flux of both NH3-N and NOx-N (3.5 and 5.8 Pg, respectively). Livestock production and biofuel burning are responsible for emissions of 3.3 and 1.2 Pg NH3-N, respectively, while the application of synthetic fertilizers contributes 0.26 Pg NH3-N. The different duration of biofuel and fossil fuel use (10,000 versus ˜150 years) causes the higher cumulative NOx-N emissions from biofuel than from fossil fuel use (1.9 versus 1.1 Pg). The cumulative Nr emissions on a land area basis are 1.3 and 3.0 Mg N ha-1 globally and in Europe, respectively. Since an estimated 60% of Nr emitted in Europe is also deposited there, the average cumulative anthropogenic Nr deposition would be ˜1.8 Mg N ha-1, representing ˜30% of the current N pools in forest and alpine meadow soils of European glaciated areas (i.e., soils of similar age as the emissions). Despite large uncertainties in the model (13.7-30.5 Pg N over the last 10,000 years), the relative temporal distributions of total cumulative Nr emissions vary within relatively narrow ranges for different assumptions, with 70%-84% of the emissions occurring prior to 1850 A.D. We conclude that the majority of the total cumulative Nr flux from anthropogenic sources over the last 10,000 years occurred in the preindustrial period and could have increased soil N pools of some remote ecosystems much earlier than is currently assumed.

A novel disease affecting the predatory mite Phytoseiulus persimilis (Acari, Phytoseiidae): 2. Disease transmission by adult females.

PubMed

Schütte, Conny; Poitevin, Olivier; Negash, Tesfaye; Dicke, Marcel

2006-01-01

Adult female Phytoseiulus persimilis Athias-Henriot (Acari, Phytoseiidae) of one of our laboratory populations (=NR-population), show the following set of symptoms: predators shrink several days after mating, cease egg production and die several days after shrinking, show a lower degree of attraction to herbivore-induced plant volatiles and a shorter choice time in olfactometer tests, have the tendency to leave a prey patch with ample food, may carry excretory crystals in the legs, may cease prey consumption, and have a lower excretion rate. We hypothesized earlier that this characteristic syndrome, called non-responding (=NR-) syndrome, is caused by a pathogen infecting P. persimilis. To further support this hypothesis we here study several transmission modes of the factor causing the NR-syndrome. In all tests we measured size, short-term fecundity, mortality, predator position, response to plant odors and crystal location, thus including 6 of the 9 symptoms known yet. No evidence was found for vertical transmission from parent to offspring. Eggs from symptomatic females of the NR-population mated by males of the NR-population gave rise to normal-sized, well performing predators, when they had been surface sterilized or transferred to a new leaf. However, such eggs gave rise to shrunken females (17%) when left on the leaf where they had been laid. In the latter case transmission via products deposited on the leaf by the mothers was possible. We therefore tested several modes of horizontal transmission by exposing females of a commercial population that never showed the NR-syndrome (=R1-population) to products related to the symptomatic NR-population. No evidence was found for transmission via food or via squashed adult females. However, symptoms were induced in adult females of the R1-population after a 3-day exposure to a live adult female of the NR-population (incubation period=3-7 days, fraction shrunken females=53%) and after a 1-day exposure to feces and debris collected from such females (incubation period=2-4 days, fraction shrunken females=65%). Contact with live females and feces of the R1-population did not induce the syndrome. These results clearly indicate that the NR-syndrome is a contagious phenomenon and that the factor inducing the syndrome is transmitted horizontally among and between generations via feces and debris deposited by symptomatic females. The results are discussed in the context of mite pathology and biological control.

Cu(II)-Doped Polydopamine-Coated Gold Nanorods for Tumor Theranostics.

PubMed

Liu, Shuwei; Wang, Lu; Lin, Min; Wang, Dandan; Song, Ziqi; Li, Shuyao; Ge, Rui; Zhang, Xue; Liu, Yi; Li, Zhimin; Sun, Hongchen; Yang, Bai; Zhang, Hao

2017-12-27

Gold nanorods (AuNRs) are potentially useful in tumor theranostics, but the poor stability, high toxicity, and rapid removal by the immune system seriously limit their theranostic applications. In our study, we demonstrate the fabrication of Cu(II)-doped polydopamine-coated AuNR (AuNR@CuPDA), which significantly improves the potentials in tumor theranostics. Besides the improvement of physiological stability and biocompatibility, the PDA shell increases the photothermal performance and prolongs the blood circulation time of AuNRs. The half-life of AuNRs during blood circulation increases from 0.7 to 4.5 h after PDA coating, and the injected dose per gram of tumor tissue is 4.6% ID g -1 for AuNR@CuPDA. In addition to computer tomography imaging, the loading of Cu(II) in PDA shell endows AuNR@CuPDA with magnetic resonance imaging function. Cu(II) doped in PDA shell also exhibits chemotherapeutic behavior, and the tumor inhibitor rate is 31.2%. Further combining 808 nm laser-driven photothermal therapy, tumors were completely ablated, and no recurrence was observed. Liver and renal functions tests and histological analysis of major organs confirm that AuNR@CuPDA is in good safety.

Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain.

PubMed

Chen, Lei; Liu, Jin-cheng; Zhang, Xiao-nan; Guo, Yan-yan; Xu, Zhao-hui; Cao, Wei; Sun, Xiao-li; Sun, Wen-ji; Zhao, Ming-Gao

2008-06-01

Gentiopicroside is one of the secoiridoid compound isolated from Gentiana lutea. It exhibits analgesic activities in the mice. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission and induce glutamate NMDA NR2B receptor expression in the ACC. But little is known about Gentiopicroside on the persistent inflammatory pain and chronic pain-induced synaptic transmission changes in the ACC. The present study was undertaken to investigate its analgesic activities and central synaptic modulation to the peripheral painful inflammation. Gentiopicroside produced significant analgesic effects against persistent inflammatory pain stimuli in mice. Systemic administration of Gentiopicroside significantly reversed NR2B over-expression during the chronic phases of persistent inflammation caused by hind-paw administration of complete Freunds adjuvant (CFA) in mice. Whole-cell patch clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents in the ACC. Our findings provide strong evidence that analgesic effects of Gentiopicroside involve down-regulation of NR2B receptors in the ACC to persistent inflammatory pain.

Characterization of the association of nitrate reductase with barley (Hordeum vulgare L.) root membranes

NASA Technical Reports Server (NTRS)

Meyerhoff, P. A.; Fox, T. C.; Travis, R. L.; Huffaker, R. C.

1994-01-01

The nature of the association between nitrate reductase (NR) and membranes was examined. Nitrate reductase activity (NRA) associated with the microsomal fraction of barley (Hordeum vulgare L.) roots amounted to 0.6 to 0.8% of soluble NRA following sonication in the presence of 250 mM KI and repeated osmotic shock. This treatment removed all contaminating soluble NRA from microsomes of uninduced barley roots that had been homogenized in a soluble extract from roots of NO3(-)-induced plants. On continuous sucrose gradients, NRA co-migrated specifically with VO4(-)-sensitive ATPase activity, a plasma membrane (PM) marker; activity of glucose-6-phosphate dehydrogenase, assayed as cytosolic marker, co-migrated with NRA. Microsomal NRA was absent in barley deficient in soluble NR. Perturbation and trypsinolysis experiments with PM vesicles isolated by aqueous two-phase partitioning indicated that NR is associated with the periphery of the cytoplasmic face of the bilayer. These results demonstrate that PM and soluble NRs are essentially the same protein but that the membrane-associated form is tightly bound. Although it is possible that PM-associated NR exists in vivo, unequivocal evidence for this has yet to be shown. However, PM NR is definitely present in vitro.

Neuropsychiatric lupus and auto-antibodies against ionotropic glutamate receptor (NMDAR)

PubMed Central

Cohen-Solal, J.F.G.; Diamond, B.

2010-01-01

Almost half of lupus patients will experience neuropsychiatric symptoms during the course of their disease. The etiology of the neuronal damages are still uncertain and probably multiple. Auto-antibodies reactive with brain have been postulated to play a role. The observation of pathogenic auto-antibodies binding the NR2A and NR2B subunits of the ionotropic glutamate receptor (NMDAR) illustrates this hypothesis. First studies showed that 40% of lupus patients possess serum titers of anti-NR2A/B antibody, but the presence of these auto-antibodies is not always associated with the occurrence of neuronal damages or neuropsychiatric symptoms. Nevertheless, their presence is observed in the cerebro-spinal fluid (CSF) of one half of the patients suffering from neurolupus. The presence in the serum of these auto-antibodies anti-NR2A/B of the NMDAR is preliminary to their presence in the CSF where their deleterious effect is observable. Their entry into the brain is dependent on a breach of the blood brain barrier (BBB). In conclusion, the serum titer of auto-antibodies against NR2A/B subunits is an indication of the potential for neuro-psychiatric manifestations during the course of the disease. PMID:20605660

Self-Healing Natural Rubber with Tailorable Mechanical Properties Based on Ionic Supramolecular Hybrid Network.

PubMed

Xu, Chuanhui; Cao, Liming; Huang, Xunhui; Chen, Yukun; Lin, Baofeng; Fu, Lihua

2017-08-30

In most cases, the strength of self-healing supramolecular rubber based on noncovalent bonds is in the order of KPa, which is a challenge for their further applications. Incorporation of conventional fillers can effectively enhance the strength of rubbers, but usually accompanied by a sacrifice of self-healing capability due to that the filler system is independent of the reversible supramolecular network. In the present work, in situ reaction of methacrylic acid (MAA) and excess zinc oxide (ZnO) was realized in natural rubber (NR). Ionic cross-links in NR matrix were obtained by limiting the covalent cross-linking of NR molecules and allowing the in situ polymerization of MAA/ZnO. Because of the natural affinity between Zn 2+ ion-rich domains and ZnO, the residual nano ZnO participated in formation of a reversible ionic supramolecular hybrid network, thus having little obstructions on the reconstruction of ionic cross-links. Meanwhile, the well dispersed residual ZnO could tailor the mechanical properties of NR by changing the MAA/ZnO molar ratios. The present study thus provides a simple method to fabricate a new self-healing NR with tailorable mechanical properties that may have more potential applications.

