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Sample records for d1 receptor-dependent 3hgaba

  1. Single exposure to cocaine impairs aspartate uptake in the pre-frontal cortex via dopamine D1-receptor dependent mechanisms.

    PubMed

    Sathler, Matheus Figueiredo; Stutz, Bernardo; Martins, Robertta Silva; Dos Santos Pereira, Maurício; Pecinalli, Ney Roner; Santos, Luis E; Taveira-da-Silva, Rosilane; Lowe, Jennifer; de Freitas, Isis Grigorio; de Melo Reis, Ricardo Augusto; Manhães, Alex C; Kubrusly, Regina C C

    2016-08-01

    Dopamine and glutamate play critical roles in the reinforcing effects of cocaine. We demonstrated that a single intraperitoneal administration of cocaine induces a significant decrease in [(3)H]-d-aspartate uptake in the pre-frontal cortex (PFC). This decrease is associated with elevated dopamine levels, and requires dopamine D1-receptor signaling (D1R) and adenylyl cyclase activation. The effect was observed within 10min of cocaine administration and lasted for up to 30min. This rapid response is related to D1R-mediated cAMP-mediated activation of PKA and phosphorylation of the excitatory amino acid transporters EAAT1, EAAT2 and EAAT3. We also demonstrated that cocaine exposure increases extracellular d-aspartate, l-glutamate and d-serine in the PFC. Our data suggest that cocaine activates dopamine D1 receptor signaling and PKA pathway to regulate EAATs function and extracellular EAA level in the PFC. PMID:27208619

  2. Adolescent nicotine-induced dendrite remodeling in the nucleus accumbens is rapid, persistent, and D1-dopamine receptor dependent.

    PubMed

    Ehlinger, D G; Bergstrom, H C; Burke, J C; Fernandez, G M; McDonald, C G; Smith, R F

    2016-01-01

    Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) shell. While nicotine-induced dendritic remodeling has frequently been described as persistent, the trajectory of dendrite remodeling is unknown. Specifically, no study to date has characterized the structural plasticity of dendrites in the NAcc immediately following chronic nicotine, leaving open the possibility that dendrite remodeling emerges gradually over time. Further, the neuropharmacological mechanisms through which nicotine induces dendrite remodeling are not well understood. To address these questions, rats were co-administered chronic nicotine (0.5 mg/kg) and the D1-dopamine receptor (D1DR) antagonist SCH-23390 (0.05 mg/kg) subcutaneously every other day during adolescence. Brains were then processed for Golgi-Cox staining either 1 day or 21 days following drug exposure and dendrites from MSNs in the NAcc shell digitally reconstructed in 3D. Spine density was also measured at both time points. Our morphometric results show (1) the formation of new dendritic branches and spines 1 day following nicotine exposure, (2) new dendritic branches, but not spine density, remains relatively stable for at least 21 days, (3) the co-administration of SCH-23390 completely blocked nicotine-induced dendritic remodeling of MSNs at both early and late time points, suggesting the formation of new dendritic branches in response to nicotine is D1DR-dependent, and (4) SCH-23390 failed to block nicotine-induced increases in spine density. Overall this study provides new insight into how nicotine influences the normal trajectory of adolescent brain development and demonstrates a persistent form of nicotine-induced neuroplasticity in the NAcc shell that develops rapidly and is D1DR dependent. PMID:25257604

  3. PSD-95 Uncouples Dopamine-Glutamate Interaction in the D1/PSD-95/NMDA Receptor Complex

    PubMed Central

    Zhang, Jingping; Xu, Tai-Xiang; Hallett, Penelope J.; Watanabe, Masahiko; Grant, Seth G. N.; Isacson, Ole; Yao, Wei-Dong

    2008-01-01

    Classical dopaminergic signaling paradigms and emerging studies on direct physical interactions between the D1 dopamine (DA) receptor and the N-Methyl-D-Aspartate (NMDA) glutamate receptor predict a reciprocally facilitating, positive feedback loop. This loop, if not controlled, may cause concomitant overactivation of both D1 and NMDA receptors, triggering neurotoxicity. Endogenous protective mechanisms must exist. Here we show that PSD-95, a prototypical structural and signaling scaffold in the postsynaptic density, inhibits D1-NMDA receptor association and uncouples NMDA receptor-dependent enhancement of D1 signaling. This uncoupling is achieved, at least in part, via a disinhibition mechanism by which PSD-95 abolishes NMDA receptor-dependent inhibition of D1 internalization. Knockdown of PSD-95 immobilizes D1 receptors on the cell surface and escalates NMDA receptor-dependent D1 cAMP signaling in neurons. Thus, in addition to its role in receptor stabilization and synaptic plasticity, PSD-95 acts as a brake on the D1-NMDA receptor complex and dampens the interaction between them. PMID:19261890

  4. Spacelab D-1 mission

    NASA Technical Reports Server (NTRS)

    Dunbar, Bonnie J.

    1990-01-01

    The Spacelab D-1 (Deutchland Eins) Mission is discussed from the points of view of safety, materials handling, and toxic materials; the laboratory and equipment used; and some of the different philosophies utilized on this flight. How to enhance scientific return at the same time as being safe was examined.

  5. Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression.

    PubMed

    Wissmann, Melanie; Yin, Na; Müller, Judith M; Greschik, Holger; Fodor, Barna D; Jenuwein, Thomas; Vogler, Christine; Schneider, Robert; Günther, Thomas; Buettner, Reinhard; Metzger, Eric; Schüle, Roland

    2007-03-01

    Posttranslational modifications of histones, such as methylation, regulate chromatin structure and gene expression. Recently, lysine-specific demethylase 1 (LSD1), the first histone demethylase, was identified. LSD1 interacts with the androgen receptor and promotes androgen-dependent transcription of target genes by ligand-induced demethylation of mono- and dimethylated histone H3 at Lys 9 (H3K9) only. Here, we identify the Jumonji C (JMJC) domain-containing protein JMJD2C as the first histone tridemethylase regulating androgen receptor function. JMJD2C interacts with androgen receptor in vitro and in vivo. Assembly of ligand-bound androgen receptor and JMJD2C on androgen receptor-target genes results in demethylation of trimethyl H3K9 and in stimulation of androgen receptor-dependent transcription. Conversely, knockdown of JMJD2C inhibits androgen-induced removal of trimethyl H3K9, transcriptional activation and tumour cell proliferation. Importantly, JMJD2C colocalizes with androgen receptor and LSD1 in normal prostate and in prostate carcinomas. JMJD2C and LSD1 interact and both demethylases cooperatively stimulate androgen receptor-dependent gene transcription. In addition, androgen receptor, JMJD2C and LSD1 assemble on chromatin to remove methyl groups from mono, di and trimethylated H3K9. Thus, our data suggest that specific gene regulation requires the assembly and coordinate action of demethylases with distinct substrate specificities. PMID:17277772

  6. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration.

    PubMed

    Huang, Wendong; Ma, Ke; Zhang, Jun; Qatanani, Mohammed; Cuvillier, James; Liu, Jun; Dong, Bingning; Huang, Xiongfei; Moore, David D

    2006-04-14

    Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor-dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth. PMID:16614213

  7. IL12-mediated sensitizing of T-cell receptor-dependent and -independent tumor cell killing.

    PubMed

    Braun, Matthias; Ress, Marie L; Yoo, Young-Eun; Scholz, Claus J; Eyrich, Matthias; Schlegel, Paul G; Wölfl, Matthias

    2016-07-01

    Interleukin 12 (IL12) is a key inflammatory cytokine critically influencing Th1/Tc1-T-cell responses at the time of initial antigen encounter. Therefore, it may be exploited for cancer immunotherapy. Here, we investigated how IL12, and other inflammatory cytokines, shape effector functions of human T-cells. Using a defined culture system, we followed the gradual differentiation and function of antigen-specific CD8(+) T cells from their initial activation as naïve T cells through their expansion phase as early memory cells to full differentiation as clonally expanded effector T cells. The addition of IL12 8 days after the initial priming event initiated two mechanistically separate events: First, IL12 sensitized the T-cell receptor (TCR) for antigen-specific activation, leading to an approximately 10-fold increase in peptide sensitivity and, in consequence, enhanced tumor cell killing. Secondly, IL12 enabled TCR/HLA-independent activation and cytotoxicity: this "non-specific" effect was mediated by the NK cell receptor DNAM1 (CD226) and dependent on ligand expression of the target cells. This IL12 regulated, DNAM1-mediated killing is dependent on src-kinases as well as on PTPRC (CD45) activity. Thus, besides enhancing TCR-mediated activation, we here identified for the first time a second IL12 mediated mechanism leading to activation of a receptor-dependent killing pathway via DNAM1. PMID:27622043

  8. β-caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner

    PubMed Central

    Horváth, Béla; Mukhopadhyay, Partha; Kechrid, Malek; Patel, Vivek; Tanashian, Galin; Wink, David A.; Gertsch, Jürg; Pacher, Pál

    2012-01-01

    (E)-β-caryophyllene (BCP) is a natural sequiterpene found in many essential oils of spice (best known for contributing to the spiciness of black pepper) and food plants with recognized anti-inflammatory properties. Recently it was shown that BCP is a natural agonist of endogenous cannabinoid 2 (CB2) receptors, which are expressed in immune cells and mediate anti-inflammatory effects. In this study we aimed to test the effects of BCP in a clinically relevant murine model of nephropathy (induced by the widely used antineoplastic drug cisplatin) in which the tubular injury is largely dependent on inflammation and oxidative/nitrative stress. β-caryophyllene dose-dependently ameliorated cisplatin-induced kidney dysfunction, morphological damage, and renal inflammatory response (chemokines MCP-1 and MIP-2, cytokines TNF-α and IL-1β, adhesion molecule ICAM-1, and neutrophil and macrophage infiltration). It also markedly mitigated oxidative/nitrative stress (NOX-2, NOX-4 expression, 4-HNE and 3-NT content) and cell death. The protective effects of BCP against biochemical and histological markers of nephropathy were absent in CB2 knockout mice. Thus, BCP may be an excellent therapeutic agent to prevent cisplatin-induced nephrotoxicity through a CB2 receptor dependent pathway. Given the excellent safety profile of BCP in humans it has tremendous therapeutic potential in multitude of diseases associated with inflammation and oxidative stress. PMID:22326488

  9. Cyclin D1 expression in prostate carcinoma

    PubMed Central

    Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S.; Tucci, S.; Muglia, V.F.; Reis, R.B. Dos; Silva, G.E.B.

    2014-01-01

    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness. PMID:24820071

  10. CoRILISA: a local similarity based receptor dependent QSAR method.

    PubMed

    Khedkar, Vijay M; Coutinho, Evans C

    2015-01-26

    Molecular similarity methods have played a crucial role in the success of structure-based and computer-assisted drug design. However, with the exception of CoMSIA, the current approaches for estimating molecular similarity yield a global picture thereby providing limited information about the local spatial molecular features responsible for the variation of activity with the 3D structure. Application of molecular similarity measures, each related to the functional "pieces" of a ligand-receptor complex, is advantageous over a composite molecular similarity alone and will provide more insights to rationally interpret the activity based on the receptor and ligand structural features. Building on the ideas of our previously published methodologies-CoRIA and LISA, we present here a local molecular similarity based receptor dependent QSAR method termed CoRILISA which is a hybrid of the two approaches. The method improves on previous techniques by inclusion of receptor attributes for the calculation and comparison of similarity between molecules. For validation studies, the CoRILISA methodology was applied on three large and diverse data sets-glycogen phosphorylase b (GPb), human immunodeficiency virus-1 protease (HIV PR), and cyclin dependent kinase 2 (CDK2) inhibitors. The statistics of the CoRILISA models were benchmarked against the standard CoRIA approach and with other published approaches. The CoRILISA models were found to be significantly better, especially in terms of the predictivity for the test set. CoRILISA is able to identify the thermodynamic properties associated with residues that define the active site and modulate the variation in the activity of the molecules. It is a useful tool in the fragment-based drug discovery approach for ligand activity prediction. PMID:25535645

  11. Blueberry-enriched diet ameliorates age-related declines in NMDA receptor-dependent LTP

    PubMed Central

    Bickford, Paula C.; Browning, Michael D.

    2008-01-01

    NMDA receptor-dependent long-term potentiation (LTP) in the hippocampus is widely accepted as a cellular substrate for memory formation. Age-related declines in the expression of both NMDAR-dependent LTP and NMDAR subunit proteins in the CA1 region of the hippocampus have been well characterized and likely underlie age-related memory impairment. In the current study, we examined NMDAR-dependent LTP in young Fischer 344 rats (4 months old) and aged rats (24 months old) given either a control diet or a diet supplemented with blueberry extract for 6–8 weeks. NMDAR-dependent LTP was evoked by high-frequency stimulation (HFS) in the presence of nifedipine, to eliminate voltage-gated calcium channel LTP. Field excitatory postsynaptic potentials (fEPSPs) were increased by 57% 1 h after HFS in young animals, but this potentiation was reduced to 31% in aged animals. Supplementation of the diet with blueberry extract elevated LTP (63%) in aged animals to levels seen in young. The normalization of LTP may be due to the blueberry diet preventing a decline in synaptic strength, as measured by the slope of the fEPSP for a given fiber potential. The blueberry diet did not prevent age-related declines in NMDAR protein expression. However, phosphorylation of a key tyrosine residue on the NR2B subunit, important for increasing NMDAR function, was enhanced by the diet, suggesting that an increase in NMDAR function might overcome the loss in protein. This report provides evidence that dietary alterations later in life may prevent or postpone the cognitive declines associated with aging. PMID:19424850

  12. Interdicting Gq Activation in Airway Disease by Receptor-Dependent and Receptor-Independent Mechanisms.

    PubMed

    Carr, Richard; Koziol-White, Cynthia; Zhang, Jie; Lam, Hong; An, Steven S; Tall, Gregory G; Panettieri, Reynold A; Benovic, Jeffrey L

    2016-01-01

    Gαqβγ heterotrimer (Gq), an important mediator in the pathology of airway disease, plays a central role in bronchoconstriction and airway remodeling, including airway smooth muscle growth and inflammation. Current therapeutic strategies to treat airway disease include the use of muscarinic and leukotriene receptor antagonists; however, these pharmaceuticals demonstrate a limited clinical efficacy as multiple Gq-coupled receptor subtypes contribute to these pathologies. Thus, broadly inhibiting the activation of Gq may be an advantageous therapeutic approach. Here, we investigated the effects of broadly inhibiting Gq activation in vitro and ex vivo using receptor-dependent and receptor-independent strategies. P4pal-10 is a protease activated receptor 4-derived pepducin that exhibits efficacy toward multiple Gq-coupled receptors. Mechanistic studies demonstrated that P4pal-10 selectively inhibits all G protein coupling to several Gq-coupled receptors, including protease activated receptor 1, muscarinic acetylcholine M3, and histamine H1 receptors, while demonstrating no direct effect on Gq. We also evaluated the ability of FR900359, also known as UBO-QIC, to directly inhibit Gq activation. FR900359 inhibited spontaneous Gαq nucleotide exchange, while having little effect on Gαsβγ, Gαiβγ, or Gα12/13βγ heterotrimer activity. Both P4pal-10 and FR900359 inhibited Gq-mediated intracellular signaling and primary human airway smooth muscle growth, whereas only FR900359 effectively interdicted agonist-promoted airway contraction in human precision cut lung slices. These studies serve as a proof of concept that the broad-based inhibition of Gq activation may be a useful therapeutic approach to treat multiple common pathologies of airway disease. PMID:26464325

  13. The flavonoid baicalein promotes NMDA receptor-dependent long-term potentiation and enhances memory

    PubMed Central

    Wang, Wei; Wang, Fang; Yang, Yuan-Jian; Hu, Zhuang-Li; Long, Li-Hong; Fu, Hui; Xie, Na; Chen, Jian-Guo

    2011-01-01

    BACKGROUND AND PURPOSE There is growing interest in the physiological functions of flavonoids, especially in their effects on cognitive function and on neurodegenerative diseases. The aim of the current investigation was to evaluate the role of the flavonoid baicalein in long-term potentiation (LTP) in the hippocampal CA1 region and cognitive behavioural performance. EXPERIMENTAL APPROACH Effects of baicalein on LTP in rat hippocampal slices were investigated by electrophysiological methods. Phosphorylation of Akt (at Ser473), the extracellular signal-regulated kinase (ERK1/2) and the transcription factor cAMP response element-binding protein (CREB) (at Ser133) were analysed by Western blot. Fear conditioning was used to determine whether baicalein could improve learning and memory in rats. KEY RESULTS Baicalein enhanced the N-methyl-d-aspartate glutamate receptor-dependent LTP in a bell-shaped concentration-dependent manner. Addition of the lipoxygenase metabolites 12(S)-HETE and 12(S)-HPETE did not reverse these effects of baicalein. Baicalein treatment enhanced phosphorylation of Akt during induction of LTP with the same bell-shaped dose–response curve. LTP potentiation induced by baicalein was blocked by inhibitors of phosphoinositide 3-kinase. CREB phosphorylation was also increased in the CA1 region of baicalein-treated slices. Baicalein-treated rats performed significantly better than controls in a hippocampus-dependent contextual fear conditioning task. Furthermore, baicalein treatment selectively increased the phosphorylation of Akt and CREB in the CA1 region of hippocampus, but not in the prefrontal cortex, after fear conditioning training. CONCLUSIONS AND IMPLICATIONS Our results demonstrate that the flavonoid baicalein can facilitate memory, and therefore it might be useful in the treatment of patients with memory disorders. PMID:21133890

  14. Catabolism of low density lipoproteins by perfused rabbit livers: cholestyramine promotes receptor-dependent hepatic catabolism of low density lipoproteins.

    PubMed

    Chao, Y S; Yamin, T T; Alberts, A W

    1982-07-01

    Rabbits fed a wheat starch/casein diet develop a marked hypercholesterolemia accompanied by a decrease in the number of EDTA-sensitive binding sites on plasma membrane fractions of the liver for low density lipoproteins (LDL) and beta-migrating very low density lipoproteins [Chao, Y.-S., Yamin, T.-T. & Alberts, A. W. (1982) J. Biol. Chem., in press]. Inclusion of 1% cholestyramine resin in this diet prevents the increase in plasma cholesterol, increases the removal of LDL from plasma, and increases the number of hepatic plasma membrane LDL-binding sites. To determine the functional role of hepatic LDL-binding sites in the catabolism of LDL, we studied the catabolism of (125)I-labeled LDL ((125)I-LDL) by in situ perfused rabbit livers in a recirculating system. The rate of catabolism was measured from the increment of nonprotein-bound radioiodine in the perfusate. The receptor-dependent catabolism of LDL by the liver was calculated from the difference of hepatic catabolism of (125)I-LDL and catabolism of (125)I-labeled cyclohexanedione-modified LDL, which does not bind to LDL receptors. The data show that about 74% of LDL catabolized by perfused livers from chow-fed rabbits is through the receptor-dependent pathway and 26% is through the receptor-independent pathway. In rabbits fed a cholesterol diet, the hepatic catabolism of (125)I-LDL is reduced, and the receptor-dependent catabolism of (125)I-LDL is abolished. In rabbits fed the wheat starch/casein diet, the receptor-dependent catabolism of (125)I-LDL is reduced by 40% when compared with hepatic catabolism in chow-fed rabbits. Perfused livers from rabbits fed the wheat starch/casein diet supplemented with 1% cholestyramine show a 5,4-fold increase of receptor-dependent catabolism of (125)I-LDL when compared with that of livers from rabbits fed the wheat starch/casein diet alone. Thus, these studies demonstrate that the change in the number of rabbit hepatic membrane LDL receptors induced by dietary manipulation

  15. 42 CFR 52d.1 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.1 Applicability. The regulations in this part apply to grants under the Clinical Cancer Education Program authorized by section 404(a)(4) of the Public Health Service Act,...

  16. 42 CFR 52d.1 - Applicability.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.1 Applicability. The regulations in this part apply to grants under the Clinical Cancer Education Program authorized by section 404(a)(4) of the Public Health Service Act,...

  17. 42 CFR 52d.1 - Applicability.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.1 Applicability. The regulations in this part apply to grants under the Clinical Cancer Education Program authorized by section 404(a)(4) of the Public Health Service Act,...

  18. 42 CFR 52d.1 - Applicability.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.1 Applicability. The regulations in this part apply to grants under the Clinical Cancer Education Program authorized by section 404(a)(4) of the Public Health Service Act,...

  19. 42 CFR 52d.1 - Applicability.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.1 Applicability. The regulations in this part apply to grants under the Clinical Cancer Education Program authorized by section 404(a)(4) of the Public Health Service Act,...

  20. Retrieval-induced NMDA receptor-dependent Arc expression in two models of cocaine-cue memory.

    PubMed

    Alaghband, Yasaman; O'Dell, Steven J; Azarnia, Siavash; Khalaj, Anna J; Guzowski, John F; Marshall, John F

    2014-12-01

    The association of environmental cues with drugs of abuse results in persistent drug-cue memories. These memories contribute significantly to relapse among addicts. While conditioned place preference (CPP) is a well-established paradigm frequently used to examine the modulation of drug-cue memories, very few studies have used the non-preference-based model conditioned activity (CA) for this purpose. Here, we used both experimental approaches to investigate the neural substrates of cocaine-cue memories. First, we directly compared, in a consistent setting, the involvement of cortical and subcortical brain regions in cocaine-cue memory retrieval by quantifying activity-regulated cytoskeletal-associated (Arc) protein expression in both the CPP and CA models. Second, because NMDA receptor activation is required for Arc expression, we investigated the NMDA receptor dependency of memory persistence using the CA model. In both the CPP and CA models, drug-paired animals showed significant increases in Arc immunoreactivity in regions of the frontal cortex and amygdala compared to unpaired controls. Additionally, administration of a NMDA receptor antagonist (MK-801 or memantine) immediately after cocaine-CA memory reactivation impaired the subsequent conditioned locomotion associated with the cocaine-paired environment. The enhanced Arc expression evident in a subset of corticolimbic regions after retrieval of a cocaine-context memory, observed in both the CPP and CA paradigms, likely signifies that these regions: (i) are activated during retrieval of these memories irrespective of preference-based decisions, and (ii) undergo neuroplasticity in order to update information about cues previously associated with cocaine. This study also establishes the involvement of NMDA receptors in maintaining memories established using the CA model, a characteristic previously demonstrated using CPP. Overall, these results demonstrate the utility of the CA model for studies of cocaine

  1. Coherence structure of D1 scattering

    NASA Astrophysics Data System (ADS)

    Stenflo, Jan Olof

    2015-10-01

    The extensive literature on the physics of polarized scattering may give the impression that we have a solid theoretical foundation for the interpretation of spectro-polarimetric data. This theoretical framework has however not been sufficiently tested by experiments under controlled conditions. While the solar atmosphere may be viewed as a physics laboratory, the observed solar polarization depends on too many environmental factors that are beyond our control. The existence of a symmetric polarization peak at the center of the solar Na D1 line has remained an enigma for two decades, in spite of persistent efforts to explain it with available quantum theory. A decade ago a laboratory experiment was set up to determine whether this was a problem for solar physics or quantum physics. The experiment revealed a rich polarization structure of D1 scattering, although available quantum theory predicted null results. It has now finally been possible to formulate a well-defined and self-consistent extension of the theory of quantum scattering that can reproduce in great quantitative detail the main polarization structures that were found in the laboratory experiment. Here we give a brief overview of the new physical ingredients that were missing before. The extended theory reveals that multi-level atomic systems have a far richer coherence structure than previously believed.

  2. Epidermal growth factor receptor-dependent stimulation of amphiregulin expression in androgen-stimulated human prostate cancer cells.

    PubMed Central

    Sehgal, I; Bailey, J; Hitzemann, K; Pittelkow, M R; Maihle, N J

    1994-01-01

    Amphiregulin is a heparin-binding epidermal growth factor (EGF)-related peptide that binds to the EGF receptor (EGF-R) with high affinity. In this study, we report a role for amphiregulin in androgen-stimulated regulation of prostate cancer cell growth. Androgen is known to enhance EGF-R expression in the androgen-sensitive LNCaP human prostate carcinoma cell line, and it has been suggested that androgenic stimuli may regulate proliferation, in part, through autocrine mechanisms involving the EGF-R. In this study, we demonstrate that LNCaP cells express amphiregulin mRNA and peptide and that this expression is elevated by androgenic stimulation. We also show that ligand-dependent EGF-R stimulation induces amphiregulin expression and that androgenic effects on amphiregulin synthesis are mediated through this EGF-R pathway. Parallel studies using the estrogen-responsive breast carcinoma cell line, MCF-7, suggest that regulation of amphiregulin by estrogen may also be mediated via an EGF-R pathway. In addition, heparin treatment of LNCaP cells inhibits androgen-stimulated cell growth further suggesting that amphiregulin can mediate androgen-stimulated LNCaP proliferation. Together, these results implicate an androgen-regulated autocrine loop composed of amphiregulin and its receptor in prostate cancer cell growth and suggest that the mechanism of steroid hormone regulation of amphiregulin synthesis may occur through androgen upregulation of the EGF-R and subsequent receptor-dependent pathways. Images PMID:8049525

  3. Synergism of aromatic amines and benzo[a]pyrene in induction of Ah receptor-dependent genes.

    PubMed

    Borza, Alexandra; Plöttner, Sabine; Wolf, Alexander; Behm, Claudia; Selinski, Silvia; Hengstler, Jan G; Roos, Peter H; Bolt, Hermann M; Kuhlmann, Jürgen; Föllmann, Wolfram

    2008-12-01

    Aromatic amines have been shown to cause bladder cancer. However, epithelial cells of the urinary bladder, cells of origin of bladder cancer, may be exposed to numerous substances besides aromatic amines. In the present study, we analysed possible interactions between the aromatic amines 4-aminobiphenyl (4-ABP) as well as 2-naphthylamine (2-NA) and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). For this purpose we incubated primary porcine urinary bladder epithelial cells (PUBEC) with concentrations of 1 to 50 microM 4-ABP with and without co-exposure to B[a]P. As expected B[a]P increased mRNA expression of cytochrome P450 1A1 (CYP1A1), whereas 4-ABP had no effect. However, when co-exposed 4-ABP enhanced the induction of CYP1A1 by B[a]P. This result was confirmed by Western blot analysis of CYP1A1 protein expression. A similar effect as for CYP1A1 was also observed for cyclooxygenase-2 (COX-2) and UDP-glucuronosyltransferase 1 (UGT1). Next, we studied co-exposures of 2-NA and B[a]P. Similar as for 4-ABP also 2-NA enhanced B[a]P-mediated induction of CYP1A1. Our results demonstrate that some aromatic amines may enhance the influence of B[a]P on Ah receptor-dependent genes. PMID:18989657

  4. 26 CFR 31.3231(d)-1 - Service.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Service. 31.3231(d)-1 Section 31.3231(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND... Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(d)-1 Service....