Thermo- and pH-Responsive Copolymers Bearing Cholic Acid and Oligo(ethylene glycol) Pendants: Self-Assembly and pH-Controlled Release.

PubMed

Jia, Yong-Guang; Zhu, X X

2015-11-11

A family of block and random copolymers of norbornene derivatives bearing cholic acid and oligo(ethylene glycol) pendants were prepared in the presence of Grubbs' catalyst. The phase transition temperature of the copolymers in aqueous solutions may be tuned by the variation of comonomer ratios and pH values. Both types of copolymers formed micellar nanostructures with a hydrophilic poly(ethylene glycol) shell and a hydrophobic core containing cholic acid residues. The micellar size increased gradually with increasing pH due to the deprotonation of the carboxylic acid groups. These micelles were capable of encapsulating hydrophobic compounds such as Nile Red (NR). A higher hydrophobicity/hydrophilicity ratio in both copolymers resulted in a higher loading capacity for NR. With similar molecular weights and monomer compositions, the block copolymers showed a higher loading capacity for NR than the random copolymers. The NR-loaded micelles exhibited a pH-triggered release behavior. At pH 7.4 within 96 h, the micelles formed by the block and random of copolymers released 56 and 97% NR, respectively. Therefore, these micelles may have promise for use as therapeutic nanocarriers in drug delivery systems.

Safety Evaluation of Turmeric Polysaccharide Extract: Assessment of Mutagenicity and Acute Oral Toxicity

PubMed Central

Velusami, Chandrasekaran Chinampudur; Boddapati, Srinivasa Rao; Hongasandra Srinivasa, Srikanth; Richard, Edwin Jothie; Balasubramanian, Murali

2013-01-01

Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight. PMID:24455673

Correlation between the dielectric and the mechanical behavior of cellulose nanocomposites extracted from the rachis of the date palm tree

NASA Astrophysics Data System (ADS)

Ladhar, A.; Arous, M.; Kaddami, H.; Ayadi, Z.; Kallel, A.

2017-10-01

In the present study, the dielectric and mechanical properties of natural rubber (NR) based nanocomposites are investigated. Cellulose nanofillers are used in two forms as reinforcing phase: nanofibrillated cellulose (NFC) and cellulose nanocrystals (CNC). In the dielectric study, different relaxation phenomena are detected: the α dipolar relaxation, the lignin and hemicelluloses relaxation, the water dipoles relaxation, the interfacial polarization and the ionic conduction. For the interfacial polarization, the dielectric strength Δε showed lower values for NFC-filled nanocomposites than CNC-filled samples. It was explained with higher interactions between induced dipoles and lower mobility, assuring a better adhesion between the NR and the NFC. Moreover, in tensile tests, the elastic modulus increases with filling indicating the reinforcement effect of nanofillers. In addition, the NR-NFC nanocomposites display the highest tensile modulus. This result shows the higher compatibility of NFC with the NR matrix, and the ensuing higher filler/matrix adhesion. In dynamic mechanical analysis (DMA), a significant reinforcing effect of NFC was shown. This effect is manifested with the high storage modulus E‧, suggesting that the interactions between the NR matrix and the NFC fibers were stronger.

Systematic Domain Swaps of Iterative, Nonreducing Polyketide Synthases Provide a Mechanistic Understanding and Rationale For Catalytic Reprogramming

PubMed Central

2015-01-01

Iterative, nonreducing polyketide synthases (NR-PKSs) are multidomain enzymes responsible for the construction of the core architecture of aromatic polyketide natural products in fungi. Engineering these enzymes for the production of non-native metabolites has been a long-standing goal. We conducted a systematic survey of in vitro “domain swapped” NR-PKSs using an enzyme deconstruction approach. The NR-PKSs were dissected into mono- to multidomain fragments and recombined as noncognate pairs in vitro, reconstituting enzymatic activity. The enzymes used in this study produce aromatic polyketides that are representative of the four main chemical features set by the individual NR-PKS: starter unit selection, chain-length control, cyclization register control, and product release mechanism. We found that boundary conditions limit successful chemistry, which are dependent on a set of underlying enzymatic mechanisms. Crucial for successful redirection of catalysis, the rate of productive chemistry must outpace the rate of spontaneous derailment and thioesterase-mediated editing. Additionally, all of the domains in a noncognate system must interact efficiently if chemical redirection is to proceed. These observations refine and further substantiate current understanding of the mechanisms governing NR-PKS catalysis. PMID:24815013

NMDA and AMPA receptors in the anterior cingulate cortex mediates visceral pain in visceral hypersensitivity rats.