  5. 26 CFR 31.3231(d)-1 - Service.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 false Service. 31.3231(d)-1 Section 31.3231(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND... Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(d)-1 Service....

  6. 26 CFR 31.3231(d)-1 - Service.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false Service. 31.3231(d)-1 Section 31.3231(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND... Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(d)-1 Service....

  7. 26 CFR 31.3231(d)-1 - Service.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Service. 31.3231(d)-1 Section 31.3231(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND... Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(d)-1 Service....

  8. D1-protein dynamics in photosystem II: the lingering enigma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The D1/D2 heterodimer core dominates the photosystem II reaction center. A characteristic feature of this heterodimer is the differentially rapid, light-dependent degradation of the D1 protein. The D1 protein is possibly the most researched photosynthetic polypeptide, with aspects of structure–funct...

  9. 26 CFR 31.3231(d)-1 - Service.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Service. 31.3231(d)-1 Section 31.3231(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND... Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(d)-1 Service....

  10. 26 CFR 1.927(d)-1 - Other definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 10 2010-04-01 2010-04-01 false Other definitions. 1.927(d)-1 Section 1.927(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Earned Income of Citizens of United States § 1.927(d)-1 Other definitions. (a) Carrying Charges. Q-1. Under what circumstances...

  11. 26 CFR 25.2522(d)-1 - Additional cross references.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 14 2014-04-01 2013-04-01 true Additional cross references. 25.2522(d)-1 Section 25.2522(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Deductions § 25.2522(d)-1...

  12. 26 CFR 25.2522(d)-1 - Additional cross references.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 14 2012-04-01 2012-04-01 false Additional cross references. 25.2522(d)-1 Section 25.2522(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Deductions § 25.2522(d)-1...

  13. 26 CFR 25.2522(d)-1 - Additional cross references.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 14 2013-04-01 2013-04-01 false Additional cross references. 25.2522(d)-1 Section 25.2522(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Deductions § 25.2522(d)-1...

  14. Opioid Receptor-Dependent Sex Differences in Synaptic Plasticity in the Hippocampal Mossy Fiber Pathway of the Adult Rat

    PubMed Central

    Harte-Hargrove, Lauren C.; Varga-Wesson, Ada; Duffy, Aine M.; Milner, Teresa A.

    2015-01-01

    The mossy fiber (MF) pathway is critical to hippocampal function and influenced by gonadal hormones. Physiological data are limited, so we asked whether basal transmission and long-term potentiation (LTP) differed in slices of adult male and female rats. The results showed small sex differences in basal transmission but striking sex differences in opioid receptor sensitivity and LTP. When slices were made from females on proestrous morning, when serum levels of 17β-estradiol peak, the nonspecific opioid receptor antagonist naloxone (1 μm) enhanced MF transmission but there was no effect in males, suggesting preferential opioid receptor-dependent inhibition in females when 17β-estradiol levels are elevated. The μ-opioid receptor (MOR) antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP; 300 nm) had a similar effect but the δ-opioid receptor (DOR) antagonist naltrindole (NTI; 1 μm) did not, implicating MORs in female MF transmission. The GABAB receptor antagonist saclofen (200 μm) occluded effects of CTOP but the GABAA receptor antagonist bicuculline (10 μm) did not. For LTP, a low-frequency (LF) protocol was used because higher frequencies elicited hyperexcitability in females. Proestrous females exhibited LF-LTP but males did not, suggesting a lower threshold for synaptic plasticity when 17β-estradiol is elevated. NTI blocked LF-LTP in proestrous females, but CTOP did not. Electron microscopy revealed more DOR-labeled spines of pyramidal cells in proestrous females than males. Therefore, we suggest that increased postsynaptic DORs mediate LF-LTP in proestrous females. The results show strong MOR regulation of MF transmission only in females and identify a novel DOR-dependent form of MF LTP specific to proestrus. PMID:25632146

  15. The clearance of human fibrinogen fragments D1, D2, D3 and fibrin fragment D1 dimer in mice.

    PubMed

    Pizzo, S V; Pasqua, J J

    1982-10-01

    The clearance of human fibrinogen fragments D1, D2, D3 and fibrin fragment D1 dimer were studied in the mouse model. Clearance of these fragments is a complex process involving clearance from blood into three other compartments. The overall clearance of fragment D1 and its dimer were essentially identical. Fragments D2 and D3 cleared at a progressively slower rate. Competition studies were performed between 125I-labeled fragment D1 and large molar excesses of unlabeled human fragments D1, D2, D3, D1 dimer, fragment E, fibrinogen, macroalbumin, mannan and asialoorosomucoid. Of these ligands only the fragment D variants competed for the clearance of 125I-labeled fragment D1. Cross-competition was observed when 125I-labeled fragment D1 dimer was cleared in the presence of a large molar excesses of fragment D1. Autopsies demonstrated that injected fragments D1, D2, D3 and D1 dimer cleared primarily in liver and kidneys. In some clearance studies, livers were perfused with tissue culture fluid, subjected to light microscopic autoradiography, and silver grain counts performed to localize cleared fragment D1. These experiments indicated that 80% of the liver uptake was in hepatocytes. However, when silver grain counts were normalized for the number of parenchymal and nonparenchymal cells, the distribution of silver grains was essentially identical (1.8 and 1.6 grains per cells, respectively). It is concluded that fragments D1, D2, D3 and D1 dimer are recognized by a similar clearance pathway. Since neither fibrinogen nor fragment E competed for the clearance of fragment D1, it is suggested that determinants present in the fragment D domain become exposed after plasmin attack on fibrinogen and are responsible for clearance. PMID:7138910

  16. Nucleic acid sequences encoding D1 and D1/D2 domains of human coxsackievirus and adenovirus receptor (CAR)

    DOEpatents

    Freimuth, Paul I.

    2010-04-06

    The invention provides recombinant human CAR (coxsackievirus and adenovirus receptor) polypeptides which bind adenovirus. Specifically, polypeptides corresponding to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2 are provided. In another aspect, the invention provides nucleic acid sequences encoding these domains and expression vectors for producing the domains and bacterial cells containing such vectors. The invention also includes an isolated fusion protein comprised of the D1 polypeptide fused to a polypeptide which facilitates folding of D1 when expressed in bacteria. The functional D1 domain finds application in a therapeutic method for treating a patient infected with a CAR D1-binding virus, and also in a method for identifying an antiviral compound which interferes with viral attachment. The invention also provides a method for specifically targeting a cell for infection by a virus which binds to D1.

  17. Phosphorylation-dependent regulation of cyclin D1 nuclear export and cyclin D1–dependent cellular transformation

    PubMed Central

    Alt, Jodi R.; Cleveland, John L.; Hannink, Mark; Diehl, J. Alan

    2000-01-01

    GSK-3β-dependent phosphorylation of cyclin D1 at Thr-286 promotes the nuclear-to-cytoplasmic redistribution of cyclin D1 during S phase of the cell cycle, but how phosphorylation regulates redistribution has not been resolved. For example, phosphorylation of nuclear cyclin D1 could increase its rate of nuclear export relative to nuclear import; alternatively, phosphorylation of cytoplasmic cyclin D1 by GSK-3β could inhibit nuclear import. Here, we report that GSK-3β-dependent phosphorylation promotes cyclin D1 nuclear export by facilitating the association of cyclin D1 with the nuclear exportin CRM1. D1-T286A, a cyclin D1 mutant that cannot be phosphorylated by GSK-3β, remains nuclear throughout the cell cycle, a consequence of its reduced binding to CRM1. Constitutive overexpression of the nuclear cyclin D1-T286A in murine fibroblasts results in cellular transformation and promotes tumor growth in immune compromised mice. Thus, removal of cyclin D1 from the nucleus during S phase appears essential for regulated cell division. PMID:11124803

  18. Attenuation of D-1 antagonist-induced D-1 receptor upregulation by conccomitant D-2 receptor blockade

    SciTech Connect

    Parashos, S.A.; Barone, P.; Tucci, I.; Chase, T.N.

    1987-11-16

    The effect of chronic selective D-1 and/or D-2 dopamine receptor blockade on regional D-1 receptor binding was studied in rat brain following chronic treatment with the specific D-1 antagonist SCH 23390 and/or the predominantly D-2 antagonist haloperidol. D-1 receptor density and affinity were evaluated by quantitative autoradiography using /sup 125/I-SCH 23982. Chronic SCH 23390 treatment increased D-1 receptor density by 30 to 40% in the striatum, accumbens and tuberculum olfactorium; receptor affinity remained unchanged. Haloperidol had no effect on D-1 receptor Bmax or Kd values, although, when administered with SCH 23390, reduced the D-1 receptor upregulation induced by the D-1 antagonist in striatum and tuberculum olfactorium, but not in nucleus accumbens, These results may be attributable to D-1/D-2 dopamine receptor interactions occurring in the striatum and tuberculum olfactorium and may have implications for the prevention and treatment of drug-induced extrapyramidal disorders. 34 references, 1 figure, 2 tables.

  19. Transferrin D1: identity in Australian aborigines and American Negroes.

    PubMed

    Wang, A C; Sutton, H E; Scott, I D

    1967-05-19

    Human transferrin D(1) obtained from an Australian aborigine was found to have the same substitution of glycine for aspartic acid in peptide 1C previously shown in transferrin D(1) from an American Negro. This finding is relevant to formation of distinct Australoid and African populations. PMID:6023254

  20. Development of specific dopamine D-1 agonists and antagonists

    SciTech Connect

    Sakolchai, S.

    1987-01-01

    To develop potentially selective dopamine D-1 agonists and to investigate on the structural requirement for D-1 activity, the derivatives of dibenzocycloheptadiene are synthesized and pharmacologically evaluated. The target compounds are 5-aminomethyl-10,11-dihydro-1,2-dihydroxy-5H-dibenzo(a,d)cycloheptene hydrobromide 10 and 9,10-dihydroxy-1,2,3,7,8,12b-hexahydrobenzo(1,2)cyclohepta(3,4,5d,e)isoquinoline hydrobromide 11. In a dopamine-sensitive rat retinal adenylate cyclase assay, a model for D-1 activity, compound 10 is essentially inert for both agonist and antagonist activity. In contrast, compound 11 is approximately equipotent to dopamine in activation of the D-1 receptor. Based on radioligand and binding data, IC{sub 50} of compound 11 for displacement of {sup 3}H-SCH 23390, a D-1 ligand, is about 7 fold less than that for displacement of {sup 3}H-spiperone, a D-2 ligand. These data indicate that compound 11 is a potent selective dopamine D-1 agonist. This study provides a new structural class of dopamine D-1 acting agent: dihydroxy-benzocycloheptadiene analog which can serve as a lead compound for further drug development and as a probe for investigation on the nature of dopamine D-1 receptor.

  1. 26 CFR 31.3402(d)-1 - Failure to withhold.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false Failure to withhold. 31.3402(d)-1 Section 31... Collection of Income Tax at Source § 31.3402(d)-1 Failure to withhold. If the employer in violation of the... penalties or additions to the tax applicable in respect of such failure to deduct and withhold. The...

  2. 26 CFR 31.3402(d)-1 - Failure to withhold.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Failure to withhold. 31.3402(d)-1 Section 31... Collection of Income Tax at Source § 31.3402(d)-1 Failure to withhold. If the employer in violation of the... penalties or additions to the tax applicable in respect of such failure to deduct and withhold. The...

  3. 26 CFR 31.3402(d)-1 - Failure to withhold.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Failure to withhold. 31.3402(d)-1 Section 31... Collection of Income Tax at Source § 31.3402(d)-1 Failure to withhold. If the employer in violation of the... penalties or additions to the tax applicable in respect of such failure to deduct and withhold. The...

  4. 26 CFR 31.3402(d)-1 - Failure to withhold.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Failure to withhold. 31.3402(d)-1 Section 31... Collection of Income Tax at Source § 31.3402(d)-1 Failure to withhold. If the employer in violation of the... penalties or additions to the tax applicable in respect of such failure to deduct and withhold. The...

  5. 26 CFR 31.3121(d)-1 - Who are employees.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Who are employees. 31.3121(d)-1 Section 31.3121(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Insurance Contributions Act (Chapter...

  6. 26 CFR 31.3121(d)-1 - Who are employees.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 false Who are employees. 31.3121(d)-1 Section 31.3121(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Insurance Contributions Act (Chapter...

  7. 26 CFR 31.3402(d)-1 - Failure to withhold.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 false Failure to withhold. 31.3402(d)-1 Section 31... Collection of Income Tax at Source § 31.3402(d)-1 Failure to withhold. If the employer in violation of the... penalties or additions to the tax applicable in respect of such failure to deduct and withhold. The...

  8. 26 CFR 1.927(d)-1 - Other definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 10 2011-04-01 2011-04-01 false Other definitions. 1.927(d)-1 Section 1.927(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX... determined for purposes of section 1274(d) and which is published in the Internal Revenue Bulletin....

  9. 26 CFR 1.927(d)-1 - Other definitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 10 2014-04-01 2013-04-01 true Other definitions. 1.927(d)-1 Section 1.927(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED... determined for purposes of section 1274(d) and which is published in the Internal Revenue Bulletin....

  10. 26 CFR 1.927(d)-1 - Other definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 10 2012-04-01 2012-04-01 false Other definitions. 1.927(d)-1 Section 1.927(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX... determined for purposes of section 1274(d) and which is published in the Internal Revenue Bulletin....

  11. 26 CFR 1.927(d)-1 - Other definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 10 2013-04-01 2013-04-01 false Other definitions. 1.927(d)-1 Section 1.927(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX... determined for purposes of section 1274(d) and which is published in the Internal Revenue Bulletin....

  12. 26 CFR 25.2523(d)-1 - Joint interests.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 14 2013-04-01 2013-04-01 false Joint interests. 25.2523(d)-1 Section 25.2523(d... TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Deductions § 25.2523(d)-1 Joint interests. Section 2523(d) provides that if a property interest is transferred to the donee spouse as sole joint...

  13. 26 CFR 25.2523(d)-1 - Joint interests.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 14 2012-04-01 2012-04-01 false Joint interests. 25.2523(d)-1 Section 25.2523(d... TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Deductions § 25.2523(d)-1 Joint interests. Section 2523(d) provides that if a property interest is transferred to the donee spouse as sole joint...

  14. 26 CFR 25.2523(d)-1 - Joint interests.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 14 2011-04-01 2010-04-01 true Joint interests. 25.2523(d)-1 Section 25.2523(d... TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Deductions § 25.2523(d)-1 Joint interests. Section 2523(d) provides that if a property interest is transferred to the donee spouse as sole joint...

  15. 26 CFR 25.2523(d)-1 - Joint interests.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 14 2014-04-01 2013-04-01 true Joint interests. 25.2523(d)-1 Section 25.2523(d... TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Deductions § 25.2523(d)-1 Joint interests. Section 2523(d) provides that if a property interest is transferred to the donee spouse as sole joint...

  16. 26 CFR 25.2523(d)-1 - Joint interests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Joint interests. 25.2523(d)-1 Section 25.2523(d... TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Deductions § 25.2523(d)-1 Joint interests. Section 2523(d) provides that if a property interest is transferred to the donee spouse as sole joint...

  17. The D 1Σ+ state of 7LiH

    NASA Astrophysics Data System (ADS)

    Huang, Yen-Ling; Luh, Wei-Tzou; Jeung, Gwang-Hi; Gadéa, F. Xavier

    2000-07-01

    The 7LiH D 1Σ+ excited electronic state has been observed for the first time by a pulsed optical-optical double resonance fluorescence depletion spectroscopic technique. Several rovibrational levels of the A 1Σ+ and B 1Π electronic states have been used as the intermediate states. Among 22 vibrational levels, 128 rovibrational levels have been observed. The spectral assignment is identified by the observed rotational structures and term values and by a comparison between the derived vibrational and rotational constants with the theoretical values. An ab initio adiabatic potential energy curve for the D 1Σ+ state and relevant D 1Σ+-A1Σ+ and D 1Σ+-B 1Π transition moment functions are presented. An overall measure of three different aspects, the energetics, the spectral line shape, and the transition probability, strongly favors the argument that the vibronic approach is a better approach for characterizing the excited D 1Σ+ electronic state.

  18. Paradoxical roles of cyclin D1 in DNA stability.

    PubMed

    Jirawatnotai, Siwanon; Sittithumcharee, Gunya

    2016-06-01

    Maintenance of DNA integrity is vital for all of the living organisms. Consequence of DNA damaging ranges from, introducing harmless synonymous mutations, to causing disease-associated mutations, genome instability, and cell death. A cell cycle protein cyclin D1 is an established cancer-driving protein. However, contribution of cyclin D1 to cancer formation and cancer survival is not entirely known. In cancer tissues, overexpression of cyclin D1 is associated with both cancer genome instability, and resistance to DNA-damaging cancer drugs. Emerging evidence indicated that cyclin D1 may play novel direct roles in regulating DNA repair. Here we provide an insight how cyclin D1 expression may contribute to DNA repair and chromosome instability, and how these functions may facilitate cancer formation, and drug resistance. PMID:27155130

  19. Interaction of environmental contaminants with zebrafish organic anion transporting polypeptide, Oatp1d1 (Slco1d1)

    SciTech Connect

    Popovic, Marta; Zaja, Roko; Fent, Karl; Smital, Tvrtko

    2014-10-01

    Polyspecific transporters from the organic anion transporting polypeptide (OATP/Oatp) superfamily mediate the uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol. It is predominantly expressed in the liver, brain and testes. In this study we have characterized the transport of xenobiotics by the zebrafish Oatp1d1 transporter. We developed a novel assay for assessing Oatp1d1 interactors using the fluorescent probe Lucifer yellow and transient transfection in HEK293 cells. Our data showed that numerous environmental contaminants interact with zebrafish Oatp1d1. Oatp1d1 mediated the transport of diclofenac with very high affinity, followed by high affinity towards perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil and 17α-ethinylestradiol; moderate affinity towards carbaryl, diazinon and caffeine; and low affinity towards metolachlor. Importantly, many environmental chemicals acted as strong inhibitors of Oatp1d1. A strong inhibition of Oatp1d1 transport activity was found by perfluorooctanoic acid (PFOA), chlorpyrifos-methyl, estrone (E1) and 17β-estradiol (E2), followed by moderate to low inhibition by diethyl phthalate, bisphenol A, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronapthalene and clofibrate. In this study we identified Oatp1d1 as a first Solute Carrier (SLC) transporter involved in the transport of a wide range of xenobiotics in fish. Considering that Oatps in zebrafish have not been characterized before, our work on zebrafish Oatp1d1 offers important new insights on the understanding of uptake processes of environmental contaminants, and contributes to the better characterization of zebrafish as a model species. - Highlights: • We optimized a novel assay for determination of Oatp1d1 interactors • Oatp1d1 is the first SLC characterized fish xenobiotic transporter • PFOS, nonylphenol, diclofenac, EE2, caffeine are high affinity Oatp1d1substrates • PFOA, chlorpyrifos

  20. Dopamine D1 signaling organizes network dynamics underlying working memory

    PubMed Central

    Roffman, Joshua L.; Tanner, Alexandra S.; Eryilmaz, Hamdi; Rodriguez-Thompson, Anais; Silverstein, Noah J.; Ho, New Fei; Nitenson, Adam Z.; Chonde, Daniel B.; Greve, Douglas N.; Abi-Dargham, Anissa; Buckner, Randy L.; Manoach, Dara S.; Rosen, Bruce R.; Hooker, Jacob M.; Catana, Ciprian

    2016-01-01

    Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory–emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits. PMID:27386561

  1. Interaction of environmental contaminants with zebrafish organic anion transporting polypeptide, Oatp1d1 (Slco1d1).

    PubMed

    Popovic, Marta; Zaja, Roko; Fent, Karl; Smital, Tvrtko

    2014-10-01

    Polyspecific transporters from the organic anion transporting polypeptide (OATP/Oatp) superfamily mediate the uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol. It is predominantly expressed in the liver, brain and testes. In this study we have characterized the transport of xenobiotics by the zebrafish Oatp1d1 transporter. We developed a novel assay for assessing Oatp1d1 interactors using the fluorescent probe Lucifer yellow and transient transfection in HEK293 cells. Our data showed that numerous environmental contaminants interact with zebrafish Oatp1d1. Oatp1d1 mediated the transport of diclofenac with very high affinity, followed by high affinity towards perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil and 17α-ethinylestradiol; moderate affinity towards carbaryl, diazinon and caffeine; and low affinity towards metolachlor. Importantly, many environmental chemicals acted as strong inhibitors of Oatp1d1. A strong inhibition of Oatp1d1 transport activity was found by perfluorooctanoic acid (PFOA), chlorpyrifos-methyl, estrone (E1) and 17β-estradiol (E2), followed by moderate to low inhibition by diethyl phthalate, bisphenol A, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronapthalene and clofibrate. In this study we identified Oatp1d1 as a first Solute Carrier (SLC) transporter involved in the transport of a wide range of xenobiotics in fish. Considering that Oatps in zebrafish have not been characterized before, our work on zebrafish Oatp1d1 offers important new insights on the understanding of uptake processes of environmental contaminants, and contributes to the better characterization of zebrafish as a model species. PMID:25088042

  2. Phylogeography of mitochondrial haplogroup D1: an early spread of subhaplogroup D1j from Central Argentina.

    PubMed

    García, Angelina; Pauro, Maia; Nores, Rodrigo; Bravi, Claudio M; Demarchi, Darío A

    2012-12-01

    We analyzed the patterns of variation of haplogroup D1 in central Argentina, including new data and published information from other populations of South America. Almost 28% (107/388) of the individuals sampled in the region belong to haplogroup D1, whereas more than 52% of them correspond to the recently described subhaplogroup D1j (Bodner et al.: Genome Res 22 (2012) 811-820), defined by the presence of additional transitions at np T152C-C16242T-T16311C to the nodal D1 motif. This lineage was found at high frequencies across a wide territory with marked geographical-ecological differences. Additionally, 12 individuals present the mutation C16187T that defines the recently named subhaplogroup D1g (Bodner et al.: Genome Res 22 (2012) 811-820), previously described in populations of Patagonia and Tierra del Fuego. Based on our results and additional data already published, we postulate that the most likely origin of subhaplogroup D1j is the region of Sierras Pampeanas, which occupies the center and part of the northwestern portion of Argentina. The extensive yet restricted geographical distribution, the relatively large internal diversity, and the absence or low incidence of D1j in other regions of South America suggest the existence of an ancient metapopulation covering the Sierras Pampeanas, being this lineage its genetic signature. Further support for a scenario of local origin for D1j in the Sierras Pampeanas stems from the fact that early derivatives from a putative ancestral lineage carrying the transitions T16311C-T152C have only been found in this region, supporting the hypothesis that it might represent an ancestral motif previous to the appearance of D1j-specific change C16242T. PMID:23114854

  3. Underground storage tank 291-D1U1: Closure plan

    SciTech Connect

    Mancieri, S.; Giuntoli, N.

    1993-09-01

    The 291-D1U1 tank system was installed in 1983 on the north side of Building 291. It supplies diesel fuel to the Building 291 emergency generator and air compressor. The emergency generator and air compressor are located southwest and southeast, respectively, of the tank (see Appendix B, Figure 2). The tank system consists of a single-walled, 2,000- gallon, fiberglass tank and a fuel pump system, fill pipe, vent pipe, electrical conduit, and fuel supply and return piping. The area to be excavated is paved with asphalt and concrete. It is not known whether a concrete anchor pad is associated with this tank. Additionally, this closure plan assumes that the diesel tank is below the fill pad. The emergency generator and air compressor for Building 291 and its associated UST, 291-D1U1, are currently in use. The generator and air compressor will be supplied by a temporary above-ground fuel tank prior to the removal of 291-D1U1. An above-ground fuel tank will be installed as a permanent replacement for 291-D1U1. The system was registered with the State Water Resources Control Board on June 27, 1984, as 291-41D and has subsequently been renamed 291-D1U1. Figure 1 (see Appendix B) shows the location of the 291-D1U1 tank system in relation to the Lawrence Livermore National Laboratory (LLNL). Figure 2 (see Appendix B) shows the 291-D1U1 tank system in relation to Building 291. Figure 3 (see Appendix B) shows a plan view of the 291-D1U1 tank system.

  4. Evidence against dopamine D1/D2 receptor heteromers

    PubMed Central

    Frederick, Aliya L.; Yano, Hideaki; Trifilieff, Pierre; Vishwasrao, Harshad D.; Biezonski, Dominik; Mészáros, József; Sibley, David R.; Kellendonk, Christoph; Sonntag, Kai C.; Graham, Devon L.; Colbran, Roger J.; Stanwood, Gregg D.; Javitch, Jonathan A.

    2014-01-01

    Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer (BRET), ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect Gαq or Gα11 protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and Gαq knockout mice, as well as in knock-in mice expressing a mutant Ala286-CaMKIIα, that cannot autophosphorylate to become active. Moreover, we found that in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through Gαq or through a D1–D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies. PMID:25560761

  5. Linoleic acid attenuates cardioprotection induced by resolvin D1.

    PubMed

    Gilbert, Kim; Malick, Mandy; Madingou, Ness; Bourque-Riel, Valérie; Touchette, Charles; Rousseau, Guy

    2016-05-01

    We previously observed that resolvin D1 (RvD1), a metabolite of the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid, reduces infarct size by a mechanism involving the PI3-K/Akt pathway. In parallel, the beneficial effect of a high omega-3 PUFA diet on infarct size can be attenuated by increased omega-6 PUFA consumption. The present study was designed to determine if augmented linoleic acid (LA), an omega-6 PUFA administered at the same time, attenuates the cardioprotective action of RvD1. Male Sprague-Dawley rats received 0.1μg RvD1 alone or with one of three LA doses (1, 5 or 10μg) directly into the left ventricle chamber 5min before ischemia. The animals underwent 40min of ischemia by occlusion of the left descending coronary artery followed by 30min or 24h of reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion, while caspase-3, -8 and -9 and Akt activities were assessed at 30min of reperfusion. LA attenuated cardioprotection afforded by RvD1, resulting in significantly increased infarct size. Neutrophil accumulation and Akt activity were similar between groups. Caspase activities, especially caspase-9, which could be activated by ischemia, were stimulated in the presence of LA, suggesting that this omega-6 PUFA accentuates ischemia intensity. The present results indicate that LA significantly attenuates the beneficial effect of RvD1 on infarct size. Therefore, reduction of omega-6 intake should be considered to maintain the protection afforded by RvD1. PMID:27133431

  6. Loss of inhibition by formate in newly constructed photosystem II D1 mutants, D1-R257E and D1-R257M, of Chlamydomonas reinhardtii.

    PubMed

    Xiong, J; Minagawa, J; Crofts, A; Govindjee

    1998-07-20

    Formate is known to cause significant inhibition in the electron and proton transfers in photosystem II (PSII); this inhibition is uniquely reversed by bicarbonate. It has been suggested that bicarbonate functions by providing ligands to the non-heme iron and by facilitating protonation of the secondary plastoquinone QB. Numerous lines of evidence indicate an intimate relationship of bicarbonate and formate binding of PSII. To investigate the potential amino acid binding environment of bicarbonate/formate in the QB niche, arginine 257 of the PSII D1 polypeptide in the unicellular green alga Chlamydomonas reinhardtii was mutated into a glutamate (D1-R257E) and a methionine (DQ-R257M). The two mutants share the following characteristics. (1) Both have a drastically reduced sensitivity to formate. (2) A larger fraction of QA- persists after flash illumination, which indicates an altered equilibrium constant of the reaction QA-QB<-->QA QB-, in the direction of [QA-], or a larger fraction of non-QB centers. However, there appears to be no significant difference in the rate of electron transfer from QA- to QB. (3) The overall rate of oxygen evolution is significantly reduced, most likely due to changes in the equilibrium constant on the electron acceptor side of PSII or due to a larger fraction in non-QB centers. Additional effects on the donor side cannot yet be excluded. (4) The binding affinity for the herbicide DCMU is unaltered. (5) The mutants grow photosynthetically, but at a decreased (approximately 70% of the wild type) level. (6) The Fo level was elevated (approximately 40-50%) which could be due to a decrease in the excitation energy transfer from the antenna to the PSII reaction center, and/or to an increased level of [QA-] in the dark. (7) A decreased (approximately 10%) ratio of F685 (mainly from CP43) and F695 (mainly from CP47) to F715 (mainly from PSI) emission bands at 77 K suggests a change in the antenna complex. Taken together these results lead to

  7. Geoscience for Alaska's D-1 Lands: A preliminary report

    USGS Publications Warehouse

    Schmidt, Jeanine M.; Gamble, B.M.; Labay, K.A.

    2007-01-01

    Purpose of This Report This interim report follows from the June 2006 recommendations to Congress by the BLM concerning disposition of the d-1 lands. That report recommended lifting of a significant number of d-1 PLOs, through the ongoing land management process within the BLM (e.g. resource management planning areas), or through Congressional action. The strategic actions outlined in this document refer only to Federal lands under US Bureau of Land Management (BLM) jurisdiction that 1) are affected by temporary withdrawals from mineral entry and mineral leasing by PLOs made pursuant to the Section 17(d)(1) of the ANCSA; 2) have been identified by the BLM as candidates for possible lifting of these PLOs and restrictions (U.S. Bureau of Land Management, 2006); and 3) lie outside of current Federal parks, preserves, monuments, refuges, reserves, wilderness areas and military installations that are closed to mineral entry, because within those areas the potential lifting of the d-1 restrictions has no practical effect. The resulting lands discussed here comprise approximately 121,000 km2 (29.9 million acres) of Alaska (Table 1) that, pending final resolution of Native and State land claims, will or may remain under Federal (BLM) control, and could be opened to mineral entry. For the purposes of this report, only these 29.9 million acres will hereafter be referred to as 'd-1' lands. This report gives a brief overview of the spatial distribution and physiographic setting, mineral occurrences, and mineral resource potential of the d-1lands. It outlines further geoscience information which could be compiled, collected, and evaluated in order to make a more accurate and comprehensive examination of the potential for undiscovered, locatable mineral resources on these Federal lands. This information is intended to provide guidance to USGS program managers and Federal land managers on matters of future exploration, access needs, and consequences of land status changes.

  8. D-1A nose fairing separation fitting load test

    NASA Technical Reports Server (NTRS)

    Vanvleet, J. O.

    1976-01-01

    Structural testing of the D-1A Centaur nose fairing was completed to determine the loads imposed during flight on the latch bolts of the fairing separation system. This testing was conducted to supplement and/or verify the analytic techniques used in calculating bolt loads for the D-1A, and to gain insight into the general structural behavior of separation latch systems. It was shown that the assumed bolt load magnification due to prying action of the latch fittings on the bolt does occur, but is strongly dependent on fairing shell stiffness.

  9. In adult female hamsters hypothyroidism stimulates D1 receptor-mediated breathing without altering D1 receptor expression.

    PubMed

    Schlenker, Evelyn H; Del Rio, Rodrigo; Schultz, Harold D

    2015-11-01

    Hypothyroidism affects cardiopulmonary regulation and function of dopaminergic receptors. Here we evaluated effects of 5 months of hypothyroidism on dopamine D1 receptor modulation of breathing in female hamsters using a D1 receptor antagonist SCH 23390. Euthyroid hamsters (EH) served as controls. Results indicated that hypothyroid female hamsters (HH) exhibited decreased body weights and minute ventilation (VE) following hypoxia due to decreased frequency of breathing (F). Moreover, SCH 23390 administration in HH increased VE by increasing tidal volume during exposure to air, hypoxia and following hypoxia. Relative to vehicle, SCH 23390 treatment decreased body temperature and hypoxic VE responsiveness in both groups. In EH, SCH 23390 decreased F in air, hypoxia and post hypoxia, and VE during hypoxia trended to decrease (P=0.053). Finally, expression of D1 receptor protein was not different between the two groups in any region evaluated. Thus, hypothyroidism in older female hamsters affected D1 receptor modulation of ventilation differently relative to euthyroid animals, but not expression of D1 receptors. PMID:26232642

  10. Evolution of Dopamine Receptor Genes of the D1 Class in Vertebrates

    PubMed Central

    Yamamoto, Kei; Mirabeau, Olivier; Bureau, Charlotte; Blin, Maryline; Michon-Coudouel, Sophie; Demarque, Michaël; Vernier, Philippe

    2013-01-01

    The receptors of the dopamine neurotransmitter belong to two unrelated classes named D1 and D2. For the D1 receptor class, only two subtypes are found in mammals, the D1A and D1B, receptors, whereas additional subtypes, named D1C, D1D, and D1X, have been found in other vertebrate species. Here, we analyzed molecular phylogeny, gene synteny, and gene expression pattern of the D1 receptor subtypes in a large range of vertebrate species, which leads us to propose a new view of the evolution of D1 dopamine receptor genes. First, we show that D1C and D1D receptor sequences are encoded by orthologous genes. Second, the previously identified Cypriniform D1X sequence is a teleost-specific paralog of the D1B sequences found in all groups of jawed vertebrates. Third, zebrafish and several sauropsid species possess an additional D1-like gene, which is likely to form another orthology group of vertebrate ancestral genes, which we propose to name D1E. Ancestral jawed vertebrates are thus likely to have possessed four classes of D1 receptor genes—D1A, D1B(X), D1C(D), and D1E—which arose from large-scale gene duplications. The D1C receptor gene would have been secondarily lost in the mammalian lineage, whereas the D1E receptor gene would have been lost independently in several lineages of modern vertebrates. The D1A receptors are well conserved throughout jawed vertebrates, whereas sauropsid D1C receptors have rapidly diverged, to the point that they were misidentified as D1D. The functional significance of the D1C receptor loss is not known. It is possible that the function may have been substituted with D1A or D1B receptors in mammals, following the disappearance of D1C receptors in these species. PMID:23197594

  11. The role of dopamine D1 receptor transmission in effort-related choice behavior: Effects of D1 agonists.

    PubMed

    Yohn, Samantha E; Santerre, Jessica L; Nunes, Eric J; Kozak, Rouba; Podurgiel, Samantha J; Correa, Mercè; Salamone, John D

    2015-08-01

    Mesolimbic dopamine (DA), particularly in the nucleus accumbens, is a critical component of the brain circuitry involved in behavioral activation and effort-related processes. Although much is known about the characteristics of DA D2 receptor antagonism on effort-related choice behavior, less is known about the effects of D1 antagonism, and agonist/antagonist interactions. The highly selective D1 antagonist ecopipam was studied for its effects on effort-related choice behavior using the concurrent fixed ratio (FR) 5/chow feeding choice and T-maze barrier choice procedures. In rats tested on the FR5/chow feeding choice task, ecopipam shifted choice behavior, decreasing lever pressing for preferred high carbohydrate pellets but increasing consumption of lab chow. Also, ecopipam decreased selection of the high effort option (i.e., climbing the barrier to obtain a larger reward) in rats tested on the T-maze task, but did not disrupt arm preference or discrimination when no barrier was present. The D1 agonists SKF38393, SKF81297 and A77636 were assessed for their ability to reverse the effects of ecopipam, and in each case the D1 agonist significantly attenuated the effects of ecopipam, typically with an inverted-u shaped dose/response curve. SKF81297 also was able to reverse the effects of the catecholamine depleting agent tetrabenazine on T-maze performance. In summary, the present results implicate DA D1 receptors in the regulation of behavioral activation and effort-related functions, and demonstrate the utility of using tests of effort-related choice behavior for assessing the effects of D1 agonists. PMID:26022661

  12. Hydrodynamics of R-charged D1-branes

    NASA Astrophysics Data System (ADS)

    David, Justin R.; Mahato, Manavendra; Thakur, Somyadip; Wadia, Spenta R.

    2011-01-01

    We study the hydrodynamic properties of strongly coupled SU( N) Yang-Mills theory of the D1-brane at finite temperature and at a non-zero density of R-charge in the framework of gauge/gravity duality. The gravity dual description involves a charged black hole solution of an Einstein-Maxwell-dilaton system in 3 dimensions which is obtained by a consistent truncation of the spinning D1-brane in 10 dimensions. We evaluate thermal and electrical conductivity as well as the bulk viscosity as a function of the chemical potential conjugate to the R-charges of the D1-brane. We show that the ratio of bulk viscosity to entropy density is independent of the chemical potential and is equal to 1/ π4. The thermal conductivity and bulk viscosity obey a relationship similar to the Wiedemann-Franz law. We show that at the boundary of thermodynamic stability, the charge diffusion mode becomes unstable and the transport coefficients exhibit critical behaviour. Our method for evaluating the transport coefficients relies on expressing the second order differential equations in terms of a first order equation which dictates the radial evolution of the transport coefficient. The radial evolution equations can be solved exactly for the transport coefficients of our interest. We observe that transport coefficients of the D1-brane theory are related to that of the M2-brane by an overall proportionality constant which sets the dimensions.

  13. 17 CFR 270.35d-1 - Investment company names.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Investment company names. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.35d-1 Investment company names. (a... name of a Fund includes: (1) Names suggesting guarantee or approval by the United States government....

  14. 17 CFR 270.35d-1 - Investment company names.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Investment company names. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.35d-1 Investment company names. (a... name of a Fund includes: (1) Names suggesting guarantee or approval by the United States government....

  15. 17 CFR 270.35d-1 - Investment company names.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Investment company names. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.35d-1 Investment company names. (a... words “United States” or “U.S. government.” (2) Names suggesting investment in certain investments...

  16. 17 CFR 270.35d-1 - Investment company names.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Investment company names. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.35d-1 Investment company names. (a... words “United States” or “U.S. government.” (2) Names suggesting investment in certain investments...

  17. 17 CFR 270.35d-1 - Investment company names.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Investment company names. 270... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.35d-1 Investment company names. (a... words “United States” or “U.S. government.” (2) Names suggesting investment in certain investments...

  18. Underground storage tank 511-D1U1 closure plan

    SciTech Connect

    Mancieri, S.; Giuntoli, N.

    1993-09-01

    This document contains the closure plan for diesel fuel underground storage tank 511-D1U1 and appendices containing supplemental information such as staff training certification and task summaries. Precision tank test data, a site health and safety plan, and material safety data sheets are also included.

  19. CD14 as a Mediator of the Mineralocorticoid Receptor-Dependent Anti-apolipoprotein A-1 IgG Chronotropic Effect on Cardiomyocytes.

    PubMed

    Mannic, Tiphaine; Satta, Nathalie; Pagano, Sabrina; Python, Magaly; Virzi, Julien; Montecucco, Fabrizio; Frias, Miguel A; James, Richard W; Maturana, Andres D; Rossier, Michel F; Vuilleumier, Nicolas

    2015-12-01

    In vitro and animal studies point to autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) as possible mediators of cardiovascular (CV) disease involving several mechanisms such as basal heart rate interference mediated by a mineralocorticoid receptor-dependent L-type calcium channel activation, and a direct pro-inflammatory effect through the engagement of the toll-like receptor (TLR) 2/CD14 complex. Nevertheless, the possible implication of these receptors in the pro-arrhythmogenic effect of anti-apoA-1 antibodies remains elusive. We aimed at determining whether CD14 and TLRs could mediate the anti-apoA-1 IgG chronotropic response in neonatal rat ventricular cardiomyocytes (NRVC). Blocking CD14 suppressed anti-apoA-1 IgG binding to NRVC and the related positive chronotropic response. Anti-apoA-1 IgG alone induced the formation of a TLR2/TLR4/CD14 complex, followed by the phosphorylation of Src, whereas aldosterone alone promoted the phosphorylation of Akt by phosphatidylinositol 3-kinase (PI3K), without affecting the chronotropic response. In the presence of both aldosterone and anti-apoA-1 IgG, the localization of TLR2/TLR4/CD14 was increased in membrane lipid rafts, followed by PI3K and Src activation, leading to an L-type calcium channel-dependent positive chronotropic response. Pharmacological inhibition of the Src pathway led to the decrease of L-type calcium channel activity and abrogated the NRVC chronotropic response. Activation of CD14 seems to be a key regulator of the mineralocorticoid receptor-dependent anti-apoA-1 IgG positive chronotropic effect on NRVCs, involving relocation of the CD14/TLR2/TLR4 complex into lipid rafts followed by PI3K and Src-dependent L-type calcium channel activation. PMID:26393305

  20. Dopamine D1 receptors control exercise hyperpnoea in mice.

    PubMed

    Iwase, Michiko; Izumizaki, Masahiko; Tsuchiya, Naoto; Homma, Ikuo

    2013-02-01

    Previously, we undertook simultaneous recording of ventilation and pulmonary gas exchange in mice and revealed that dopamine D(2) receptors participate in exercise hyperpnoea via behavioural control of ventilation with unchanged pulmonary gas exchange. Here, we examined the hypothesis that D(1) receptors also contribute to exercise hyperpnoea using a D(1) receptor antagonist (SCH 23390; SCH) that crosses the blood-brain barrier, with the same recording technique and protocol as in the previous study. The respiratory responses of mice injected with saline or SCH (50 μg (kg body weight)(-1), i.p.) were compared during constant-load exercise at 6 m min(-1). Each mouse was set in an airtight treadmill chamber equipped with a differential pressure transducer and open-circuit system with a mass spectrometer. At rest, SCH-injected mice had significantly reduced respiratory frequency, minute ventilation and pulmonary gas exchange compared with saline-injected mice. Ventilation during hyperoxic gas inhalation and hypercapnic ventilatory responses between groups were similar. Abrupt increases and sequential declines to the steady-state level were produced by treadmill exercise in both groups of mice. Treatment with SCH lowered the increased levels of respiratory frequency, tidal volume and minute ventilation during the steady state, as well as reducing the O(2) uptake, CO(2) output and body temperature throughout treadmill exercise. These data suggest that D(1) receptors contribute to a resting ventilation level and exercise hyperpnoea during the steady state in parallel with metabolic changes. Notably, the metabolic control of D(1) receptors was important for maintenance of the steady state, and D(1) receptors in hypothalamic nuclei could be involved in this modulation. PMID:23024370

  1. D1 dopamine receptor activity of anti-parkinsonian drugs.

    PubMed

    Fici, G J; Wu, H; VonVoigtlander, P F; Sethy, V H

    1997-01-01

    Clinical and preclinical investigations suggest that stimulation of D1 dopamine receptors may be responsible for dyskinesias induced by dopamine agonist treatment of Parkinson's Disease (PD), and that these dyskinesias may be decreased by treatment with a D1 antagonist (clozapine). Therefore, the effects of dopamine agonists and antagonists have been investigated in a primary cerebellar granule cell model of cAMP formation that seems to be highly responsive to the D1 receptors. SKF 38393, lisuride, apomorphine, pergolide, dopamine, bromocriptine and 7-OH-DPAT showed concentration-dependent increases in cAMP formation, with EC50s (in microM) of 0.013, 0.053, 0.25, 1.04, 2.18, 50.9 and 54.4, respectively. SKF 38393, apomorphine, dopamine and pergolide had similar intrinsic activity (100%), while the intrinsic activities of 7-OH-DPAT, bromocriptine and lisuride were 28.0%, 20.7% and 17.2%, respectively. SCH 23390, a selective D1 dopamine receptor antagonist, blocked an increase in cAMP formation produced by EC50 concentrations of all of the dopamine agonists investigated in this study. Clozapine concentration-dependently blocked pergolide-induced increases in cAMP and was approximately 1700-fold less potent than SCH 23390 (IC50: 0.97 microM and 0.56 nM, respectively). U-95666A (1-1000 microM), selective for the D2 receptors, showed no significant effect on cAMP, while pramipexole (0.1-100 microM), a D3 preferring agonist, did not elevate cAMP. These data suggest that primary cerebellar granule cell cultures are an excellent model for measuring D1 dopamine receptor-mediated changes in cellular cAMP. The results are discussed with reference to the relationship between the D1 receptor-stimulated increase in cAMP formation and the induction of dyskinesia in humans by these anti-parkinsonian drugs. PMID:9126882

  2. Centaur D-1A nose fairing jettison test

    NASA Technical Reports Server (NTRS)

    Prati, W. M.

    1976-01-01

    An experimental investigation was conducted to verify the functional and structural capability of the Centaur D-1A nose fairing. A full-scale flight-type nose fairing was jettisoned at the Lewis Research Center Space Power Chamber at simulated altitude. Two complete jettisons of the nose fairing were performed, one without aft helper springs and one with aft helper springs. A ''static'' rotation test was also performed to verify capability of the helper springs and to allow clearance measurements between the nose fairing and spacecraft envelope mock-up at certain discrete nose fairing rotation angles. Nose fairing trajectories, structural deflections, clearances, and hinge forces during jettison are presented. Data from subsequent Centaur D-1A flights, relative to nose fairing jettisons, are compared with the experimental results.

  3. Redesign of Glenn Research Center D1 Flywheel Module

    NASA Technical Reports Server (NTRS)

    Jansen, Ralph H.; Wagner, Robert C.; Duffy, Kirsten P.; Hervol, David S.; Storozuk, Ronald J.; Dever, Timothy P.; Anzalone, Salvatore M.; Trudell, Jeffrey J.; Konno, Kevin E.; Kenny, Andrew

    2002-01-01

    Glenn Research Center has completed the redesign of the D1 flywheel module. The redesign includes a new rotor with a composite rim, motor/generator, touchdown bearings, sensors, and a magnetic actuator. The purpose of the relatively low cost module upgrade is to enable it to continuously operate throughout its speed range of 0 to 60,000 RPM. The module will be used as part of a combined attitude control and bus regulation experiment.

  4. Underground storage tank 431-D1U1, Closure Plan

    SciTech Connect

    Mancieri, S.

    1993-09-01

    This document contains information about the decommissioning of Tank 431-D1U1. This tank was installed in 1965 for diesel fuel storage. This tank will remain in active usage until closure procedures begin. Soils and ground water around the tank will be sampled to check for leakage. Appendices include; proof of proper training for workers, health and safety briefing record, task hazard analysis summary, and emergency plans.

  5. Evaluation of D-1 tape and cassette characteristics: Moisture content of Sony and Ampex D-1 tapes when delivered

    NASA Technical Reports Server (NTRS)

    Ashton, Gary

    1993-01-01

    Commercial D-1 cassette tapes and their associated recorders were designed to operate in broadcast studios and record in accordance with the International Radio Consultative Committee (CCIR) 607 digital video standards. The D-1 recorder resulted in the Society of Motion Picture and Television Engineers (SMPTE) standards 224 to 228 and is the first digital video recorder to be standardized for the broadcast industry. The D-1 cassette and associated media are currently marketed for broadcast use. The recorder was redesigned for data applications and is in the early stages of being evaluated. The digital data formats used are specified in MIL-STD-2179 and the American National Standards Institute (ANSI) X3.175-190 standard. In early 1990, the National Media Laboratory (NML) was asked to study the effects of time, temperature, and relative humidity on commercial D-1 cassettes. The environmental range to be studied was the one selected for the Advanced Tactical Air Reconnaissance System (ATARS) program. Several discussions between NML personnel, ATARS representatives, recorder contractors, and other interested parties were held to decide upon the experimental plan to be implemented. Review meetings were held periodically during the course of the experiment. The experiments were designed to determine the dimensional stability of the media and cassette since this is one of the major limiting factors of helical recorders when the media or recorders are subjected to non-broadcasting environments. Measurements were also made to characterize each sample of cassettes to give preliminary information on which purchase specifications could be developed. The actual tests performed on the cassettes and media before and after aging fall into the general categories listed.

  6. Evaluation of D-1 tape and cassette characteristics: Moisture content of Sony and Ampex D-1 tapes when delivered

    NASA Astrophysics Data System (ADS)

    Ashton, Gary

    Commercial D-1 cassette tapes and their associated recorders were designed to operate in broadcast studios and record in accordance with the International Radio Consultative Committee (CCIR) 607 digital video standards. The D-1 recorder resulted in the Society of Motion Picture and Television Engineers (SMPTE) standards 224 to 228 and is the first digital video recorder to be standardized for the broadcast industry. The D-1 cassette and associated media are currently marketed for broadcast use. The recorder was redesigned for data applications and is in the early stages of being evaluated. The digital data formats used are specified in MIL-STD-2179 and the American National Standards Institute (ANSI) X3.175-190 standard. In early 1990, the National Media Laboratory (NML) was asked to study the effects of time, temperature, and relative humidity on commercial D-1 cassettes. The environmental range to be studied was the one selected for the Advanced Tactical Air Reconnaissance System (ATARS) program. Several discussions between NML personnel, ATARS representatives, recorder contractors, and other interested parties were held to decide upon the experimental plan to be implemented. Review meetings were held periodically during the course of the experiment. The experiments were designed to determine the dimensional stability of the media and cassette since this is one of the major limiting factors of helical recorders when the media or recorders are subjected to non-broadcasting environments. Measurements were also made to characterize each sample of cassettes to give preliminary information on which purchase specifications could be developed. The actual tests performed on the cassettes and media before and after aging fall into the general categories listed.

  7. Titan 3E/Centaur D-1T Systems Summary

    NASA Technical Reports Server (NTRS)

    1973-01-01

    A systems and operational summary of the Titan 3E/Centaur D-1T program is presented which describes vehicle assembly facilities, launch facilities, and management responsibilities, and also provides detailed information on the following separate systems: (1) mechanical systems, including structural components, insulation, propulsion units, reaction control, thrust vector control, hydraulic systems, and pneumatic equipment; (2) astrionics systems, such as instrumentation and telemetry, navigation and guidance, C-Band tracking system, and range safety command system; (3) digital computer unit software; (4) flight control systems; (5) electrical/electronic systems; and (6) ground support equipment, including checkout equipment.