PubMed

Zhou, Lin; Huang, Junjing; Gao, Jun; Zhang, Guanpo; Jiang, Jinjin

2014-02-01

Several studies have shown that N-methyl-D-aspartate (NMDA)-receptor activation in anterior cingulate cortex (ACC) neurons plays critical roles in modulating visceral pain responses in visceral hypersensitivity (VH) rats. However, there are few reports about the expressions of NMDA and α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic-acid (AMPA) receptor subtypes in ACC of VH model rats at different time points. The current study was undertaken to investigate NR2A, NR2B and GluR2 expressions in ACC of VH rats that were induced by administration with 5% mustard oil. Our results indicated that NR2B, but not NR2A, was highly expressed in VH model group on day 15, 22, and 36 compared with normal group (p < 0.05). GluR2 expression was also higher in VH model group on day 15, 22, and 36 than that of normal group (p < 0.05). These findings suggested increased expression of NR2B and GluR2 might be key mechanisms for long-term synaptic plastic changes in VH rats. Copyright © 2014. Published by Elsevier Inc.

Objective measures of listening effort: effects of background noise and noise reduction.

PubMed

Sarampalis, Anastasios; Kalluri, Sridhar; Edwards, Brent; Hafter, Ervin

2009-10-01

This work is aimed at addressing a seeming contradiction related to the use of noise-reduction (NR) algorithms in hearing aids. The problem is that although some listeners claim a subjective improvement from NR, it has not been shown to improve speech intelligibility, often even making it worse. To address this, the hypothesis tested here is that the positive effects of NR might be to reduce cognitive effort directed toward speech reception, making it available for other tasks. Normal-hearing individuals participated in 2 dual-task experiments, in which 1 task was to report sentences or words in noise set to various signal-to-noise ratios. Secondary tasks involved either holding words in short-term memory or responding in a complex visual reaction-time task. At low values of signal-to-noise ratio, although NR had no positive effect on speech reception thresholds, it led to better performance on the word-memory task and quicker responses in visual reaction times. Results from both dual tasks support the hypothesis that NR reduces listening effort and frees up cognitive resources for other tasks. Future hearing aid research should incorporate objective measurements of cognitive benefits.

Origin of negative resistance in anion migration controlled resistive memory

NASA Astrophysics Data System (ADS)

Banerjee, Writam; Wu, Facai; Hu, Yuan; Wu, Quantan; Wu, Zuheng; Liu, Qi; Liu, Ming

2018-03-01

Resistive random access memory (RRAM) is one of the most promising emerging nonvolatile technologies for the futuristic memory devices. Resistive switching behavior often shows negative resistance (NR), either voltage controlled or current controlled. In this work, the origin of a current compliance dependent voltage controlled NR effect during the resetting of anion migration based RRAM devices is discussed. The N-type voltage controlled NR is a high field driven phenomena. The current conduction within the range of a certain negative voltage is mostly dominated by space charge limited current. But with the higher negative voltage, a field induced tunneling effect is generated in the NR region. The voltage controlled NR is strongly dependent on the compliance current. The area independent behavior indicates the filamentary switching. The peak to valley ratio (PVR) is > 5. The variation of PVR as a function of the conduction band offset is achieved. Compared to other reported works, based on the PVR, it is possible to distinguish the RRAM types. Generally, due to the higher electric field effect on the metallic bridge during RESET, the electrochemical metallization type RRAM shows much higher PVR than the valance change type RRAM.

Highly reproducible and sensitive silver nanorod array for the rapid detection of Allura Red in candy

NASA Astrophysics Data System (ADS)

Yao, Yue; Wang, Wen; Tian, Kangzhen; Ingram, Whitney Marvella; Cheng, Jie; Qu, Lulu; Li, Haitao; Han, Caiqin

2018-04-01

Allura Red (AR) is a highly stable synthetic red azo dye, which is widely used in the food industry to dye food and increase its attraction to consumers. However, the excessive consumption of AR can result in adverse health effects to humans. Therefore, a highly reproducible silver nanorod (AgNR) array was developed for surface enhanced Raman scattering (SERS) detection of AR in candy. The relative standard deviation (RSD) of AgNR substrate obtained from the same batch and different batches were 5.7% and 11.0%, respectively, demonstrating the high reproducibility. Using these highly reproducible AgNR arrays as the SERS substrates, AR was detected successfully, and its characteristic peaks were assigned by the density function theory (DFT) calculation. The limit of detection (LOD) of AR was determined to be 0.05 mg/L with a wide linear range of 0.8-100 mg/L. Furthermore, the AgNR SERS arrays can detect AR directly in different candy samples within 3 min without any complicated pretreatment. These results suggest the AgNR array can be used for rapid and qualitative SERS detection of AR, holding a great promise for expanding SERS application in food safety control field.

Human T lymphocytes express N-methyl-D-aspartate receptors functionally active in controlling T cell activation

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

Miglio, Gianluca; Varsaldi, Federica; Lombardi, Grazia

2005-12-30

The aim of this study was to investigate the expression and the functional role of N-methyl-D-aspartate (NMDA) receptors in human T cells. RT-PCR analysis showed that human resting peripheral blood lymphocytes (PBL) and Jurkat T cells express genes encoding for both NR1 and NR2B subunits: phytohemagglutinin (PHA)-activated PBL also expresses both these genes and the NR2A and NR2D genes. Cytofluorimetric analysis showed that NR1 expression increases as a consequence of PHA (10 {mu}g/ml) treatment. D-(-)-2-Amino-5-phosphonopentanoic acid (D-AP5), and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+)-MK 801], competitive and non-competitive NMDA receptor antagonists, respectively, inhibited PHA-induced T cell proliferation, whereas they did not affect IL-2 (10more » U/ml)-induced proliferation of PHA blasts. These effects were due to the prevention of T cell activation (inhibition of cell aggregate formation and CD25 expression), but not to cell cycle arrest or death. These results demonstrate that human T lymphocytes express NMDA receptors, which are functionally active in controlling cell activation.« less

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.

Prevalence of tidal expiratory flow limitation in preschool children with and without respiratory symptoms: application of the negative expiratory pressure (NEP) method.

PubMed

JIRICKOVA, A; SULC, J; POHUNEK, P; KITTNAR, O; DOHNALOVA, A; KOFRANEK, J

2009-01-01

Negative expiratory pressure (NEP) applied at the mouth during tidal expiration provides a non-invasive method for detecting expiratory flow limitation. Forty-two children were studied, i.e. 25 children with different respiratory symptoms (R) and 17 without any respiratory symptoms (NR). Children were examined without any sedation. A preset NEP of -5 cm H(2)O was applied; its duration did not exceed duration of tidal expiration. A significance of FL was judged by determining of a flow-limited range (in % of tidal volume). FL was found in 48 % children of R group. No patient of the NR group elicited FL (P<0.001 R vs. NR). The frequency of upper airway collapses was higher in R group (12 children) than in NR group (5 children). In conclusion, a high frequency of tidal FL in the R group was found, while it was not present in NR group. A relatively high frequency of expiratory upper airway collapses was found in both groups, but it did not differ significantly. NEP method represents a reasonable approach for tidal flow limitation testing in non-sedated preschool children.

Partielle Geschlechtertrennung--Enttauschte Hoffnungen? Monoedukative Lernumgebungen zum Chancenausgleich im Unterricht auf dem Prufstand (Partial Separation of the Sexes--Disappointed Hopes? An Assessment of Non-Educative Learning Environments for Equalizing Educational Opportunities).

ERIC Educational Resources Information Center

Ludwig, Peter H.

2003-01-01

Argues that the thesis of discrimination against girls in coeducation schools has been replaced by a belief that, during certain phases or in specific subjects, abandonment of coeducation would promote equal opportunities. Questions whether classic or recent surveys provide empirical evidence for this moderate skeptical attitude towards…

Ebenen des Verstehens: Überlegungen zu einem Verfahren zum Wurzelziehen

NASA Astrophysics Data System (ADS)

Winter, Martin

Wir bemühen uns, insbesondere bei Kindern, den Lernprozess auch im Mathematikunterricht durch den Einsatz von Materialien zu unterstützen. Die Arbeitsschritte dienen dabei oft der Vorbereitung oder Herleitung von Verfahren - in der Hoffnung, dass durch die Veranschaulichung Zusammenhänge besser verstanden werden. Worin dann das Verstehen besteht, wenn im Ergebnis ein Verfahren von den Kindern erfolgreich abgearbeitet wird, ist nicht unmittelbar zu sehen.

Konfektionierung und Individualisierung im Fernstudium (Ready-Made and Individualized Systems in Distance Study). Bericht zum ZIFF-Projekt 2.23. ZIFF Papiere-58.

ERIC Educational Resources Information Center

Lehner, H.; Weingartz, M.

The typical traits of a ready-made system as well as those of an individualized system are constituent characteristics of distance education. Within the framework set by these qualities and the extent to which they differ from one another, one seeks to achieve the fundamental educational aim of distance students' autonomy. The way institutions see…

"Land der Berge, Land der Seen": Zum Oesterreichbild in amerikanischen Deutsch-Lehrbuechern ("Land of Mountains, Land of Lakes": On the Picture of Austria Presented by German Textbooks in the USA).

ERIC Educational Resources Information Center

Koppensteiner, Juergen

1978-01-01

Nearly all German textbooks currently used in the USA either entirely fail to mention Austria, or else portray it by means of myths, cliches (Apfelstrudel, Sachertorte, Gemuetlichkeit), and often with outright untruths. The American student gets a picture of Austria as an "underdeveloped Disneyland of Europe". (WGA)

Video: einige Bemerkungen zum medien-spezifischen Ort und zur didaktischen Basis (Video: Some Notes on Its Place among Teaching Media and on Its Theoretical Basis in FL Teaching)

ERIC Educational Resources Information Center

Bauer, Hans-Ludwig

1976-01-01

Reports on the introduction of video recorders at various branches of the Goethe Institute. The characteristics of video are compared with those of films, tapes and printed matter. Video's advantage is that through it authentic, unprepared material can be presented, and it provides strong motivation. (Text is in German.) (IFS/WGA)

Neue Lautzeichen im Advanced Learners Dictionary (ALD). Stellungnahmen zum Pro und Kontra (New Sound Symbols in the Advanced Learners Dictionary [ALD]. Considerations Pro and Con)

ERIC Educational Resources Information Center

Zielsprache Englisch, 1976

1976-01-01

The phonetic symbols in the "Advanced Learners Dictionary" (Oxford University Press, London) are discussed critically in articles by L. Alfes, H. Arndt, E. Bauch, G. Dahlmann-Resing, W. Friedrich, E. Germer, B. Haycraft, H. P. Kelz. Reference is made to an earlier article "Neue Zeichen", by H. G. Hoffmann. (Text is in German.)…

Forschung Zum Prozess des Mathematiklernens. Reihe: Materialien und Studien, Band 2. (Research on the Process of Mathematics Learning. Series: Materials and Studies, Volume 2.)