  8. Levinson theorem for the Dirac equation in D+1 dimensions

    SciTech Connect

    Gu Xiaoyan; Ma Zhongqi; Dong Shihai

    2003-06-01

    In terms of the generalized Sturm-Liouville theorem, the Levinson theorem for the Dirac equation with a spherically symmetric potential in D+1 dimensions is uniformly established as a relation between the total number of bound states and the sum of the phase shifts of the scattering states at E={+-}M with a given angular momentum. The critical case, where the Dirac equation has a half bound state, is analyzed in detail. A half bound state is a zero-momentum solution if its wave function is finite but does not decay fast enough at infinity to be square integrable.

  9. Quantitative structure-activity relationship models with receptor-dependent descriptors for predicting peroxisome proliferator-activated receptor activities of thiazolidinedione and oxazolidinedione derivatives.

    PubMed

    Lather, Viney; Kairys, Visvaldas; Fernandes, Miguel X

    2009-04-01

    A quantitative structure-activity relationship study has been carried out, in which the relationship between the peroxisome proliferator-activated receptor alpha and the peroxisome proliferator-activated receptor gamma agonistic activities of thiazolidinedione and oxazolidinedione derivatives and quantitative descriptors, V(site) calculated in a receptor-dependent manner is modeled. These descriptors quantify the volume occupied by the optimized ligands in regions that are either common or specific to the superimposed binding sites of the targets under consideration. The quantitative structure-activity relationship models were built by forward stepwise linear regression modeling for a training set of 27 compounds and validated for a test set of seven compounds, resulting in a squared correlation coefficient value of 0.90 for peroxisome proliferator-activated receptor alpha and of 0.89 for peroxisome proliferator-activated receptor gamma. The leave-one-out cross-validation and test set predictability squared correlation coefficient values for these models were 0.85 and 0.62 for peroxisome proliferator-activated receptor alpha and 0.89 and 0.50 for peroxisome proliferator-activated receptor gamma respectively. A dual peroxisome proliferator-activated receptor model has also been developed, and it indicates the structural features required for the design of ligands with dual peroxisome proliferator-activated receptor activity. These quantitative structure-activity relationship models show the importance of the descriptors here introduced in the prediction and interpretation of the compounds affinity and selectivity. PMID:19243388

  10. A systematic investigation of the protein kinases involved in NMDA receptor-dependent LTD: evidence for a role of GSK-3 but not other serine/threonine kinases

    PubMed Central

    Peineau, Stéphane; Nicolas, Céline S; Bortolotto, Zuner A; Bhat, Ratan V; Ryves, W Jonathan; Harwood, Adrian J; Dournaud, Pascal; Fitzjohn, Stephen M; Collingridge, Graham L

    2009-01-01

    Background The signalling mechanisms involved in the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression (LTD) in the hippocampus are poorly understood. Numerous studies have presented evidence both for and against a variety of second messengers systems being involved in LTD induction. Here we provide the first systematic investigation of the involvement of serine/threonine (ser/thr) protein kinases in NMDAR-LTD, using whole-cell recordings from CA1 pyramidal neurons. Results Using a panel of 23 inhibitors individually loaded into the recorded neurons, we can discount the involvement of at least 57 kinases, including PKA, PKC, CaMKII, p38 MAPK and DYRK1A. However, we have been able to confirm a role for the ser/thr protein kinase, glycogen synthase kinase 3 (GSK-3). Conclusion The present study is the first to investigate the role of 58 ser/thr protein kinases in LTD in the same study. Of these 58 protein kinases, we have found evidence for the involvement of only one, GSK-3, in LTD. PMID:19583853

  11. Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence.

    PubMed Central

    Chiaradonna, F; Fontana, L; Iavarone, C; Carriero, M V; Scholz, G; Barone, M V; Stoppelli, M P

    1999-01-01

    Anchorage-independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N-terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)-anchored receptor. Here, we report that urokinase-treated differentiating U937 monocyte-like cells exhibit a rapid and transient inhibition of p56/59(hck) and p55(fgr) whereas no changes in the activity of other Src family kinases, such as p53/56(lyn) and p59(fyn) were observed. U937 transfectants expressing a kinase-defective (Lys267 to Met) p56/59(hck) variant exhibit enhanced adhesiveness and a marked F-actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild-type or constitutively active (Tyr499 to Phe) p56/59(hck) stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59(hck) selectively prevents urokinase receptor-dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59(hck) is required for each cell response. In conclusion, modulation of the intracellular p56/59(hck) tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo. PMID:10357814

  12. Comparison of D1´- and D1-containing PS II reaction centre complexes under different environmental conditions in Synechocystis sp. PCC 6803.

    PubMed

    Crawford, Tim S; Hanning, Kyrin R; Chua, Jocelyn P S; Eaton-Rye, Julian J; Summerfield, Tina C

    2016-08-01

    In oxygenic photosynthesis, the D1 protein of Photosystem II is the primary target of photodamage and environmental stress can accelerate this process. The cyanobacterial response to stress includes transcriptional regulation of genes encoding D1, including low-oxygen-induction of psbA1 encoding the D1´ protein in Synechocystis sp. PCC 6803. The psbA1 gene is also transiently up-regulated in high light, and its deletion has been reported to increase ammonium-induced photoinhibition. Therefore we investigated the role of D1´-containing PS II centres under different environmental conditions. A strain containing only D1´-PS II centres under aerobic conditions exhibited increased sensitivity to ammonium chloride and high light compared to a D1-containing strain. Additionally a D1´-PS II strain was outperformed by a D1-PS II strain under normal conditions; however, a strain containing low-oxygen-induced D1´-PS II centres was more resilient under high light than an equivalent D1 strain. These D1´-containing centres had chlorophyll a fluorescence characteristics indicative of altered forward electron transport and back charge recombination with the donor side of PS II. Our results indicate D1´-PS II centres are important in the reconfiguration of thylakoid electron transport in response to high light and low oxygen. PMID:26991994

  13. Haplotype variation of Glu-D1 locus and the origin of Glu-D1d allele conferring superior end-use qualities in common wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In common wheat (Triticum aestivum, AABBDD), the Glu-D1 locus possesses multiple alleles, with Glu-D1a (coding for 1Dx2 and 1Dy12 subunits) and Glu-D1d (encoding 1Dx5 and 1Dy10 subunits) being intensively used in the genetic improvement of end-use qualities. Here, we studied the molecular variatio...

  14. 16 CFR Appendix D1 to Part 305 - Water Heaters-Gas

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Water Heaters-Gas D1 Appendix D1 to Part 305... DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS REQUIRED UNDER THE ENERGY POLICY AND CONSERVATION ACT (âAPPLIANCE LABELING RULEâ) Pt. 305, App. D1 Appendix D1...

  15. Role of the D1-D2 Linker of Human VCP/p97 in the Asymmetry and ATPase Activity of the D1-domain

    PubMed Central

    Tang, Wai Kwan; Xia, Di

    2016-01-01

    Human AAA+ protein p97 consists of an N-domain and two tandem ATPase domains D1 and D2, which are connected by the N-D1 and the D1-D2 linkers. Inclusion of the D1-D2 linker, a 22-amino acid peptide, at the end of p97 N-D1 truncate has been shown to activate ATP hydrolysis of its D1-domain, although the mechanism of activation remains unclear. Here, we identify the N-terminal half of this linker, highly conserved from human to fungi, is essential for the ATPase activation. By analyzing available crystal structures, we observed that the D1-D2 linker is capable of inducing asymmetry in subunit association into a p97 hexamer. This observation is reinforced by two new crystal structures, determined in the present work. The effect of D1-D2 linker on the ATPase activity of the D1-domain is correlated to the side-chain conformation of residue R359, a trans-acting arginine-finger residue essential for ATP hydrolysis of the D1-domain. The activation in D1-domain ATPase activity by breaking perfect six-fold symmetry implies functional importance of asymmetric association of p97 subunits, the extent of which can be determined quantitatively by the metric Asymmetric Index. PMID:26818443

  16. Canonical D = 1 supergravity framework for FLRW cosmology

    NASA Astrophysics Data System (ADS)

    Bogers, M. P.; van Holten, J. W.

    2015-05-01

    We construct an extension of standard flat FLRW cosmology with matter, possessing local D = 1, N=1 proper-time supersymmetry. The fundamental equation for the resulting mini-superspace models of quantum universes is a Dirac-like analogue of the Friedmann and Wheeler-DeWitt equations. We provide solutions of this equation for specific matter configurations based on the supersymmetric O(3) and O(2,1) σ-models. It turns out that in the compact model the volume rate of growth of the universe is quantized and non-vanishing due to the zero-point energy of the scalar fields. In the non-compact model the spectrum of the growth rates is continuous but subject to an uncertainty relation involving the scale and the growth factor.

  17. Control of βAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons.

    PubMed

    Chay, Andrew; Zamparo, Ilaria; Koschinski, Andreas; Zaccolo, Manuela; Blackwell, Kim T

    2016-02-01

    Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory. PMID:26901880

  18. Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus.

    PubMed

    Lauderdale, Kelli; Murphy, Thomas; Tung, Tina; Davila, David; Binder, Devin K; Fiacco, Todd A

    2015-01-01

    Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of slow inward currents (SICs), which initiate after approximately 1 min. Frequency of SICs increased as osmolarity decreased in a dose-dependent manner. Imaging of real-time volume changes in astrocytes revealed that neuronal SICs occurred while astrocytes were still in the process of swelling. SICs evoked by cell swelling were mainly nonsynaptic in origin and NMDA receptor-dependent. To better understand the relationship between SICs and changes in neuronal excitability, recordings were performed in increasingly physiological conditions. In the absence of any added pharmacological reagents or imposed voltage clamp, osmotic edema induced excitatory postsynaptic potentials and burst firing over the same timecourse as SICs. Like SICs, action potentials were blocked by NMDAR antagonists. Effects were more pronounced in adult (8-20 weeks old) compared with juvenile (P15-P21) mice. Together, our results indicate that cell swelling triggered by reduced osmolarity rapidly increases neuronal excitability through activation of NMDA receptors. Our findings have important implications for understanding nonsynaptic mechanisms of epilepsy in relation to cell swelling and reduction of the extracellular space. PMID:26489684

  19. β-Arrestin 2 is required for B1 receptor-dependent post-translational activation of inducible nitric oxide synthase

    PubMed Central

    Kuhr, Frank K.; Zhang, Yongkang; Brovkovych, Viktor; Skidgel, Randal A.

    2010-01-01

    A major source of “high-output” NO in inflammation is inducible nitric oxide synthase (iNOS). iNOS is primarily transcriptionally regulated and is thought to function as an uncontrolled generator of high NO. We found that iNOS in cytokine-stimulated human lung microvascular endothelial cells (HLMVECs) is highly regulated post-translationally via activation of the B1 kinin G protein-coupled receptor (B1R). We report here that B1R-mediated iNOS activation was significantly inhibited by knockdown of β-arrestin 2 with siRNA in cytokine-treated HLMVECs or HEK293 cells transfected with iNOS and B1R. In contrast, β-arrestin 1 siRNA had no effect. The prolonged phase of B1R-dependent ERK activation was also inhibited by β-arrestin 2 knockdown. Furthermore, robust ERK activation by the epidermal growth factor receptor (a β-arrestin 2 independent pathway) had no effect on iNOS-derived NO production. β-arrestin 2 and iNOS coimmunoprecipitated, and there was significant fluorescence resonance energy transfer between CFP-iNOS and β-arrestin 2-YFP (but not β-arrestin 1-YFP) that increased 3-fold after B1R stimulation. These data show that β-arrestin 2 mediates B1R-dependent high-output NO by scaffolding iNOS and ERK to allow post-translational activation of iNOS. This could play a critical role in mediating endothelial function in inflammation.—Kuhr, F. K., Zhang, Y., Brovkovych, V., Skidgel, R. A. β-Arrestin 2 is required for B1 receptor-dependent post-translational activation of inducible nitric oxide synthase. PMID:20228252

  20. Notoginsenoside R1-mediated neuroprotection involves estrogen receptor-dependent crosstalk between Akt and ERK1/2 pathways: a novel mechanism of Nrf2/ARE signaling activation.

    PubMed

    Meng, X; Sun, G; Ye, J; Xu, H; Wang, H; Sun, X

    2014-04-01

    Notoginsenoside R1 (NGR1), a novel phytoestrogen isolated from Panax notoginseng, has antioxidant and anti-apoptotic properties. Oxidative stress plays a pivotal role in neurodegenerative diseases. To mimic oxidative stress in neurons and explore the neuroprotection of NGR1, H₂O₂-induced neurotoxicity in NGF-induced differentiation of PC12 cells was used. In this study, NGR1 preconditioning provided neuroprotective effects via suppressing H₂O₂-induced the intracellular ROS accumulation, the increase in the product of lipid peroxidation (MDA), protein oxidation (protein carbonyl), and DNA fragmentation (8-OHdG), and mitochondrial membrane depolarization as well as caspase-3 activation. Moreover, NGR1 treatment alone potently increased the nuclear translocation of Nrf2, augmented ARE enhancer activity, and upregulated the expression and activity of phase II antioxidant enzymes including HO-1, NQO-1, and γ-GCSc. NGR1 could also increase the ERE activity and activate Akt and ERK1/2 pathways. NGR1-mediated activation of Nrf2/ARE signaling and neuroprotection were abolished by genetic silencing of Nrf2 using siRNA or the pharmacological blockade of estrogen receptors using ICI-182780, and partially inhibited by Akt siRNA or ERK siRNA transfection. In addition, the phosphorylation of ERK1/2 mediated by NGR1 was markedly inhibited in PC12 cells transfected with Akt siRNA. On the contrary, ERK1/2 siRNA transfection hardly had any effect on the phosphorylation of Akt mediated by NGR1. NGR1-mediated activation of Akt and ERK1/2 pathways was blocked by ICI-182780. In conclusion, NGR1 provided neuroprotection via inducing an estrogen receptor-dependent crosstalk between Akt and ERK1/2 pathways, subsequently activating Nrf2/ARE signaling and thereby up-regulating phase II antioxidant enzymes. PMID:24437944

  1. Characterization of the liver X receptor-dependent regulatory mechanism of goat stearoyl-coenzyme A desaturase 1 gene by linoleic acid.

    PubMed

    Yao, D W; Luo, J; He, Q Y; Li, J; Wang, H; Shi, H B; Xu, H F; Wang, M; Loor, J J

    2016-05-01

    Stearoyl-coenzyme A desaturase 1 (SCD1) is a key enzyme in the biosynthesis of palmitoleic and oleic acid. Although the transcriptional regulatory mechanism of SCD1 via polyunsaturated fatty acids (PUFA) has been extensively explored in nonruminants, the existence of such mechanism in ruminant mammary gland remains unknown. In this study, we used goat genomic DNA to clone and sequence a 1,713-bp fragment of the SCD1 5' flanking region. Deletion assays revealed a core region of the promoter located between -415 and -109 bp upstream of the transcription start site, and contained the highly conserved PUFA response region. An intact PUFA response region was required for the basal transcriptional activity of SCD1. Linoleic acid reduced endogenous expression of SCD1 and sterol regulatory element binding factor-1 (SREBF1) in goat mammary epithelial cells. Further analysis indicated that both the sterol response element (SRE) and the nuclear factor Y (NF-Y) binding site in the SCD1 promoter were responsible for the inhibition effect by linoleic acid, whereas the effect was abrogated once NF-Y was deleted. In addition, SRE and NF-Y were partly responsible for the transcriptional activation induced via the liver X receptor agonist T 4506585 (Sigma-Aldrich, St. Louis, MO). When goat mammary epithelial cells were cultured with linoleic acid, addition of T 4506585 markedly increased SCD1 transcription in controls, but had no effect on cells with a deleted SRE promoter. These results demonstrated that linoleic acid can regulate SCD1 expression at the transcriptional level through SRE and NF-Y in a liver X receptor-dependent fashion in the goat mammary gland. PMID:26947306

  2. E2F1 in neurons is cleaved by calpain in an NMDA receptor-dependent manner in a model of HIV-induced neurotoxicity

    PubMed Central

    Zyskind, Jacob W.; Wang, Ying; Cho, Giyong; Ting, Jenhao H.; Kolson, Dennis L.; Lynch, David R.; Jordan-Sciutto, Kelly L.

    2014-01-01

    The transcription factor E2F1 activates gene targets required for G1-S phase progression and for apoptosis, and exhibits increased expression levels in neurons in several CNS diseases including HIV encephalitis, Alzheimer disease, and Parkinson Disease. While E2F1 is known to regulate cell viability through activation of caspases, here we present evidence supporting the involvement of E2F1 in NMDA receptor-dependent, HIV-induced neuronal death mediated by calpains. Using an in vitro model of HIV-induced neurotoxicity that is dependent on NMDA receptor and calpain activation, we have shown that cortical neurons lacking functional E2F1 are less susceptible to neuronal death. Additionally, we report that neuronal E2F1 is cleaved by calpain to a stable 55-kiloDalton fragment following NR2B-dependent NMDA receptor stimulation. This cleavage of E2F1 is protein conformation-dependent and involves at least two cleavage events, one at each terminus of the protein. Intriguingly, the stabilized E2F1 cleavage product is produced in postmitotic neurons of all ages, but fails to be stabilized in cycling cells. Finally, we show that a matching E2F1 cleavage product is produced in human fetal neurons, suggesting that calpain cleavage of E2F1 may be produced in human cortical tissue. These results suggest neuronal E2F1 is processed in a novel manner in response to NMDA receptor-mediated toxicity, a mechanism implicated in HAND pathogenesis as well as several other diseases of the CNS. PMID:25279448

  3. Changes in mGlu5 receptor-dependent synaptic plasticity and coupling to homer proteins in the hippocampus of Ube3A hemizygous mice modeling angelman syndrome.

    PubMed

    Pignatelli, Marco; Piccinin, Sonia; Molinaro, Gemma; Di Menna, Luisa; Riozzi, Barbara; Cannella, Milena; Motolese, Marta; Vetere, Gisella; Catania, Maria Vincenza; Battaglia, Giuseppe; Nicoletti, Ferdinando; Nisticò, Robert; Bruno, Valeria

    2014-03-26

    Angelman syndrome (AS) is caused by the loss of Ube3A, an ubiquitin ligase that commits specific proteins to proteasomal degradation. How this defect causes autism and other pathological phenotypes associated with AS is unknown. Long-term depression (LTD) of excitatory synaptic transmission mediated by type 5 metabotropic glutamate (mGlu5) receptors was enhanced in hippocampal slices of Ube3A(m-/p+) mice, which model AS. No changes were found in NMDA-dependent LTD induced by low-frequency stimulation. mGlu5 receptor-dependent LTD in AS mice was sensitive to the protein synthesis inhibitor anisomycin, and relied on the same signaling pathways as in wild-type mice, e.g., the mitogen-activated protein kinase (MAPK) pathway, the phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycine pathway, and protein tyrosine phosphatase. Neither the stimulation of MAPK and PI3K nor the increase in Arc (activity-regulated cytoskeleton-associated protein) levels in response to mGlu5 receptor activation were abnormal in hippocampal slices from AS mice compared with wild-type mice. mGlu5 receptor expression and mGlu1/5 receptor-mediated polyphosphoinositide hydrolysis were also unchanged in the hippocampus of AS mice. In contrast, AS mice showed a reduced expression of the short Homer protein isoform Homer 1a, and an increased coupling of mGlu5 receptors to Homer 1b/c proteins in the hippocampus. These findings support the link between Homer proteins and monogenic autism, and lay the groundwork for the use of mGlu5 receptor antagonists in AS. PMID:24672001

  4. Ethanol withdrawal is required to produce persisting N-methyl-D-aspartate receptor-dependent hippocampal cytotoxicity during chronic intermittent ethanol exposure

    PubMed Central

    Reynolds, Anna R.; Berry, B. Jennifer N.; Sharrett-Field, Lynda; Prendergast, Mark A.

    2015-01-01

    Chronic intermittent ethanol consumption is associated with neurodegeneration and cognitive deficits in preclinical laboratory animals and in the clinical population. While previous work suggests a role for neuroadaptations in the N-methyl-D-aspartate (NMDA) receptor in the development of ethanol dependence and manifestation of withdrawal, the relative roles of ethanol exposure and ethanol withdrawal in producing these effects have not been fully characterized. To examine underlying cytotoxic mechanisms associated with CIE exposure, organotypic hippocampal slices were exposed to 1–3 cycles of ethanol (50 mM) in cell culture medium for 5 days, followed by 24-hours of ethanol withdrawal in which a portion of slices were exposed to competitive NMDA receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV; 40 µM). Cytotoxicity was assessed using immunohistochemical labeling of neuron specific nuclear protein (NeuN; Fox-3), a marker of mature neurons, and thionine (2%) staining of Nissl bodies. Multiple cycles of CIE produced neurotoxicity, as reflected in persisting losses of neuron NeuN immunoreactivity and thionine staining in each of the primary cell layers of the hippocampal formation. Hippocampi aged in vitro were significantly more sensitive to the toxic effects of multiple CIEs than were non-aged hippocampi. This effect was not demonstrated in slices exposed to continuous ethanol, in the absence of withdrawal, or to a single exposure/withdrawal regimen. Exposure to APV significantly attenuated the cytotoxicity observed in the primary cell layers of the hippocampus. The present findings suggest that ethanol withdrawal is required to produce NMDA receptor-dependent hippocampal cytotoxicity, particularly in the aging hippocampus in vitro. PMID:25746220

  5. Technetium-99m labelled LDL as a tracer for quantitative LDL scintigraphy. II. In vivo validation, LDL receptor-dependent and unspecific hepatic uptake and scintigraphic results.

    PubMed

    Leitha, T; Staudenherz, A; Gmeiner, B; Hermann, M; Hüttinger, M; Dudczak, R

    1993-08-01

    The purpose of this study was to determine whether the hepatic uptake of dialysed technetium-99m labelled low-density lipoprotein (99mTc-LDL) reflects the hepatic LDL receptor activity and to what extent the non-LDL receptor-dependent 99mTc-LDL uptake by non-parenchymal cells relates to the diagnostic utility of quantitative 99mTc-LDL scintigraphy of the liver. New Zealand White rabbits and Watanabe Heritable Hyperlipidaemic rabbits, which were sacrificed 24 h after simultaneous injection of 99mTc-LDL and iodine-125 labelled LDL, were clearly discriminated by their hepatic 99mTc-LDL uptake according to their genetically different hepatic LDL receptor activity. Yet the hepatic 99mTc-LDL uptake exceeded the 125I-LDL uptake in all animals. The different hepatic uptake of the tracers was elucidated in the isolated perfused rat liver and was due to rapid intracellular degradation and the release of low molecular catabolites of 125I-LDL. In contrast, 99mTc activity was trapped in the liver. Analysis of biliary 99mTc activity provided evidence for the excretion of 99mTc-labelled apolipoprotein B. The amount of biliary excreted protein-bound 99mTc was linked to total hepatic 99mTc-LDL uptake and presumably reflected LDL receptor-mediated apolipoprotein excretion. Collagenase liver perfusion in Sprague-Dawley rats 90 min following simultaneous injection of 99mTc- and 125I-LDL and subsequent cell separation by gradient centrifugation revealed that 99mTc-LDL and 125I-LDL had a comparably low uptake into non-parenchymal cells; thus its contribution can be neglected for scintigraphic purposes. Planar scintigraphy was performed in New Zealand White and Watanabe Heritable Hyperlipidaemic rabbits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8404953

  6. Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus

    PubMed Central

    Lauderdale, Kelli; Murphy, Thomas; Tung, Tina; Davila, David; Binder, Devin K.

    2015-01-01

    Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of slow inward currents (SICs), which initiate after approximately 1 min. Frequency of SICs increased as osmolarity decreased in a dose-dependent manner. Imaging of real-time volume changes in astrocytes revealed that neuronal SICs occurred while astrocytes were still in the process of swelling. SICs evoked by cell swelling were mainly nonsynaptic in origin and NMDA receptor-dependent. To better understand the relationship between SICs and changes in neuronal excitability, recordings were performed in increasingly physiological conditions. In the absence of any added pharmacological reagents or imposed voltage clamp, osmotic edema induced excitatory postsynaptic potentials and burst firing over the same timecourse as SICs. Like SICs, action potentials were blocked by NMDAR antagonists. Effects were more pronounced in adult (8–20 weeks old) compared with juvenile (P15–P21) mice. Together, our results indicate that cell swelling triggered by reduced osmolarity rapidly increases neuronal excitability through activation of NMDA receptors. Our findings have important implications for understanding nonsynaptic mechanisms of epilepsy in relation to cell swelling and reduction of the extracellular space. PMID:26489684

  7. Control of βAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons

    PubMed Central

    Chay, Andrew; Zamparo, Ilaria; Koschinski, Andreas; Zaccolo, Manuela; Blackwell, Kim T.

    2016-01-01

    Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory. PMID:26901880

  8. Validation of 3D/1D Analysis of ICRF Antennas

    NASA Astrophysics Data System (ADS)

    Milanesio, D.; Lancellotti, V.; Kyrytsya, V.; Maggiora, R.; Vecchi, G.; Parisot, A.; Wukitch, S. J.