ERIC Educational Resources Information Center

Bielefeld Univ. (West Germany).

The ten papers in this document were developed for a meeting prepared for the Third International Congress on Mathematical Education. Each paper is concerned with research from 1970-1975 related to the mathematical learning process. The first paper describes projects conducted in England on both content and process learning. The second paper…

Chirurgie angeborener Herzfehler

NASA Astrophysics Data System (ADS)

Schreiber, Christian; Libera, Paul; Lange, Rüdiger

Störungen der embryonalen Entwicklung in der frühen Phase der Schwangerschaft können zu Fehlbildungen am Herz- und Gefäßsystem führen. Die Häufigkeit liegt bei 0.8-1 % aller lebend geborenen Kinder. In Deutschland werden jedes Jahr etwa 6.000 Kinder mit einem Herzfehler geboren (Quelle: http://www.kompetenznetzahf.de). Das Spektrum reicht von einfachen Fehlern, die das Herz-Kreislauf-System wenig beeinträchtigen, bis zu sehr schweren Herzerkrankungen, die unbehandelt zum Tode führen. Fortschritte der Kinderkardiologie, Herzchirurgie und Anästhesie ermöglichen heute ein Überleben bei über 90 % der Patienten. Auch die spezialisierte Pränataldiagnostik (vorgeburtliche Diagnostik) ermöglicht schon die frühe Weichenstellung für mögliche Therapieoptionen. Bei der chirurgischen Therapie ist jedoch festzuhalten, dass ein Herzfehler entweder korrigierend behandelt wird oder nur "palliiert“ werden kann. Bei letzterer Therapie wird bei einem Patienten eine medizinische Maßnahme durchgeführt, die nicht die Herstellung normaler Körperfunktionen zum Ziel hat, sondern in Anpassung an die physiologischen Besonderheiten des Patienten dessen Zustand lediglich stabilisiert und optimiert. Dies kann beispielsweise bei einer nicht korrigierbaren angeborenen Fehlbildung notwendig sein, bei der lediglich eine funktionelle Herzkammer vorhanden ist (z. B. hypoplastisches Linksherz). Hierbei muss eine prothetische Verbindung zur Lungenstrombahn in der Folgezeit entfernt werden.

Light-Dark Changes in Cytosolic Nitrate Pools Depend on Nitrate Reductase Activity in Arabidopsis Leaf Cells1[w

PubMed Central

Cookson, Sarah J.; Williams, Lorraine E.; Miller, Anthony J.

2005-01-01

Several different cellular processes determine the size of the metabolically available nitrate pool in the cytoplasm. These processes include not only ion fluxes across the plasma membrane and tonoplast but also assimilation by the activity of nitrate reductase (NR). In roots, the maintenance of cytosolic nitrate activity during periods of nitrate starvation and resupply (M. van der Leij, S.J. Smith, A.J. Miller [1998] Planta 205: 64–72; R.-G. Zhen, H.-W. Koyro, R.A. Leigh, A.D. Tomos, A.J. Miller [1991] Planta 185: 356–361) suggests that this pool is regulated. Under nitrate-replete conditions vacuolar nitrate is a membrane-bound store that can release nitrate to the cytoplasm; after depletion of cytosolic nitrate, tonoplast transporters would serve to restore this pool. To study the role of assimilation, specifically the activity of NR in regulating the size of the cytosolic nitrate pool, we have compared wild-type and mutant plants. In leaf mesophyll cells, light-to-dark transitions increase cytosolic nitrate activity (1.5–2.8 mm), and these changes were reversed by dark-to-light transitions. Such changes were not observed in nia1nia2 NR-deficient plants indicating that this change in cytosolic nitrate activity was dependent on the presence of functional NR. Furthermore, in the dark, the steady-state cytosolic nitrate activities were not statistically different between the two types of plant, indicating that NR has little role in determining resting levels of nitrate. Epidermal cells of both wild type and NR mutants had cytosolic nitrate activities that were not significantly different from mesophyll cells in the dark and were unaltered by dark-to-light transitions. We propose that the NR-dependent changes in cytosolic nitrate provide a cellular mechanism for the diurnal changes in vacuolar nitrate storage, and the results are discussed in terms of the possible signaling role of cytosolic nitrate. PMID:15908593

Site-directed mutagenesis in Petunia × hybrida protoplast system using direct delivery of purified recombinant Cas9 ribonucleoproteins.