    2004-11-01

    An innovative tool has been realized for the 3D/1D simulation of Ion Cyclotron Radio Frequency (ICRF), i.e. accounting for antennas in a realistic 3D geometry and with an accurate 1D plasma model. The approach to the problem is based on an integral-equation formulation for the self-consistent evaluation of the current distribution on the conductors. The environment has been subdivided in two coupled region: the plasma region and the vacuum region. The two problems are linked by means of electromagnetic current distribution on the aperture between the two regions. The plasma enters the formalism via a surface impedance matrix for this reason any plasma model can be used. The source term directly models the TEM mode of the coax feeding the antenna and the current in the coax is determined self-consistently, giving the input impedance/admittance of the antenna itself. The suite, called TOPICA, has been used in the design of various ICRF antennas and also for the performance prediction of the ALCATOR C-MOD D and E antenna. An extensive set of comparisons between measured and simulated antenna parameters during ALCATOR C-MOD operation will be presented.

  9. The microgravity environment of the D1 mission

    NASA Technical Reports Server (NTRS)

    Hamacher, H.; Merbold, U.; Jilg, R.

    1990-01-01

    Some characteristic features and results of D1 microgravity measurements are discussed as performed in the Material Science Double Rack (MSDR) and the Materials Science Double Rack for Experiment Modules and Apparatus (MEDEA). Starting with a brief review of the main potential disturbances, the payload aspects of interest to the analysis and the accelerometer measuring systems are described. The microgravity data are analyzed with respect to selected mission events such as thruster firings for attitude control, operations of Spacelab experiment facilities, vestibular experiments and crew activities. The origins are divided into orbit, vehicle, and experiment induced perturbations. It has been found that the microgravity-environment is dictated mainly by payload-induced perturbations. To reduce the microgravity-level, the design of some experiment facilities has to be improved by minimizing the number of moving parts, decoupling of disturbing units from experiment facilities, by taking damping measures, etc. In addition, strongly disturbing experiments and very sensitive investigations should be performed in separate mission phases.

  10. Perfect magnetic conductor Casimir piston in d+1 dimensions

    SciTech Connect

    Edery, Ariel; Marachevsky, Valery

    2008-07-15

    Perfect magnetic conductor (PMC) boundary conditions are dual to the more familiar perfect electric conductor (PEC) conditions and can be viewed as the electromagnetic analog of the boundary conditions in the bag model for hadrons in QCD. Recent advances and requirements in communication technologies have attracted great interest in PMC's, and Casimir experiments involving structures that approximate PMC's may be carried out in the not-too-distant future. In this paper, we make a study of the zero-temperature PMC Casimir piston in d+1 dimensions. The PMC Casimir energy is explicitly evaluated by summing over p+1-dimensional Dirichlet energies where p ranges from 2 to d inclusively. We derive two exact d-dimensional expressions for the Casimir force on the piston and find that the force is negative (attractive) in all dimensions. Both expressions are applied to the case of 2+1 and 3+1 dimensions. A spin-off from our work is a contribution to the PEC literature: we obtain a useful alternative expression for the PEC Casimir piston in 3+1 dimensions and also evaluate the Casimir force per unit area on an infinite strip, a geometry of experimental interest.

  11. Consequence of the tumor-associated conversion to cyclin D1b

    PubMed Central

    Augello, Michael A; Berman-Booty, Lisa D; Carr, Richard; Yoshida, Akihiro; Dean, Jeffry L; Schiewer, Matthew J; Feng, Felix Y; Tomlins, Scott A; Gao, Erhe; Koch, Walter J; Benovic, Jeffrey L; Diehl, John Alan; Knudsen, Karen E

    2015-01-01

    Clinical evidence suggests that cyclin D1b, a variant of cyclin D1, is associated with tumor progression and poor outcome. However, the underlying molecular basis was unknown. Here, novel models were created to generate a genetic switch from cyclin D1 to cyclin D1b. Extensive analyses uncovered overlapping but non-redundant functions of cyclin D1b compared to cyclin D1 on developmental phenotypes, and illustrated the importance of the transcriptional regulatory functions of cyclin D1b in vivo. Data obtained identify cyclin D1b as an oncogene, wherein cyclin D1b expression under the endogenous promoter induced cellular transformation and further cooperated with known oncogenes to promote tumor growth in vivo. Further molecular interrogation uncovered unexpected links between cyclin D1b and the DNA damage/PARP1 regulatory networks, which could be exploited to suppress cyclin D1b-driven tumors. Collectively, these data are the first to define the consequence of cyclin D1b expression on normal cellular function, present evidence for cyclin D1b as an oncogene, and provide pre-clinical evidence of effective methods to thwart growth of cells dependent upon this oncogenic variant. PMID:25787974

  12. Amphetamine elevates phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the rat forebrain via activating dopamine D1 and D2 receptors.

    PubMed

    Xue, Bing; Fitzgerald, Cole A; Jin, Dao-Zhong; Mao, Li-Min; Wang, John Q

    2016-09-01

    Psychostimulants have an impact on protein synthesis, although underlying molecular mechanisms are unclear. Eukaryotic initiation factor 2α-subunit (eIF2α) is a key player in initiation of protein translation and is regulated by phosphorylation. While this factor is sensitive to changing synaptic input and is critical for synaptic plasticity, its sensitivity to stimulants is poorly understood. Here we systematically characterized responses of eIF2α to a systemic administration of the stimulant amphetamine (AMPH) in dopamine responsive regions of adult rat brains. Intraperitoneal injection of AMPH at 5mg/kg increased eIF2α phosphorylation at serine 51 in the striatum. This increase was transient. In the medial prefrontal cortex (mPFC), AMPH induced a relatively delayed phosphorylation of the factor. Pretreatment with a dopamine D1 receptor antagonist SCH23390 blocked the AMPH-stimulated eIF2α phosphorylation in both the striatum and mPFC. Similarly, a dopamine D2 receptor antagonist eticlopride reduced the effect of AMPH in the two regions. Two antagonists alone did not alter basal eIF2α phosphorylation. AMPH and two antagonists did not change the amount of total eIF2α proteins in both regions. These results demonstrate the sensitivity of eIF2α to stimulant exposure. AMPH possesses the ability to stimulate eIF2α phosphorylation in striatal and mPFC neurons in vivo in a D1 and D2 receptor-dependent manner. PMID:27338925

  13. The relationship between dopamine receptor D1 and cognitive performance

    PubMed Central

    Tsang, Jonathan; Fullard, John F; Giakoumaki, Stella G; Katsel, Pavel; Katsel, Pavel; Karagiorga, Vasiliki Eirini; Greenwood, Tiffany A; Braff, David L; Siever, Larry J; Bitsios, Panos; Haroutunian, Vahram; Roussos, Panos

    2015-01-01

    Background: Cognitive impairment cuts across traditional diagnostic boundaries and is one of the most typical symptoms in various psychiatric and neurobiological disorders. Aims: The objective of this study was to examine the genetic association between 94 candidate genes, including receptors and enzymes that participate in neurotransmission, with measures of cognition. Methods: The Clinical Dementia Rating (CDR), a global measure of cognition, and genotypes derived from a custom array of 1,536 single-nucleotide polymorphisms (SNPs) in 94 genes were available for a large postmortem cohort of Caucasian cases with Alzheimer’s disease (AD), schizophrenia and controls (n=727). A cohort of healthy young males (n=1,493) originating from the LOGOS project (Learning On Genetics Of Schizophrenia Spectrum) profiled across multiple cognitive domains was available for targeted SNP genotyping. Gene expression was quantified in the superior temporal gyrus of control samples (n=109). The regulatory effect on transcriptional activity was assessed using the luciferase reporter system. Results: The rs5326-A allele at the promoter region of dopamine receptor D1 (DRD1) locus was associated with: (i) poorer cognition (higher CDR) in the postmortem cohort (P=9.325×10−4); (ii) worse cognitive performance relevant to strategic planning in the LOGOS cohort (P=0.008); (iii) lower DRD1 gene expression in the superior temporal gyrus of controls (P=0.038); and (iv) decreased transcriptional activity in human neuroblastoma (SH-SY5Y) cells (P=0.026). Conclusions: An interdisciplinary approach combining genetics with cognitive and molecular neuroscience provided a possible mechanistic link among DRD1 and alterations in cognitive performance. PMID:27336024

  14. Hepatitis B Virus X Protein Stabilizes Cyclin D1 and Increases Cyclin D1 Nuclear Accumulation through ERK-Mediated Inactivation of GSK-3β.

    PubMed

    Chen, Xiangmei; Zhang, Ling; Zheng, Sujun; Zhang, Ting; Li, Meng; Zhang, Xiaolei; Zeng, Zhenzhen; McCrae, Malcolm A; Zhao, Jingmin; Zhuang, Hui; Lu, Fengmin

    2015-05-01

    The Hepatitis B virus X protein (HBx) contributes centrally to the pathogenesis of hepatocellular carcinoma (HCC). It has been suggested that the transcriptional activation of cyclin D1 by HBx is implicated in the development of HCC. However, numerous studies have shown that overexpression of cyclin D1 alone is not sufficient to drive oncogenic transformation. Herein, we investigated whether HBx can stabilize cyclin D1 and induce cyclin D1 protein nuclear accumulation, and thereby accelerate hepatocarcinogenesis. The effects of HBx on cyclin D1 stabilization were assessed in cell-based transfection, Western blot, immunoprecipitation, immunocytofluorescence staining, and flow-cytometric assays. The results demonstrated that ectopic expression of HBx in HCC cells could extend the half-life of cyclin D1 protein from 40-60 minutes to 80-110 minutes. HBx stabilized cyclin D1 primarily in the S phase of the cell cycle, in a manner dependent on the inactivation of GSK-3β, which was mediated by ERK activation. HBx also prompted the nuclear accumulation of cyclin D1, and cotransfection of the constitutively active mutant of GSK-3β along with HBx could reverse the nuclear accumulation and subsequent cell proliferation induced by HBx. Further, a positive correlation between HBx and nuclear cyclin D1 level was established in HCC specimens detected by an immunohistochemical assay. Taken together, our results indicated that HBx could stabilize and increase cyclin D1 nuclear accumulation through ERK-mediated inactivation of GSK-3β. This HBx-induced cyclin D1 upregulation might play an important role in HCC development and progression. PMID:25712050

  15. 16 CFR Appendix D1 to Part 305 - Water Heaters-Gas

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS REQUIRED UNDER THE ENERGY POLICY AND CONSERVATION ACT (âAPPLIANCE LABELING RULEâ) Pt. 305, App. D1 Appendix D1...

  16. 1. CAPTIVE TEST STAND D1 FROM THE FERROCEMENT APRON, VIEW ...

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

    1. CAPTIVE TEST STAND D-1 FROM THE FERROCEMENT APRON, VIEW TOWARDS SOUTHEAST. - Glenn L. Martin Company, Titan Missile Test Facilities, Captive Test Stand D-1, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  17. Proresolving actions of a new resolvin D1 analog mimetic qualifies as an immunoresolvent

    PubMed Central

    Orr, Sarah K.; Colas, Romain A.; Dalli, Jesmond; Chiang, Nan

    2015-01-01

    Resolution of inflammation is an active process driven by several new families of endogenous lipid mediators collectively coined specialized proresolving mediators (SPM). Here, we report a synthetic analog of resolvin D1 (RvD1) and aspirin-triggered RvD1, benzo-diacetylenic-17R-RvD1-methyl ester (BDA-RvD1), which was prepared using fewer steps than required for total organic synthesis of natural SPM. BDA-RvD1 was resistant to further metabolism by human recombinant 15-prostaglandin dehydrogenase, a major inactivation pathway for RvD1. In ischemia-reperfusion-initiated second organ injury, BDA-RvD1 intravenously (1 μg) reduced neutrophil infiltration into the lungs by 58 ± 9% and was significantly more potent than native RvD1. BDA-RvD1 at 100 ng/mouse also shortened the resolution interval, Ri, of Escherichia coli peritonitis with a similar potency as RvD1, by ∼57%, from Ri 10.5 h to 4.5 h. With isolated human phagocytes, BDA-RvD1 at picomolar concentrations (10−12 M) stimulated phagocytosis of zymosan A particles. BDA-RvD1 activated human recombinant G protein-coupled receptor 32/DRV1, an RvD1 receptor, in a dose-dependent manner. These results indicate that, both in vivo in mice and with isolated human cells, BDA-RvD1 shares defining proresolving actions of RvD1, including inhibiting leukocyte infiltration and stimulating phagocytosis. Moreover, they provide evidence for a new analog mimetic and example of an immunoresolvent, namely an agent that stimulates active resolution of inflammation, for a potential new therapeutic class. PMID:25770181

  18. Proresolving actions of a new resolvin D1 analog mimetic qualifies as an immunoresolvent.

    PubMed

    Orr, Sarah K; Colas, Romain A; Dalli, Jesmond; Chiang, Nan; Serhan, Charles N

    2015-05-01

    Resolution of inflammation is an active process driven by several new families of endogenous lipid mediators collectively coined specialized proresolving mediators (SPM). Here, we report a synthetic analog of resolvin D1 (RvD1) and aspirin-triggered RvD1, benzo-diacetylenic-17R-RvD1-methyl ester (BDA-RvD1), which was prepared using fewer steps than required for total organic synthesis of natural SPM. BDA-RvD1 was resistant to further metabolism by human recombinant 15-prostaglandin dehydrogenase, a major inactivation pathway for RvD1. In ischemia-reperfusion-initiated second organ injury, BDA-RvD1 intravenously (1 μg) reduced neutrophil infiltration into the lungs by 58 ± 9% and was significantly more potent than native RvD1. BDA-RvD1 at 100 ng/mouse also shortened the resolution interval, Ri, of Escherichia coli peritonitis with a similar potency as RvD1, by ~57%, from Ri 10.5 h to 4.5 h. With isolated human phagocytes, BDA-RvD1 at picomolar concentrations (10(-12) M) stimulated phagocytosis of zymosan A particles. BDA-RvD1 activated human recombinant G protein-coupled receptor 32/DRV1, an RvD1 receptor, in a dose-dependent manner. These results indicate that, both in vivo in mice and with isolated human cells, BDA-RvD1 shares defining proresolving actions of RvD1, including inhibiting leukocyte infiltration and stimulating phagocytosis. Moreover, they provide evidence for a new analog mimetic and example of an immunoresolvent, namely an agent that stimulates active resolution of inflammation, for a potential new therapeutic class. PMID:25770181

  19. 17 CFR 240.14d-102 - Schedule 14D-1F. Tender offer statement pursuant to rule 14d-1(b) under the Securities Exchange...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Schedule 14D-1F. Tender offer statement pursuant to rule 14d-1(b) under the Securities Exchange Act of 1934. 240.14d-102 Section 240.14d-102 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL...

  20. 17 CFR 240.14d-102 - Schedule 14D-1F. Tender offer statement pursuant to rule 14d-1(b) under the Securities Exchange...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Schedule 14D-1F. Tender offer statement pursuant to rule 14d-1(b) under the Securities Exchange Act of 1934. 240.14d-102 Section 240.14d-102 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL...

  1. 26 CFR 1.1033(d)-1 - Destruction or disposition of livestock because of disease.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of disease. 1.1033(d)-1 Section 1.1033(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... § 1.1033(d)-1 Destruction or disposition of livestock because of disease. (a) The destruction... account of, disease, or the sale or exchange, in such a year, of livestock because of disease, shall...

  2. 26 CFR 1.1033(d)-1 - Destruction or disposition of livestock because of disease.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... of disease. 1.1033(d)-1 Section 1.1033(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... § 1.1033(d)-1 Destruction or disposition of livestock because of disease. (a) The destruction... account of, disease, or the sale or exchange, in such a year, of livestock because of disease, shall...

  3. 26 CFR 1.1033(d)-1 - Destruction or disposition of livestock because of disease.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... of disease. 1.1033(d)-1 Section 1.1033(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... § 1.1033(d)-1 Destruction or disposition of livestock because of disease. (a) The destruction... account of, disease, or the sale or exchange, in such a year, of livestock because of disease, shall...

  4. 26 CFR 1.1033(d)-1 - Destruction or disposition of livestock because of disease.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... of disease. 1.1033(d)-1 Section 1.1033(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... § 1.1033(d)-1 Destruction or disposition of livestock because of disease. (a) The destruction... account of, disease, or the sale or exchange, in such a year, of livestock because of disease, shall...

  5. 26 CFR 1.337(d)-1 - Transitional loss limitation rule.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Transitional loss limitation rule. 1.337(d)-1 Section 1.337(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Effects on Corporation § 1.337(d)-1 Transitional loss limitation rule. (a) Loss limitation rule for...

  6. 26 CFR 1.337(d)-1 - Transitional loss limitation rule.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 4 2011-04-01 2011-04-01 false Transitional loss limitation rule. 1.337(d)-1 Section 1.337(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Effects on Corporation § 1.337(d)-1 Transitional loss limitation rule. (a) Loss limitation rule for...

  7. 26 CFR 1.666(d)-1A - Information required from trusts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Information required from trusts. 1.666(d)-1A Section 1.666(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Taxable Years Beginning Before January 1, 1969 § 1.666(d)-1A Information required from trusts....

  8. 26 CFR 1.669(d)-1A - Total taxes deemed distributed.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Total taxes deemed distributed. 1.669(d)-1A Section 1.669(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Taxable Years Beginning Before January 1, 1969 § 1.669(d)-1A Total taxes deemed distributed. (a) If...

  9. 26 CFR 301.6323(d)-1 - 45-day period for making disbursements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....6323(d)-1 45-day period for making disbursements. (a) In general. Even though a notice of a lien... 26 Internal Revenue 18 2012-04-01 2012-04-01 false 45-day period for making disbursements. 301.6323(d)-1 Section 301.6323(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...

  10. 26 CFR 31.3306(d)-1 - Included and excluded service.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Included and excluded service. 31.3306(d)-1 Section 31.3306(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(d)-1...

  11. 26 CFR 301.6323(d)-1 - 45-day period for making disbursements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....6323(d)-1 45-day period for making disbursements. (a) In general. Even though a notice of a lien... 26 Internal Revenue 18 2011-04-01 2011-04-01 false 45-day period for making disbursements. 301.6323(d)-1 Section 301.6323(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...

  12. 26 CFR 48.4216(d)-1 - Sales of installment accounts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 16 2013-04-01 2013-04-01 false Sales of installment accounts. 48.4216(d)-1 Section 48.4216(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Manufacturers Taxes § 48.4216(d)-1 Sales of installment accounts. (a) In general. Except as provided...

  13. 26 CFR 1.669(d)-1A - Total taxes deemed distributed.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Total taxes deemed distributed. 1.669(d)-1A Section 1.669(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Taxable Years Beginning Before January 1, 1969 § 1.669(d)-1A Total taxes deemed distributed. (a) If...

  14. 26 CFR 301.6323(d)-1 - 45-day period for making disbursements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....6323(d)-1 45-day period for making disbursements. (a) In general. Even though a notice of a lien... 26 Internal Revenue 18 2013-04-01 2013-04-01 false 45-day period for making disbursements. 301.6323(d)-1 Section 301.6323(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...

  15. 26 CFR 1.665(d)-1 - Taxes imposed on the trust.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Taxes imposed on the trust. 1.665(d)-1 Section 1.665(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX... Beginning Before January 1, 1969 § 1.665(d)-1 Taxes imposed on the trust. (a) For the purpose of subpart...

  16. 26 CFR 1.669(d)-1A - Total taxes deemed distributed.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Total taxes deemed distributed. 1.669(d)-1A Section 1.669(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Taxable Years Beginning Before January 1, 1969 § 1.669(d)-1A Total taxes deemed distributed. (a) If...

  17. 26 CFR 31.3306(d)-1 - Included and excluded service.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 false Included and excluded service. 31.3306(d)-1 Section 31.3306(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(d)-1...

  18. 26 CFR 1.665(d)-1 - Taxes imposed on the trust.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Taxes imposed on the trust. 1.665(d)-1 Section 1.665(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX... Before January 1, 1969 § 1.665(d)-1 Taxes imposed on the trust. (a) For the purpose of subpart D...

  19. 26 CFR 1.665(d)-1 - Taxes imposed on the trust.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Taxes imposed on the trust. 1.665(d)-1 Section 1.665(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX... Beginning Before January 1, 1969 § 1.665(d)-1 Taxes imposed on the trust. (a) For the purpose of subpart...

  20. 26 CFR 1.665(d)-1 - Taxes imposed on the trust.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Taxes imposed on the trust. 1.665(d)-1 Section 1.665(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX... Beginning Before January 1, 1969 § 1.665(d)-1 Taxes imposed on the trust. (a) For the purpose of subpart...

  1. 26 CFR 1.669(d)-1A - Total taxes deemed distributed.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Total taxes deemed distributed. 1.669(d)-1A Section 1.669(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Years Beginning Before January 1, 1969 § 1.669(d)-1A Total taxes deemed distributed. (a) If a...

  2. 26 CFR 1.669(d)-1A - Total taxes deemed distributed.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Total taxes deemed distributed. 1.669(d)-1A Section 1.669(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Taxable Years Beginning Before January 1, 1969 § 1.669(d)-1A Total taxes deemed distributed. (a) If...

  3. 26 CFR 1.665(d)-1 - Taxes imposed on the trust.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Taxes imposed on the trust. 1.665(d)-1 Section 1.665(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX... Beginning Before January 1, 1969 § 1.665(d)-1 Taxes imposed on the trust. (a) For the purpose of subpart...

  4. 26 CFR 31.3306(d)-1 - Included and excluded service.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false Included and excluded service. 31.3306(d)-1 Section 31.3306(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(d)-1...

  5. 26 CFR 301.6323(d)-1 - 45-day period for making disbursements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....6323(d)-1 45-day period for making disbursements. (a) In general. Even though a notice of a lien... 26 Internal Revenue 18 2014-04-01 2014-04-01 false 45-day period for making disbursements. 301.6323(d)-1 Section 301.6323(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...

  6. 26 CFR 1.149(d)-1 - Limitations on advance refundings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Limitations on advance refundings. 1.149(d)-1 Section 1.149(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED....149(d)-1 Limitations on advance refundings. (a) General rule. Under section 149(d) and this...

  7. 26 CFR 1.45D-1 - New markets tax credit.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 1 2011-04-01 2009-04-01 true New markets tax credit. 1.45D-1 Section 1.45D-1... Computing Credit for Investment in Certain Depreciable Property § 1.45D-1 New markets tax credit. (a) Table...) Allowance of credit (1) In general (2) Credit allowance date (3) Applicable percentage (4) Amount paid...

  8. 26 CFR 1.45D-1 - New markets tax credit.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 1 2014-04-01 2013-04-01 true New markets tax credit. 1.45D-1 Section 1.45D-1... Computing Credit for Investment in Certain Depreciable Property § 1.45D-1 New markets tax credit. (a) Current year credit. The current year general business credit under section 38(b)(13) includes the...

  9. 26 CFR 1.1092(d)-1 - Definitions and special rules.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Definitions and special rules. 1.1092(d)-1 Section 1.1092(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Wash Sales of Stock Or Securities § 1.1092(d)-1 Definitions...

  10. ATM is required for rapid degradation of cyclin D1 in response to {gamma}-irradiation

    SciTech Connect

    Choo, Dong Wan; Baek, Hye Jung; Motoyama, Noboru; Cho, Kwan Ho; Kim, Hye Sun; Kim, Sang Soo

    2009-01-23

    The cellular response to DNA damage induced by {gamma}-irradiation activates cell-cycle arrest to permit DNA repair and to prevent replication. Cyclin D1 is the key molecule for transition between the G1 and S phases of the cell-cycle, and amplification or overexpression of cyclin D1 plays pivotal roles in the development of several human cancers. To study the regulation of cyclin D1 in the DNA-damaged condition, we analyzed the proteolytic regulation of cyclin D1 expression upon {gamma}-irradiation. Upon {gamma}-irradiation, a rapid reduction in cyclin D1 levels was observed prior to p53 stabilization, indicating that the stability of cyclin D1 is controlled in a p53-independent manner. Further analysis revealed that irradiation facilitated ubiquitination of cyclin D1 and that a proteasome inhibitor blocked cyclin D1 degradation under the same conditions. Interestingly, after mutation of threonine residue 286 of cyclin D1, which is reported to be the GSK-3{beta} phosphorylation site, the mutant protein showed resistance to irradiation-induced proteolysis although inhibitors of GSK-3{beta} failed to prevent cyclin D1 degradation. Rather, ATM inhibition markedly prevented cyclin D1 degradation induced by {gamma}-irradiation. Our data indicate that communication between ATM and cyclin D1 may be required for maintenance of genomic integrity achieved by rapid arrest of the cell-cycle, and that disruption of this crosstalk may increase susceptibility to cancer.

  11. 17 CFR 270.6d-1 - Exemption for certain closed-end investment companies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-end investment companies. 270.6d-1 Section 270.6d-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.6d-1 Exemption for certain closed-end investment companies. (a) An application under section 6(d) of the Act...

  12. 26 CFR 1.666(d)-1A - Information required from trusts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Information required from trusts. 1.666(d)-1A Section 1.666(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Taxable Years Beginning Before January 1, 1969 § 1.666(d)-1A Information required from trusts....

  13. 26 CFR 1.666(d)-1A - Information required from trusts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Information required from trusts. 1.666(d)-1A Section 1.666(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Years Beginning Before January 1, 1969 § 1.666(d)-1A Information required from trusts. (a)...

  14. 26 CFR 1.666(d)-1A - Information required from trusts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Information required from trusts. 1.666(d)-1A Section 1.666(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Taxable Years Beginning Before January 1, 1969 § 1.666(d)-1A Information required from trusts....