PubMed

Subburaj, Saminathan; Chung, Sung Jin; Lee, Choongil; Ryu, Seuk-Min; Kim, Duk Hyoung; Kim, Jin-Soo; Bae, Sangsu; Lee, Geung-Joo

2016-07-01

Site-directed mutagenesis of nitrate reductase genes using direct delivery of purified Cas9 protein preassembled with guide RNA produces mutations efficiently in Petunia × hybrida protoplast system. The clustered, regularly interspaced, short palindromic repeat (CRISPR)-CRISPR associated endonuclease 9 (CRISPR/Cas9) system has been recently announced as a powerful molecular breeding tool for site-directed mutagenesis in higher plants. Here, we report a site-directed mutagenesis method targeting Petunia nitrate reductase (NR) gene locus. This method could create mutations efficiently using direct delivery of purified Cas9 protein and single guide RNA (sgRNA) into protoplast cells. After transient introduction of RNA-guided endonuclease (RGEN) ribonucleoproteins (RNPs) with different sgRNAs targeting NR genes, mutagenesis at the targeted loci was detected by T7E1 assay and confirmed by targeted deep sequencing. T7E1 assay showed that RGEN RNPs induced site-specific mutations at frequencies ranging from 2.4 to 21 % at four different sites (NR1, 2, 4 and 6) in the PhNR gene locus with average mutation efficiency of 14.9 ± 2.2 %. Targeted deep DNA sequencing revealed mutation rates of 5.3-17.8 % with average mutation rate of 11.5 ± 2 % at the same NR gene target sites in DNA fragments of analyzed protoplast transfectants. Further analysis from targeted deep sequencing showed that the average ratio of deletion to insertion produced collectively by the four NR-RGEN target sites (NR1, 2, 4, and 6) was about 63:37. Our results demonstrated that direct delivery of RGEN RNPs into protoplast cells of Petunia can be exploited as an efficient tool for site-directed mutagenesis of genes or genome editing in plant systems.

NR4A2 genetic variation and Parkinson's disease: Evidence from a systematic review and meta-analysis.

PubMed

Liu, Hongmei; Liu, Hongbo; Li, Ting; Cui, Jiayi; Fu, Yingmei; Ren, Juanjuan; Sun, Xiujia; Jiang, Ping; Yu, Shunying; Li, Chunbo

2017-05-22

The homo sapiens nuclear receptor subfamily 4, group A (NR4A2) genetic variation has been implicated as a risk factor for Parkinson's disease (PD). Nevertheless, the results are inconclusive. We conducted a comprehensive systematic review and meta-analysis to quantify the impact of NR4A2 variation on the risk of PD. All eligible case-control studies published up to June 2016 by searching Pubmed, OVID, EBSCO, PsycINFO, ISI Web of Knowledge, Chinese Biomedical Literature Database and China Academic Journals Database were identified. Pooled odds ratio (OR) with 95% confidence interval (CI) were used to access the strength of the association in fixed- or random-effects model. Eighteen studies reported 24 genetic variants with a total of 6150 cases and 5919 controls were included. Twelve studies for NR4A2 rs35479735 polymorphism and 4 studies for rs12803 were available for meta-analysis. A significant association was observed for rs35479735 under the homozygous model (OR=1.31, 95% CI: 1.10-1.56, P=0.003), whereas no significant association for rs12803 was detected. In subgroup analysis stratified by ethnicity, age onset and familial history, we found no significant association except one in sporadic PD subgroup under the recessive (OR=3.30, 95% CI: 1.23-8.84, P=0.02) and homozygous model (OR=3.43, 95% CI: 1.26-9.33, P=0.02) for rs35479735. The study comprehensively evaluated the association of NR4A2 variation with PD, and the results failed to demonstrate that the NR4A2 polymorphisms significantly associated with PD except for rs35479735, suggesting that more studies are needed to elucidate if NR4A2 is a risk of PD. Copyright © 2017 Elsevier B.V. All rights reserved.

Incorporation of a recombinant Eimeria maxima IMP1 antigen into nanoparticles confers protective immunity against E. Maxima challenge infection.

PubMed

Jenkins, Mark C; Stevens, Laura; O'Brien, Celia; Parker, Carolyn; Miska, Katrzyna; Konjufca, Vjollca

2018-02-14

The purpose of this study was to determine if conjugating a recombinant Eimeria maxima protein, namely EmaxIMP1, into 20 nm polystyrene nanoparticles (NP) could improve the level of protective immunity against E. maxima challenge infection. Recombinant EmaxIMP1 was expressed in Escherichia coli as a poly-His fusion protein, purified by NiNTA chromatography, and conjugated to 20 nm polystyrene NP (NP-EmaxIMP1). NP-EMaxIMP1 or control non-recombinant (NP-NR) protein were delivered per os to newly-hatched broiler chicks with subsequent booster immunizations at 3 and 21 days of age. In battery cage studies (n = 4), chickens immunized with NP-EMaxIMP1 displayed complete protection as measured by weight gain (WG) against E. maxima challenge compared to chickens immunized with NP-NR. WG in the NP-EMaxIMP1-immunized groups was identical to WG in chickens that were not infected with E. maxima infected chickens. In floor pen studies (n = 2), chickens immunized with NP-EMaxIMP1 displayed partial protection as measured by WG against E. maxima challenge compared to chickens immunized with NP-NR. In order to understand the basis for immune stimulation, newly-hatched chicks were inoculated per os with NP-EMaxIMP1 or NP-NR protein, and the small intestine, bursa, and spleen, were examined for NP localization at 1 h and 6 h post-inoculation. Within 1 h, both NP-EMaxIMP1 and NP-NR were observed in all 3 tissues. An increase was observed in the level of NP-EmaxIMP1 and NP-NR in all tissues at 6 h post-inoculation. These data indicate that 20 nm NP-EmaxIMP1 or NP-NR reached deeper tissues within hours of oral inoculation and elicited complete to partial immunity against E. maxima challenge infection. Published by Elsevier Ltd.

Hyperglycemia Suppresses Calcium Phosphate-Induced Aneurysm Formation Through Inhibition of Macrophage Activation.

PubMed

Tanaka, Teruyoshi; Takei, Yuichiro; Yamanouchi, Dai

2016-03-28

The aim of this study was to elucidate aspects of diabetes mellitus-induced suppression of aneurysm. We hypothesized that high glucose suppresses aneurysm by inhibiting macrophage activation via activation of Nr1h2 (also known as liver X receptor β), recently characterized as a glucose-sensing nuclear receptor. Calcium phosphate (CaPO4)-induced aneurysm formation was significantly suppressed in the arterial wall in type 1 and 2 diabetic mice. A murine macrophage cell line, RAW264.7, was treated with tumor necrosis factor α (TNF-α) plus CaPO4 and showed a significant increase in matrix metalloproteinase 9 (Mmp9) mRNA and secreted protein expression compared with TNF-α alone. Elevated Mmp9 expression was significantly suppressed by hyperglycemic conditions (15.5 mmol/L glucose) compared with normoglycemic conditions (5.5 mmol/L glucose) or normoglycemic conditions with high osmotic pressure (5.5 mmol/L glucose +10.0 mmol/L mannitol). Nr1h2 mRNA and protein expression were suppressed by treatment with TNF-α plus CaPO4 but were restored by hyperglycemic conditions. Activation of Nr1h2 by the antagonist GW3965 during stimulation with TNF-α plus CaPO4 mimicked hyperglycemic conditions and inhibited Mmp9 upregulation, whereas the deactivation of Nr1h2 by small interfering RNA (siRNA) under hyperglycemic conditions canceled the suppressive effect and restored Mmp9 expression induced by TNF-α plus CaPO4. Moreover, Nr1h2 activation with GW3965 significantly suppressed CaPO4-induced aneurysm in mice compared with vehicle-injected control mice. Our results show that hyperglycemia suppresses macrophage activation and aneurysmal degeneration through the activation of Nr1h2. Although further validation of the underlying pathway is necessary, targeting Nr1h2 is a potential therapeutic approach to treating aneurysm. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Regulation of the Trigeminal NR1 Subunit Expression Induced by Inflammation of the Temporomandibular Joint Region in Rats

PubMed Central

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Mao, Jianren

2012-01-01

Expression of the N-methyl-D-aspartate receptor (NMDA) receptor in trigeminal nuclei has been shown to play a role in the mechanisms of trigeminal pain. Here, we examined the hypothesis that the upregulation of the NR1 subunit of the NMDA receptor (NR1) in the trigeminal subnucleus caudalis (Sp5c) following inflammation of the temporomandibular joint (TMJ) region would be regulated by interleukin-6 (IL-6) and the nuclear factor kappa B (NF-κB). Inflammation of a unilateral TMJ region was produced in rats by injecting 50 μl of complete Freund’s adjuvant (CFA) into a TMJ and adjacent tissues, which resulted in persistent pain behavior as assessed using algometer before (baseline) and on day 1, 3 and 7 after the CFA injection. The CFA injection also induced a significant upregulation of NR1 and NF-κB on day 3 and 7, and of IL-6 on day 1, 3, and 7, within the ipsilateral Sp5c, as compared with the sham TMJ injection group. Once daily intracisternal injection of an IL-6 antiserum or NF-κB inhibitor (PDTC) for six days, beginning on day 1 immediately after the CFA injection, prevented both the upregulation of NR1 in the ipsilateral Sp5C and pain behavior. Moreover, once daily intracisternal IL-6 administration for six days in naïve rats induced the NR1 upregulation and pain behavior similar to that after TMJ inflammation. These results indicate that the upregulation of IL-6 and NF-κB after inflammation of the unilateral TMJ region is a critical regulatory mechanism for the expression of NR1 in the ipsilateral Sp5c, which contributed to the development of TMJ pain behavior in rats. PMID:19058915

38. From Final Construction Report on the Haleakala Road ProjectNR7, ...

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

38. From Final Construction Report on the Haleakala Road Project--NR-7, Hawaii National Park, Island of Maui, Territory of Hawaii. BRIDGE AT STATION 85+. - Haleakala National Park Roads, Pukalani, Maui County, HI