  15. 26 CFR 1.666(d)-1A - Information required from trusts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Information required from trusts. 1.666(d)-1A Section 1.666(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Taxable Years Beginning Before January 1, 1969 § 1.666(d)-1A Information required from trusts....

  16. 17 CFR 270.6d-1 - Exemption for certain closed-end investment companies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-end investment companies. 270.6d-1 Section 270.6d-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.6d-1 Exemption for certain closed-end investment companies. (a) An application under section 6(d) of the Act...

  17. 17 CFR 270.6d-1 - Exemption for certain closed-end investment companies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-end investment companies. 270.6d-1 Section 270.6d-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.6d-1 Exemption for certain closed-end investment companies. (a) An application under section 6(d) of the Act...

  18. 17 CFR 270.6d-1 - Exemption for certain closed-end investment companies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-end investment companies. 270.6d-1 Section 270.6d-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.6d-1 Exemption for certain closed-end investment companies. (a) An application under section 6(d) of the Act...

  19. 17 CFR 270.6d-1 - Exemption for certain closed-end investment companies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-end investment companies. 270.6d-1 Section 270.6d-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.6d-1 Exemption for certain closed-end investment companies. (a) An application under section 6(d) of the Act...

  20. 3D/1D Analysis of ICRF Antennas

    NASA Astrophysics Data System (ADS)

    Maggiora, Riccardo; Lancellotti, Vito; Vecchi, Giuseppe

    2003-10-01

    An innovative tool has been realized for the 3D/1D simulation of Ion Cyclotron Radio Frequency (ICRF), i.e. accounting for antennas in a realistic 3D geometry and with an accurate 1D plasma model. The approach to the problem is based on an integral-equation formulation for the self-consistent evaluation of the current distribution on the conductors. The environment has been subdivided in two coupled region: the plasma region and the vacuum region. The two problems are linked by means of a magnetic current (electric field) distribution on the aperture between the two regions. In the vacuum region all the calculations are executed in the spatial domain while in the plasma region an extraction in the spectral domain of some integrals is employed that permits to significantly reduce the integration support and to obtain a high numerical efficiency leading to the practical possibility of using a large number of sub-domain (rectangular or triangular) basis functions on each solid conductor of the system. The plasma enters the formalism of the plasma region via a surface impedance matrix; for this reason any plasma model can be used; at present the FELICE code has been adopted, that affords density and temperature profiles, and FLR effects. The source term directly models the TEM mode of the coax feeding the antenna and the current in the coax is determined self-consistently, giving the input impedance/admittance of the antenna itself. Calculation of field distributions (both magnetic and electric), useful for sheath considerations, is included. This tool has been implemented in a suite, called TOPICA, that is modular and applicable to ICRF antenna structures of arbitrary shape. This new simulation tool can assist during the detailed design phase and for this reason can be considered a "Virtual Prototyping Laboratory" (VPL). The TOPICA suite has been tested against assessed codes and against measurements and data of mock-ups and existing antennas. The VPL is being used in

  1. Genetic variation in aldo-keto reductase 1D1 (AKR1D1) affects the expression and activity of multiple cytochrome P450s.

    PubMed

    Chaudhry, Amarjit S; Thirumaran, Ranjit K; Yasuda, Kazuto; Yang, Xia; Fan, Yiping; Strom, Stephen C; Schuetz, Erin G

    2013-08-01

    Human liver gene regulatory (Bayesian) network analysis was previously used to identify a cytochrome P450 (P450) gene subnetwork with Aldo-keto reductase 1D1 (AKR1D1) as a key regulatory driver of this subnetwork. This study assessed the biologic importance of AKR1D1 [a key enzyme in the synthesis of bile acids, ligand activators of farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR), known transcriptional regulators of P450s] to hepatic P450 expression. Overexpression of AKR1D1 in primary human hepatocytes led to increased expression of CYP3A4, CYP2C8, CYP2C9, CYP2C19, and CYP2B6. Conversely, AKR1D1 knockdown decreased expression of these P450s. We resequenced AKR1D1 from 98 donor livers and identified a 3'-untranslated region (UTR) (rs1872930) single nucleotide polymorphism (SNP) significantly associated with higher AKR1D1 mRNA expression. AKR1D1 3'-UTR-luciferase reporter studies showed that the variant allele resulted in higher luciferase activity, suggesting that the SNP increases AKR1D1 mRNA stability and/or translation efficiency. Consistent with AKR1D1's putative role as a driver of the P450 subnetwork, the AKR1D1 3'-UTR SNP was significantly associated with increased hepatic mRNA expression of multiple P450s (CYP3A4, CYP2C8, CYP2C9, CYP2C19, and CYP2B6) and CYP3A4, CYP2C8, CYP2C19, and CYP2B6 activities. After adjusting for multiple testing, the association remained significant for AKR1D1, CYP2C9, and CYP2C8 mRNA expression and CYP2C8 activity. These results provide new insights into the variation in expression and activity of P450s that can account for interindividual differences in drug metabolism/efficacy and adverse drug events. In conclusion, we provide the first experimental evidence supporting a role for AKR1D1 as a key genetic regulator of the P450 network. PMID:23704699

  2. Delimitation of the Earliness per se D1 (Eps-D1) flowering gene to a subtelomeric chromosomal deletion in bread wheat (Triticum aestivum)

    PubMed Central

    Zikhali, Meluleki; Wingen, Luzie U.; Griffiths, Simon

    2016-01-01

    Earliness per se (Eps) genes account for the variation in flowering time when vernalization and photoperiod requirements are satisfied. Genomics and bioinformatics approaches were used to describe allelic variation for 40 Triticum aestivum genes predicted, by synteny with Brachypodium distachyon, to be in the 1DL Eps region. Re-sequencing 1DL genes revealed that varieties carrying early heading alleles at this locus, Spark and Cadenza, carry a subtelomeric deletion including several genes. The equivalent region in Rialto and Avalon is intact. A bimodal distribution in the segregating Spark X Rialto single seed descent (SSD) populations enabled the 1DL QTL to be defined as a discrete Mendelian factor, which we named Eps-D1. Near isogenic lines (NILs) and NIL derived key recombinants between markers flanking Eps-D1 suggest that the 1DL deletion contains the gene(s) underlying Eps-D1. The deletion spans the equivalent of the Triticum monoccocum Eps-A m 1 locus, and hence includes MODIFIER OF TRANSCRIPTION 1 (MOT1) and FTSH PROTEASE 4 (FTSH4), the candidates for Eps-A m 1. The deletion also contains T. aestivum EARLY FLOWERING 3-D1 (TaELF3-D1) a homologue of the Arabidopsis thaliana circadian clock gene EARLY FLOWERING 3. Eps-D1 is possibly a homologue of Eps-B1 on chromosome 1BL. NILs carrying the Eps-D1 deletion have significantly reduced total TaELF3 expression and altered TaGIGANTEA (TaGI) expression compared with wild type. Altered TaGI expression is consistent with an ELF3 mutant, hence we propose TaELF3-D1 as the more likely candidate for Eps-D1. This is the first direct fine mapping of Eps effect in bread wheat. PMID:26476691

  3. Effects of D1 receptor knockout on fear and reward learning.

    PubMed

    Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

    2016-09-01

    Dopamine signaling is involved in a variety of neurobiological processes that contribute to learning and memory. D1-like dopamine receptors (including D1 and D5 receptors) are thought to be involved in memory and reward processes, but pharmacological approaches have been limited in their ability to distinguish between D1 and D5 receptors. Here, we examine the effects of a specific knockout of D1 receptors in associative learning tasks involving aversive (shock) or appetitive (cocaine) unconditioned stimuli. We find that D1 knockout mice show similar levels of cued and contextual fear conditioning to WT controls following conditioning protocols involving one, two, or four shocks. D1 knockout mice show increased generalization of fear conditioning and extinction across contexts, revealed as increased freezing to a novel context following conditioning and decreased freezing to an extinguished cue during a contextual renewal test. Further, D1 knockout mice show mild enhancements in extinction following an injection of SKF81297, a D1/D5 receptor agonist, suggesting a role for D5 receptors in extinction enhancements induced by nonspecific pharmacological agonists. Finally, although D1 knockout mice show decreased locomotion induced by cocaine, they are able to form a cocaine-induced conditioned place preference. We discuss these findings in terms of the role of dopamine D1 receptors in general learning and memory processes. PMID:27423521

  4. Resolvin D1 prevents smoking-induced emphysema and promotes lung tissue regeneration

    PubMed Central

    Kim, Kang-Hyun; Park, Tai Sun; Kim, You-Sun; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

    2016-01-01

    Purpose Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1), derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration. Materials and methods C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C) or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid. Results Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking. Conclusion RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema. PMID:27313451

  5. 17(R)-resolvin D1 ameliorates bleomycin-induced pulmonary fibrosis in mice.

    PubMed

    Yatomi, Masakiyo; Hisada, Takeshi; Ishizuka, Tamotsu; Koga, Yasuhiko; Ono, Akihiro; Kamide, Yosuke; Seki, Kaori; Aoki-Saito, Haruka; Tsurumaki, Hiroaki; Sunaga, Noriaki; Kaira, Kyoichi; Dobashi, Kunio; Yamada, Masanobu; Okajima, Fumikazu

    2015-12-01

    Idiopathic pulmonary fibrosis (IPF) is a destructive inflammatory disease with limited therapeutic options. Inflammation plays an integral role in the development of pulmonary fibrosis. Unresolved inflammatory responses can lead to substantial tissue injury, chronic inflammation, and fibrosis. The resolvins are a family of endogenous ω-3 fatty acid derived-lipid mediators of inflammation resolution. Resolvin D1 (RvD1) displays potent anti-inflammatory, pro-resolving activity, without causing immunosuppression. Its epimer, 17(R)-resolvin D1 (17(R)-RvD1), exhibits equivalent functionality to RvD1. In addition, 17(R)-RvD1 is resistant to rapid inactivation by eicosanoid oxidoreductases. In the present study, we tested the hypothesis that 17(R)-RvD1 can provide a therapeutic benefit in IPF by reducing inflammation and pulmonary fibrosis, while leaving the normal immune response intact. Mice were exposed to bleomycin (BLM) via micro-osmotic pump to induce pulmonary fibrosis, and were then treated with 17(R)-RvD1 or vehicle by intraperitoneal injection. Administration of 17(R)-RvD1 from the start of BLM treatment attenuated neutrophil alveolar infiltration, lung collagen content, and Interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and type I collagen mRNA expression, along with subsequent reduction in histologically detectable fibrosis. The 17(R)-RvD1-induced infiltration of inflammatory cells was inhibited by an antagonist of lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2). The administration of 17(R)-RvD1 at the later fibrotic stage also improved the lung failure. These results suggest that 17(R)-RvD1 attenuates pulmonary fibrosis by promoting the resolution of neutrophilic inflammation and also provides pulmonary restoration. These data highlight the therapeutic potential of 17(R)-RvD1 in the management of this intractable disease. PMID:26660549

  6. 17 CFR 270.12d1-2 - Exemptions for investment companies relying on section 12(d)(1)(G) of the Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... by an investment company); and (3) Securities issued by a money market fund, when the acquisition is in reliance on § 270.12d1-1. (b) Definitions. For purposes of this section, money market fund has...

  7. Cyclin D1 and Ewing's sarcoma/PNET: A microarray analysis.

    PubMed

    Fagone, Paolo; Nicoletti, Ferdinando; Salvatorelli, Lucia; Musumeci, Giuseppe; Magro, Gaetano

    2015-10-01

    Recent immunohistochemical analyses have showed that cyclin D1 is expressed in soft tissue Ewing's sarcoma/peripheral neuroectodermal tumor (PNET) of childhood and adolescents, while it is undetectable in both embryonal and alveolar rhabdomyosarcoma. In the present paper, microarray analysis provided evidence of a significant upregulation of cyclin D1 in Ewing's sarcoma as compared to normal tissues. In addition, we confirmed our previous findings of a significant over-expression of cyclin D1 in Ewing sarcoma as compared to rhabdomyosarcoma. Bioinformatic analysis also allowed to identify some other genes, strongly correlated to cyclin D1, which, although not previously studied in pediatric tumors, could represent novel markers for the diagnosis and prognosis of Ewing's sarcoma/PNET. The data herein provided support not only the use of cyclin D1 as a diagnostic marker of Ewing sarcoma/PNET but also the possibility of using drugs targeting cyclin D1 as potential therapeutic strategies. PMID:26363896

  8. Efficient source for the production of ultradense deuterium D(-1) for laser-induced fusion (ICF)

    SciTech Connect

    Andersson, Patrik U.; Loenn, Benny; Holmlid, Leif

    2011-01-15

    A novel source which simplifies the study of ultradense deuterium D(-1) is now described. This means one step further toward deuterium fusion energy production. The source uses internal gas feed and D(-1) can now be studied without time-of-flight spectral overlap from the related dense phase D(1). The main aim here is to understand the material production parameters, and thus a relatively weak laser with focused intensity {<=}10{sup 12} W cm{sup -2} is employed for analyzing the D(-1) material. The properties of the D(-1) material at the source are studied as a function of laser focus position outside the emitter, deuterium gas feed, laser pulse repetition frequency and laser power, and temperature of the source. These parameters influence the D(-1) cluster size, the ionization mode, and the laser fragmentation patterns.

  9. Immunohistological recognition of cyclin D1 expression by non-lymphoid cells among lymphoid neoplastic cells.

    PubMed

    Abdulla, Zainalabideen; Turley, Helen; Gatter, Kevin; Pezzella, Francesco

    2014-03-01

    Cyclin D1 immunostaining of non-neoplastic cells has been a source of diagnostic confusion especially in lymphoproliferative lesions. This study has reviewed these in two hundred and thirty-one haematopathological samples stained for cyclin D1. Most cases were formalin-fixed except for a few bone marrow trephines, which were B-5 fixed, and EDTA decalcified. Overall, 94% (216/231) of cases showed one or more types of non-neoplastic cells expressing Cyclin D1 of variable intensity. Endothelial cells and histiocytes were the most commonly identified Cyclin D1 positive cells being positive in 92% (214/231) of cases. Other normal cell types identified included fat cells, stromal fibroblasts, glial cells, spermatocytes, smooth muscle cells, osteoblasts and where present epithelial cells. Many normal cell types can express cyclinD1. Knowledge of these is useful to prevent misinterpretation of cyclin D1 positive tumours. PMID:23758159

  10. Cyclin D1 interacts and collaborates with Ral GTPases enhancing cell detachment and motility.

    PubMed

    Fernández, R M H; Ruiz-Miró, M; Dolcet, X; Aldea, M; Garí, E

    2011-04-21

    Alterations in the levels of adhesion and motility of cells are critical events in the development of metastasis. Cyclin D1 (CycD1) is one of the most frequently amplified oncogenes in many types of cancers and it is also associated with the development of metastasis. Despite this, we still do not know which are all the relevant pathways by which CycD1 induces oncogenic processes. CycD1 functions can be either dependent or independent of the cyclin-dependent kinase Cdk4, and they affect several cellular aspects such as proliferation, cell attachment and migration. In this work, we reveal a novel function of CycD1 that fosters our understanding of the oncogenic potential of CycD1. We show that CycD1 binds to the small GTPases Ral A and B, which are involved, through exocyst regulation, in the progression of metastatic cancers, inducing anchorage-independent growth and cell survival of transformed cells. We show that CycD1 binds active Ral complexes and the exocyst protein Sec6, and co-localizes with Ral GTPases in trans-Golgi and exocyst-rich regions. We have also observed that CycD1-Cdk4 phosphorylates the Ral GEF Rgl2 'in vitro' and that CycD1-Cdk4 activity stimulates accumulation of the Ral GTP active forms. In accordance with this, our data suggest that CycD1-Cdk4 enhances cell detachment and motility in collaboration with Ral GTPases. This new function may help explain the contribution of CycD1 to tumor spreading. PMID:21242975

  11. Altered striatal function in a mutant mouse lacking D1A dopamine receptors.

    PubMed Central

    Drago, J; Gerfen, C R; Lachowicz, J E; Steiner, H; Hollon, T R; Love, P E; Ooi, G T; Grinberg, A; Lee, E J; Huang, S P

    1994-01-01

    Of the five known dopamine receptors, D1A and D2 represent the major subtypes expressed in the striatum of the adult brain. Within the striatum, these two subtypes are differentially distributed in the two main neuronal populations that provide direct and indirect pathways between the striatum and the output nuclei of the basal ganglia. Movement disorders, including Parkinson disease and various dystonias, are thought to result from imbalanced activity in these pathways. Dopamine regulates movement through its differential effects on D1A receptors expressed by direct output neurons and D2 receptors expressed by indirect output neurons. To further examine the interaction of D1A and D2 neuronal pathways in the striatum, we used homologous recombination to generate mutant mice lacking functional D1A receptors (D1A-/-). D1A-/- mutants are growth retarded and die shortly after weaning age unless their diet is supplemented with hydrated food. With such treatment the mice gain weight and survive to adulthood. Neurologically, D1A-/- mice exhibit normal coordination and locomotion, although they display a significant decrease in rearing behavior. Examination of the striatum revealed changes associated with the altered phenotype of these mutants. D1A receptor binding was absent in striatal sections from D1A-/- mice. Striatal neurons normally expressing functional D1A receptors are formed and persist in adult homozygous mutants. Moreover, substance P mRNA, which is colocalized specifically in striatal neurons with D1A receptors, is expressed at a reduced level. In contrast, levels of enkephalin mRNA, which is expressed in striatal neurons with D2 receptors, are unaffected. These findings show that D1A-/- mice exhibit selective functional alterations in the striatal neurons giving rise to the direct striatal output pathway. Images Fig. 2 Fig. 4 PMID:7809078

  12. Hypoallergenic derivatives of Fel d 1 obtained by rational reassembly for allergy vaccination and tolerance induction

    PubMed Central

    Curin, M.; Weber, M.; Thalhamer, T.; Swoboda, I.; Focke-Tejkl, M.; Blatt, K.; Valent, P.; Marth, K.; Garmatiuk, T.; Grönlund, H.; Thalhamer, J.; Spitzauer, S.; Valenta, R.

    2015-01-01

    Summary Background and objective The major cat allergen Fel d 1 represents one of the most important respiratory allergens. Aim of this study was to engineer recombinant Fel d 1 derivatives with reduced IgE reactivity and preserved T cell epitopes for vaccination and tolerance induction. Methods Seven recombinant mosaic proteins were generated by reassembly of non-IgE-reactive peptides of Fel d 1 which contained the sequence elements for induction of allergen-specific blocking IgG antibodies and T cell epitopes. Mosaic proteins were expressed in Escherichia coli using codon-optimized synthetic genes and compared with Fel d 1 regarding structural fold by circular dichroism, IgE-binding capacity, activation of allergic patients’ basophils and ability to induce allergen-specific blocking IgG antibodies upon immunization. Results Although each of the mosaic proteins had lost the alpha-helical fold typical for Fel d 1, a strong reduction in IgE reactivity as well as allergenic activity in basophil activation assays was only obtained for three constructs, two reassembled fragments (Fel d 1 MB, Fel d 1 MC) and a fusion of the latter two (Fel d 1 MF) in which the cysteines of Fel d 1 MC were replaced by serines. Immunization of rabbits with Fel d 1 MB, MC and MF induced high levels of IgG antibodies that inhibited IgE reactivity of cat-allergic patients to Fel d 1 in a comparable manner as IgG induced with the wild-type allergen. Conclusions We report the development of hypoallergenic reassembled Fel d 1 proteins suitable for vaccination and tolerance induction in cat-allergic patients. PMID:24552249

  13. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice.

    PubMed

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-01

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice. PMID:26771609

  14. Cyclin K and cyclin D1b are oncogenic in myeloma cells

    PubMed Central

    2010-01-01

    Background Aberrant expression of cyclin D1 is a common feature in multiple myeloma (MM) and always associated with mantle cell lymphoma (MCL). CCND1 gene is alternatively spliced to produce two cyclin D1 mRNA isoforms which are translated in two proteins: cyclin D1a and cyclin D1b. Both isoforms are present in MM cell lines and primary cells but their relative role in the tumorigenic process is still elusive. Results To test the tumorigenic potential of cyclin D1b in vivo, we generated cell clones derived from the non-CCND1 expressing MM LP-1 cell line, synthesizing either cyclin D1b or cyclin K, a structural homolog and viral oncogenic form of cyclin D1a. Immunocompromised mice injected s.c. with LP-1K or LP-1D1b cells develop tumors at the site of injection. Genome-wide analysis of LP-1-derived cells indicated that several cellular processes were altered by cyclin D1b and/or cyclin K expression such as cell metabolism, signal transduction, regulation of transcription and translation. Importantly, cyclin K and cyclin D1b have no major action on cell cycle or apoptosis regulatory genes. Moreover, they impact differently cell functions. Cyclin K-expressing cells have lost their migration properties and display enhanced clonogenic capacities. Cyclin D1b promotes tumorigenesis through the stimulation of angiogenesis. Conclusions Our study indicates that cyclin D1b participates into MM pathogenesis via previously unrevealed actions. PMID:20459741

  15. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice

    PubMed Central

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-01

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice. PMID:26771609

  16. 26 CFR 1.45D-1 - New markets tax credit.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 1 2013-04-01 2013-04-01 false New markets tax credit. 1.45D-1 Section 1.45D-1... Computing Credit for Investment in Certain Depreciable Property § 1.45D-1 New markets tax credit. (a... markets tax credit under section 45D(a). (b) Allowance of credit—(1) In general. A taxpayer holding...

  17. 26 CFR 1.45D-1 - New markets tax credit.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 1 2012-04-01 2012-04-01 false New markets tax credit. 1.45D-1 Section 1.45D-1... Computing Credit for Investment in Certain Depreciable Property § 1.45D-1 New markets tax credit. (a... markets tax credit under section 45D(a). (b) Allowance of credit—(1) In general. A taxpayer holding...

  18. Cooperation between Dmp1 Loss and Cyclin D1 Overexpression in Breast Cancer

    PubMed Central

    Zhu, Sinan; Mott, Ryan T.; Fry, Elizabeth A.; Taneja, Pankaj; Kulik, George; Sui, Guangchao; Inoue, Kazushi

    2014-01-01

    Cyclin D1 is a component of the core cell-cycle machinery and is frequently overexpressed in breast cancer. It physically interacts with the tumor suppressor Dmp1 that attenuates the oncogenic signals from Ras and HER2 by inducing Arf/p53-dependent cell-cycle arrest. Currently, the biological significance of Dmp1–cyclin D1 interplay in breast cancer has not been determined. Here, we show that cyclin D1 bound to Dmp1 to activate both Arf and Ink4a promoters and, consequently, induced apoptosis or G2/M cell-cycle delay in normal cells to protect them from neoplastic transformation. The cyclin D1–induced Ink4a/Arf gene expression was dependent on Dmp1 because the induction was not detected in Dmp1-deficient or DMP1-depleted cells. Arf/Ink4a expression was increased in pre-malignant mammary glands from Dmp1+/+;MMTV-cyclin D1 and Dmp1+/+;MMTV-D1T286A mice but significantly down-regulated in those from Dmp1-deficient mice. Selective Dmp1 deletion was found in 21% of the MMTV-D1 and D1T286A mammary carcinomas, and the Dmp1 heterozygous status significantly accelerated mouse mammary tumorigenesis with reduced apoptosis and increased metastasis. Overall, our study reveals a pivotal role of combined Dmp1 loss and cyclin D1 overexpression in breast cancer. PMID:23938323

  19. [Pronostic value of the immunohistochemical expression of cyclin D1 (DCS6) in epidermoid larynx carcinoma].

    PubMed

    García Lozano, M C; Orradre Romero, J L; Sánchez Carrión, S; Caro Garcia, M; Lasso Luis, O; Piris Pinilla, M A

    2006-01-01

    In this paper we carried out an immunohistochemical study of cyclin D1 (DCS6 ) expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain) for a time of 5 years. In the cases with lymph node metastasis we also studied cyclin D1 expression at this level. Furthermore we have analysed the value of cyclin D1 expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between cyclin D1 expression and other clinic and pathologic parameters. PMID:16881553

  20. Phenotypical characterization of the rat striatal neurons expressing the D1 dopamine receptor gene.

    PubMed Central

    Le Moine, C; Normand, E; Bloch, B

    1991-01-01

    In situ hybridization experiments were performed in rat brain sections from normal and 6-hydroxydopamine-treated rats in order to map and identify the neurons expressing the D1 receptor gene in the striatum and the substantia nigra. Procedures of combined in situ hybridization, allowing the simultaneous detection of two mRNAs in the same section or in adjacent sections, were used to characterize the phenotypes of the neurons expressing the D1 receptor gene. D1 receptor mRNA was found in neurons all over the caudate-putamen, the accumbens nucleus, and the olfactory tubercle but not in the substantia nigra. In the caudate-putamen and accumbens nucleus, most of the neurons containing D1 receptor mRNA were characterized as medium-sized substance P neurons and distinct from those containing D2 receptor mRNA. Nevertheless, 15-20% of the substance P neurons did not contain D1 receptor mRNA. The neurons containing preproenkephalin A mRNA did not contain D1 receptor mRNA but contained D2 receptor mRNA. A small number of cholinergic and somatostatinergic neurons exhibited a weak reaction for D1 receptor mRNA. These results demonstrate that dopamine acts on efferent striatal neurons through expression of distinct receptors--namely, D1 and D2 in separate cell populations (substance P and preproenkephalin A neurons, respectively)--and can also act on nonprojecting neurons through D1 receptor expression. Images PMID:1827915

  1. Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer.

    PubMed

    Borcherding, D C; Tong, W; Hugo, E R; Barnard, D F; Fox, S; LaSance, K; Shaughnessy, E; Ben-Jonathan, N

    2016-06-16

    Patients with advanced breast cancer often fail to respond to treatment, creating a need to develop novel biomarkers and effective therapeutics. Dopamine (DA) is a catecholamine that binds to five G protein-coupled receptors. We discovered expression of DA type-1 receptors (D1Rs) in breast cancer, thereby identifying these receptors as novel therapeutic targets in this disease. Strong to moderate immunoreactive D1R expression was found in 30% of 751 primary breast carcinomas, and was associated with larger tumors, higher tumor grades, node metastasis and shorter patient survival. DA and D1R agonists, signaling through the cGMP/protein kinase G (PKG) pathway, suppressed cell viability, inhibited invasion and induced apoptosis in multiple breast cancer cell lines. Fenoldopam, a peripheral D1R agonist that does not penetrate the brain, dramatically suppressed tumor growth in two mouse models with D1R-expressing xenografts by increasing both necrosis and apoptosis. D1R-expressing primary tumors and metastases in mice were detected by fluorescence imaging. In conclusion, D1R overexpression is associated with advanced breast cancer and poor prognosis. Activation of the D1R/cGMP/PKG pathway induces apoptosis in vitro and causes tumor shrinkage in vivo. Fenoldopam, which is FDA (Food and Drug Administration) approved to treat renal hypertension, could be repurposed as a novel therapeutic agent for patients with D1R-expressing tumors. PMID:26477316

  2. Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

    PubMed Central

    Norling, Lucy V.; Headland, Sarah E.; Dalli, Jesmond; Arnardottir, Hildur H.; Haworth, Oliver; Jones, Hefin R.; Irimia, Daniel; Serhan, Charles N.; Perretti, Mauro

    2016-01-01

    Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which — once applied to human neutrophils — attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor–deficient mice termed ALX/fpr2/3−/−. These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA. PMID:27158677

  3. Comparative effects of nodularin and microcystin-LR in zebrafish: 1. Uptake by organic anion transporting polypeptide Oatp1d1 (Slco1d1).

    PubMed

    Faltermann, Susanne; Prétôt, René; Pernthaler, Jakob; Fent, Karl

    2016-02-01

    Microcystin-LR (MC-LR) and nodularin are hepatotoxins produced by several cyanobacterial species. Their toxicity is based on active cellular uptake and subsequent inhibition of protein phosphatases PP1/2A, leading to hyperphosphorylation and cell death. To date, uptake of MC-LR and nodularin in fish is poorly understood. Here, we investigated the role of the organic anion transporting polypeptide Oatp1d1 in zebrafish (drOatp1d1, Slco1d1) in cellular uptake in zebrafish. We stably transfected CHO and HEK293 cell lines expressing drOatp1d1. In both transfectants, uptake of MC-LR and nodularin was demonstrated by competitive inhibition of uptake with fluorescent substrate lucifer yellow. Direct uptake of MC-LR was demonstrated by immunostaining, and indirectly by the high cytotoxicity in stable transfectants. By means of a synthesized fluorescent labeled MC-LR derivative, direct uptake was further confirmed in HEK293 cells expressing drOatp1d1. Additionally, uptake and toxicity was investigated in the permanent zebrafish liver cell line ZFL. These cells had only a low relative abundance of drOatp1d1, drOatp2b1 and drOatp1f transcripts, which correlated with the lack of MC-LR induced cytotoxicity and transcriptional changes of genes indicative of endoplasmic reticulum stress, a known effect of this toxin. Our study demonstrates that drOatp1d1 functions as an uptake transporter for both MC-LR and nodularin in zebrafish. PMID:26769064

  4. Inhibition of the Dopamine D1 Receptor Signaling by PSD-95*◆

    PubMed Central

    Zhang, Jingping; Vinuela, Angel; Neely, Mark H.; Hallett, Penelope J.; Grant, Seth G. N.; Miller, Gregory M.; Isacson, Ole; Caron, Marc G.; Yao, Wei-Dong

    2008-01-01

    Dopamine D1 receptors play an important role in movement, reward, and learning and are implicated in a number of neurological and psychiatric disorders. These receptors are concentrated in dendritic spines of neurons, including the spine head and the postsynaptic density. D1 within spines is thought to modulate the local channels and receptors to control the excitability and synaptic properties of spines. The molecular mechanisms mediating D1 trafficking, anchorage, and function in spines remain elusive. Here we show that the synaptic scaffolding protein PSD-95 thought to play a role in stabilizing gluta-mate receptors in the postsynaptic density, interacts with D1 and regulates its trafficking and function. Interestingly, the D1-PSD-95 interaction does not require the well characterized domains of PSD-95 but is mediated by the carboxyl-terminal tail of D1 and the NH2terminus of PSD-95, a region that is recognized only recently to participate in protein-protein interaction. Co-expression of PSD-95 with D1 in mammalian cells inhibits the D1-mediated cAMP accumulation without altering the total expression level or the agonist binding properties of the receptor. The diminished D1 signaling is mediated by reduced D1 expression at the cell surface as a consequence of an enhanced constitutive, dynamin-dependent endocytosis. In addition, genetically engineered mice lacking PSD-95 show a heightened behavioral response to either a D1 agonist or the psychostimulant amphetamine. These studies demonstrate a role for a glutamatergic scaffold in dopamine receptor signaling and trafficking and identify a new potential target for the modulation of abnormal dopaminergic function. PMID:17369255

  5. Automated structure verification based on a combination of 1D (1)H NMR and 2D (1)H - (13)C HSQC spectra.

    PubMed

    Golotvin, Sergey S; Vodopianov, Eugene; Pol, Rostislav; Lefebvre, Brent A; Williams, Antony J; Rutkowske, Randy D; Spitzer, Timothy D

    2007-10-01

    A method for structure validation based on the simultaneous analysis of a 1D (1)H NMR and 2D (1)H - (13)C single-bond correlation spectrum such as HSQC or HMQC is presented here. When compared with the validation of a structure by a 1D (1)H NMR spectrum alone, the advantage of including a 2D HSQC spectrum in structure validation is that it adds not only the information of (13)C shifts, but also which proton shifts they are directly coupled to, and an indication of which methylene protons are diastereotopic. The lack of corresponding peaks in the 2D spectrum that appear in the 1D (1)H spectrum, also gives a clear picture of which protons are attached to heteroatoms. For all these benefits, combined NMR verification was expected and found by all metrics to be superior to validation by 1D (1)H NMR alone. Using multiple real-life data sets of chemical structures and the corresponding 1D and 2D data, it was possible to unambiguously identify at least 90% of the correct structures. As part of this test, challenging incorrect structures, mostly regioisomers, were also matched with each spectrum set. For these incorrect structures, the false positive rate was observed as low as 6%. PMID:17694570

  6. 26 CFR 1.1033(d)-1 - Destruction or disposition of livestock because of disease.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... of disease. 1.1033(d)-1 Section 1.1033(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Destruction or disposition of livestock because of disease. (a) The destruction occurring in a taxable year to which the Internal Revenue Code of 1954 applies, of livestock by, or on account of, disease, or the...

  7. 26 CFR 1.665(d)-1A - Taxes imposed on the trust.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Taxes imposed on the trust. 1.665(d)-1A Section 1.665(d)-1A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning on Or After January...

  8. 26 CFR 48.4222(d)-1 - Registration in the case of certain other exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... procedure set forth in § 48.4222 (a)-1 also applies in the following cases: (a) Tax-free sales on or after... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Registration in the case of certain other exemptions. 48.4222(d)-1 Section 48.4222(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF...

  9. 17 CFR 270.12d1-1 - Exemptions for investments in money market funds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... money market funds. 270.12d1-1 Section 270.12d1-1 Commodity and Securities Exchanges SECURITIES AND... Exemptions for investments in money market funds. (a) Exemptions for acquisition of money market fund shares... issued by a money market fund; and (2) A money market fund, any principal underwriter thereof, and...

  10. 26 CFR 31.3306(d)-1 - Included and excluded service.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Included and excluded service. 31.3306(d)-1 Section 31.3306(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Unemployment Tax Act...

  11. 7 CFR Exhibits D-D-1 to Subpart A... - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 14 2013-01-01 2013-01-01 false D Exhibits D-D-1 to Subpart A of Part 1962...) PROGRAM REGULATIONS (CONTINUED) PERSONAL PROPERTY Servicing and Liquidation of Chattel Security Exhibits D—D-1 to Subpart A of Part 1962...

  12. 7 CFR Exhibits D-D-1 to Subpart A... - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 14 2011-01-01 2011-01-01 false D Exhibits D-D-1 to Subpart A of Part 1962...) PROGRAM REGULATIONS (CONTINUED) PERSONAL PROPERTY Servicing and Liquidation of Chattel Security Exhibits D—D-1 to Subpart A of Part 1962...

  13. 7 CFR Exhibits D-D-1 to Subpart A... - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 14 2012-01-01 2012-01-01 false D Exhibits D-D-1 to Subpart A of Part 1962...) PROGRAM REGULATIONS (CONTINUED) PERSONAL PROPERTY Servicing and Liquidation of Chattel Security Exhibits D—D-1 to Subpart A of Part 1962...

  14. 7 CFR Exhibits D-D-1 to Subpart A... - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 14 2014-01-01 2014-01-01 false D Exhibits D-D-1 to Subpart A of Part 1962...) PROGRAM REGULATIONS (CONTINUED) PERSONAL PROPERTY Servicing and Liquidation of Chattel Security Exhibits D—D-1 to Subpart A of Part 1962...

  15. 7 CFR Exhibits D-D-1 to Subpart A... - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true D Exhibits D-D-1 to Subpart A of Part 1962 Agriculture... REGULATIONS (CONTINUED) PERSONAL PROPERTY Servicing and Liquidation of Chattel Security Exhibits D—D-1 to Subpart A of Part 1962...

  16. 16 CFR Appendix D1 to Part 305 - Water Heaters-Gas

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Water Heaters-Gas D1 Appendix D1 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS ENERGY AND WATER USE LABELING FOR CONSUMER PRODUCTS UNDER THE ENERGY POLICY AND CONSERVATION ACT (âENERGY...

  17. 16 CFR Appendix D1 to Part 305 - Water Heaters-Gas

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Water Heaters-Gas D1 Appendix D1 to Part 305... DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS REQUIRED... Part 305—Water Heaters—Gas Range Information CAPACITY FIRST HOUR RATING Range of Estimated...

  18. Concerted Action of ANP and Dopamine D1-Receptor to Regulate Sodium Homeostasis in Nephrotic Syndrome

    PubMed Central

    Fernandes-Cerqueira, Cátia; Quelhas-Santos, Janete; Moreira-Rodrigues, Mónica; Simões-Silva, Liliana; Blazquez-Medela, Ana M.; Martinez-Salgado, C.; Lopez-Novoa, Jose M.; Pestana, Manuel

    2013-01-01

    The edema formation in nephrotic syndrome (NS) is associated with a blunted response to atrial natriuretic peptide (ANP). The natriuretic effects of ANP have been related to renal dopamine D1-receptors (D1R). We examined the interaction between ANP and renal D1R in rats with puromycin aminonucleoside-induced NS (PAN-NS). Urinary sodium, cyclic guanosine monophosphate (cGMP) excretion, and D1R protein expression and localization in renal tubules were evaluated in PAN-NS and control rats before and during volume expansion (VE). The effects of zaprinast (phosphodiesterase type 5 inhibitor), alone or in combination with Sch-23390 (D1R antagonist), were examined in both groups. The increased natriuresis and urinary cGMP excretion evoked by acute VE were blunted in PAN-NS despite increased levels of circulating ANP. This was accompanied in PAN-NS by a marked decrease of D1R expression in the renal tubules. Infusion of zaprinast in PAN-NS resulted in increased urinary excretion of cGMP and sodium to similar levels of control rats and increased expression of D1R in the plasma membrane of renal tubular cells. Combined administration of Sch-23390 and zaprinast prevented natriuresis and increased cGMP excretion induced by zaprinast alone. We conclude that D1R may play a major role in the ANP resistance observed in PAN-NS. PMID:23956981

  19. 26 CFR 31.3406(d)-1 - Manner required for furnishing a taxpayer identification number.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Manner required for furnishing a taxpayer identification number. 31.3406(d)-1 Section 31.3406(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT...

  20. 16 CFR Appendix D1 to Part 305 - Water Heaters-Gas

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Water Heaters-Gas D1 Appendix D1 to Part 305... DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS REQUIRED... Part 305—Water Heaters—Gas Range Information CAPACITY FIRST HOUR RATING Range of Estimated...

  1. D1 LF Wind Measurements in the 90 to 100 Km Height Range

    NASA Technical Reports Server (NTRS)

    Schminder, R.; Kurschner, D.

    1984-01-01

    A short historical review of the development and use of D1 low frequency (LF) techniques for wind measurement is presented and the measuring and evaluation procedures are described. The advantages and disadvantages of D1 LF measurements are examined. Finally, the results of measurements over Central Europe acquired by the Collm Geophysical Observatory are discussed.

  2. 26 CFR 1.149(d)-1 - Limitations on advance refundings.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Limitations on advance refundings. 1.149(d)-1 Section 1.149(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... advance refunding issue that is, in turn, currently refunded with a tax-exempt issue, the taxable...

  3. 26 CFR 1.149(d)-1 - Limitations on advance refundings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Limitations on advance refundings. 1.149(d)-1 Section 1.149(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... advance refunding issue that is, in turn, currently refunded with a tax-exempt issue, the taxable...

  4. 26 CFR 48.4216(d)-1 - Sales of installment accounts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 16 2011-04-01 2011-04-01 false Sales of installment accounts. 48.4216(d)-1 Section 48.4216(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Special Provisions Applicable...

  5. 26 CFR 48.4216(d)-1 - Sales of installment accounts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 16 2012-04-01 2012-04-01 false Sales of installment accounts. 48.4216(d)-1 Section 48.4216(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Special Provisions Applicable...

  6. 26 CFR 1.149(d)-1 - Limitations on advance refundings.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 2 2012-04-01 2012-04-01 false Limitations on advance refundings. 1.149(d)-1 Section 1.149(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... advance refunding issue that is, in turn, currently refunded with a tax-exempt issue, the taxable...

  7. 26 CFR 48.4216(d)-1 - Sales of installment accounts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Sales of installment accounts. 48.4216(d)-1 Section 48.4216(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Special Provisions Applicable...

  8. 26 CFR 1.149(d)-1 - Limitations on advance refundings.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Limitations on advance refundings. 1.149(d)-1 Section 1.149(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... advance refunding issue that is, in turn, currently refunded with a tax-exempt issue, the taxable...

  9. Constitutive Phosphorylation by Protein Kinase C Regulates D1 Dopamine Receptor Signaling

    PubMed Central

    Rankin, Michele L.; Sibley, David R.

    2010-01-01

    The D1 dopamine receptor (D1DAR) is robustly phosphorylated by multiple protein kinases, yet the phosphorylation sites and functional consequences of these modifications are not fully understood. Here, we report that the D1DAR is phosphorylated by protein kinase C (PKC) in the absence of agonist stimulation. Phosphorylation of the D1DAR by PKC is constitutive in nature, can be induced by phorbol ester treatment or through activation of Gq-mediated signal transduction pathways, and is abolished by PKC inhibitors. We demonstrate that most, but not all, isoforms of PKC are capable of phosphorylating the receptor. To directly assess the functional role of PKC phosphorylation of the D1DAR, a site-directed mutagenesis approach was used to identify the PKC sites within the receptor. Five serine residues were found to mediate the PKC phosphorylation. Replacement of these residues had no effect on D1DAR expression or agonist-induced desensitization; however, G protein coupling and cAMP accumulation were significantly enhanced in PKC-null D1DAR. Thus, constitutive or heterologous PKC phosphorylation of the D1DAR dampens dopamine activation of the receptor, most likely occurring in a context-specific manner, mediated by the repertoire of PKC isozymes within the cell. PMID:20969574

  10. 26 CFR 1.415(d)-1 - Cost-of-living adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 5 2014-04-01 2014-04-01 false Cost-of-living adjustments. 1.415(d)-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.415(d)-1 Cost-of... defined benefit plans is adjusted annually to take into account increases in the cost of living....

  11. 26 CFR 1.415(d)-1 - Cost-of-living adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Cost-of-living adjustments. 1.415(d)-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.415(d)-1 Cost-of... defined benefit plans is adjusted annually to take into account increases in the cost of living....

  12. 26 CFR 1.415(d)-1 - Cost-of-living adjustments.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Cost-of-living adjustments. 1.415(d)-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.415(d)-1 Cost-of... defined benefit plans is adjusted annually to take into account increases in the cost of living....

  13. 26 CFR 1.642(d)-1 - Net operating loss deduction.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Net operating loss deduction. 1.642(d)-1 Section... TAX (CONTINUED) INCOME TAXES (CONTINUED) Estates, Trusts, and Beneficiaries § 1.642(d)-1 Net operating loss deduction. The net operating loss deduction allowed by section 172 is available to estates...

  14. 26 CFR 1.642(d)-1 - Net operating loss deduction.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Net operating loss deduction. 1.642(d)-1 Section... TAX (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(d)-1 Net operating loss deduction. The net operating loss deduction allowed by section 172 is available to estates and...

  15. Dissociable hippocampal and amygdalar D1-like receptor contribution to discriminated Pavlovian conditioned approach learning.

    PubMed

    Andrzejewski, Matthew E; Ryals, Curtis

    2016-02-15

    Pavlovian conditioning is an elementary form of reward-related behavioral adaptation. The mesolimbic dopamine system is widely considered to mediate critical aspects of reward-related learning. For example, initial acquisition of positively-reinforced operant behavior requires dopamine (DA) D1 receptor (D1R) activation in the basolateral amygdala (BLA), central nucleus of the amygdala (CeA), and the ventral subiculum (vSUB). However, the role of D1R activation in these areas on appetitive, non-drug-related, Pavlovian learning is not currently known. In separate experiments, microinfusions of the D1-like receptor antagonist SCH-23390 (3.0 nmol/0.5 μL per side) into the amygdala and subiculum preceded discriminated Pavlovian conditioned approach (dPCA) training sessions. D1-like antagonism in all three structures impaired the acquisition of discriminated approach, but had no effect on performance after conditioning was asymptotic. Moreover, dissociable effects of D1-like antagonism in the three structures on components of discriminated responding were obtained. Lastly, the lack of latent inhibition in drug-treated groups may elucidate the role of D1-like in reward-related Pavlovian conditioning. The present data suggest a role for the D1 receptors in the amygdala and hippocampus in learning the significance of conditional stimuli, but not in the expression of conditional responses. PMID:26632336

  16. New cis-regulatory elements in the Rht-D1b locus region of wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fifteen gene-containing BACs with accumulated length of 1.82-Mb from the Rht-D1b locus region weresequenced and compared in detail with the orthologous regions of rice, sorghum, and maize. Our results show that Rht-D1b represents a conserved genomic region as implied by high gene sequence identity...

  17. 17 CFR 270.12d1-1 - Exemptions for investments in money market funds.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... securities and other investments in which a money market fund may invest under § 270.2a-7; and (B) Undertakes... money market funds. 270.12d1-1 Section 270.12d1-1 Commodity and Securities Exchanges SECURITIES AND... Exemptions for investments in money market funds. (a) Exemptions for acquisition of money market fund...

  18. 17 CFR 270.12d1-1 - Exemptions for investments in money market funds.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... securities and other investments in which a money market fund may invest under § 270.2a-7; and (B) Undertakes... money market funds. 270.12d1-1 Section 270.12d1-1 Commodity and Securities Exchanges SECURITIES AND... Exemptions for investments in money market funds. (a) Exemptions for acquisition of money market fund...

  19. 17 CFR 270.12d1-1 - Exemptions for investments in money market funds.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... securities and other investments in which a money market fund may invest under § 270.2a-7; and (B) Undertakes... money market funds. 270.12d1-1 Section 270.12d1-1 Commodity and Securities Exchanges SECURITIES AND... Exemptions for investments in money market funds. (a) Exemptions for acquisition of money market fund...

  20. 17 CFR 270.12d1-1 - Exemptions for investments in money market funds.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... securities and other investments in which a money market fund may invest under § 270.2a-7; and (B) Undertakes... money market funds. 270.12d1-1 Section 270.12d1-1 Commodity and Securities Exchanges SECURITIES AND... Exemptions for investments in money market funds. (a) Exemptions for acquisition of money market fund...

  1. Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4.

    PubMed Central

    Neuman, E; Ladha, M H; Lin, N; Upton, T M; Miller, S J; DiRenzo, J; Pestell, R G; Hinds, P W; Dowdy, S F; Brown, M; Ewen, M E

    1997-01-01

    Cyclin D1 plays an important role in the development of breast cancer and is required for normal breast cell proliferation and differentiation associated with pregnancy. We show that ectopic expression of cyclin D1 can stimulate the transcriptional activity of the estrogen receptor in the absence of estradiol and that this activity can be inhibited by 4-hydroxytamoxifen and ICI 182,780. Cyclin D1 can form a specific complex with the estrogen receptor. Stimulation of the estrogen receptor by cyclin D1 is independent of cyclin-dependent kinase 4 activation. Cyclin D1 may manifest its oncogenic potential in breast cancer in part through binding to the estrogen receptor and activation of the transcriptional activity of the receptor. PMID:9271411

  2. Resolvin D1, Protectin D1, and Related Docosahexaenoic Acid-Derived Products: Analysis via Electrospray/Low Energy Tandem Mass Spectrometry based on Spectra and Fragmentation Mechanisms

    PubMed Central

    Hong, Song; Lu, Yan; Yang, Rong; Gotlinger, Katherine H.; Petasis, Nicos P.; Serhan, Charles N.

    2009-01-01

    Resolvin D1 (RvD1) and Protectin D1 (Neuroprotectin D1, PD1/NPD1) are newly identified anti-inflammatory lipid mediators biosynthesized from docosahexaenoic acid (DHA). In this report, the spectra-structure correlations and fragmentation mechanisms were studied using electrospray low-energy collision-induced dissociation tandem mass spectrometry (MS/MS) for biogenic RvD1 and PD1, as well as mono-hydroxy-DHA and related hydroperoxy-DHA. The loss of H2O and CO2 in the spectra indicates the number of functional group(s). Chain-cut ions are the signature of the positions and numbers of functional groups and double-bonds. The observed chain-cut ion is equivalent to a hypothetical homolytic-segment (cc, cm, mc, or mm) with addition or extraction of up to 2 protons (H). The α-cleavage ions are equivalent to: [cc + H], with H from the hydroxyl through a β-ene or γ-ene rearrangement; [cm - 2H], with 2H from hydroxyls of PD1 through a γ-ene rearrangement, or one H from the hydroxyl and the other H from the α-carbon of mono-HDHA through an α-H-β-ene rearrangement; [mc – H], with H from hydroxyl through a β-ene or γ-ene rearrangement, or from the α-carbon through an α-H-β-ene rearrangement; or [mm] through charge-direct fragmentations. The β-ene or γ-ene facilitates the H shift to γ position and α-cleavage. Deuterium labeling confirmed the assignment of MS/MS ions and the fragmentation mechanisms. Based on the MS/MS spectra and fragmentation mechanisms, we identified RvD1, PD1, and mono-hydroxy-DHA products in human neutrophils and blood, trout head-kidney, and stroke-injury murine brain-tissues. PMID:17055291

  3. The role of MyoD1 and histone modifications in the activation of muscle enhancers

    PubMed Central

    Blum, Roy; Dynlacht, Brian D

    2013-01-01

    MyoD1 is a key regulator that orchestrates skeletal muscle differentiation through the regulation of gene expression. Although many studies have focused on its role in transcriptional control at gene promoters, less is known regarding the role of MyoD1 in the assembly of active enhancers. Here, we discuss novel data that point to the ability of MyoD1 to mediate the assembly of active enhancers that augment the transcription of genes essential for muscle development and lineage specification. Based on genome-wide studies of epigenetic marks that typify active enhancers, we recently identified the compendium of distal regulatory elements that dictate transcriptional programs during myogenesis. Superimposition of MyoD1 binding sites upon the locations of muscle enhancers revealed its unequivocal binding to a core region of nearly a third of condition-specific muscle enhancers. Further studies exploring deposition of enhancer-related epigenetic marks in myoblasts lacking MyoD1 demonstrate the dependence of muscle enhancer assembly on the presence of MyoD1. We propose a model wherein MyoD1 mediates recruitment of Set7, H3K4me1, H3K27ac, p300, and RNAP II to MyoD1-bound enhancers to establish condition-specific activation of muscle genes. Moreover, muscle enhancers are modulated through coordinated binding of transcription factors, including c-Jun, Jdp2, Meis, and Runx1, which are recruited to muscle enhancers in a MyoD1-dependent manner. Thus, MyoD1 and enhancer-associated transcription factors function coordinately to assemble and regulate enhancers, thereby augmenting expression of muscle-related genes. PMID:23880568

  4. Schizophrenia susceptibility gene product dysbindin-1 regulates the homeostasis of cyclin D1.

    PubMed

    Ito, Hidenori; Morishita, Rika; Nagata, Koh-Ichi

    2016-08-01

    Dysbindin-1 (dystrobrevin binding protein-1, DTNBP1) is now widely accepted as a potential schizophrenia susceptibility gene and accumulating evidence indicates its functions in the neural development. In this study, we tried to identify new binding partners for dysbindin-1 to clarify the novel function of this molecule. When consulted with BioGRID protein interaction database, cyclin D3 was found to be a possible binding partner for dysbindin-1. We then examined the interaction between various dysbindin-1 isoforms (dysbindin-1A, -1B and -1C) and all three D-type cyclins (cyclin D1, D2, and D3) by immunoprecipitation with the COS7 cell expression system, and found that dysbindin-1A preferentially interacts with cyclin D1. The mode of interaction between these molecules was considered as direct binding since recombinant dysbindin-1A and cyclin D1 formed a complex in vitro. Mapping analyses revealed that the C-terminal region of dysbindin-1A binds to the C-terminal of cyclin D1. Consistent with the results of the biochemical analyses, endogenous dysbindin-1was partially colocalized with cyclin D1 in NIH3T3 fibroblast cells and in neuronal stem and/or progenitor cells in embryonic mouse brain. While co-expression of dysbindin-1A with cyclin D1 changed the localization of the latter from the nucleus to cytosol, cyclin D1-binding partner CDK4 inhibited the dysbindin-cyclin D1 interaction. Meanwhile, depletion of endogenous dysbindin-1A increased cyclin D1 expression. These results indicate that dysbindin-1A may control the cyclin D1 function spatiotemporally and might contribute to better understanding of the pathophysiology of dysbindin-1-associated disorders. PMID:27130439

  5. Treatment of BG-1 Ovarian Cancer Cells Expressing Estrogen Receptors with Lambda-cyhalothrin and Cypermethrin Caused a Partial Estrogenicity Via an Estrogen Receptor-dependent Pathway

    PubMed Central

    Kim, Cho-Won; Go, Ryeo-Eun

    2015-01-01

    Synthetic pyrethroids (SPs) are the most common pesticides which are recently used for indoor pest control. The widespread use of SPs has resulted in the increased exposure to wild animals and humans. Recently, some SPs are suspected as endocrine disrupting chemicals (EDCs) and have been assessed for their potential estrogenicity by adopting various analyzing assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LC) and cypermethrin (CP), the most commonly used pesticides in Korea, using BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To evaluate the estrogenic activities of two SPs, LC and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT-PCR) in LC or CP treated BG-1 ovarian cancer cells. In MTT assay, LC (10−6 M) and CP (10−5 M) significantly induced the growth of BG-1 cancer cells. LC or CP-induced cell growth was antagonized by addition of ICI 182,720 (10−8 M), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT-PCR results showed that transcriptional level of cyclin D1, a cell cycle-regulating gene, was significantly up-regulated by LC and CP, while these effects were reversed by co-treatment of ICI 182,780. However, p21, a cyclin D-ckd-4 inhibitor gene, was not altered by LC or CP. Moreover, ERα expression was not significantly changed by LC and CP, while downregulated by E2. Finally, in xenografted mouse model transplanted with human BG-1 ovarian cancer cells, E2 significantly increased the tumor volume compare to a negative control, but LC did not. Taken together, these results suggest that LC and CP may possess estrogenic potentials by stimulating the growth of BG-1 ovarian cancer cells via partially ER signaling pathway associated with cell cycle as did E2, but this estrogenic effect was not found in in vivo mouse model. PMID:26877835

  6. 26 CFR 1.1503(d)-1 - Definitions and special rules for filings under section 1503(d).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... section 1503(d). 1.1503(d)-1 Section 1.1503(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Other Rules § 1.1503(d)-1 Definitions and special rules for filings under section 1503(d). (a) In general. This section and §§ 1.1503(d)-2 through 1.1503(d)-8 provide rules concerning the...

  7. 26 CFR 1.1503(d)-1 - Definitions and special rules for filings under section 1503(d).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... section 1503(d). 1.1503(d)-1 Section 1.1503(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Other Rules § 1.1503(d)-1 Definitions and special rules for filings under section 1503(d). (a) In general. This section and §§ 1.1503(d)-2 through 1.1503(d)-8 provide rules concerning the...

  8. 26 CFR 1.1503(d)-1 - Definitions and special rules for filings under section 1503(d).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... section 1503(d). 1.1503(d)-1 Section 1.1503(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Other Rules § 1.1503(d)-1 Definitions and special rules for filings under section 1503(d). (a) In general. This section and §§ 1.1503(d)-2 through 1.1503(d)-8 provide rules concerning the...

  9. 17 CFR 240.11d1-2 - Exemption from section 11(d)(1) for certain investment company securities held by broker-dealers...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemption from section 11(d)(1) for certain investment company securities held by broker-dealers as collateral in margin accounts. 240... margin accounts. Any securities issued by a registered open-end investment company or unit...

  10. 17 CFR 240.11d1-2 - Exemption from section 11(d)(1) for certain investment company securities held by broker-dealers...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Exemption from section 11(d)(1) for certain investment company securities held by broker-dealers as collateral in margin accounts. 240... margin accounts. Any securities issued by a registered open-end investment company or unit...

  11. Structure-affinity relationships of halogenated predicentrine and glaucine derivatives at D1 and D2 dopaminergic receptors: halogenation and D1 receptor selectivity.

    PubMed

    Asencio, Marcelo; Hurtado-Guzmán, Claudio; López, John J; Cassels, Bruce K; Protais, Philippe; Chagraoui, Abdeslam

    2005-06-01

    Halogenation of the aporphine alkaloid boldine at the 3-position leads to increased affinity for rat brain D(1)-like dopaminergic receptors with some selectivity over D(2)-like receptors. A series of 3-halogenated and 3,8-dihalogenated (halogen=Cl, Br or I) derivatives of predicentrine (9-O-methylboldine) and glaucine (2,9-di-O-methylboldine) were prepared and assayed for binding at D(1) and D(2) sites. Halogenation of predicentrine led to strong increases in affinity for D(1)-like receptors, while the affinities for D(2)-like receptors were either practically unchanged or reduced three- to fourfold. Halogenated glaucine derivatives did not show any clear trend towards enhanced selectivity, and the affinities were poor and similar to or worse than the values previously recorded for glaucine itself. Together with earlier work on boldine derivatives, these results suggest that the 2-hydroxy group on the aporphine skeleton may determine a binding mode favoring D(1)-like over D(2)-like receptors, with enhanced affinity when the C-3 position is halogenated. PMID:15862999

  12. Expression of cyclin D1 correlates with malignancy in human ovarian tumours.

    PubMed Central

    Barbieri, F.; Cagnoli, M.; Ragni, N.; Pedullà, F.; Foglia, G.; Alama, A.

    1997-01-01

    Cyclin D1 is a cell cycle regulator of G1 progression that has been suggested to play a relevant role in the pathogenesis of several human cancer types. In the current study, the expression of cyclin D1 has been investigated in a series of 33 patients, with benign (10 patients), borderline (five patients) and malignant (18 patients) ovarian disease. Cyclin D1 protein and mRNA content were analysed by Western blotting and reverse transcriptase polymerase chain reaction respectively. The levels of cyclin D1 protein were undetectable in patients with benign disease, detectable in the majority of patients with borderline disease and elevated in those with ovarian carcinomas, being significantly related to the degree of malignancy (carcinoma vs benign, P = 0.0001; benign vs borderline, P = 0.0238). A significant relationship between cyclin D1 expression and tumour proliferative activity was also found (P = 0.000001). Moreover, eight benign lesions, two borderline tumours and 11 carcinomas proved to be suitable for the analysis of cyclin D1 transcript, and emerging data demonstrated significant agreement between protein abundance and mRNA expression. Results from the current study suggest that cyclin D1 expression is associated with the degree of transformation and most probably plays a role in the early development of ovarian malignancy. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:9155044

  13. D1 dopamine receptor stimulation impairs striatal proteasome activity in Parkinsonism through 26S proteasome disassembly.

    PubMed

    Barroso-Chinea, Pedro; Thiolat, Marie-Laure; Bido, Simone; Martinez, Audrey; Doudnikoff, Evelyne; Baufreton, Jérôme; Bourdenx, Mathieu; Bloch, Bertrand; Bezard, Erwan; Martin-Negrier, Marie-Laure

    2015-06-01

    Among the mechanisms underlying the development of L-dopa-induced dyskinesia (LID) in Parkinson's disease, complex alterations in dopamine signaling in D1 receptor (D1R)-expressing medium spiny striatal neurons have been unraveled such as, but not limited to, dysregulation of D1R expression, lateral diffusion, intraneuronal trafficking, subcellular localization and desensitization, leading to a pathological anchorage of D1R at the plasma membrane. Such anchorage is partly due to a decreased proteasomal activity that is specific of the L-dopa-exposed dopamine-depleted striatum, results from D1R activation and feeds-back the D1R exaggerated cell surface abundance. The precise mechanisms by which L-dopa affects striatal proteasome activity remained however unknown. We here show, in a series of in vitro ex vivo and in vivo models, that such rapid modulation of striatal proteasome activity intervenes through D1R-mediated disassembly of the 26S proteasome rather than change in transcription or translation of proteasome or proteasome subunits intraneuronal relocalization. PMID:25766677

  14. Cytoplasmic sequestration of cyclin D1 associated with cell cycle withdrawal of neuroblastoma cells

    SciTech Connect

    Sumrejkanchanakij, Piyamas; Eto, Kazuhiro; Ikeda, Masa-Aki . E-mail: mikeda.emb@tmd.ac.jp

    2006-02-03

    The regulation of D-type cyclin-dependent kinase activity is critical for neuronal differentiation and apoptosis. We recently showed that cyclin D1 is sequestered in the cytoplasm and that its nuclear localization induces apoptosis in postmitotic primary neurons. Here, we further investigated the role of the subcellular localization of cyclin D1 in cell cycle withdrawal during the differentiation of N1E-115 neuroblastoma cells. We show that cyclin D1 became predominantly cytoplasmic after differentiation. Targeting cyclin D1 expression to the nucleus induced phosphorylation of Rb and cdk2 kinase activity. Furthermore, cyclin D1 nuclear localization promoted differentiated N1E-115 cells to reenter the cell cycle, a process that was inhibited by p16{sup INK4a}, a specific inhibitor of D-type cyclin activity. These results indicate that cytoplasmic sequestration of cyclin D1 plays a role in neuronal cell cycle withdrawal, and suggests that the abrogation of machinery involved in monitoring aberrant nuclear cyclin D1 activity contributes to neuronal tumorigenesis.

  15. Structure and Catalytic Mechanism of Human Steroid 5-Reductase (AKR1D1)

    SciTech Connect

    Costanzo, L.; Drury, J; Christianson, D; Penning, T

    2009-01-01

    Human steroid 5{beta}-reductase (aldo-keto reductase (AKR) 1D1) catalyzes reduction of {Delta}{sup 4}-ene double bonds in steroid hormones and bile acid precursors. We have reported the structures of an AKR1D1-NADP{sup +} binary complex, and AKR1D1-NADP{sup +}-cortisone, AKR1D1-NADP{sup +}-progesterone and AKR1D1-NADP{sup +}-testosterone ternary complexes at high resolutions. Recently, structures of AKR1D1-NADP{sup +}-5{beta}-dihydroprogesterone complexes showed that the product is bound unproductively. Two quite different mechanisms of steroid double bond reduction have since been proposed. However, site-directed mutagenesis supports only one mechanism. In this mechanism, the 4-pro-R hydride is transferred from the re-face of the nicotinamide ring to C5 of the steroid substrate. E120, a unique substitution in the AKR catalytic tetrad, permits a deeper penetration of the steroid substrate into the active site to promote optimal reactant positioning. It participates with Y58 to create a 'superacidic' oxyanion hole for polarization of the C3 ketone. A role for K87 in the proton relay proposed using the AKR1D1-NADP{sup +}-5{beta}-dihydroprogesterone structure is not supported.

  16. Dimerization of Plant Defensin NaD1 Enhances Its Antifungal Activity*

    PubMed Central

    Lay, Fung T.; Mills, Grant D.; Poon, Ivan K. H.; Cowieson, Nathan P.; Kirby, Nigel; Baxter, Amy A.; van der Weerden, Nicole L.; Dogovski, Con; Perugini, Matthew A.; Anderson, Marilyn A.; Kvansakul, Marc; Hulett, Mark D.

    2012-01-01

    The plant defensin, NaD1, from the flowers of Nicotiana alata, is a member of a family of cationic peptides that displays growth inhibitory activity against several filamentous fungi, including Fusarium oxysporum. The antifungal activity of NaD1 has been attributed to its ability to permeabilize membranes; however, the molecular basis of this function remains poorly defined. In this study, we have solved the structure of NaD1 from two crystal forms to high resolution (1.4 and 1.58 Å, respectively), both of which contain NaD1 in a dimeric configuration. Using protein cross-linking experiments as well as small angle x-ray scattering analysis and analytical ultracentrifugation, we show that NaD1 forms dimers in solution. The structural studies identified Lys4 as critical in formation of the NaD1 dimer. This was confirmed by site-directed mutagenesis of Lys4 that resulted in substantially reduced dimer formation. Significantly, the reduced ability of the Lys4 mutant to dimerize correlated with diminished antifungal activity. These data demonstrate the importance of dimerization in NaD1 function and have implications for the use of defensins in agribiotechnology applications such as enhancing plant crop protection against fungal pathogens. PMID:22511788

  17. Cyclin D1 as a universally expressed mantle cell lymphoma-associated tumor antigen for immunotherapy.

    PubMed

    Wang, M; Sun, L; Qian, J; Han, X; Zhang, L; Lin, P; Cai, Z; Yi, Q

    2009-07-01

    Mantle cell lymphoma (MCL) accounts for 5-10% of all non-Hodgkin lymphomas and has the worst prognosis among all lymphomas. The hallmark of MCL is a t(11;14) translocation that results in overexpression of cyclin D1 by tumor cells of virtually all patients. In this study, we examined whether cyclin D1 could be an effective tumor-associated antigen for immunotherapy. We identified cyclin D1 peptides for HLA-A(*)0201 and generated peptide-specific CD8(+) T-cell lines from HLA-A(*)0201(+) blood donors and MCL patients. These cell lines proliferated in response to cyclin D1 peptide-pulsed stimulatory cells. Moreover, the T cells efficiently lysed peptide-pulsed but not unpulsed T2 cells and autologous dendritic cells; cyclin D1(+) and HLA-A(*)0201(+) human MCL lines MINO, SP53, Jeko-1 and Granta 519; and more importantly, HLA-A(*)0201(+) primary lymphoma cells from MCL patients. No killing was observed with HLA-A(*)0201(-) primary lymphoma cells or HLA-A(*)0201(+) normal blood cells, including B cells. These results indicate that these T cells are potent cytotoxic T cells and recognize cyclin D1 peptides naturally presented by patient lymphoma cells in the context of HLA-A(*)0201 molecules. Taken together, our work identifies cyclin D1 as a potentially important antigen for immunotherapy of MCL. PMID:19225534

  18. Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies.

    PubMed

    Levey, A I; Hersch, S M; Rye, D B; Sunahara, R K; Niznik, H B; Kitt, C A; Price, D L; Maggio, R; Brann, M R; Ciliax, B J

    1993-10-01

    Five or more dopamine receptor genes are expressed in brain. However, the pharmacological similarities of the encoded D1-D5 receptors have hindered studies of the localization and functions of the subtypes. To better understand the roles of the individual receptors, antibodies were raised against recombinant D1 and D2 proteins and were shown to bind to the receptor subtypes specifically in Western blot and immunoprecipitation studies. Each antibody reacted selectively with the respective receptor protein expressed both in cells transfected with the cDNAs and in brain. By immunocytochemistry, D1 and D2 had similar regional distributions in rat, monkey, and human brain, with the most intense staining in striatum, olfactory bulb, and substantia nigra. Within each region, however, the precise distributions of each subtype were distinct and often complementary. D1 and D2 were differentially enriched in striatal patch and matrix compartments, in selective layers of the olfactory bulb, and in either substantia nigra pars compacta or reticulata. Electron microscopy demonstrated that D1 and D2 also had highly selective subcellular distributions. In the rat neostriatum, the majority of D1 and D2 immunoreactivity was localized in postsynaptic sites in subsets of spiny dendrites and spine heads in rat neostriatum. Presynaptic D1 and D2 receptors were also observed, indicating both subtypes may regulate neurotransmitter release. D1 was also present in axon terminals in the substantia nigra. These results provide a morphological substrate for understanding the pre- and postsynaptic functions of the genetically defined D1 and D2 receptors in discrete neuronal circuits in mammalian brain. PMID:8415621

  19. Cyclin D1 splice variants: polymorphism, risk, and isoform specific regulation in prostate cancer

    PubMed Central

    Comstock, Clay E.S.; Augello, Michael A.; Benito, Ruth Pe; Karch, Jason; Tran, Thai H.; Utama, Fransiscus E.; Tindall, Elizabeth A.; Wang, Ying; Burd, Craig J.; Groh, Eric M.; Hoang, Hoa N.; Giles, Graham G.; Severi, Gianluca; Hayes, Vanessa M.; Henderson, Brian E.; Marchand, Loic Le; Kolonel, Laurence N.; Haiman, Christopher A.; Baffa, Raffaele; Gomella, Leonard G.; Knudsen, Erik S.; Rui, Hallgeir; Henshall, Susan M.; Sutherland, Robert L.; Knudsen, Karen E.

    2010-01-01

    Purpose Alternative CCND1 splicing results in cyclin D1b, which has specialized, pro-tumorigenic functions in prostate not shared by the cyclin D1a (full-length) isoform. Here, the frequency, tumor relevance, and mechanisms controlling cyclin D1b were challenged. Experimental Design First, relative expression of both cyclin D1 isoforms was determined in prostate adenocarcinomas. Second, relevance of the androgen axis was determined. Third, minigenes were created to interrogate the role of the G/A870 polymorphism (within the splice site), and findings validated in primary tissue. Fourth, impact of G/A870 on cancer risk was assessed in two large case-control studies. Results Cyclin D1b is induced in tumors, and a significant subset expressed this isoform in the absence of detectable cyclin D1a. Accordingly, the isoforms showed non-correlated expression patterns, and hormone status did not alter splicing. While G/A870 was not independently predictive of cancer risk, A870 predisposed for transcript-b production in cells and in normal prostate. The influence of A870 on overall transcript-b levels was relieved in tumors, indicating that aberrations in tumorigenesis likely alter the influence of the polymorphism. Conclusions These studies reveal that cyclin D1b is specifically elevated in prostate tumorigenesis. Cyclin D1b expression patterns are distinct from that observed with cyclin D1a. The A870 allele predisposes for transcript-b production in a context-specific manner. While A870 does not independently predict cancer risk, tumor cells can bypass the influence of the polymorphism. These findings have major implications for the analyses of D-cyclin function in the prostate, and provide the foundation for future studies directed at identifying potential modifiers of the G/A870 polymorphism. PMID:19706803

  20. The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention

    PubMed Central

    Alao, John P

    2007-01-01

    Cyclin D1 is an important regulator of cell cycle progression and can function as a transcriptionl co-regulator. The overexpression of cyclin D1 has been linked to the development and progression of cancer. Deregulated cyclin D1 degradation appears to be responsible for the increased levels of cyclin D1 in several cancers. Recent findings have identified novel mechanisms involved in the regulation of cyclin D1 stability. A number of therapeutic agents have been shown to induce cyclin D1 degradation. The therapeutic ablation of cyclin D1 may be useful for the prevention and treatment of cancer. In this review, current knowledge on the regulation of cyclin D1 degradation is discussed. Novel insights into cyclin D1 degradation are also discussed in the context of ablative therapy. A number of unresolved questions regarding the regulation of cellular cyclin D1 levels are also addressed. PMID:17407548

  1. Synthesis and herbicidal evaluation of novel benzothiazole derivatives as potential inhibitors of D1 protease.

    PubMed

    Huang, Tonghui; Sun, Jie; An, Lin; Zhang, Lixian; Han, Cuiping

    2016-04-01

    D1 protease is a C-terminal processing protease that has been predicted to be an ideal herbicidal target. Three novel series of benzothiazole derivatives were synthesized and evaluated for their herbicidal activities against Brassica napus (rape) and Echinochloa crusgalli (barnyard grass). The preliminary bioassay indicated that most of the synthesized compounds possess promising D1 protease inhibitory activities and considerable herbicidal activities. Molecular docking was performed to position representative compounds into the active site of D1 protease to determine a probable binding model. PMID:26905829

  2. The D1-173 amino acid is a structural determinant of the critical interaction between D1-Tyr161 (TyrZ) and D1-His190 in Photosystem II.

    PubMed

    Sugiura, Miwa; Ozaki, Yui; Nakamura, Masato; Cox, Nicholas; Rappaport, Fabrice; Boussac, Alain

    2014-12-01

    The main cofactors of Photosystem II (PSII) are borne by the D1 and D2 subunits. In the thermophilic cyanobacterium Thermosynechococcus elongatus, three psbA genes encoding D1 are found in the genome. Among the 344 residues constituting the mature form of D1, there are 21 substitutions between PsbA1 and PsbA3, 31 between PsbA1 and PsbA2, and 27 between PsbA2 and PsbA3. In a previous study (Sugiura et al., J. Biol. Chem. 287 (2012), 13336-13347) we found that the oxidation kinetics and spectroscopic properties of TyrZ were altered in PsbA2-PSII when compared to PsbA(1/3)-PSII. The comparison of the different amino acid sequences identified the residues Cys144 and Pro173 found in PsbA1 and PsbA3, as being substituted in PsbA2 by Pro144 and Met173, and thus possible candidates accounting for the changes in the geometry and/or the environment of the TyrZ/His190 phenol/imidizol motif. Indeed, these amino acids are located upstream of the α-helix bearing TyrZ and between the two α-helices bearing TyrZ and its hydrogen-bonded partner, D1/His190. Here, site-directed mutants of PSII, PsbA3/Pro173Met and PsbA2/Met173Pro, were analyzed using X- and W-band EPR and UV-visible time-resolved absorption spectroscopy. The Pro173Met substitution in PsbA2-PSII versus PsbA3-PSII is shown to be the main structural determinant of the previously described functional differences between PsbA2-PSII and PsbA3-PSII. In PsbA2-PSII and PsbA3/Pro173Met-PSII, we found that the oxidation of TyrZ by P680+● was specifically slowed during the transition between S-states associated with proton release. We thus propose that the increase of the electrostatic charge of the Mn4CaO5 cluster in the S2 and S3 states could weaken the strength of the H-bond interaction between TyrZ● and D1/His190 in PsbA2 versus PsbA3 and/or induce structural modification(s) of the water molecules network around TyrZ. PMID:25193561

  3. The new powder diffractometer D1B of the Institut Laue Langevin

    NASA Astrophysics Data System (ADS)

    Puente Orench, I.; Clergeau, J. F.; Martínez, S.; Olmos, M.; Fabelo, O.; Campo, J.

    2014-11-01

    D1B is a medium resolution high flux powder diffractometer located at the Institut Laue Langevin, ILL. D1B a suitable instrument for studying a large variety of polycrystalline materials. D1B runs since 1998 as a CRG (collaborating research group) instrument, being exploited by the CNRS (Centre National de la Recherche Scientifique, France) and CSIC (Consejo Superior de Investigaciones Cientificas, Spain). In 2008 the Spanish CRG started an updating program which included a new detector and a radial oscillating collimator (ROC). The detector, which has a sensitive height of 100mm, covers an angular range of 128°. Its 1280 gold wires provide a neutron detection point every 0.1°. The ROC is made of 198 gadolinium- based absorbing collimation blades, regular placed every 0.67°. Here the present characteristics of D1B are reviewed and the different experimental performances will be presented.

  4. Origin of the Scaling Constant "d" = 1.7 in Item Response Theory.

    ERIC Educational Resources Information Center

    Camilli, Gregory

    1994-01-01

    Describes the scaling constant "d" = 1.702, used in Item Response Theory, which minimizes the maximum difference between the normal and logistic distribution functions. Recapitulates the theoretical and numerical derivation of "d" given by D. Haley (1952). (SLD)

  5. 42 CFR 51d.1 - To what does this subpart apply?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.1 To what does this subpart apply? The... communities created by mental health or substance abuse emergencies, as authorized under section 501(m) of...

  6. 42 CFR 51d.1 - To what does this subpart apply?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.1 To what does this subpart apply? The... communities created by mental health or substance abuse emergencies, as authorized under section 501(m) of...

  7. 42 CFR 51d.1 - To what does this subpart apply?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.1 To what does this subpart apply? The... communities created by mental health or substance abuse emergencies, as authorized under section 501(m) of...

  8. 42 CFR 51d.1 - To what does this subpart apply?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.1 To what does this subpart apply? The... communities created by mental health or substance abuse emergencies, as authorized under section 501(m) of...

  9. 42 CFR 51d.1 - To what does this subpart apply?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.1 To what does this subpart apply? The... communities created by mental health or substance abuse emergencies, as authorized under section 501(m) of...

  10. Diverse functions for the semaphorin receptor PlexinD1 in development and disease

    PubMed Central

    Gay, Carl M.; Zygmunt, Tomasz; Torres-Vázquez, Jesús

    2010-01-01

    SUMMARY Plexins are a family of single pass transmembrane proteins that serve as cell surface receptors for Semaphorins during the embryonic development of animals. Semaphorin-Plexin signaling is critical for many cellular aspects of organogenesis, including cell migration, proliferation and survival. Until recently, little was known about the function of PlexinD1, the sole member of the vertebrate-specific PlexinD (PlxnD1) subfamily. Here we review novel findings about PlxnD1’s roles in the development of the cardiovascular, nervous and immune systems and salivary gland branching morphogenesis and discuss new insights concerning the molecular mechanisms of PlxnD1 activity. PMID:20880496